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    Carlos Hernández
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    31.txt

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    80 views211 pages

    31

    Uploaded by

    Carlos Hernández

    Copyright:

    © All Rights Reserved
    Download as TXT, PDF, TXT or read online from Scribd
    Flag for inappropriate content
    of 211

    var title_f0_31_496="Hemangioma PI";

    var content_f0_31_496=[" <div id=\"graphicsToolbar\">",


    " <div id=\"graphicsCopy\">",
    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
    " </div>",
    " <div id=\"graphicsLinks\">",
    " <a href=\"?imageKey=PI
    %2F87009&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\">",
    " <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
    title=\"Print this page\"/>",
    " </a>",
    " <a class=\"icontxt textLink\" href=\"?imageKey=PI
    %2F87009&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\"
    title=\"Print this page\">",
    " Print",
    " </a>",
    " <a class=\"etacLink\" href=\"#\">",
    " <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
    title=\"Email graphic(s)\"/>",
    " </a>",
    " <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
    " Email",
    " </a>",
    " </div>",
    " </div>",
    " <div class=\"graphic\">",
    " <div class=\"figure\" style=\"width: 470px\">",
    " <div class=\"ttl\">",
    " Hemangioma on lip",
    " </div>",
    " <div class=\"cntnt\" style=\"width: 370px; height: 277px; background-image:
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    " </div>",
    " <div class=\"lgnd\">",
    " This is an example of a hemangioma.",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " Courtesy of Denise W Metry, MD.",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f0_31_496=[""].join("\n");
    var outline_f0_31_496=null;
    var title_f0_31_497="Brooke end ileostomy";
    var content_f0_31_497=[" <div id=\"graphicsToolbar\">",
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    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
    " </div>",
    " <div id=\"graphicsLinks\">",
    " <a href=\"?imageKey=SURG
    %2F72724&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\">",
    " <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
    title=\"Print this page\"/>",
    " </a>",
    " <a class=\"icontxt textLink\" href=\"?imageKey=SURG
    %2F72724&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\"
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    " </a>",
    " <a class=\"etacLink\" href=\"#\">",
    " <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
    title=\"Email graphic(s)\"/>",
    " </a>",
    " <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
    " Email",
    " </a>",
    " </div>",
    " </div>",
    " <div class=\"graphic\">",
    " <div class=\"figure\" style=\"width: 562px\">",
    " <div class=\"ttl\">",
    " End ileostomy (Brooke ileostomy)",
    " </div>",
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    " </div>",
    " <div class=\"lgnd\">",
    " (A) Absorbable sutures are placed full thickness through the distal end of the
    bowel, 2 cm proximally through the seromuscular layer, and then through
    subcuticular space.",
    " <br>",
    " (B) During the tying of the sutures, the distal end is everted unto itself.",
    " <br>",
    " (C) The matured, everted, Brooke end ileostomy with the sutures at the
    mucocutaneous junction.",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " </div>",
    " </br>",
    " </br>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
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    var outline_f0_31_497=null;
    var title_f0_31_498="Subjective global assessment form";
    var content_f0_31_498=[" <div id=\"graphicsToolbar\">",
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    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
    " </div>",
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    " </a>",
    " <a class=\"icontxt textLink\" href=\"?imageKey=GAST
    %2F63581&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=2\" onclick=\"\"
    title=\"Print this page\">",
    " Print",
    " </a>",
    " <a class=\"etacLink\" href=\"#\">",
    " <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
    title=\"Email graphic(s)\"/>",
    " </a>",
    " <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
    " Email",
    " </a>",
    " </div>",
    " </div>",
    " <div class=\"graphic\">",
    " <div class=\"figure\" style=\"width: 615px\">",
    " <div class=\"ttl\">",
    " Evaluation form for subjective global assessment",
    " </div>",
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    k6KpwBiBhnkzyH33GbGT4bzIkS1QTwH1HJIHYexWpaZZ8ncDNDzxiy90wCiQiBQahtFalyAjwo5wE+3nSJ6
    AElsJQCzGOd+GwBKzvA7gLwuyWtRzzUJfBc2Aa/8L+EAIO2M0gqLqZW+tFENB+VvWO6G1ZhiPZMBBa3DNRg
    zW3voX7KO7AahshqFUEqLn0wA0WisQ7fYbjjKSqa+EtDrUWUGevQese5agDa8MyBvyEgOH7oQSXMho6RGOt
    D75BJTeBvmM5aysPUiGughLLhfEq4ae2aCDFuoi0vJ+NfSeH194W9P/4bfXzh//fpTGUH/fSTuD0Ar9c8V2
    htOAQOIQDoMkEH5S6ADL7dA+2XvgRSE4P069L8KalANB+RgBCHkgQ2KUAwh5EUJd3FCXXggCAA7);\">",
    " </div>",
    " <div class=\"lgnd\">",
    " <strong>",
    " (A) Well nourished",
    " </strong>",
    " _____.",
    " <br>",
    " <strong>",
    " (B) Mild/moderate undernutrition",
    " </strong>",
    " _____.",
    " <br>",
    " <strong>",
    " (C) Severe undernutrition",
    " </strong>",
    " _____.",
    " <br>",
    " The subjective global assessment (SGA) score is a subjective score. Each
    medical history and physical examination paramater is rated by the clinician as A
    (well-nourished), B (moderately malnourished), or C (severly malnourished). The
    ratings for each of the parameters are then used as a guide to determine the
    patient's subjecitve SGA score. For example, if a patient has more B or C ratings
    than A ratings, the patient is more likely to be malnourished.",
    " <div class=\"footnotes\">",
    " %: percent.",
    " </div>",
    " <div class=\"reference\">",
    " Reproduced with permission from: Sacks GS, Dearman K, Replogle WH, et al.
    Use of subjective global assessment to identify nutrition-associated complications
    and death in geriatric long-term care facility residents. J Am Coll Nutr 2000;
    19:570. Copyright &copy; 2000 American College of Nutrition.",
    " </div>",
    " </br>",
    " </br>",
    " </br>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f0_31_498=[""].join("\n");
    var outline_f0_31_498=null;
    var title_f0_31_499="Medications for the prevention of breast cancer";
    var content_f0_31_499=[" <h1 id=\"patTopicTitle\">",
    " Patient information: Medications for the prevention of breast cancer (Beyond the
    Basics)",
    " </h1>",
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    " <div>",
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    " <table>",
    " <tr>",
    " <td>",
    " <a class=\"contributor contributor_credentials patTopicContributorsType\"
    href=\"UTD.htm?0/31/499/contributors\">",
    " Authors",
    " </a>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/31/499/contributors\" id=\"au4385\">",
    " Wendy Y Chen, MD, MPH",
    " </a>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/31/499/contributors\" id=\"au4356\">",
    " Graham A Colditz, MD, DrPh",
    " </a>",
    " </td>",
    " <td>",
    " <a class=\"contributor contributor_credentials patTopicContributorsType\"
    href=\"UTD.htm?0/31/499/contributors\">",
    " Section Editor",
    " </a>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/31/499/contributors\" id=\"se4959\">",
    " Daniel F Hayes, MD",
    " </a>",
    " </td>",
    " <td>",
    " <a class=\"contributor contributor_credentials patTopicContributorsType\"
    href=\"UTD.htm?0/31/499/contributors\">",
    " Deputy Editor",
    " </a>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/31/499/contributors\" id=\"de8229\">",
    " Don S Dizon, MD, FACP",
    " </a>",
    " </td>",
    " </tr>",
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    " </div>",
    " <div class=\"rcBottom\">",
    " <div>",
    " </div>",
    " </div>",
    " </div>",
    " <div class=\"patTopicTool\" id=\"patTopicToolTop\">",
    " <a class=\"toolbutton findicon findInPageLink\" href=\"#\" title=\"Find in
    Topic\">",
    " Find",
    " </a>",
    " <a class=\"toolbutton printicon\" href=\"UTD.htm?0/31/499?view=print\"
    title=\"Print This Topic\">",
    " Print",
    " </a>",
    " <script src=\"file://w.sharethis.com/button/sharethis.js#publisher=357881b8-
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    " <div id=\"topicText\">",
    " <p class=\"headingAnchor\" id=\"H1\">",
    " <span class=\"h1\">",
    " INTRODUCTION",
    " </span>",
    " </p>",
    " <p>",
    " Approximately 210,000 women in the United States are newly diagnosed with
    breast cancer each year. Certain risk factors may increase the likelihood that a
    woman will develop breast cancer, including advancing age, a strong family history
    of breast cancer, and having a precancerous breast condition, such as lobular
    carcinoma in situ (LCIS).",
    " </p>",
    " <p>",
    " Based upon a careful risk assessment, healthcare providers sometimes
    recommend therapy with one of several medications to reduce the chance of
    developing breast cancer for women at increased risk. These medications are called
    selective estrogen receptor modulator (SERM), of which there are two: tamoxifen and
    raloxifene. Another group of medications, called the aromatase inhibitors, such as
    exemestane, are also being studied for breast cancer prevention, though none are
    approved for this indication.",
    " </p>",
    " <p>",
    " These medications only work to prevent tumors that are known to be responsive
    to female hormones, which can be identified by the presence of hormone receptors.
    Tumors that have hormone receptors are called either ER-positive (short for
    estrogen-receptor positive) or PR-positive (short for progestin-receptor
    positive).",
    " </p>",
    " <p>",
    " The following is a discussion of studies evaluating the effectiveness of both
    SERMs and aromatase inhibitors for breast cancer prevention in women without a
    history of breast cancer, possible adverse effects of treatment, and information
    about which women should consider taking one of these agents. The role of SERMs and
    the aromatase inhibitors in women with a history of breast cancer is covered
    separately. (See",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?25/52/26437?
    source=see_link\">",
    " \"Patient information: Early stage breast cancer treatment in postmenopausal
    women (Beyond the Basics)\"",
    " </a>",
    " and",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?39/2/39970?
    source=see_link\">",
    " \"Patient information: Early stage breast cancer treatment in premenopausal
    women (Beyond the Basics)\"",
    " </a>",
    " .) &nbsp;",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H2\">",
    " <span class=\"h1\">",
    " HOW DO PREVENTIVE AGENTS WORK?",
    " </span>",
    " </p>",
    " <p>",
    " The preventive agents all work by interfering with the effects of the female
    hormone estrogen. SERMs work by blocking the effects of estrogen on breast tissue.
    Aromatase inhibitors work by blocking an enzyme (aromatase) that is responsible for
    producing estrogen within the body in postmenopausal women (or women after
    menopause).",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H3\">",
    " <span class=\"h1\">",
    " EFFECTIVENESS",
    " </span>",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H14120212\">",
    " <span class=\"h2\">",
    " SERMs",
    " </span>",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H4\">",
    " <span class=\"h3\">",
    " Tamoxifen",
    " </span>",
    " &nbsp;&mdash;&nbsp;Multiple studies have examined the effectiveness of
    tamoxifen for the prevention of breast cancer. Overall, these studies suggest that
    tamoxifen can prevent hormone positive breast cancers from developing in women at
    risk for the disease. In general, tamoxifen, given daily for five years, reduces
    the risk of developing breast cancer by about one-half. Tamoxifen can be used in
    women before and after menopause. &nbsp;",
    " </p>",
    " <p>",
    " Despite the evidence that it reduces the risk of developing breast cancer in
    high-risk women, tamoxifen has not been widely accepted for breast cancer
    prevention. That is largely because there is no evidence that tamoxifen improves
    survival when given as a preventive treatment and because the medication has a
    small risk of serious adverse events, including uterine cancer and blood clots in
    the legs or lungs.",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H5\">",
    " <span class=\"h3\">",
    " Raloxifene",
    " </span>",
    " &nbsp;&mdash;&nbsp;Raloxifene is currently used for the prevention and
    treatment of osteoporosis (low bone density) in postmenopausal women. Several
    studies suggest that in postmenopausal women at high risk of developing breast
    cancer, raloxifene can reduce the risk of developing an invasive hormone-positive
    (ER-positive) breast cancer.",
    " </p>",
    " <p>",
    " In the STAR Breast Cancer Prevention Trial that directly compared tamoxifen
    and raloxifene, raloxifene was slightly less effective than tamoxifen at preventing
    breast cancer. On the other hand, raloxifene was associated with fewer of the most
    serious side effects associated with tamoxifen, including a lower risk of uterine
    cancer. Raloxifene has been tested only in postmenopausal women; its benefit in
    premenopausal women is unknown.",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H6\">",
    " <span class=\"h2\">",
    " Precautions",
    " </span>",
    " &nbsp;&mdash;&nbsp;Tamoxifen and raloxifene are not recommended for some
    women, including those who:",
    " </p>",
    " <p>",
    " <ul class=\"bulletCompact-block\">",
    " <li>",
    " Have a history of blood clots in the legs or lungs (known as &ldquo;deep
    vein thrombosis&rdquo; or &ldquo;pulmonary embolism&rdquo;)",
    " </li>",
    " <li>",
    " Require anticoagulant or blood-thinning medications",
    " </li>",
    " <li>",
    " Smoke",
    " </li>",
    " <li>",
    " Are pregnant, planning on becoming pregnant, or breastfeeding (tamoxifen
    may cause birth defects if taken during pregnancy)",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " Women who use tamoxifen prior to menopause should use a non-hormonal method
    of birth control (such as condoms and a diaphragm), since hormonal methods of birth
    control, such as oral contraceptives, may alter the effectiveness of tamoxifen. A
    woman should immediately notify her doctor if she becomes pregnant while on
    tamoxifen. (See",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?8/60/9157?
    source=see_link\">",
    " \"Patient information: Birth control; which method is right for me? (Beyond
    the Basics)\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Women who use tamoxifen or raloxifene should be closely monitored by their
    healthcare provider. In particular, women should:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Have an annual gynecologic examination, including a breast examination and,
    if recommended, a yearly mammogram and Pap smear (screening of the cervix for
    cancerous or precancerous cells). Any woman who finds a new breast lump should
    speak with her healthcare provider about the need for diagnostic testing
    (mammogram, ultrasound, biopsy).",
    " </li>",
    " <li>",
    " Immediately report any abnormal gynecologic symptoms, such as menstrual
    irregularities, abnormal vaginal bleeding or spotting, staining, or pelvic pressure
    or pain. (See",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?22/18/22820?
    source=see_link\">",
    " \"Patient information: Abnormal uterine bleeding (Beyond the Basics)\"",
    " </a>",
    " .)",
    " </li>",
    " <li>",
    " Seek immediate medical care if they develop signs or symptoms of a blood
    clot, such as calf tenderness, swelling, pain, or severe, unexplained
    breathlessness or a fast heart rate.",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H14120244\">",
    " <span class=\"h2\">",
    " Aromatase inhibitors",
    " </span>",
    " &nbsp;&mdash;&nbsp;Of the aromatase inhibitors used in the treatment of
    breast cancer (ie, anastrazole, letrozole, exemestane), only one trial that looked
    at exemestane has been published. In this trial, exemestane reduced the risk of
    breast cancer by approximately 65 percent. Questions remain as to long-term effects
    of these drugs on bone loss and cardiovascular risk. Furthermore, joint and muscle
    symptoms associated with aromatase inhibitors may limit patient acceptance of this
    medication for preventive purposes. However, none of the aromatase inhibitors,
    including exemestane, are approved for breast cancer prevention.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H8\">",
    " <span class=\"h1\">",
    " SUMMARY",
    " </span>",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H9\">",
    " <span class=\"h2\">",
    " Who should consider medication for breast cancer prevention?",
    " </span>",
    " &nbsp;&mdash;&nbsp;Guidelines from expert groups recommend that the risks and
    benefits of breast cancer prevention be discussed with premenopausal and
    postmenopausal women who are at high risk for the disease [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/499/abstract/1-3\">",
    " 1-3",
    " </a>",
    " ]. Appropriate candidates for breast cancer prevention include the following
    groups: &nbsp;",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Women over the age of 60.",
    " </li>",
    " <li>",
    " Women with certain high-risk conditions found on breast biopsy, such as
    lobular carcinoma in situ (LCIS) or atypical ductal or lobular hyperplasia.",
    " </li>",
    " <li>",
    " Women between the ages of 35 and 59 years who have a calculated five-year
    risk of developing breast cancer of 1.66 percent or higher, according to a system
    called the Gail model. The Gail model uses a woman's current age, age at first
    menstrual period, age at first live birth, the number of first-degree relatives
    with breast cancer, and the number and pathologic findings of any breast biopsies
    to estimate the probability of breast cancer over time.",
    " <br/>",
    " <br/>",
    " A program called the Breast Cancer Risk Assessment Tool is available to
    calculate an individual woman's risk according to the Gail model [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/499/abstract/4\">",
    " 4",
    " </a>",
    " ]. Risk assessment tools such as these were developed for health
    professionals; patients who use them on their own should speak with their clinician
    for help interpreting the results. In addition, the presence of breast cancer risk
    factors does",
    " <strong>",
    " not",
    " </strong>",
    " mean that cancer is inevitable. Many women with risk factors never develop
    breast cancer.",
    " <br/>",
    " <br/>",
    " An important issue is that the Gail model does not consider the risk of
    cancer associated with inherited breast cancer-predisposing genes such as BRCA1 and
    BRCA2. Preliminary data suggest that tamoxifen helps reduce the risk of breast
    cancer in women with BRCA mutations, but benefit may be limited to certain women
    who inherit these mutations. (See",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?30/15/30963?
    source=see_link\">",
    " \"Patient information: Genetic testing for breast and ovarian cancer
    (Beyond the Basics)\"",
    " </a>",
    " .)",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H10\">",
    " <span class=\"h2\">",
    " Choice of agent: tamoxifen, raloxifene, or an aromatase inhibitor?",
    " </span>",
    " </p>",
    " <p>",
    " For women who choose to pursue breast cancer prevention, the choice of agent
    depends on a number of factors, including her menopausal status, the side effects
    expected with each agent, and cost. &nbsp;",
    " </p>",
    " <p>",
    " Postmenopausal women have the choice between tamoxifen or raloxifene. There
    are no studies comparing them against each other as primary prevention. In
    addition, aromatase inhibitors are not approved for primary prevention. Questions
    remain as to long-term effects of an aromatase inhibitor on bone loss and
    cardiovascular risk.",
    " </p>",
    " <p>",
    " If a SERM is chosen, tamoxifen appears to be more effective than raloxifene
    in preventing breast cancer. However, raloxifene has fewer serious side effects.
    Models to assess benefit and risk of tamoxifen versus raloxifene in individual
    women are available. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?43/13/44246?
    source=see_link\">",
    " \"Selective estrogen receptor modulators and aromatase inhibitors for breast
    cancer prevention\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Tamoxifen is the only option for premenopausal women who choose to pursue
    breast cancer prevention. At present, raloxifene is not used for breast cancer
    prevention in premenopausal women because of the lack of data regarding safety in
    this population. In addition, aromatase inhibitors are generally not used in
    premenopausal women because they can actually increase estrogen production in women
    whose ovaries are still producing the hormone.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H11\">",
    " <span class=\"h1\">",
    " WHERE TO GET MORE INFORMATION",
    " </span>",
    " </p>",
    " <p>",
    " Your healthcare provider is the best source of information for questions and
    concerns related to your medical problem.",
    " </p>",
    " <p>",
    " This article will be updated as needed on our web site (",
    " <a class=\"external\" href=\"file://www.uptodate.com/patients\">",
    " www.uptodate.com/patients",
    " </a>",
    " ). Related topics for patients, as well as selected articles written for
    healthcare professionals, are also available. Some of the most relevant are listed
    below.",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H864777681\">",
    " <span class=\"h2\">",
    " Patient level information",
    " </span>",
    " &nbsp;&mdash;&nbsp;UpToDate offers two types of patient education
    materials.",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H5513621\">",
    " <span class=\"h3\">",
    " The Basics",
    " </span>",
    " &nbsp;&mdash;&nbsp;The Basics patient education pieces answer the four or
    five key questions a patient might have about a given condition. These articles are
    best for patients who want a general overview and who prefer short, easy-to-read
    materials.",
    " </p>",
    " <p>",
    " <a class=\"medical medical_basics\" href=\"UTD.htm?26/26/27043?
    source=see_link\">",
    " Patient information: Genetic testing for breast and ovarian cancer (The
    Basics)",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_basics\" href=\"UTD.htm?3/26/3492?
    source=see_link\">",
    " Patient information: Ductal carcinoma in situ (DCIS) (The Basics)",
    " </a>",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H5513629\">",
    " <span class=\"h3\">",
    " Beyond the Basics",
    " </span>",
    " &nbsp;&mdash;&nbsp;Beyond the Basics patient education pieces are longer,
    more sophisticated, and more detailed. These articles are best for patients who
    want in-depth information and are comfortable with some medical jargon.",
    " </p>",
    " <p>",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?43/6/44134?
    source=see_link\">",
    " Patient information: Factors that modify breast cancer risk in women (Beyond
    the Basics)",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?1/29/1491?
    source=see_link\">",
    " Patient information: Bone density testing (Beyond the Basics)",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?24/49/25366?
    source=see_link\">",
    " Patient information: Osteoporosis prevention and treatment (Beyond the
    Basics)",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?12/44/12998?
    source=see_link\">",
    " Patient information: Deep vein thrombosis (DVT) (Beyond the Basics)",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?8/60/9157?
    source=see_link\">",
    " Patient information: Birth control; which method is right for me? (Beyond
    the Basics)",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?22/18/22820?
    source=see_link\">",
    " Patient information: Abnormal uterine bleeding (Beyond the Basics)",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_patient\" href=\"UTD.htm?30/15/30963?
    source=see_link\">",
    " Patient information: Genetic testing for breast and ovarian cancer (Beyond
    the Basics)",
    " </a>",
    " <br/>",
    " </p>",
    " <p class=\"headingAnchor2\" id=\"H864777688\">",
    " <span class=\"h2\">",
    " Professional-level information",
    " </span>",
    " &nbsp;&mdash;&nbsp;Professional level articles are designed to keep doctors
    and other health professionals up-to-date on the latest medical findings. These
    articles are thorough, long, and complex, and they contain multiple references to
    the research on which they are based. Professional level articles are best for
    people who are comfortable with a lot of medical terminology and who want to read
    the same materials their doctors are reading.",
    " </p>",
    " <p>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?28/17/28954?
    source=see_link\">",
    " Factors that modify breast cancer risk in women",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?31/31/32249?
    source=see_link\">",
    " Genetic testing for hereditary breast and ovarian cancer syndrome",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?40/38/41576?
    source=see_link\">",
    " Managing the side effects of tamoxifen",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?17/0/17418?
    source=see_link\">",
    " Management of hereditary breast and ovarian cancer syndrome and patients
    with BRCA mutations",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?11/11/11449?
    source=see_link\">",
    " Postmenopausal hormone therapy and the risk of breast cancer",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?42/63/44025?
    source=see_link\">",
    " Characteristics of hereditary breast and ovarian cancer syndromes",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?40/49/41754?
    source=see_link\">",
    " Screening for breast cancer",
    " </a>",
    " <br/>",
    " <a class=\"medical medical_review\" href=\"UTD.htm?43/13/44246?
    source=see_link\">",
    " Selective estrogen receptor modulators and aromatase inhibitors for breast
    cancer prevention",
    " </a>",
    " <br/>",
    " <br/>",
    " The following organizations also provide reliable health information.",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " People Living With Cancer: The official patient information",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " &nbsp; &nbsp; &nbsp;Web site of the American Society of Clinical Oncology",
    " <br/>",
    " &nbsp; &nbsp; &nbsp;(",
    " <a class=\"external\" href=\"file://www.cancer.net/portal/site/patient\">",
    " www.cancer.net/portal/site/patient",
    " </a>",
    " )",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " National Comprehensive Cancer Network",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " &nbsp; &nbsp; &nbsp;(",
    " <a class=\"external\" href=\"file://www.nccn.com/\">",
    " www.nccn.com",
    " </a>",
    " )",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " National Cancer Institute",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " &nbsp; &nbsp; &nbsp; 1-800-4-CANCER",
    " <br/>",
    " &nbsp; &nbsp; &nbsp; (",
    " <a class=\"external\" href=\"file://www.nci.nih.gov/\">",
    " www.nci.nih.gov",
    " </a>",
    " )",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " American Cancer Society",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " &nbsp; &nbsp; &nbsp; 1-800-ACS-2345",
    " <br/>",
    " &nbsp; &nbsp; &nbsp;(",
    " <a class=\"external\" href=\"file://www.cancer.org/\">",
    " www.cancer.org",
    " </a>",
    " )",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Susan G. Komen Breast Cancer Foundation",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " &nbsp; &nbsp; &nbsp; (",
    " <a class=\"external\" href=\"file://www.komen.org/\">",
    " www.komen.org",
    " </a>",
    " )",
    " </p>",
    " </div>",
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    " <div id=\"literatureReviewDate\">",
    " <span class=\"emphasis\">",
    " Literature review current through:",
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    " Oct 2013.",
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    " </div>",
    " <ol id=\"reference\">",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/499/abstract/1\">",
    " U.S. Preventive Services Task Force. Chemoprevention of breast cancer:
    recommendations and rationale. Ann Intern Med 2002; 137:56.",
    " </a>",
    " </li>",
    " <li>",
    " Guidelines for cancer prevention from the National Comprehensive Cancer
    Network (NCCN) available online at www.nccn.org (Accessed on June 10, 2011).",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/499/abstract/3\">",
    " Visvanathan K, Chlebowski RT, Hurley P, et al. American society of clinical
    oncology clinical practice guideline update on the use of pharmacologic
    interventions including tamoxifen, raloxifene, and aromatase inhibition for breast
    cancer risk reduction. J Clin Oncol 2009; 27:3235.",
    " </a>",
    " </li>",
    " <li>",
    " Breast cancer risk asssessment tool. www.cancer.gov/bcrisktool/ (Accessed on
    March 20, 2012).",
    " </li>",
    " </ol>",
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    " Contents of this article",
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    " <li class=\"plainItem\">",
    " <a href=\"#H1\">",
    " INTRODUCTION",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#H2\">",
    " HOW DO PREVENTIVE AGENTS WORK?",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#H3\">",
    " EFFECTIVENESS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#H8\">",
    " SUMMARY",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#H11\">",
    " WHERE TO GET MORE INFORMATION",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#references\">",
    " REFERENCES",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
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    ;\">",
    " </div>",
    " <div class=\"lgnd\">",
    " A prominent venous pattern on the chest, facial edema, and a plethoric
    appearance is present in this man with SVC obstruction from lung cancer.",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " Reproduced with permission from: Midthun, DE, et al. Clinical presentation of
    lung cancer. Lung Cancer 1996; :421. Copyright &copy; Elsevier Science, Inc.",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f0_31_500=[""].join("\n");
    var outline_f0_31_500=null;
    var title_f0_31_501="Magnesium chloride: Pediatric drug information";
    var content_f0_31_501=[" <noscript>",
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    here to print\">",
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    " <!-- TC:TOPIC_PAGE -->",
    " <div id=\"topicContent\">",
    " <div id=\"drugTitle\">",
    " Magnesium chloride: Pediatric drug information",
    " </div>",
    " <div id=\"lexiTitleImg\">",
    " <img height=\"17\" src=\"./../images/lexiComp/Lexicomp_2012_71x17.myextg\"
    width=\"71\"/>",
    " </div>",
    " <div class=\"clear\">",
    " </div>",
    " <div id=\"drugCopy\">",
    " Copyright 1978-2013 Lexicomp, Inc. All rights reserved.",
    " </div>",
    " <div id=\"topicText\">",
    " (For additional information",
    " <a class=\"drug drug_general\" href=\"UTD.htm?24/22/24933?source=see_link\">",
    " see \"Magnesium chloride: Drug information\"",
    " </a>",
    " and",
    " <a class=\"drug drug_patient\" href=\"UTD.htm?23/28/24004?source=see_link\">",
    " see \"Magnesium chloride: Patient drug information\"",
    " </a>",
    " )",
    " <br/>",
    " For abbreviations and symbols that may be used in Lexicomp (",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?23/39/24183\">",
    " show table",
    " </a>",
    " )",
    " <div class=\"list ubnlist drugH1Div drugBrandNames\" id=\"F190783\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Brand Names: U.S.",
    " </span>",
    " <ul>",
    " <li>",
    " Chloromag&reg;;",
    " </li>",
    " <li>",
    " Mag 64&reg; [OTC];",
    " </li>",
    " <li>",
    " Mag Delay&trade; [OTC];",
    " </li>",
    " <li>",
    " Slow-Mag&reg; [OTC]",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"list_set htclist drugH1Div drugBrandNames\" id=\"F1022932\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Therapeutic Category",
    " </span>",
    " <ul>",
    " <li>",
    " <span class=\"list-set-name\">",
    " Electrolyte Supplement, Oral",
    " </span>",
    " </li>",
    " <li>",
    " <span class=\"list-set-name\">",
    " Electrolyte Supplement, Parenteral",
    " </span>",
    " </li>",
    " <li>",
    " <span class=\"list-set-name\">",
    " Magnesium Salt",
    " </span>",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"block don drugH1Div\" id=\"F11443859\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Neonatal",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Hypomagnesemia: I.V.: Magnesium chloride: 0.2-0.4 mEq/kg/dose every 8-12
    hours for 2-3 doses",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Daily maintenance magnesium: I.V.: 0.25-0.5 mEq magnesium/kg/day (",
    " <b>",
    " Note:",
    " </b>",
    " mEq denotes amount of magnesium ion only not the total salt form.)",
    " </p>",
    " </div>",
    " <div class=\"block dos drugH1Div\" id=\"F1022941\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Usual",
    " </span>",
    " <p>",
    " (For additional information",
    " <a class=\"drug drug_general\" href=\"UTD.htm?24/22/24933?
    source=see_link\">",
    " see \"Magnesium chloride: Drug information\"",
    " </a>",
    " )",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Hypomagnesemia: Children:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;\">",
    " I.M., I.V.: Magnesium chloride: 0.2-0.4 mEq/kg/dose every 4-6 hours for 3-4
    doses; maximum single dose: 16 mEq",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;\">",
    " Oral:",
    " <b>",
    " Note:",
    " </b>",
    " Achieving optimal magnesium levels using oral therapy may be difficult due to
    the propensity for magnesium to cause diarrhea; I.V. replacement may be more
    appropriate particularly in situations of severe deficit:",
    " <b>",
    " Magnesium chloride:",
    " </b>",
    " 10-20 mg/kg elemental magnesium per dose up to 4 times/day",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Dietary supplement: Adults: Oral: (Mag 64&reg;, Mag Delay&trade;, Slow-
    Mag&reg;): 2 tablets once daily",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Daily maintenance magnesium: I.V.: Magnesium chloride:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;\">",
    " Infants and Children &le;45 kg: 0.25-0.5 mEq/kg/day",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;\">",
    " Adolescents &gt;45 kg and Adults: 0.2-0.5 mEq/kg/day or 3-10 mEq/1000
    kcal/day (maximum: 8-20 mEq/day)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " <b>",
    " Dosing adjustment in renal impairment:",
    " </b>",
    " Patients in severe renal failure should not receive magnesium due to toxicity
    from accumulation. Patients with a Cl",
    " <sub>",
    " cr",
    " </sub>",
    " &lt;25 mL/minute receiving magnesium should have serum magnesium levels
    monitored.",
    " </p>",
    " </div>",
    " <div class=\"block foc drugH1Div\" id=\"F190777\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosage Forms: U.S.",
    " </span>",
    " <p style=\"text-indent:0em;text-align:justify;display:inline\">",
    " Excipient information presented when available (limited, particularly for
    generics); consult specific product labeling.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Injection, solution, as hexahydrate: 200 mg/mL (50 mL) [equivalent to
    elemental magnesium 1.97 mEq/mL]",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Chloromag&reg;: 200 mg/mL (50 mL) [contains aluminum, benzyl alcohol;
    equivalent to elemental magnesium 1.97 mEq/mL]",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Tablet, delayed release, enteric coated, oral:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Mag 64&reg;: Elemental magnesium 64 mg [sugar free; contains elemental
    calcium 112 mg]",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Mag Delay&trade;: Elemental magnesium 64 mg [contains elemental calcium 112
    mg]",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Tablet, enteric coated, oral:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Slow-Mag&reg;: Elemental magnesium 71.5 mg [contains elemental calcium 119
    mg]",
    " </p>",
    " </div>",
    " <div class=\"block geq drugH1Div\" id=\"F190767\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Generic Equivalent Available: U.S.",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Yes",
    " </p>",
    " </div>",
    " <div class=\"block adm drugH1Div\" id=\"F3416485\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Administration",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Oral: Tablet: Take with full glass of water; do not chew or crush sustained
    release formulations",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Parenteral: Intermittent infusion: Dilute to a concentration of 0.5 mEq/mL
    (maximum concentration: 1.6 mEq/mL, and infuse over 2-4 hours; do not exceed 1
    mEq/kg/hour; in severe circumstances, half of the dosage to be administered may be
    infused over the first 15-20 minutes",
    " </p>",
    " </div>",
    " <div class=\"block use drugH1Div\" id=\"F1022933\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Use",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Treatment and prevention of hypomagnesemia; dietary supplement",
    " </p>",
    " </div>",
    " <div class=\"block arm drugH1Div\" id=\"F190795\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Adverse Reactions",
    " </span>",
    " <p style=\"text-indent:0em;text-align:justify;display:inline\">",
    " Gastrointestinal: Diarrhea (excessive oral doses)",
    " </p>",
    " </div>",
    " <div class=\"block coi drugH1Div\" id=\"F3416478\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Contraindications",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Hypersensitivity to magnesium salt(s) or any component; serious renal
    impairment, myocardial damage, heart block; patients with colostomy or ileostomy,
    intestinal obstruction, impaction, or perforation, appendicitis, abdominal pain",
    " </p>",
    " </div>",
    " <div class=\"block pre drugH1Div\" id=\"F3416480\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Precautions",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Use with caution in patients with impaired renal function (accumulation of
    magnesium may lead to magnesium intoxication); use with caution in digitalized
    patients (may alter cardiac conduction leading to heart block). The parenteral
    product may contain aluminum; toxic aluminum concentrations may be seen with high
    doses, prolonged use, or renal dysfunction. Premature neonates are at higher risk
    due to immature renal function and aluminum intake from other parenteral sources.
    Parenteral aluminum exposure of &gt;4-5 mcg/kg/day is associated with CNS and bone
    toxicity and tissue loading may occur at lower doses.",
    " </p>",
    " </div>",
    " <div class=\"block war drugH1Div\" id=\"F3416479\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Warnings",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Multiple salt forms of magnesium exist; close attention must be paid to the
    salt form when ordering and administering magnesium;",
    " <b>",
    " incorrect selection or substitution of one salt for another without proper
    dosage adjustment may result in serious over- or under-dosing",
    " </b>",
    " </p>",
    " <p style=\"text-indent:0em;margin-top:2em;\">",
    " Magnesium chloride injection contains benzyl alcohol which may cause allergic
    reactions in susceptible individuals; large amounts of benzyl alcohol (&ge;99
    mg/kg/day) have been associated with a potentially fatal toxicity (&ldquo;gasping
    syndrome&rdquo;) in neonates; the &ldquo;gasping syndrome&rdquo; consists of
    metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction
    (including convulsions, intracranial hemorrhage), hypotension and cardiovascular
    collapse; avoid or use magnesium chloride injection with caution in neonates",
    " </p>",
    " </div>",
    " <div class=\"block cyt drugH1Div\" id=\"F13299630\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Metabolism/Transport Effects",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " None known.",
    " </p>",
    " </div>",
    " <div class=\"block dri drugH1Div\" id=\"F3011375\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Drug Interactions",
    " </span>",
    " <br/>",
    " <br/>",
    " <div class=\"lexi\" id=\"lexiInteractAddInfo\">",
    " (For additional information:",
    " <a class=\"dip\" href=\"./drug-interaction\" target=\"_blank\">",
    " Launch Lexi-Interact&trade; Drug Interactions Program",
    " </a>",
    " )",
    " </div>",
    " <div class=\"lexi\" id=\"lexiInteractImgB\">",
    " <img border=\"0\" height=\"17\"
    src=\"./../images/lexiComp/Lexicomp_2012_71x17.myextg\" width=\"71\"/>",
    " </div>",
    " <div class=\"clear\">",
    " </div>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Alfacalcidol: May increase the serum concentration of Magnesium Salts.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Bisphosphonate Derivatives: Magnesium Salts may decrease the serum
    concentration of Bisphosphonate Derivatives. Management: Avoid administration of
    oral magnesium salts within: 2 hours before or after
    tiludronate/clodronate/etidronate; 60 minutes after oral ibandronate; or 30 minutes
    after alendronate/risedronate.",
    " <b>",
    " Exceptions:",
    " </b>",
    " Pamidronate; Zoledronic Acid.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Calcitriol: May increase the serum concentration of Magnesium Salts.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Calcium Channel Blockers: May enhance the adverse/toxic effect of Magnesium
    Salts. Magnesium Salts may enhance the hypotensive effect of Calcium Channel
    Blockers.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Deferiprone: Magnesium Salts may decrease the serum concentration of
    Deferiprone. Management: Separate administration of deferiprone and oral
    medications or supplements that contain polyvalent cations by at least 4 hours.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Eltrombopag: Magnesium Salts may decrease the serum concentration of
    Eltrombopag. Management: Separate administration of eltrombopag and any polyvalent
    cation (e.g., magnesium-containing products) by at least 4 hours.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Mycophenolate: Magnesium Salts may decrease the serum concentration of
    Mycophenolate. Management: Separate doses of mycophenolate and oral magnesium
    salts. Monitor for reduced effects of mycophenolate if taken concomitant with oral
    magnesium salts.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Neuromuscular-Blocking Agents: Magnesium Salts may enhance the neuromuscular-
    blocking effect of Neuromuscular-Blocking Agents.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Phosphate Supplements: Magnesium Salts may decrease the serum concentration
    of Phosphate Supplements. Management: Administer oral phosphate supplements at
    least 1 hour before, or 2 hours after, oral magnesium salt administration.",
    " <b>",
    " Exceptions:",
    " </b>",
    " Potassium Phosphate.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Quinolone Antibiotics: Magnesium Salts may decrease the absorption of
    Quinolone Antibiotics. Of concern only with oral administration of both agents.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Tetracycline Derivatives: Magnesium Salts may decrease the absorption of
    Tetracycline Derivatives. Only applicable to oral preparations of each agent.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Trientine: Magnesium Salts may decrease the serum concentration of Trientine.
    Trientine may decrease the serum concentration of Magnesium Salts.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " </div>",
    " <div class=\"block prf drugH1Div\" id=\"F190774\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pregnancy Risk Factor",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " C (",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?16/42/17068\">",
    " show table",
    " </a>",
    " )",
    " </p>",
    " </div>",
    " <div class=\"block pri drugH1Div\" id=\"F3011366\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pregnancy Implications",
    " </span>",
    " <p style=\"text-indent:0em;text-align:justify;display:inline\">",
    " Animal reproduction studies have not been conducted. Magnesium crosses the
    placenta; serum levels in the fetus correlate with those in the mother (Idama,
    1998; Osada, 2002).",
    " </p>",
    " </div>",
    " <div class=\"block mop drugH1Div\" id=\"F3416486\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Monitoring Parameters",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Serum magnesium, deep tendon reflexes, respiratory rate, renal function,
    blood pressure, stool output (laxative use)",
    " </p>",
    " </div>",
    " <div class=\"block rer drugH1Div\" id=\"F1022940\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Reference Range",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Neonates and Infants: 1.5-2.3 mEq/L",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Children: 1.5-2.0 mEq/L",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Adults: 1.4-2.0 mEq/L",
    " </p>",
    " </div>",
    " <div class=\"block pha drugH1Div\" id=\"F3416482\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Mechanism of Action",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Magnesium is important as a cofactor in many enzymatic reactions in the body.
    There are at least 300 enzymes which are dependent upon magnesium for normal
    functioning. Actions on lipoprotein lipase have been found to be important in
    reducing serum cholesterol. Magnesium is necessary for the maintaining of serum
    potassium and calcium levels due to its effect on the renal tubule. In the heart,
    magnesium acts as a calcium channel blocker. It also activates sodium potassium
    ATPase in the cell membrane to promote resting polarization and produce
    arrhythmias.",
    " </p>",
    " </div>",
    " <div class=\"block phk drugH1Div\" id=\"F3416484\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pharmacokinetics (Adult data unless noted)",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Absorption: Oral: Up to 30%",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Elimination: Renal with unabsorbed drug excreted in feces",
    " </p>",
    " </div>",
    " <div class=\"block adi drugH1Div\" id=\"F3426352\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Additional Information",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Magnesium chloride 500 mg = 59 mg",
    " <b>",
    " elemental",
    " </b>",
    " magnesium= 4.9 mEq magnesium",
    " </p>",
    " <table border=\"1\" frame=\"border\" rules=\"all\">",
    " <caption style=\"text-align:center;\">",
    " Elemental Magnesium Content of Magnesium Salts",
    " </caption>",
    " <col align=\"left\" width=\"190\">",
    " </col>",
    " <col align=\"center\" width=\"150\">",
    " </col>",
    " <col align=\"center\" width=\"160\">",
    " </col>",
    " <thead valign=\"middle\">",
    " <tr>",
    " <th align=\"center\">",
    " <p style=\"text-indent:0em;\">",
    " Magnesium Salt",
    " </p>",
    " </th>",
    " <th align=\"center\">",
    " <p style=\"text-indent:0em;\">",
    " Elemental Magnesium",
    " </p>",
    " <p style=\"text-indent:0em;\">",
    " (mg/500 mg salt)",
    " </p>",
    " </th>",
    " <th align=\"center\">",
    " <p style=\"text-indent:0em;\">",
    " Magnesium",
    " </p>",
    " <p style=\"text-indent:0em;\">",
    " (mEq/500 mg salt)",
    " </p>",
    " </th>",
    " </tr>",
    " </thead>",
    " <tbody valign=\"middle\">",
    " <tr>",
    " <td align=\"left\">",
    " <p style=\"text-indent:0em;\">",
    " Magnesium chloride",
    " </p>",
    " </td>",
    " <td align=\"center\">",
    " <p style=\"text-indent:0em;\">",
    " 59",
    " </p>",
    " </td>",
    " <td align=\"center\">",
    " <p style=\"text-indent:0em;\">",
    " 4.9",
    " </p>",
    " </td>",
    " </tr>",
    " <tr>",
    " <td align=\"left\">",
    " <p style=\"text-indent:0em;\">",
    " Magnesium gluconate",
    " </p>",
    " </td>",
    " <td align=\"center\">",
    " <p style=\"text-indent:0em;\">",
    " 27",
    " </p>",
    " </td>",
    " <td align=\"center\">",
    " <p style=\"text-indent:0em;\">",
    " 2.4",
    " </p>",
    " </td>",
    " </tr>",
    " <tr>",
    " <td align=\"left\">",
    " <p style=\"text-indent:0em;\">",
    " Magnesium L-aspartate",
    " </p>",
    " </td>",
    " <td align=\"center\">",
    " <p style=\"text-indent:0em;\">",
    " 49.6",
    " </p>",
    " </td>",
    " <td align=\"center\">",
    " <p style=\"text-indent:0em;\">",
    " 4.1",
    " </p>",
    " </td>",
    " </tr>",
    " <tr>",
    " <td align=\"left\">",
    " <p style=\"text-indent:0em;\">",
    " Magnesium oxide",
    " </p>",
    " </td>",
    " <td align=\"center\">",
    " <p style=\"text-indent:0em;\">",
    " 302",
    " </p>",
    " </td>",
    " <td align=\"center\">",
    " <p style=\"text-indent:0em;\">",
    " 25",
    " </p>",
    " </td>",
    " </tr>",
    " <tr>",
    " <td align=\"left\">",
    " <p style=\"text-indent:0em;\">",
    " Magnesium sulfate",
    " </p>",
    " </td>",
    " <td align=\"center\">",
    " <p style=\"text-indent:0em;\">",
    " 49.3",
    " </p>",
    " </td>",
    " <td align=\"center\">",
    " <p style=\"text-indent:0em;\">",
    " 4.1",
    " </p>",
    " </td>",
    " </tr>",
    " </tbody>",
    " </table>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Adverse effects associated with elevated serum magnesium concentrations may
    include:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;\">",
    " &gt;3 mg/dL: Blocked peripheral neuromuscular transmission leading to
    anticonvulsant effects, depressed CNS",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;\">",
    " &gt;5 mg/dL: Depressed deep tendon reflexes, flushing, somnolence",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;\">",
    " &gt;12 mg/dL: Complete heart block, respiratory paralysis",
    " </p>",
    " </div>",
    " </div>",
    " <div id=\"topicAgreement\">",
    " Use of UpToDate is subject to the",
    " <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
    target=\"_blank\">",
    " Subscription and License Agreement",
    " </a>",
    " .",
    " </div>",
    " <div class=\"headingAnchor\" id=\"references\">",
    " <h1>",
    " REFERENCES",
    " </h1>",
    " <ol id=\"reference\">",
    " <li>",
    " <div class=\"reference\">",
    " Department Health &amp; Human Services, Food Drug Administration, \"Aluminum
    in Large and Small Volume Parenterals Used in Total Parenteral Nutrition,\"",
    " <i>",
    " Federal Register",
    " </i>",
    " , 2000, 65(17):4103-11.",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Idama TO and Lindow SW, &ldquo;Magnesium Sulphate: A Review of Clinical
    Pharmacology Applied to Obstetrics,&rdquo;",
    " <i>",
    " Br J Obstet Gynaecol",
    " </i>",
    " , 1998, 105(3):260-8.",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " IOM (Institute of Medicine),",
    " <i>",
    " Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D,
    and Fluoride",
    " </i>",
    " , National Academy of Sciences, Washington, DC, 1997.",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Osada H, Watanabe Y, Nishimura Y, at al, \"Profile of Trace Element
    Concentrations in the Feto-Placental Unit in Relation to Fetal Growth,\"",
    " <i>",
    " Acta Obstet Gynecol Scand",
    " </i>",
    " , 2002, 81(10):931-7.",
    " <span class=\"pubmed-id\">",
    " [PubMed",
    " <a href=\"UTD.htm?0/31/501/abstract-text/12366483/pubmed\" id=\"12366483\"
    target=\"_blank\">",
    " 12366483",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " </ol>",
    " </div>",
    " <div id=\"topicVersionRevision\">",
    " Topic 12976 Version 39.0",
    " </div>",
    " </div>",
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    " <h1>",
    " TOPIC OUTLINE",
    " </h1>",
    " <div id=\"outline\">",
    " <ul>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F190783\">",
    " Brand Names: U.S.",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F1022932\">",
    " Therapeutic Category",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F11443859\">",
    " Dosing: Neonatal",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F1022941\">",
    " Dosing: Usual",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F190777\">",
    " Dosage Forms: U.S.",
    " </a>",
    " </li>",
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    " <a class=\"outlineLink\" href=\"#F190767\">",
    " Generic Equivalent Available: U.S.",
    " </a>",
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    " Administration",
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    " <a class=\"outlineLink\" href=\"#F1022933\">",
    " Use",
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    " <a class=\"outlineLink\" href=\"#F190795\">",
    " Adverse Reactions",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F3416478\">",
    " Contraindications",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F3416480\">",
    " Precautions",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F3416479\">",
    " Warnings",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F13299630\">",
    " Metabolism/Transport Effects",
    " </a>",
    " </li>",
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    " <a class=\"outlineLink\" href=\"#F3011375\">",
    " Drug Interactions",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F190774\">",
    " Pregnancy Risk Factor",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F3011366\">",
    " Pregnancy Implications",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F3416486\">",
    " Monitoring Parameters",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F1022940\">",
    " Reference Range",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F3416482\">",
    " Mechanism of Action",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F3416484\">",
    " Pharmacokinetics (Adult data unless noted)",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F3426352\">",
    " Additional Information",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#references\">",
    " REFERENCES",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " <div class=\"openRelatedGraphics\" id=\"DRUG_PED/12976\"
    rel=\"outline_link\">",
    " GRAPHICS",
    " <a class=\"graphics_icon\" href=\"#\" title=\"View All Related Graphics\">",
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    " </a>",
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    " TABLES",
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    " </li>",
    " <li class=\"bulletItem\">",
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    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " RELATED TOPICS",
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    " <ul>",
    " <li class=\"plainItem\">",
    " <a class=\"drug drug_general\" href=\"UTD.htm?24/22/24933?
    source=related_link\">",
    " Magnesium chloride: Drug information",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"drug drug_patient\" href=\"UTD.htm?23/28/24004?
    source=related_link\">",
    " Magnesium chloride: Patient drug information",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " </div>"].join("\n");
    var title_f0_31_502="Diuretic-induced hyponatremia";
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    " <div id=\"topicContent\">",
    " <div id=\"topicTitle\">",
    " Diuretic-induced hyponatremia",
    " </div>",
    " <div id=\"topicContributors\">",
    " <div>",
    " <a id=\"authors\">",
    " </a>",
    " <a class=\"contributor contributor_credentials contributorType\"
    href=\"UTD.htm?0/31/502/contributors\">",
    " Author",
    " </a>",
    " <br/>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/31/502/contributors\">",
    " Richard H Sterns, MD",
    " </a>",
    " <br/>",
    " </div>",
    " <div>",
    " <a class=\"contributor contributor_credentials contributorType\"
    href=\"UTD.htm?0/31/502/contributors\">",
    " Section Editor",
    " </a>",
    " <br/>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/31/502/contributors\">",
    " Michael Emmett, MD",
    " </a>",
    " <br/>",
    " </div>",
    " <div>",
    " <a class=\"contributor contributor_credentials contributorType\"
    href=\"UTD.htm?0/31/502/contributors\">",
    " Deputy Editor",
    " </a>",
    " <br/>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/31/502/contributors\">",
    " John P Forman, MD, MSc",
    " </a>",
    " <br/>",
    " </div>",
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    " <div id=\"disclosures\">",
    " <a href=\"UTD.htm?0/31/502/contributor-disclosure\" target=\"_blank\">",
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    " peer review process",
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    " is complete.",
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    " <span class=\"emphasis\">",
    " Literature review current through:",
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    " Oct 2013.",
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    " This topic last updated:",
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    " Sep 26, 2012.",
    " </div>",
    " <div id=\"topicText\">",
    " <p class=\"headingAnchor\" id=\"H1\">",
    " <span class=\"h1\">",
    " INTRODUCTION",
    " </span>",
    " &nbsp;&mdash;&nbsp;Hyponatremia is an occasional but potentially fatal
    complication of diuretic therapy. Virtually all cases of severe diuretic-induced
    hyponatremia have been due to a thiazide-type diuretic [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/502/abstract/1-7\">",
    " 1-7",
    " </a>",
    " ]. A loop diuretic is much less likely to induce this problem unless the
    diuretic has induced volume depletion [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/502/abstract/8\">",
    " 8",
    " </a>",
    " ] or water intake is very high (since loop diuretics partially impair urinary
    diluting capacity).",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H2\">",
    " <span class=\"h1\">",
    " PATHOGENESIS",
    " </span>",
    " &nbsp;&mdash;&nbsp;The difference in hyponatremic risk between thiazide-type
    and loop diuretics may be related to differences in their tubular site of action.
    (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?38/13/39128?
    source=see_link\">",
    " \"Mechanism of action of diuretics\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Loop diuretics inhibit sodium chloride (NaCl) reabsorption in the thick
    ascending limb of the loop of Henle. The reabsorption of NaCl without water in the
    medullary aspect of this segment is normally the first step in the generation of
    the hyperosmotic gradient in the medullary interstitium. In the presence of
    antidiuretic hormone (ADH), the highly concentrated interstitium allows water to be
    reabsorbed in the medullary collecting tubule down the favorable osmotic gradient
    between the tubular lumen and the interstitium, resulting in the excretion of a
    concentrated urine.",
    " <br/>",
    " <br/>",
    " Administration of a loop diuretic interferes with this process by impairing
    the accumulation of NaCl in the medulla. Thus, although the loop diuretic can
    increase ADH levels by inducing volume depletion, responsiveness to ADH is reduced
    because of the impairment in the medullary gradient [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/502/abstract/9\">",
    " 9",
    " </a>",
    " ]. As a result, water retention and the development of hyponatremia will be
    limited, unless distal delivery is very low or water intake is very high.",
    " </li>",
    " <li>",
    " The thiazides, in comparison, act in the cortex in the distal tubule; as a
    result, they do not interfere with medullary function or with ADH-induced water
    retention. In addition, in vitro data indicate that thiazides increase water
    permeability and water reabsorption in the inner medullary collecting duct, an
    effect that is independent of ADH [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/502/abstract/10\">",
    " 10",
    " </a>",
    " ]. In addition to water retention, the combination of increased sodium and
    potassium excretion (due to the diuretic) and enhanced water reabsorption (due to
    ADH) can result in the excretion of urine with a sodium plus potassium
    concentration higher than that of the plasma [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/502/abstract/3\">",
    " 3",
    " </a>",
    " ]. Loss of this fluid can directly promote the development of hyponatremia
    independent of the degree of water intake. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?2/52/2886?
    source=see_link&amp;anchor=H5#H5\">",
    " \"Chapter 9B: Renal water excretion and reabsorption\", section on
    'Electrolyte-free water reabsorption'",
    " </a>",
    " .)",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " As with other diuretic-induced fluid and electrolyte complications,
    hyponatremia often develops within the",
    " <strong>",
    " first one to two weeks of therapy",
    " </strong>",
    " if diuretic dose and dietary intake remain relatively constant (",
    " <a class=\"graphic graphic_figure graphicRef74940 \" href=\"UTD.htm?
    15/33/15901\">",
    " figure 1",
    " </a>",
    " ) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/502/abstract/1,3,11\">",
    " 1,3,11",
    " </a>",
    " ]. After this period, the patient is in a new steady state in which further
    sodium and water losses do not occur. However, in many patients with diuretic-
    induced hyponatremia, the disorder first appears after many months of uncomplicated
    thiazide therapy [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/502/abstract/5,12\">",
    " 5,12",
    " </a>",
    " ]. In these patients, perturbation of the steady state, such as an acute
    gastrointestinal or respiratory illness, an increase in diuretic dose, or the
    development of heart failure, may explain the hyponatremia. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?6/45/6868?
    source=see_link\">",
    " \"Time course of loop and thiazide diuretic-induced electrolyte
    complications\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " The reproducibility of thiazide-induced hyponatremia was evaluated in a study
    of 11 elderly patients with a history of thiazide-induced hyponatremia to below
    130",
    " <span class=\"nowrap\">",
    " meq/L",
    " </span>",
    " [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/502/abstract/2\">",
    " 2",
    " </a>",
    " ]. Rechallenge with a single 50 mg dose of",
    " <a class=\"drug drug_general\" href=\"UTD.htm?8/4/8263?source=see_link\">",
    " hydrochlorothiazide",
    " </a>",
    " lowered the plasma sodium concentration by 5 to 6",
    " <span class=\"nowrap\">",
    " meq/L",
    " </span>",
    " in the first six hours [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/502/abstract/2\">",
    " 2",
    " </a>",
    " ]. A more pronounced effect was noted in another study of two elderly patients
    who had recovered from episodes of severe thiazide-induced hyponatremia (serum
    sodiums of 109 and 116",
    " <span class=\"nowrap\">",
    " meq/L)",
    " </span>",
    " [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/502/abstract/3\">",
    " 3",
    " </a>",
    " ]. Rechallenge with either",
    " <a class=\"drug drug_general\" href=\"UTD.htm?1/32/1542?source=see_link\">",
    " metolazone",
    " </a>",
    " (10",
    " <span class=\"nowrap\">",
    " mg/day)",
    " </span>",
    " or hydrochlorothiazide (100",
    " <span class=\"nowrap\">",
    " mg/day)",
    " </span>",
    " resulted in a decrease in serum sodium from 142 to 124",
    " <span class=\"nowrap\">",
    " meq/L",
    " </span>",
    " in 36 hours in one patient, and from 133 to 120",
    " <span class=\"nowrap\">",
    " meq/L",
    " </span>",
    " in 37 hours in the other patient [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/502/abstract/3\">",
    " 3",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H1983318\">",
    " <span class=\"h2\">",
    " Increased water intake",
    " </span>",
    " &nbsp;&mdash;&nbsp;Many patients with thiazide-induced hyponatremia appear to
    have an underlying tendency to increased water intake (polydipsia). As an example,
    a study of 11 elderly patients with thiazide-induced hyponatremia and 10 healthy
    controls found that both the pre-thiazide serum sodium concentration (mean 138
    versus 141",
    " <span class=\"nowrap\">",
    " meq/L)",
    " </span>",
    " and the urine osmolality (306 versus 513",
    " <span class=\"nowrap\">",
    " mosmol/kg)",
    " </span>",
    " were lower in those who developed hyponatremia [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/502/abstract/2\">",
    " 2",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H4\">",
    " <span class=\"h2\">",
    " Impaired water excretion",
    " </span>",
    " &nbsp;&mdash;&nbsp;In most patients, increased water intake will not lead to
    hyponatremia unless there is an impairment in water excretion. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?3/30/3562?
    source=see_link\">",
    " \"Causes of hyponatremia\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " At least four different mechanisms may contribute to diuretic-induced
    hyponatremia:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Volume depletion can stimulate the release of ADH, leading to the production
    of a concentrated urine [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/502/abstract/1,3,8\">",
    " 1,3,8",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " Enhanced ADH release may be a secondary event induced by nausea and other
    neurologic symptoms.",
    " </li>",
    " <li>",
    " Thiazide diuretics may be associated with water retention that is
    independent of ADH [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/502/abstract/10\">",
    " 10",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " Patients treated with diuretics may have a reduced glomerular filtration
    rate. This is a common contributor in the elderly. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?35/45/36570?
    source=see_link&amp;anchor=H20658511#H20658511\">",
    " \"Assessment of kidney function\", section on 'Change in GFR with aging'",
    " </a>",
    " .)",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " Elderly patients generally have a reduced ability to excrete a water load, an
    effect that is most prominent in those who have previously developed thiazide-
    induced hyponatremia [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/502/abstract/13\">",
    " 13",
    " </a>",
    " ]. Why this occurs is not clear, but decreased intrarenal generation of
    prostaglandins may be important [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/502/abstract/13\">",
    " 13",
    " </a>",
    " ]. A defect in water excretion due to prostaglandin deficiency would be
    amplified by thiazides, since the reabsorption of NaCl without water at the
    thiazide-sensitive site in the distal tubule normally lowers the urine osmolality.
    However, this mechanism would not explain the seeming rarity of hyponatremia with
    loop diuretics, which also inhibit urinary dilution. Perhaps the shorter duration
    of action of the loop diuretics protects against hyponatremia.",
    " </p>",
    " <p>",
    " Retention of water as a primary event can explain why many patients with
    thiazide-induced hyponatremia behave as if they are volume expanded: the body
    weight may initially increase [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/502/abstract/2\">",
    " 2",
    " </a>",
    " ]; the blood urea nitrogen and plasma creatinine concentration are generally
    low-normal [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/502/abstract/4,14\">",
    " 4,14",
    " </a>",
    " ]; and hypouricemia due to enhanced urinary uric acid excretion may be present
    [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/502/abstract/8,14\">",
    " 8,14",
    " </a>",
    " ]. All of these findings are similar to those in the syndrome of inappropriate
    ADH secretion (SIADH), which is also associated with initial volume expansion.
    (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?21/20/21832?
    source=see_link\">",
    " \"Evaluation of the patient with hyponatremia\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?7/46/7913?
    source=see_link&amp;anchor=H3#H3\">",
    " \"Pathophysiology and etiology of the syndrome of inappropriate antidiuretic
    hormone secretion (SIADH)\", section on 'Pathogenesis of hyponatremia'",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " In the aggregate, these observations suggest that there are two different
    forms of diuretic-induced hyponatremia: one in which volume depletion stimulates
    the release of ADH; and another in which the patient may be slightly volume
    expanded [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/502/abstract/14\">",
    " 14",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " In most patients, the combination of sodium plus potassium loss and water
    retention accounts for essentially all of the fall in the plasma sodium
    concentration [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/502/abstract/2,4\">",
    " 2,4",
    " </a>",
    " ]. However, there are patients in whom this does not appear to be the case,
    raising the possibility that the hyponatremia is due in part to osmotic
    inactivation of sodium in the cells or perhaps bone [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/502/abstract/15\">",
    " 15",
    " </a>",
    " ]. How or if this actually occurs is not clear. A similar hypothesis was
    proposed in the syndrome of inappropriate ADH and then seemingly excluded by
    careful balance studies [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/502/abstract/16,17\">",
    " 16,17",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H18442563\">",
    " <span class=\"h1\">",
    " INCIDENCE AND PATIENTS AT RISK",
    " </span>",
    " &nbsp;&mdash;&nbsp;The incidence of thiazide-induced hyponatremia is uncertain
    [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/502/abstract/18,19\">",
    " 18,19",
    " </a>",
    " ]. The best data come from a retrospective cohort study of 2613 newly treated
    hypertensive patients followed for 10 years [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/502/abstract/18\">",
    " 18",
    " </a>",
    " ]. Hyponatremia, defined as a serum sodium of 130",
    " <span class=\"nowrap\">",
    " meq/L",
    " </span>",
    " or less, developed in 66 of 220 patients initiated on a thiazide (30 percent)
    compared with 422 of 2393 patients started on alternate therapy (18 percent). Most
    cases of hyponatremia in patients taking thiazides occurred in the first three
    months of treatment. However, the risk of hyponatremia continued to be higher in
    the group exposed to thiazides throughout the 10 years of observation. Among those
    that developed hyponatremia, the median time to diagnosis was 1.75 years,
    emphasizing the importance of continued follow-up of patients started on thiazide
    diuretics. The incidence of hyponatremia associated with thiazide therapy was
    slightly, but not significantly, more common with advancing age (ie, 37 versus 24
    percent comparing those above and below 60 years of age). After taking into account
    other risk factors for hyponatremia, thiazide therapy was associated with one
    excess case of hyponatremia for every 15 patients treated. &nbsp;",
    " </p>",
    " <p>",
    " The association of thiazide-induced hyponatremia with older age, particularly
    those with low body weight, has been noted in other studies as well [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/502/abstract/1-5,12,20\">",
    " 1-5,12,20",
    " </a>",
    " ]. As an example, a case controlled study in hospitalized patients found that
    patient age and body mass were independent risk factors for thiazide-induced
    hyponatremia [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/502/abstract/5\">",
    " 5",
    " </a>",
    " ]. Each 10-year increment of age was associated with a twofold increase in
    risk, and every 5 kg increment in body mass decreased the odds ratio by 27 percent.
    Alcoholics, particularly beer drinkers, and patients with psychogenic polydipsia
    who depend on the excretion of maximally dilute urine to maintain water balance are
    also at risk.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H6\">",
    " <span class=\"h1\">",
    " CLINICAL MANIFESTATIONS",
    " </span>",
    " &nbsp;&mdash;&nbsp;The clinical manifestations of diuretic-induced
    hyponatremia are similar to those of other causes of hyponatremia. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?22/58/23464?
    source=see_link\">",
    " \"Manifestations of hyponatremia and hypernatremia\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " The hyponatremia typically begins soon after the onset of thiazide therapy and
    corrects over a period of days to two weeks after the cessation of therapy [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/502/abstract/2,3\">",
    " 2,3",
    " </a>",
    " ]. Most patients do not exhibit signs of volume depletion [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/502/abstract/2,6\">",
    " 2,6",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Diuretic-induced hyponatremia is rarely, if ever, associated with cerebral
    edema severe enough to cause herniation of the brain. This was illustrated in a
    series of 223 patients hospitalized for symptomatic hyponatremia due to thiazide
    diuretics; the mean plasma sodium was 115",
    " <span class=\"nowrap\">",
    " meq/L",
    " </span>",
    " [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/502/abstract/6\">",
    " 6",
    " </a>",
    " ]. The major symptoms were malaise, lethargy, dizzy spells, and vomiting, all
    of which are well described manifestations of severe hyponatremia. There was only a
    1 percent incidence of seizures and no cases of herniation [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/502/abstract/6\">",
    " 6",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " The older literature includes reports of brain damage in outpatients with
    thiazide-induced hyponatremia [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/502/abstract/3,7\">",
    " 3,7",
    " </a>",
    " ]. However, at the time of the study, the consequences of overly rapid
    correction were unknown. The reported patients were all treated with hypertonic
    saline, increasing the plasma sodium concentration by more than 25",
    " <span class=\"nowrap\">",
    " meq/L",
    " </span>",
    " in 48 hours, a rate of correction now known to be associated with osmotic
    demyelination in the brain. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?9/53/10074?
    source=see_link\">",
    " \"Osmotic demyelination syndrome and overly rapid correction of
    hyponatremia\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H7\">",
    " <span class=\"h1\">",
    " TREATMENT",
    " </span>",
    " &nbsp;&mdash;&nbsp;Treatment of diuretic-induced hyponatremia consists of
    discontinuing the diuretic and administering either isotonic saline or, if the
    hyponatremia is severe or symptomatic, hypertonic saline. There is a potential risk
    of overly rapid correction of the hyponatremia with either regimen. Once the
    diuretic has been cleared and the patient becomes euvolemic, ADH release will be
    appropriately suppressed, resulting in the excretion of a dilute urine, which can
    lead to rapid excretion of the excess water. Thus, patients with moderate to severe
    hyponatremia must be monitored carefully during treatment to minimize the risk of
    osmotic demyelination [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/502/abstract/1\">",
    " 1",
    " </a>",
    " ]. Preemptive administration of",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?source=see_link\">",
    " desmopressin",
    " </a>",
    " has been used to prevent the excretion of dilute urine. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?18/34/18986?
    source=see_link\">",
    " \"Overview of the treatment of hyponatremia\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H8\">",
    " <span class=\"h2\">",
    " Prevention",
    " </span>",
    " &nbsp;&mdash;&nbsp;There is no proven way to identify patients at risk of
    developing hyponatremia after diuretic therapy, making prevention difficult.
    Nevertheless, it may be prudent to avoid thiazide diuretics in beer drinkers and
    patients with psychogenic polydipsia and to measure the plasma sodium concentration
    within a few days after therapy has begun in elderly patients, especially those
    with a low body mass [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/502/abstract/5,19\">",
    " 5,19",
    " </a>",
    " ]. A thiazide diuretic should generally",
    " <strong>",
    " not",
    " </strong>",
    " be used in patients who have had a previous episode of hyponatremia.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"PATIENT_INFORMATION\">",
    " <span class=\"h1\">",
    " INFORMATION FOR PATIENTS",
    " </span>",
    " &nbsp;&mdash;&nbsp;UpToDate offers two types of patient education
    materials, \"The Basics\" and \"Beyond the Basics.\" The Basics patient education
    pieces are written in plain language, at the 5",
    " <sup>",
    " th",
    " </sup>",
    " to 6",
    " <sup>",
    " th",
    " </sup>",
    " grade reading level, and they answer the four or five key questions a patient
    might have about a given condition. These articles are best for patients who want a
    general overview and who prefer short, easy-to-read materials. Beyond the Basics
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    articles are written at the 10",
    " <sup>",
    " th",
    " </sup>",
    " to 12",
    " <sup>",
    " th",
    " </sup>",
    " grade reading level and are best for patients who want in-depth information
    and are comfortable with some medical jargon.",
    " </p>",
    " <p>",
    " Here are the patient education articles that are relevant to this topic. We
    encourage you to print or e-mail these topics to your patients. (You can also
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    on \"patient info\" and the keyword(s) of interest.)",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Basics topics (see",
    " <a class=\"medical medical_basics\" href=\"UTD.htm?9/20/9537?
    source=see_link\">",
    " \"Patient information: Hyponatremia (The Basics)\"",
    " </a>",
    " )",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H9602708\">",
    " <span class=\"h1\">",
    " SUMMARY AND RECOMMENDATIONS",
    " </span>",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Thiazide diuretics are more likely to cause hyponatremia than loop diuretics
    because they impair NaCl reabsorption in the distal convoluted tubule. As a result,
    there is an intact medullary concentration gradient, which is dependent on NaCl
    reabsorption in the loop, and patients treated with thiazide diuretics can excrete
    a concentrated urine if ADH is present. (See",
    " <a class=\"local\" href=\"#H2\">",
    " 'Pathogenesis'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " Thiazide-induced hyponatremia most commonly occurs in elderly patients,
    particularly those with a low body mass. (See",
    " <a class=\"local\" href=\"#H18442563\">",
    " 'Incidence and patients at risk'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " Patients with thiazide-induced hyponatremia often appear clinically
    euvolemic, sharing many features in common with patients with the syndrome of
    inappropriate ADH secretion. (See",
    " <a class=\"local\" href=\"#H6\">",
    " 'Clinical manifestations'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " Treatment consists of stopping the diuretic and administering either
    isotonic saline or, if the hyponatremia is severe or symptomatic, hypertonic
    saline. Patients with thiazide-induced hyponatremia are at risk of overly rapid
    correction because the ability to dilute the urine is restored once the effect of
    the diuretic clears and the patient becomes euvolemic. Thus, careful monitoring is
    needed during therapy to avoid osmotic demyelination. (See",
    " <a class=\"local\" href=\"#H7\">",
    " 'Treatment'",
    " </a>",
    " above.)",
    " </li>",
    " </ul>",
    " </p>",
    " </div>",
    " <div id=\"topicAgreement\">",
    " Use of UpToDate is subject to the",
    " <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
    target=\"_blank\">",
    " Subscription and License Agreement",
    " </a>",
    " .",
    " </div>",
    " <div class=\"headingAnchor\" id=\"references\">",
    " <h1>",
    " REFERENCES",
    " </h1>",
    " <ol id=\"reference\">",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/502/abstract/1\">",
    " Sonnenblick M, Friedlander Y, Rosin AJ. Diuretic-induced severe
    hyponatremia. Review and analysis of 129 reported patients. Chest 1993; 103:601.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/502/abstract/2\">",
    " Friedman E, Shadel M, Halkin H, Farfel Z. Thiazide-induced hyponatremia.
    Reproducibility by single dose rechallenge and an analysis of pathogenesis. Ann
    Intern Med 1989; 110:24.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/502/abstract/3\">",
    " Ashraf N, Locksley R, Arieff AI. Thiazide-induced hyponatremia associated
    with death or neurologic damage in outpatients. Am J Med 1981; 70:1163.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/502/abstract/4\">",
    " Fichman MP, Vorherr H, Kleeman CR, Telfer N. Diuretic-induced hyponatremia.
    Ann Intern Med 1971; 75:853.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/502/abstract/5\">",
    " Chow KM, Szeto CC, Wong TY, et al. Risk factors for thiazide-induced
    hyponatraemia. QJM 2003; 96:911.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/502/abstract/6\">",
    " Chow KM, Kwan BC, Szeto CC. Clinical studies of thiazide-induced
    hyponatremia. J Natl Med Assoc 2004; 96:1305.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/502/abstract/7\">",
    " Mozes B, Pines A, Werner D, et al. Thiazide-induced hyponatremia: an unusual
    neurologic course. South Med J 1986; 79:629.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/502/abstract/8\">",
    " Sonnenblick M, Rosin AJ. Significance of the measurement of uric acid
    fractional clearance in diuretic induced hyponatraemia. Postgrad Med J 1986;
    62:449.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/502/abstract/9\">",
    " Szatalowicz VL, Miller PD, Lacher JW, et al. Comparative effect of diuretics
    on renal water excretion in hyponatraemic oedematous disorders. Clin Sci (Lond)
    1982; 62:235.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/502/abstract/10\">",
    " C&eacute;sar KR, Magaldi AJ. Thiazide induces water absorption in the inner
    medullary collecting duct of normal and Brattleboro rats. Am J Physiol 1999;
    277:F756.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/502/abstract/11\">",
    " Maronde RF, Milgrom M, Vlachakis ND, Chan L. Response of thiazide-induced
    hypokalemia to amiloride. JAMA 1983; 249:237.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/502/abstract/12\">",
    " Sharabi Y, Illan R, Kamari Y, et al. Diuretic induced hyponatraemia in
    elderly hypertensive women. J Hum Hypertens 2002; 16:631.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/502/abstract/13\">",
    " Clark BA, Shannon RP, Rosa RM, Epstein FH. Increased susceptibility to
    thiazide-induced hyponatremia in the elderly. J Am Soc Nephrol 1994; 5:1106.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/502/abstract/14\">",
    " Decaux G, Schlesser M, Coffernils M, et al. Uric acid, anion gap and urea
    concentration in the diagnostic approach to hyponatremia. Clin Nephrol 1994;
    42:102.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/502/abstract/15\">",
    " Johnson JE, Wright LF. Thiazide-induced hyponatremia. South Med J 1983;
    76:1363.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/502/abstract/16\">",
    " Cooke CR, Turin MD, Walker WG. The syndrome of inappropriate antidiuretic
    hormone secretion (SIADH): pathophysiologic mechanisms in solute and volume
    regulation. Medicine (Baltimore) 1979; 58:240.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/502/abstract/17\">",
    " Verbalis JG. Pathogenesis of hyponatremia in an experimental model of the
    syndrome of inappropriate antidiuresis. Am J Physiol 1994; 267:R1617.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/502/abstract/18\">",
    " Leung AA, Wright A, Pazo V, et al. Risk of thiazide-induced hyponatremia in
    patients with hypertension. Am J Med 2011; 124:1064.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/502/abstract/19\">",
    " Clayton JA, Rodgers S, Blakey J, et al. Thiazide diuretic prescription and
    electrolyte abnormalities in primary care. Br J Clin Pharmacol 2006; 61:87.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/502/abstract/20\">",
    " Gross P, Palm C. Thiazides: do they kill? Nephrol Dial Transplant 2005;
    20:2299.",
    " </a>",
    " </li>",
    " </ol>",
    " </div>",
    " <div id=\"topicVersionRevision\">",
    " Topic 2288 Version 10.0",
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    " <div id=\"innerOutline\">",
    " <h1>",
    " TOPIC OUTLINE",
    " </h1>",
    " <div id=\"outline\">",
    " <ul>",
    " <li>",
    " <a class=\"sr_button\" href=\"#H9602708\" id=\"summRecButton\">",
    " <span>",
    " SUMMARY &amp; RECOMMENDATIONS",
    " </span>",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H1\">",
    " INTRODUCTION",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H2\">",
    " PATHOGENESIS",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H1983318\">",
    " Increased water intake",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H4\">",
    " Impaired water excretion",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H18442563\">",
    " INCIDENCE AND PATIENTS AT RISK",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H6\">",
    " CLINICAL MANIFESTATIONS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H7\">",
    " TREATMENT",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H8\">",
    " Prevention",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#PATIENT_INFORMATION\">",
    " INFORMATION FOR PATIENTS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H9602708\">",
    " SUMMARY AND RECOMMENDATIONS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#references\">",
    " REFERENCES",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " <div class=\"openRelatedGraphics\" id=\"NEPH/2288\" rel=\"outline_link\">",
    " GRAPHICS",
    " <a class=\"graphics_icon\" href=\"#\" title=\"View All Related Graphics\">",
    " View All",
    " </a>",
    " </div>",
    " </h1>",
    " <div id=\"relatedGraphics\">",
    " <ul>",
    " <li class=\"plainItem\">",
    " <div class=\"openRelatedGraphics\" id=\"NEPH/2288|FIG\">",
    " <a href=\"#\" title=\"FIGURES\">",
    " FIGURES",
    " </a>",
    " </div>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_figure\" href=\"UTD.htm?15/33/15901\"
    title=\"figure 1\">",
    " Time course of diuretic action",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " RELATED TOPICS",
    " </h1>",
    " <div id=\"relatedTopics\">",
    " <ul>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?35/45/36570?
    source=related_link\">",
    " Assessment of kidney function",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?3/30/3562?
    source=related_link\">",
    " Causes of hyponatremia",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?2/52/2886?
    source=related_link\">",
    " Chapter 9B: Renal water excretion and reabsorption",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?21/20/21832?
    source=related_link\">",
    " Evaluation of the patient with hyponatremia",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?22/58/23464?
    source=related_link\">",
    " Manifestations of hyponatremia and hypernatremia",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?38/13/39128?
    source=related_link\">",
    " Mechanism of action of diuretics",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?9/53/10074?
    source=related_link\">",
    " Osmotic demyelination syndrome and overly rapid correction of hyponatremia",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?18/34/18986?
    source=related_link\">",
    " Overview of the treatment of hyponatremia",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?7/46/7913?
    source=related_link\">",
    " Pathophysiology and etiology of the syndrome of inappropriate antidiuretic
    hormone secretion (SIADH)",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_basics\" href=\"UTD.htm?9/20/9537?
    source=related_link\">",
    " Patient information: Hyponatremia (The Basics)",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?6/45/6868?
    source=related_link\">",
    " Time course of loop and thiazide diuretic-induced electrolyte
    complications",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " </div>"].join("\n");
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    " </div>",
    " <div class=\"lgnd\">",
    " (A) Roticular disoposable surgical stapler with disposable loading unit. (B)
    Skin staple gun and cartridge.",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f0_31_503=[""].join("\n");
    var outline_f0_31_503=null;
    var title_f0_31_504="Minor Vibrio and Vibrio-like species associated with human
    disease";
    var content_f0_31_504=[" <noscript>",
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    " Official reprint from UpToDate",
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    " <!-- TC:TOPIC_PAGE -->",
    " <div id=\"topicContent\">",
    " <div id=\"topicTitle\">",
    " Minor Vibrio and Vibrio-like species associated with human disease",
    " </div>",
    " <div id=\"topicContributors\">",
    " <div>",
    " <a id=\"authors\">",
    " </a>",
    " <a class=\"contributor contributor_credentials contributorType\"
    href=\"UTD.htm?0/31/504/contributors\">",
    " Author",
    " </a>",
    " <br/>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/31/504/contributors\">",
    " J Glenn Morris, Jr, MD, MPH&amp;TM",
    " </a>",
    " <br/>",
    " </div>",
    " <div>",
    " <a class=\"contributor contributor_credentials contributorType\"
    href=\"UTD.htm?0/31/504/contributors\">",
    " Section Editor",
    " </a>",
    " <br/>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/31/504/contributors\">",
    " Stephen B Calderwood, MD",
    " </a>",
    " <br/>",
    " </div>",
    " <div>",
    " <a class=\"contributor contributor_credentials contributorType\"
    href=\"UTD.htm?0/31/504/contributors\">",
    " Deputy Editor",
    " </a>",
    " <br/>",
    " <a class=\"contributor contributor_credentials\" href=\"UTD.htm?
    0/31/504/contributors\">",
    " Elinor L Baron, MD, DTMH",
    " </a>",
    " <br/>",
    " </div>",
    " </div>",
    " <div id=\"disclosures\">",
    " <a href=\"UTD.htm?0/31/504/contributor-disclosure\" target=\"_blank\">",
    " Disclosures",
    " </a>",
    " </div>",
    " <div id=\"reviewProcess\">",
    " <span>",
    " All topics are updated as new evidence becomes available and our",
    " </span>",
    " <a href=\"/home/editorial-policy\" target=\"_blank\">",
    " peer review process",
    " </a>",
    " <span>",
    " is complete.",
    " </span>",
    " </div>",
    " <div id=\"literatureReviewDate\">",
    " <span class=\"emphasis\">",
    " Literature review current through:",
    " </span>",
    " Oct 2013.",
    " <span class=\"pipeSpace\">",
    " |",
    " </span>",
    " <span class=\"emphasis\">",
    " This topic last updated:",
    " </span>",
    " Apr 11, 2012.",
    " </div>",
    " <div id=\"topicText\">",
    " <p class=\"headingAnchor\" id=\"H631646146\">",
    " <span class=\"h1\">",
    " INTRODUCTION",
    " </span>",
    " &nbsp;&mdash;&nbsp;Vibrios are ubiquitous environmental Gram-negative rods,
    with well over 100 species currently recognized. Among these species, 10 have been
    isolated from humans. The species responsible for the most serious diseases are V.
    cholerae (V. cholerae",
    " <span class=\"nowrap\">",
    " O1/O139",
    " </span>",
    " strains causing the disease cholera and other V. cholerae strains linked with
    diarrhea, wound infections, and septicemia), V. parahaemolyticus, and V.
    vulnificus.",
    " </p>",
    " <p>",
    " Four additional species (V. mimicus, V. fluvialis, V. furnissii, V.
    alginolyticus) clearly have pathogenic potential for humans but cause illness that
    generally is less severe. Two closely related species that were originally
    classified in the genus Vibrio but have undergone a change in name on the basis of
    recent taxonomic studies, Grimontia hollisae (formerly Vibrio hollisae) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/1\">",
    " 1",
    " </a>",
    " ], and Photobacterium damsela (formerly Vibrio damsela) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/2\">",
    " 2",
    " </a>",
    " ], are also established human pathogens. Three species (V. metschnikovii, V.
    cincinnatiensis, and V. carchariae [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/3-7\">",
    " 3-7",
    " </a>",
    " ]) have primarily been the subject of case reports, and their significance as
    human pathogens remains to be determined.",
    " </p>",
    " <p>",
    " This topic discusses the microbiology, epidemiology, clinical manifestations,
    diagnosis and treatment of the six minor Vibrio and Vibrio-like species that have
    been associated with human disease. Infections due to the major Vibrio species are
    discussed elsewhere. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?35/14/36073?
    source=see_link\">",
    " \"Overview of Vibrio cholerae infection\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?18/4/18502?
    source=see_link\">",
    " \"Infections due to non-O1/O139 Vibrio cholerae\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?27/14/27878?
    source=see_link\">",
    " \"Vibrio parahaemolyticus infections\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?43/42/44710?
    source=see_link\">",
    " \"Vibrio vulnificus infections\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H10851452\">",
    " <span class=\"h1\">",
    " EPIDEMIOLOGY COMMON TO VIBRIO SPECIES",
    " </span>",
    " &nbsp;&mdash;&nbsp;All Vibrio species are free-living microorganisms in marine
    and estuarine environments. They are sensitive to temperature, with numbers of
    microorganisms in the environment increasing during warmer, summer months [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/8\">",
    " 8",
    " </a>",
    " ]. As an example, the number of Vibrio species isolated from human infections
    in the United States and reported to the Center for Disease Control peaks during
    the months of May to September. Approximately 25 percent of the 825 non-toxigenic
    V. cholerae Vibrio isolates reported in the US in 2009 occurred in August (",
    " <a class=\"graphic graphic_figure graphicRef82927 \" href=\"UTD.htm?
    4/60/5070\">",
    " figure 1",
    " </a>",
    " ).",
    " </p>",
    " <p>",
    " Vibrio species are associated mainly with gastroenteritis, wound infection,
    and occasionally bacteremia. V. mimicus, V. fluvialis, V. furnissii, and Grimontia
    hollisae primarily cause gastroenteritis. V. alginolyticus and Photobacterium
    damsela primarily cause wound infections (",
    " <a class=\"graphic graphic_table graphicRef82928 \" href=\"UTD.htm?
    3/15/3325\">",
    " table 1",
    " </a>",
    " ).",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H631646153\">",
    " <span class=\"h1\">",
    " SPECIES THAT PRIMARILY CAUSE DIARRHEA",
    " </span>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H631646161\">",
    " <span class=\"h2\">",
    " V. mimicus",
    " </span>",
    " &nbsp;&mdash;&nbsp;V. mimicus, identified as a separate species in 1981 [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/9\">",
    " 9",
    " </a>",
    " ], was initially classified as &ldquo;atypical sucrose-negative V.
    cholerae.&rdquo; The species &ldquo;mimics&rdquo; V. cholerae in many biochemical
    tests, hence the name. Comparative genomic analysis suggests that V. mimicus and V.
    cholerae diverged from a common ancestor derived from the strain that caused the
    sixth cholera pandemic [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/10\">",
    " 10",
    " </a>",
    " ]. Despite the close genetic relationship with V. cholerae, V. mimicus do not
    cause epidemic cholera-like disease. Fewer than 10 percent of clinical isolates,
    and less than 1 percent of environmental isolates, produce cholera toxin [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/11\">",
    " 11",
    " </a>",
    " ]. Strains do, however, carry a variety of possible virulence factors,
    including genes for a type III secretion system that can be seen in V.
    parahaemolyticus [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/12\">",
    " 12",
    " </a>",
    " ]. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?27/14/27878?
    source=see_link&amp;anchor=H2#H2\">",
    " \"Vibrio parahaemolyticus infections\", section on 'Pathogenesis'",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H631646168\">",
    " <span class=\"h3\">",
    " Epidemiology",
    " </span>",
    " &nbsp;&mdash;&nbsp;Consumption of seafood is the main risk factor for V.
    mimicus gastrointestinal infection. The microorganism has been isolated from shrimp
    and other shellfish in fish markets in Malaysia [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/13\">",
    " 13",
    " </a>",
    " ] and from mussels in Italy [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/14\">",
    " 14",
    " </a>",
    " ]. In the US, occurrence of V. mimicus diarrhea has been associated with
    eating raw oysters and other shellfish, including crayfish [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/15,16\">",
    " 15,16",
    " </a>",
    " ]. In a large Thai outbreak, &ldquo;fish soup&rdquo; was implicated as the
    vehicle of transmission [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/17\">",
    " 17",
    " </a>",
    " ], and infection has been linked to consumption of raw turtle eggs in Costa
    Rica [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/18\">",
    " 18",
    " </a>",
    " ]. In a pattern analogous to that seen with",
    " <span class=\"nowrap\">",
    " non-O1/non-O139",
    " </span>",
    " V. cholerae, the organism is likely to be introduced into communities through
    seafood, with further transmission in the developing world related to fecal
    contamination of food and water sources. Wound and ear infections occur to a lesser
    extent and are generally seen in the setting of exposure to estuarine waters [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/15\">",
    " 15",
    " </a>",
    " ], which serve as a reservoir for the microorganism.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H631646175\">",
    " <span class=\"h3\">",
    " Clinical manifestations",
    " </span>",
    " &nbsp;&mdash;&nbsp;Gastroenteritis, with typical symptoms of diarrhea, nausea,
    vomiting, and abdominal cramps, is the primary clinical manifestation of V. mimicus
    infection. Wound and ear infections occur rarely, as does bacteremia (",
    " <a class=\"graphic graphic_table graphicRef82928 \" href=\"UTD.htm?
    3/15/3325\">",
    " table 1",
    " </a>",
    " ).",
    " </p>",
    " <p>",
    " In an initial case series (which was probably biased toward more severe
    cases), median duration of illness was six days, with 44 percent of patients having
    fever, and 16 percent having bloody diarrhea [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/15\">",
    " 15",
    " </a>",
    " ]. Approximately 55 percent of V. mimicus clinical isolates in the US reported
    to CDC between 2004 and 2009 were from hospitalized patients (",
    " <a class=\"graphic graphic_table graphicRef82928 \" href=\"UTD.htm?
    3/15/3325\">",
    " table 1",
    " </a>",
    " ). In the Thai outbreak involving over 400 persons, symptoms were milder, with
    91 percent reporting diarrhea, 66 percent abdominal pain, and 27 percent vomiting
    [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/17\">",
    " 17",
    " </a>",
    " ]. Symptoms resolved in two-thirds",
    " <sup>",
    " </sup>",
    " of these patients within 36 hours, with less than a third seeking medical
    attention.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H631646204\">",
    " <span class=\"h2\">",
    " V. fluvialis",
    " </span>",
    " &nbsp;&mdash;&nbsp;V. fluvialis was identified as a separate species in 1981,
    with the name derived from the Latin for &ldquo;river,&rdquo; reflecting its early
    isolation from river and estuarine waters [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/19\">",
    " 19",
    " </a>",
    " ]. Strains do not appear to produce cholera toxin. They have been shown to
    have",
    " <span class=\"nowrap\">",
    " cytopathic/cytotoxic",
    " </span>",
    " effects on HeLa cells [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/20\">",
    " 20",
    " </a>",
    " ], and to cause fluid accumulation in rabbit ileal loops, and diarrhea and
    death in infant mice [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/21,22\">",
    " 21,22",
    " </a>",
    " ]. However, factors responsible for these effects are not well defined. V.
    fluvialis has been associated with high rates of bloody diarrhea, raising the
    possibility that it is invasive in the intestinal tract, despite reports that
    isolates are negative for invasiveness in laboratory testing [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/23\">",
    " 23",
    " </a>",
    " ]. &nbsp;",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H631646211\">",
    " <span class=\"h3\">",
    " Epidemiology",
    " </span>",
    " &nbsp;&mdash;&nbsp;V. fluvialis is widely distributed in the estuarine and
    marine environment and has been isolated from shellfish and fish, including fish in
    Turkey [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/24\">",
    " 24",
    " </a>",
    " ], shrimp and other shellfish in fish markets in Malaysia [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/13\">",
    " 13",
    " </a>",
    " ], and mussels in Italy [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/14\">",
    " 14",
    " </a>",
    " ]. It is also recognized as an important pathogen for some marine species,
    with &ldquo;V. fluvialis-like&rdquo; strains identified as the cause of &ldquo;limp
    lobster&rdquo; syndrome [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/25\">",
    " 25",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " In humans, V. fluvialis has been linked with large outbreaks in Bangladesh and
    India, including outbreaks of diarrheal disease after the major cyclone Aila [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/23,26\">",
    " 23,26",
    " </a>",
    " ]. In the US, it is a relatively common Vibrio species isolated from patients.
    In reports from Bangladesh and India, cases have been concentrated in children and
    persons aged 55 and older [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/20,26\">",
    " 20,26",
    " </a>",
    " ]. Similar age-related incidence patterns were not observed in studies in
    Indonesia [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/27\">",
    " 27",
    " </a>",
    " ]. In a pattern analogous to that seen with",
    " <span class=\"nowrap\">",
    " non-O1/non-O139",
    " </span>",
    " V. cholerae, the organism is likely to be introduced into human populations
    through seafood or water contact, with further transmission in the developing world
    related to fecal contamination of food and water sources.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H631646218\">",
    " <span class=\"h3\">",
    " Clinical manifestations",
    " </span>",
    " &nbsp;&mdash;&nbsp;Gastroenteritis is the primary clinical manifestation of V.
    fluvialis infection. Infections at other sites, including wounds and ears, also
    occur, with rare reports of bacteremia and death (",
    " <a class=\"graphic graphic_table graphicRef82928 \" href=\"UTD.htm?
    3/15/3325\">",
    " table 1",
    " </a>",
    " ). Among 100 persons with &ldquo;moderate to severe&rdquo; illness following
    cyclone Aila in whom V. fluvialis was implicated as the etiologic agent, symptoms
    included watery diarrhea (86 percent of patients), bloody diarrhea (62 percent),
    abdominal pain (57 percent), vomiting (41 percent), and fever (21 percent) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/26\">",
    " 26",
    " </a>",
    " ]. In an earlier outbreak in Bangladesh (1976-77), 75 percent of patients were
    found to have blood cells and leukocytes in their stools on microscopic examination
    [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/23\">",
    " 23",
    " </a>",
    " ]. The duration of diarrhea ranged from 16 to 80 hours, with antibiotic
    therapy.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H631646247\">",
    " <span class=\"h2\">",
    " V. furnissii",
    " </span>",
    " &nbsp;&mdash;&nbsp;V. furnissii, initially identified as biovar II for V.
    fluvialis, was designated as a separate species in 1983 [10]. A complete genome
    sequence has been reported for an environmental strain. It lacked the gene for
    cholera toxin, other cholera toxin-related toxins, and genes encoding a type III
    secretion system [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/28\">",
    " 28",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " The organism can be isolated from the environment, and has been isolated from
    mussels in Brazil [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/29\">",
    " 29",
    " </a>",
    " ]. It has been retrospectively identified as the cause of at least one
    outbreak (gastroenteritis on an airplane flight from Tokyo to Seattle [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/30\">",
    " 30",
    " </a>",
    " ]), has been linked with gastroenteritis in Peru [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/31\">",
    " 31",
    " </a>",
    " ] and Indonesia [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/27\">",
    " 27",
    " </a>",
    " ], and has been reported as the cause of bacteremia in a diabetic patient in
    Virginia [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/32\">",
    " 32",
    " </a>",
    " ]. However, its role as a pathogen remains somewhat controversial,
    particularly as in the Peru study, it was isolated more frequently from persons who
    were asymptomatic than from persons with diarrhea.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H631646262\">",
    " <span class=\"h2\">",
    " Grimontia (Vibrio) hollisae",
    " </span>",
    " &nbsp;&mdash;&nbsp;Grimontia hollisae, initially known as Vibrio hollisae, was
    designated as a separate species in 1982. G. hollisae is known to have a type III
    secretion system and produce a thermostable direct hemolysin very similar to that
    found in V. parahaemolyticus [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/33\">",
    " 33",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " G. hollisae has been isolated from the environment in Australia [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/34\">",
    " 34",
    " </a>",
    " ] and from mussels in Italy [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/35\">",
    " 35",
    " </a>",
    " ], but reports are limited; it is unclear whether this reflects a decreased
    environmental presence compared with Vibrio species or technical problems in
    environmental isolation. It has been associated primarily with sporadic cases of
    gastroenteritis (",
    " <a class=\"graphic graphic_table graphicRef82928 \" href=\"UTD.htm?
    3/15/3325\">",
    " table 1",
    " </a>",
    " ), and there is a suggestion that illness is associated with consumption of
    seafood [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/36,37\">",
    " 36,37",
    " </a>",
    " ]. Cases appear to be more common in North America, although isolation from
    patients with diarrhea has been reported from Indonesia [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/27\">",
    " 27",
    " </a>",
    " ], and a case of bacteremia has been reported from Europe [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/36\">",
    " 36",
    " </a>",
    " ]. Of five patients with bacteremia reported in the literature [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/38\">",
    " 38",
    " </a>",
    " ], three had a history of underlying liver disease, similar to the pattern
    seen with",
    " <span class=\"nowrap\">",
    " non-O1/non-O139",
    " </span>",
    " V. cholerae and V. vulnificus.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H631646285\">",
    " <span class=\"h1\">",
    " SPECIES THAT PRIMARILY CAUSE WOUND INFECTIONS",
    " </span>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H631646293\">",
    " <span class=\"h2\">",
    " V. alginolyticus",
    " </span>",
    " &nbsp;&mdash;&nbsp;V. alginolyticus is known to produce extracellular
    proteases and collagenases, which may contribute to its virulence [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/39\">",
    " 39",
    " </a>",
    " ]. It has also been found to have a type III secretion system that has been
    linked with the ability of the microorganism to cause rapid apoptosis, cell
    rounding, and osmotic lysis of fish cells [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/40\">",
    " 40",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " V. alginolyticus is widely distributed in the environment [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/41,42\">",
    " 41,42",
    " </a>",
    " ], has been isolated from fish and shellfish [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/43\">",
    " 43",
    " </a>",
    " ], and is recognized as a pathogen for fish. It is the most common cause of
    Vibrio-associated wound infections in the United States (",
    " <a class=\"graphic graphic_table graphicRef82928 \" href=\"UTD.htm?
    3/15/3325\">",
    " table 1",
    " </a>",
    " ). It has been associated with otitis, and rare cases of bacteremia are
    reported, almost always associated with wound infections, and generally in
    immunocompromised or burn patients [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/44,45\">",
    " 44,45",
    " </a>",
    " ]. Wound infections and otitis are almost all associated with exposure to
    marine or estuarine waters. In contrast to other Vibrio species, it is only rarely
    isolated from stool, and it is unclear that it is able to cause gastrointestinal
    disease in humans.",
    " </p>",
    " <p>",
    " In a study in Western Australia, V. alginolyticus was isolated from 20 of 36
    samples (56 percent) taken from infected superficial wounds contaminated with
    seawater [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/46\">",
    " 46",
    " </a>",
    " ]. Most infections cleared within one or two days without the use of
    antibiotics. The general lack of severity associated with V. alginolyticus
    infections is reflected in the fact that in the US from 2004 to 2009, only three
    deaths were reported out of the 386 patients with V. alginolyticus infection (",
    " <a class=\"graphic graphic_table graphicRef82928 \" href=\"UTD.htm?
    3/15/3325\">",
    " table 1",
    " </a>",
    " ). In a 10-year study from Florida, no deaths were reported among 131
    infections [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/8\">",
    " 8",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H631646308\">",
    " <span class=\"h2\">",
    " Photobacterium (Vibrio) damsela",
    " </span>",
    " &nbsp;&mdash;&nbsp;Photobacterium damsela has gone through several name
    changes: originally designated as Vibrio damsela (based on its pathogenicity for
    damsel fish [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/47\">",
    " 47",
    " </a>",
    " ]), it has been known as Listonella damsela, and is currently designated as P.
    damsela. It is a rare cause of wound infections in the United States (",
    " <a class=\"graphic graphic_table graphicRef82928 \" href=\"UTD.htm?
    3/15/3325\">",
    " table 1",
    " </a>",
    " ) [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/37\">",
    " 37",
    " </a>",
    " ]. It shows fairly striking virulence in mice [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/48\">",
    " 48",
    " </a>",
    " ], and has been isolated from a fatal case of necrotizing fasciitis [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/49\">",
    " 49",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H10851583\">",
    " <span class=\"h1\">",
    " DIAGNOSIS",
    " </span>",
    " &nbsp;&mdash;&nbsp;The diagnosis of these Vibrio species is established by
    isolation of the organism from the relevant clinical specimen, generally stool or
    wound culture. They can grow on standard media used for wound and blood cultures.
    Isolation of Vibrio species from stool generally requires a selective media to
    suppress growth of other organisms, such as thiosulfate, citrate, bile salts, and
    sucrose (TCBS). The laboratory should be alerted regarding cases of diarrhea in
    which illness due to Vibrio species is suspected so that the appropriate media can
    be used. Species identification is based on standard biochemical tests.",
    " </p>",
    " <p>",
    " Certain species have particular diagnostic characteristics:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " V. mimicus and P. damsela appear as green colonies on TCBS agar. V.
    cholerae, V. alginolyticus, V. fluvialis, and V. furnissii are yellow.",
    " </li>",
    " <li>",
    " V. fluvialis shows marked biochemical similarity to Aeromonas species. When
    the British Public Health Laboratories reviewed all of their old anaerogenic,
    lysine-decarboxylase-negative Aeromonas strains, they found that one-third were
    actually V. fluvialis [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/19\">",
    " 19",
    " </a>",
    " ]. Microbiologic identification schemes in current use in the United States
    will sometimes mistakenly identify V. fluvialis as Aeromonas [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/22\">",
    " 22",
    " </a>",
    " ]. Where V. fluvialis is suspected, isolates should be screened for salt
    requirements (V. fluvialis grows in 6 to 7 percent sodium chloride, while Aeromonas
    generally does not) to help differentiate the two species.",
    " </li>",
    " <li>",
    " G. hollisae does NOT grow on TCBS agar, in contrast to Vibrio species.
    Isolation is possible on blood agar or marine agar but tends to be difficult,
    particularly from stool [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/37\">",
    " 37",
    " </a>",
    " ].",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H22319510\">",
    " <span class=\"h1\">",
    " TREATMENT",
    " </span>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H22319517\">",
    " <span class=\"h2\">",
    " Diarrheal disease",
    " </span>",
    " &nbsp;&mdash;&nbsp;Volume repletion is the most important element of therapy
    in patients with diarrheal disease and is best done through the oral route with
    solutions that contain water, salt, and sugar. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?31/17/32025?
    source=see_link&amp;anchor=H14#H14\">",
    " \"Approach to the adult with acute diarrhea in developed countries\", section
    on 'Oral rehydration solutions'",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Although diarrhea associated with these Vibrio species is often mild and self-
    limited, antimicrobial therapy is reasonable in moderate to severe cases,
    particularly in V. fluvialis infections, given its association with blood and
    leukocytes in the stool. No controlled trials of therapy of these Vibrio species
    have been performed, and there are limited observational data. In the Thai outbreak
    of V. mimicus, patients were treated with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?16/9/16536?source=see_link\">",
    " norfloxacin",
    " </a>",
    " [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/17\">",
    " 17",
    " </a>",
    " ]; no outcome data were reported. Successful therapy with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?34/45/35536?source=see_link\">",
    " ciprofloxacin",
    " </a>",
    " has been reported in one case of severe diarrhea and sepsis with G. hollisae
    infection [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/38\">",
    " 38",
    " </a>",
    " ]. However, among patients with cholera, antimicrobials are known to decrease
    the duration of diarrhea and the excretion of infectious organisms and may also
    have the same benefit in these Vibrio species. Based upon clinical trials in
    cholera and in vitro susceptibility data, we suggest",
    " <a class=\"drug drug_general\" href=\"UTD.htm?2/41/2714?source=see_link\">",
    " doxycycline",
    " </a>",
    " or a fluoroquinolone. Susceptibility testing should be done to confirm
    sensitivity to these agents. We typically use a single dose of doxycycline 300 mg
    orally or ciprofloxacin 1 g orally. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?35/14/36073?
    source=see_link&amp;anchor=H12#H12\">",
    " \"Overview of Vibrio cholerae infection\", section on 'Antimicrobial
    therapy'",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H22319573\">",
    " <span class=\"h2\">",
    " Wound infection",
    " </span>",
    " &nbsp;&mdash;&nbsp;There are few data on treatment of wound infections due to
    these Vibrio species. Treatment suggestions are based upon clinical experience.
    Serious wound infections generally require debridement and antimicrobial therapy.
    Mild wound infections generally respond well to local wound care and oral
    antibiotics. In the case of V. alginolyticus infections of superficial wounds,
    antibiotics may not be necessary, as reflected by the report from Australia in
    which most cases resolved spontaneously [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/504/abstract/46\">",
    " 46",
    " </a>",
    " ]. Based upon antibiotic susceptibility patterns and clinical response of
    other Vibrio species, we suggest",
    " <a class=\"drug drug_general\" href=\"UTD.htm?2/41/2714?source=see_link\">",
    " doxycycline",
    " </a>",
    " or a fluoroquinolone for severe wound infections and infections in
    immunocompromised hosts. Susceptibility testing should be done to confirm
    sensitivity to these agents. We typically use oral doxycycline 100 mg twice daily
    or",
    " <a class=\"drug drug_general\" href=\"UTD.htm?34/45/35536?source=see_link\">",
    " ciprofloxacin",
    " </a>",
    " 500 mg twice daily. Duration of therapy is dictated by clinical response; most
    patients respond to five to seven days of antibiotics.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H22319378\">",
    " <span class=\"h1\">",
    " SUMMARY AND RECOMMENDATIONS",
    " </span>",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Vibrio species are naturally occurring marine and estuarine microorganisms
    that are found worldwide. They are sensitive to temperature, and infections peak
    during warmer, summer months. (See",
    " <a class=\"local\" href=\"#H10851452\">",
    " 'Epidemiology common to Vibrio species'",
    " </a>",
    " above.) &nbsp;",
    " </li>",
    " <li>",
    " V. mimicus primarily causes gastroenteritis and is frequently linked to
    seafood ingestion, particularly raw or undercooked shellfish. It may also occur as
    a result of fecal contamination of food and water sources. (See",
    " <a class=\"local\" href=\"#H631646161\">",
    " 'V. mimicus'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " V. fluvialis primarily causes gastroenteritis and has been associated with
    large outbreaks in Bangladesh and India. Bloody diarrhea and fecal leukocytes are
    common in V. fluvialis infection. It is very similar biochemically to Aeromonas,
    with which it may be confused in the laboratory. (See",
    " <a class=\"local\" href=\"#H631646204\">",
    " 'V. fluvialis'",
    " </a>",
    " above and",
    " <a class=\"local\" href=\"#H10851583\">",
    " 'Diagnosis'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " V. furnissii has been associated with gastroenteritis, although its role as
    a pathogen remains controversial. (See",
    " <a class=\"local\" href=\"#H631646247\">",
    " 'V. furnissii'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " Grimontia hollisae primarily causes gastroenteritis, although cases of
    bacteremia are reported. Infection has been linked to seafood ingestion. (See",
    " <a class=\"local\" href=\"#H631646262\">",
    " 'Grimontia (Vibrio) hollisae'",
    " </a>",
    " above and",
    " <a class=\"local\" href=\"#H10851583\">",
    " 'Diagnosis'",
    " </a>",
    " above.).",
    " </li>",
    " <li>",
    " V. alginolyticus is the most common cause of Vibrio-associated wound
    infections in the US, and most infections are mild. Photobacterium damsel also
    causes wound infections, although more rarely. Infections with both are linked with
    exposure to marine or estuarine waters. (See",
    " <a class=\"local\" href=\"#H631646293\">",
    " 'V. alginolyticus'",
    " </a>",
    " above and",
    " <a class=\"local\" href=\"#H631646308\">",
    " 'Photobacterium (Vibrio) damsela'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " The diagnosis of these Vibrio species is established by isolation of the
    organism from the relevant clinical specimen, generally stool or wound culture.
    Vibrio species can grow on standard media for wound and blood cultures. For
    gastroenteritis cases, the laboratory should be alerted of the suspicion for
    Vibrio, as isolation from stool requires a selective media to suppress growth of
    other organisms. In contrast to Vibrio species, G. hollisae does NOT grow on TCBS,
    the standard selective media used in isolation of Vibrios from stool. It does grow
    on blood agar. (See",
    " <a class=\"local\" href=\"#H10851583\">",
    " 'Diagnosis'",
    " </a>",
    " above.) &nbsp;",
    " </li>",
    " <li>",
    " Volume repletion is the most important element of therapy in patients with
    diarrheal disease due to Vibrio species. Wound infections require local wound care
    and possibly debridement. For patients with mild superficial wounds due to V.
    alginolyticus, we suggest initial observation without antibiotics (",
    " <a class=\"grade\" href=\"._grade_6?title=Grade 2C\">",
    " Grade 2C",
    " </a>",
    " ). Antibiotics should be given to those with moderate to severe infections
    or an underlying immunosuppressive condition. For such patients, we suggest using",
    " <a class=\"drug drug_general\" href=\"UTD.htm?2/41/2714?source=see_link\">",
    " doxycycline",
    " </a>",
    " or a fluoroquinolone (",
    " <a class=\"grade\" href=\"._grade_6?title=Grade 2C\">",
    " Grade 2C",
    " </a>",
    " ). This choice is based upon antibiotic susceptibility patterns and clinical
    response of other Vibrio species. (See",
    " <a class=\"local\" href=\"#H22319510\">",
    " 'Treatment'",
    " </a>",
    " above.)",
    " </li>",
    " </ul>",
    " </p>",
    " </div>",
    " <div id=\"topicAgreement\">",
    " Use of UpToDate is subject to the",
    " <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
    target=\"_blank\">",
    " Subscription and License Agreement",
    " </a>",
    " .",
    " </div>",
    " <div class=\"headingAnchor\" id=\"references\">",
    " <h1>",
    " REFERENCES",
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    " </ol>",
    " </div>",
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    var outline_f0_31_504=[" <div id=\"toggleOutline\">",
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    " <h1>",
    " TOPIC OUTLINE",
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    " <ul>",
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    " <a class=\"sr_button\" href=\"#H22319378\" id=\"summRecButton\">",
    " <span>",
    " SUMMARY &amp; RECOMMENDATIONS",
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    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H631646146\">",
    " INTRODUCTION",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H10851452\">",
    " EPIDEMIOLOGY COMMON TO VIBRIO SPECIES",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H631646153\">",
    " SPECIES THAT PRIMARILY CAUSE DIARRHEA",
    " </a>",
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    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H631646161\">",
    " V. mimicus",
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    " <a class=\"outlineLink\" href=\"#H631646168\">",
    " - Epidemiology",
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    " - Epidemiology",
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    " - Clinical manifestations",
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    " V. furnissii",
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    " Grimontia (Vibrio) hollisae",
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    " SPECIES THAT PRIMARILY CAUSE WOUND INFECTIONS",
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    " DIAGNOSIS",
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    " TREATMENT",
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    " Diarrheal disease",
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    " SUMMARY AND RECOMMENDATIONS",
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    " <a href=\"#references\">",
    " REFERENCES",
    " </a>",
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    " Vibrio cases by month",
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    source=related_link\">",
    " Vibrio vulnificus infections",
    " </a>",
    " </li>",
    " </ul>",
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    " </div>"].join("\n");
    var title_f0_31_505="Treatment of central diabetes insipidus";
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    " Treatment of central diabetes insipidus",
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    " Author",
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    " <p class=\"headingAnchor\" id=\"H1\">",
    " <span class=\"h1\">",
    " INTRODUCTION",
    " </span>",
    " &nbsp;&mdash;&nbsp;The major symptoms of central diabetes insipidus (DI) are
    polyuria, nocturia, and polydipsia due to the concentrating defect. Treatment of
    this disorder is primarily aimed at decreasing the urine output, usually by
    increasing the activity of antidiuretic hormone (ADH, also called arginine
    vasopressin or AVP).",
    " </p>",
    " <p>",
    " Replacement of previous and ongoing fluid losses is also important. Most
    patients with central DI have a normal or only mildly elevated plasma sodium
    concentration because concurrent stimulation of thirst minimizes the degree of net
    water loss. However, hypernatremia can occur if thirst is impaired or the patient
    has no access to water [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/505/abstract/1\">",
    " 1",
    " </a>",
    " ]. Correction of the hypernatremia requires repair of this free water deficit.
    (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?23/52/24393?
    source=see_link\">",
    " \"Treatment of hypernatremia\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " The treatment of central DI will be reviewed here. The causes of this disorder
    and the approach to the patient with polyuria are discussed separately. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?20/35/21048?
    source=see_link\">",
    " \"Clinical manifestations and causes of central diabetes insipidus\"",
    " </a>",
    " and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?23/47/24312?
    source=see_link\">",
    " \"Diagnosis of polyuria and diabetes insipidus\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H144709921\">",
    " <span class=\"h1\">",
    " CHOICE OF THERAPY",
    " </span>",
    " &nbsp;&mdash;&nbsp;There are three main options for the treatment of polyuria
    in patients with central DI:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?
    source=see_link\">",
    " Desmopressin",
    " </a>",
    " , which is an ADH analog and is the preferred drug in almost all patients.",
    " </li>",
    " <li>",
    " Other drugs, such as",
    " <a class=\"drug drug_general\" href=\"UTD.htm?6/0/6151?source=see_link\">",
    " chlorpropamide",
    " </a>",
    " ,",
    " <a class=\"drug drug_general\" href=\"UTD.htm?25/10/25770?
    source=see_link\">",
    " carbamazepine",
    " </a>",
    " , thiazide diuretics, and nonsteroidal antiinflammatory drugs.",
    " </li>",
    " <li>",
    " A low solute (mostly low sodium, low protein) diet. In normal individuals,
    the urine output is primarily determined by fluid intake, a relationship that is
    mediated by changes in the release of antidiuretic hormone (ADH). When the urine
    osmolality is fixed, as in untreated DI, the urine output is determined by the
    intake and subsequent urinary excretion of solutes (mostly sodium salts and urea),
    which has been called the renal solute load. As an example, at a fixed urine
    osmolality of 100",
    " <span class=\"nowrap\">",
    " mosmol/kg,",
    " </span>",
    " the urine output will be 6",
    " <span class=\"nowrap\">",
    " L/day",
    " </span>",
    " if urinary solute excretion is 600",
    " <span class=\"nowrap\">",
    " mosmol/day",
    " </span>",
    " and 3 L if urinary solute excretion is 300",
    " <span class=\"nowrap\">",
    " mosmol/day",
    " </span>",
    " on a low sodium, reduced protein diet. A low solute diet can be combined
    with a thiazide diuretic. (See",
    " <a class=\"local\" href=\"#H13\">",
    " 'Low solute diet and thiazide diuretics'",
    " </a>",
    " below.)",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " The choice of therapy varies with the severity of the polyuria. Patients with
    partial DI and mild to moderate polyuria and nocturia may be adequately controlled
    with a low solute diet (if acceptable to the patient) and, if necessary, a thiazide
    diuretic. Although these modalities also reduce the urine output in patients with
    marked polyuria and nocturia,",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?source=see_link\">",
    " desmopressin",
    " </a>",
    " therapy is usually required for symptom control. Desmopressin can also be used
    in patients with less severe DI who do not want to comply with a low solute diet.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H216816629\">",
    " <span class=\"h1\">",
    " THERAPEUTIC GOAL",
    " </span>",
    " &nbsp;&mdash;&nbsp;The only symptoms of DI are polyuria, nocturia, and thirst
    (unless the patient has a hypothalamic lesion causing hypodipsia). Thirst is
    essential so that the excess urinary water losses can be replaced. Patients without
    an intact thirst mechanism can develop severe hypernatremia. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?35/63/36857?
    source=see_link&amp;anchor=H9#H9\">",
    " \"Etiology and evaluation of hypernatremia\", section on 'Hypothalamic
    lesions affecting thirst or osmoreceptor function'",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " The initial aim of therapy is to reduce nocturia, thereby providing adequate
    sleep, most often by the administration at bedtime of",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?source=see_link\">",
    " desmopressin",
    " </a>",
    " , which is the",
    " <strong>",
    " preferred therapy",
    " </strong>",
    " for central DI. Once this is achieved, one aims for",
    " <strong>",
    " partial",
    " </strong>",
    " control of the diuresis during the day, since complete control can lead to
    retention of water and hyponatremia.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H216816636\">",
    " <span class=\"h2\">",
    " Risk of hyponatremia",
    " </span>",
    " &nbsp;&mdash;&nbsp;Water retention leading to the development of hyponatremia
    is a potential risk in patients with central DI who are treated with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?source=see_link\">",
    " desmopressin",
    " </a>",
    " or other therapies that increase the response to or secretion of ADH (eg,",
    " <a class=\"drug drug_general\" href=\"UTD.htm?6/0/6151?source=see_link\">",
    " chlorpropamide",
    " </a>",
    " and",
    " <a class=\"drug drug_general\" href=\"UTD.htm?25/10/25770?source=see_link\">",
    " carbamazepine",
    " </a>",
    " ). Once desmopressin is given, the patient has nonsuppressible ADH activity
    and may be unable to excrete ingested water normally, possibly leading to
    hyponatremia, as occurs in patients with the syndrome of inappropriate ADH
    secretion. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?7/46/7913?
    source=see_link&amp;anchor=H3#H3\">",
    " \"Pathophysiology and etiology of the syndrome of inappropriate antidiuretic
    hormone secretion (SIADH)\", section on 'Pathogenesis of hyponatremia'",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " Although thirst will be suppressed by effective therapy, much of the fluid
    intake during the day is not driven by thirst (eg, coffee with breakfast, soda with
    lunch and dinner). In addition, previously untreated patients may have become
    accustomed to drinking large amounts of fluids and may continue to do so for a
    short period after the initiation of effective therapy to control polyuria,
    possibly resulting in the development of hyponatremia. Thus, we suggest measuring
    the serum sodium one to two days after the initiation of",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?source=see_link\">",
    " desmopressin",
    " </a>",
    " therapy and, if the initial measurement is normal, repeating the measurement
    at four days.",
    " </p>",
    " <p>",
    " Once a stable dose of",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?source=see_link\">",
    " desmopressin",
    " </a>",
    " is achieved, annual or biannual monitoring of the serum sodium may be
    performed. If a patient treated with a stable dose of desmopressin begins
    experiencing increased urinary frequency or nocturia,",
    " <span class=\"nowrap\">",
    " and/or",
    " </span>",
    " the serum sodium is elevated, a 24-hour urine should be collected to ascertain
    whether the patient is polyuric.",
    " </p>",
    " <p>",
    " Preventing water retention is more difficult in infants and young children and
    more frequent monitoring of the serum sodium concentration is recommended. (See",
    " <a class=\"local\" href=\"#H45645699\">",
    " 'Monitoring of serum sodium'",
    " </a>",
    " below.)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H216816726\">",
    " <span class=\"h3\">",
    " Dosing to prevent hyponatremia",
    " </span>",
    " &nbsp;&mdash;&nbsp;Given the risk of hyponatremia, patients treated with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?source=see_link\">",
    " desmopressin",
    " </a>",
    " should be educated about the symptoms that may be induced by hyponatremia.
    These include nausea, vomiting, headache, lethargy, and, if severe, seizures and
    coma. Patients should be instructed to call the physician at the first sign of such
    manifestations. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?22/58/23464?
    source=see_link&amp;anchor=H2#H2\">",
    " \"Manifestations of hyponatremia and hypernatremia\", section on
    'Hyponatremia'",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?source=see_link\">",
    " Desmopressin",
    " </a>",
    " dosing is an empiric process. Hyponatremia can usually be avoided by giving
    the",
    " <strong>",
    " minimum",
    " </strong>",
    " desmopressin dose that is required to control the polyuria. The initial aim of
    therapy is to reduce nocturia, thereby permitting adequate sleep. Thus, the first
    dose (0.1 or 0.2 mg tablet or 5 to 10 microg of the nasal spray) is typically given
    at bedtime. The size of and necessity for a daytime dose is determined by the
    effectiveness of the evening dose. If, for example, polyuria does not recur until
    noon, then one-half the evening dose may be sufficient at that time.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H216816692\">",
    " <span class=\"h2\">",
    " Course of DI and duration of therapy",
    " </span>",
    " &nbsp;&mdash;&nbsp;The duration of central DI varies with the cause. As
    examples, DI is permanent in idiopathic disease, most often transient following
    neurosurgery (usually transsphenoidal) or trauma, and may be reversible with
    appropriate therapy in patients with infiltrative diseases. The supportive data are
    presented elsewhere. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?20/35/21048?
    source=see_link\">",
    " \"Clinical manifestations and causes of central diabetes insipidus\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?source=see_link\">",
    " Desmopressin",
    " </a>",
    " therapy should be continued for as long as the patient has symptomatic central
    DI. As mentioned above, the goal of therapy is control of nocturia and partial
    control of polyuria during the day since more aggressive therapy can promote the
    development of hyponatremia. The DI induced by neurosurgery or trauma is often
    transient. Thus, such patients should be questioned carefully at each visit about
    the degree of polyuria. If the polyuria is said to be less pronounced or to have
    ceased, the desmopressin dose can be gradually tapered and eventually withdrawn if
    polyuria does not recur. &nbsp;",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H2\">",
    " <span class=\"h1\">",
    " DESMOPRESSIN",
    " </span>",
    " &nbsp;&mdash;&nbsp;Since the primary problem in central DI is deficient
    secretion of ADH, control of the polyuria can be achieved by hormone replacement.
    In the past, this was achieved by intramuscular injections of vasopressin
    (Pitressin) tannate in oil, which is no longer available. This preparation had two
    problems: the requirement for intramuscular administration; and the occasional
    development of anti-vasopressin antibodies with a secondary increase in urine
    output that appears to be ADH-resistant [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/505/abstract/2\">",
    " 2",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Intramuscular vasopressin has been replaced by",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?source=see_link\">",
    " desmopressin",
    " </a>",
    " (dDAVP), a two-amino acid substitute of ADH that has potent antidiuretic but
    no vasopressor activity [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/505/abstract/3\">",
    " 3",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H144709866\">",
    " <span class=\"h2\">",
    " Preparations",
    " </span>",
    " &nbsp;&mdash;&nbsp;",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?source=see_link\">",
    " Desmopressin",
    " </a>",
    " comes in liquid form that is usually administered intranasally, in an oral
    tablet form, and a parenteral formulation. The intranasal preparation can be blown
    into the nose by the patient with a curved, dose-calibrated small plastic tube or
    delivered with a nasal spray. An initial dose of 5 microg at bedtime can be
    titrated upward in 5 microg increments depending upon the response of the nocturia
    and then additional daytime doses added. The daily maintenance dose is about 5 to
    20 microg once or twice a day.",
    " </p>",
    " <p>",
    " The",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?source=see_link\">",
    " desmopressin",
    " </a>",
    " metered spray bottle is currently used more commonly than the rhinal tube
    because of greater convenience of administration. Although flexibility is more
    limited with the metered spray bottle because the minimum dose is 10 microg, this
    does not represent a problem for most patients. The usual daily maintenance dose is
    10 to 20 microg intranasally once or twice a day. (See",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?source=see_link\">",
    " \"Desmopressin: Drug information\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " An oral tablet preparation of",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?source=see_link\">",
    " desmopressin",
    " </a>",
    " is also available [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/505/abstract/4\">",
    " 4",
    " </a>",
    " ]. The absorption of desmopressin in normal persons is decreased by 40 to 50
    percent when taken with meals [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/505/abstract/5\">",
    " 5",
    " </a>",
    " ]. This usually has little effect on the antidiuretic action but administering
    the drug in the fasting state may be tried if there is a poor response to the usual
    doses taken with meals.",
    " </p>",
    " <p>",
    " The oral form has about one-tenth to one-twentieth the potency of the nasal
    form because only about five percent is absorbed from the gut. Thus, a 0.1 mg
    tablet is the equivalent of 2.5 to 5 microg of the nasal spray. However, because
    the oral dose cannot be precisely predicted from a previous nasal dose, transfer of
    patients from nasal insufflation to oral therapy usually requires some dosage
    retitration.",
    " </p>",
    " <p>",
    " The initial dose of the tablet form is 0.05 mg (one-half a 0.1 mg tablet) at
    bedtime with titration as with the liquid form. The usual daily maintenance dose
    ranges from 0.1 mg to 0.8 mg in divided doses but may be as high as 1.2",
    " <span class=\"nowrap\">",
    " mg/day.",
    " </span>",
    " </p>",
    " <p>",
    " There are few long-term data on the use of the tablet form of",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?source=see_link\">",
    " desmopressin",
    " </a>",
    " . In one study, eight children with central DI were treated and followed for
    up to 3.5 years [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/505/abstract/6\">",
    " 6",
    " </a>",
    " ]. There was no attenuation of the antidiuretic effect and no side effects or
    antibody formation were noted. In another report, ten adults had satisfactory
    maintenance of the antidiuretic effect over one year with doses of 0.3 to 0.6",
    " <span class=\"nowrap\">",
    " mg/day",
    " </span>",
    " given in two to three doses per day; doses larger than 0.2 mg had no greater
    effect, eg, 0.4 versus 0.2 mg, but probably lasted longer [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/505/abstract/7\">",
    " 7",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Although patients generally prefer the oral preparation because of ease of
    administration, not all patients have an adequate response. As a result, we
    recommend starting with the intranasal preparation; this ensures that the patient
    understands what constitutes a good antidiuretic response prior to performing a
    trial of oral therapy.",
    " </p>",
    " <p>",
    " If",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?source=see_link\">",
    " desmopressin",
    " </a>",
    " cannot be administered intranasally or orally, it can be given subcutaneously.
    A usual antidiuretic dose is 1 microg administered subcutaneously every 12 hours.
    Some patients do not respond well to subcutaneous desmopressin due to inadequate
    absorption. Such patients can be treated with 2 microg of desmopressin acetate
    given intravenously over two minutes; the duration of action, as judged by
    increased urine osmolality, will be 12 hours or more [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/505/abstract/8,9\">",
    " 8,9",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?source=see_link\">",
    " Desmopressin",
    " </a>",
    " is",
    " <strong>",
    " safe",
    " </strong>",
    " during pregnancy for both the mother and the fetus [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/505/abstract/10\">",
    " 10",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H4\">",
    " <span class=\"h1\">",
    " OTHER DRUGS",
    " </span>",
    " &nbsp;&mdash;&nbsp;For the vast majority of patients with central DI,",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?source=see_link\">",
    " desmopressin",
    " </a>",
    " is readily available, safe, and effective. Other drugs that can be used are
    thiazide diuretics, which act independent of ADH, and, in patients with partial
    central DI (ie, there is some circulating vasopressin), drugs that increase ADH
    release or enhance ADH effect on the kidney such as",
    " <a class=\"drug drug_general\" href=\"UTD.htm?6/0/6151?source=see_link\">",
    " chlorpropamide",
    " </a>",
    " ,",
    " <a class=\"drug drug_general\" href=\"UTD.htm?25/10/25770?source=see_link\">",
    " carbamazepine",
    " </a>",
    " , clofibrate, and nonsteroidal antiinflammatory drugs. These drugs are
    associated with more side effects than desmopressin and are generally less
    effective, lowering the urine output by 25 to 60 percent, although a greater effect
    may be seen with thiazide diuretics.",
    " </p>",
    " <p>",
    " Thiazide diuretics and nonsteroidal antiinflammatory drugs also constitute the
    only effective therapy for nephrogenic DI, which is characterized by ADH
    resistance. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?23/32/24071?
    source=see_link\">",
    " \"Treatment of nephrogenic diabetes insipidus\"",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H5\">",
    " <span class=\"h2\">",
    " Chlorpropamide",
    " </span>",
    " &nbsp;&mdash;&nbsp;",
    " <a class=\"drug drug_general\" href=\"UTD.htm?6/0/6151?source=see_link\">",
    " Chlorpropamide",
    " </a>",
    " , an oral hypoglycemic agent, is the most commonly used antidiuretic drug
    after",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?source=see_link\">",
    " desmopressin",
    " </a>",
    " [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/505/abstract/11,12\">",
    " 11,12",
    " </a>",
    " ]; it appears to act by enhancing the renal response to ADH or to
    desmopressin. Studies in animals suggest that this response may be mediated by
    enhanced sodium chloride reabsorption in the thick ascending limb (thereby
    increasing the degree of medullary hypertonicity)",
    " <span class=\"nowrap\">",
    " and/or",
    " </span>",
    " by increased collecting tubule permeability to water; how these changes occur
    is unclear [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/505/abstract/13,14\">",
    " 13,14",
    " </a>",
    " ]. The usual dose is 125 to 250 mg, once or twice a day; higher doses may
    produce a somewhat greater response but also increase the risk of hypoglycemia [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/505/abstract/12\">",
    " 12",
    " </a>",
    " ]. Chlorpropamide can lower the urine output by as much as 50 percent [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/505/abstract/11\">",
    " 11",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H6\">",
    " <span class=\"h2\">",
    " Carbamazepine or clofibrate",
    " </span>",
    " &nbsp;&mdash;&nbsp;",
    " <a class=\"drug drug_general\" href=\"UTD.htm?25/10/25770?source=see_link\">",
    " Carbamazepine",
    " </a>",
    " (used to treat seizures and tic douloureux) in a dose of 100 to 300 mg twice
    daily and clofibrate (used in the treatment of hyperlipidemia) in a dose of 500 mg
    every six hours can ameliorate the polyuria in partial central DI [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/505/abstract/12,15,16\">",
    " 12,15,16",
    " </a>",
    " ]. Carbamazepine appears to enhance the response to ADH [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/505/abstract/17\">",
    " 17",
    " </a>",
    " ], whereas clofibrate may increase ADH release [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/505/abstract/16\">",
    " 16",
    " </a>",
    " ]. Carbamazepine can lower the urine output by as much as 50 to 60 percent [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/505/abstract/15\">",
    " 15",
    " </a>",
    " ] and clofibrate by a mean of 50 percent but is not as predictably effective
    as carbamazepine [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/505/abstract/16\">",
    " 16",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H8\">",
    " <span class=\"h2\">",
    " Thiazide diuretics",
    " </span>",
    " &nbsp;&mdash;&nbsp;The induction of mild volume depletion with a low sodium
    diet plus a thiazide diuretic (such as",
    " <a class=\"drug drug_general\" href=\"UTD.htm?8/4/8263?source=see_link\">",
    " hydrochlorothiazide",
    " </a>",
    " , 25 mg once or twice daily or its equivalent) is a first-line therapy in
    nephrogenic DI and is also effective in central DI [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/505/abstract/18,19\">",
    " 18,19",
    " </a>",
    " ]. As little as a 1 to 1.5 kg weight loss can reduce the urine output by more
    than 50 percent, from 10",
    " <span class=\"nowrap\">",
    " L/day",
    " </span>",
    " to below 3.5",
    " <span class=\"nowrap\">",
    " L/day",
    " </span>",
    " in one study of patients with nephrogenic DI [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/505/abstract/20\">",
    " 20",
    " </a>",
    " ]. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?23/32/24071?
    source=see_link&amp;anchor=H5#H5\">",
    " \"Treatment of nephrogenic diabetes insipidus\", section on 'Diuretics'",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " The effect of thiazide diuretics is presumably mediated by a hypovolemia-
    induced increase in proximal sodium and water reabsorption, thereby diminishing
    water delivery to the ADH-sensitive sites in the collecting tubules and reducing
    the urine output. The thiazide effect is additive to that of the other modalities.
    Thiazides also tend to modestly raise the plasma glucose concentration, thereby
    decreasing the likelihood of hypoglycemia in patients who are also treated with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?6/0/6151?source=see_link\">",
    " chlorpropamide",
    " </a>",
    " [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/505/abstract/11\">",
    " 11",
    " </a>",
    " ]. (See",
    " <a class=\"local\" href=\"#H5\">",
    " 'Chlorpropamide'",
    " </a>",
    " above.)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H9\">",
    " <span class=\"h2\">",
    " NSAIDs",
    " </span>",
    " &nbsp;&mdash;&nbsp;Nonsteroidal antiinflammatory drugs (NSAIDs) increase
    urinary concentrating ability by inhibiting the renal synthesis of prostaglandins,
    which are ADH antagonists [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/505/abstract/21\">",
    " 21",
    " </a>",
    " ]. In normal subjects, pretreatment with an NSAID increases the antidiuretic
    effect of a submaximal dose of ADH, amplifying the increase in urine osmolality by
    more than 200",
    " <span class=\"nowrap\">",
    " mosmol/kg",
    " </span>",
    " [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/505/abstract/22\">",
    " 22",
    " </a>",
    " ]. The net effect in patients with DI may be a 25 to 50 percent reduction in
    urine output [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/505/abstract/23-25\">",
    " 23-25",
    " </a>",
    " ], a response that is partially additive to that of a thiazide diuretic [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/505/abstract/24\">",
    " 24",
    " </a>",
    " ].",
    " </p>",
    " <p>",
    " Not all NSAIDs are equally effective in a given patient. As an example, some
    patients have a good response to",
    " <a class=\"drug drug_general\" href=\"UTD.htm?35/50/36649?source=see_link\">",
    " indomethacin",
    " </a>",
    " but derive little if any benefit from",
    " <a class=\"drug drug_general\" href=\"UTD.htm?15/38/15978?source=see_link\">",
    " ibuprofen",
    " </a>",
    " [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/505/abstract/23\">",
    " 23",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H10\">",
    " <span class=\"h1\">",
    " CHILDREN",
    " </span>",
    " &nbsp;&mdash;&nbsp;In addition to removing the underlying causes, if possible,
    children with DI are treated with a low solute diet to reduce urinary solute
    excretion and therefore the urine output, and pharmacologic therapy with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?source=see_link\">",
    " desmopressin",
    " </a>",
    " <span class=\"nowrap\">",
    " and/or",
    " </span>",
    " a thiazide diuretic.",
    " <a class=\"drug drug_general\" href=\"UTD.htm?6/0/6151?source=see_link\">",
    " Chlorpropamide",
    " </a>",
    " ,",
    " <a class=\"drug drug_general\" href=\"UTD.htm?25/10/25770?source=see_link\">",
    " carbamazepine",
    " </a>",
    " and clofibrate should",
    " <strong>",
    " not",
    " </strong>",
    " be used in children, since limited data suggest that they are less effective
    than desmopressin and have significant adverse effects [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/505/abstract/26\">",
    " 26",
    " </a>",
    " ]. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?20/35/21048?
    source=see_link\">",
    " \"Clinical manifestations and causes of central diabetes insipidus\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " The management of central DI varies with the age of the child.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H11\">",
    " <span class=\"h2\">",
    " Older children",
    " </span>",
    " &nbsp;&mdash;&nbsp;Older children with an intact thirst mechanism are able to
    regulate their fluid balance, and independently access free water and monitor their
    urine output. As a result they can be treated in a manner similar to adults with
    oral or intranasal",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?source=see_link\">",
    " desmopressin",
    " </a>",
    " .",
    " </p>",
    " <p>",
    " The dosing of both oral and intranasal",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?source=see_link\">",
    " desmopressin",
    " </a>",
    " in children older than 12 years of age is the same as in adults. (See",
    " <a class=\"local\" href=\"#H2\">",
    " 'Desmopressin'",
    " </a>",
    " above.)",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " The initial oral dose is 0.05 mg at bedtime and is titrated to a desired
    response to an upper daily limit of 1.2 mg (divided two to three times a day).",
    " </li>",
    " <li>",
    " The initial intranasal dose begins at 5 microg at bedtime and is titrated to
    a desired response to an upper daily dose of 40 microg (divided two times a day).",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " In children younger than 12 years of age, the same initial",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?source=see_link\">",
    " desmopressin",
    " </a>",
    " dose is used, but the upper daily limit of the oral medication is 0.8 mg
    (divided two to three times a day), and the upper daily limit of the intranasal
    preparation is 30 microg (divided two times a day).",
    " </p>",
    " <p>",
    " Thiazide diuretic therapy and a low sodium diet are used to induce mild volume
    depletion, which will reduce the urine output. The dose of the thiazide is weight-
    based. Adolescents can be treated with same dose used in adults (",
    " <a class=\"drug drug_general\" href=\"UTD.htm?8/4/8263?source=see_link\">",
    " hydrochlorothiazide",
    " </a>",
    " , 25 mg once or twice daily or its equivalent). (See",
    " <a class=\"local\" href=\"#H8\">",
    " 'Thiazide diuretics'",
    " </a>",
    " above.)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H12\">",
    " <span class=\"h2\">",
    " Infants and small children",
    " </span>",
    " &nbsp;&mdash;&nbsp;Treatment of infants and small children with central DI is
    challenging for the following reasons:",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Oral or intranasal administration of",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?
    source=see_link\">",
    " desmopressin",
    " </a>",
    " is difficult to administer accurately in infants and small children; thus,
    when used, desmopressin is often given subcutaneously. (See",
    " <a class=\"local\" href=\"#H14\">",
    " 'Subcutaneous desmopressin therapy'",
    " </a>",
    " below.)",
    " </li>",
    " <li>",
    " Infants and small children are unable to both access fluids and articulate
    thirst to care providers.",
    " </li>",
    " <li>",
    " It is often challenging to ascertain the volume of urine output in children
    who are not toilet trained.",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " Infants receive all or most of their nutrition in liquid form. As a result,
    they are at risk for hyponatremia when treated with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?source=see_link\">",
    " desmopressin",
    " </a>",
    " therapy because of their high obligatory oral fluid requirement (150",
    " <span class=\"nowrap\">",
    " mL/kg",
    " </span>",
    " per day). Thus, frequent measurement of the serum sodium concentration is
    essential at the initiation of therapy and one to two days after any change in
    desmopressin dose.",
    " </p>",
    " <p>",
    " Two approaches are used to treat infants and small children: a low solute diet
    plus thiazide diuretics, which is generally preferred; and subcutaneous",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?source=see_link\">",
    " desmopressin",
    " </a>",
    " [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/505/abstract/18\">",
    " 18",
    " </a>",
    " ]. With both of these approaches, families need to be taught to monitor urine
    output (frequency and number of wet diapers) and identify signs of hyponatremia or
    hypernatremia, which are often nonspecific and include irritability and lethargy.
    When oral intake is reduced, as occurs with intercurrent illness,",
    " <span class=\"nowrap\">",
    " and/or",
    " </span>",
    " fluid losses are increased, as occurs with vomiting and diarrhea, vigilance
    should be increased to detect signs of hypovolemia (ie, dry mucous membranes,
    decreased urine output, sunken fontanelle, and decreased weight). (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?3/33/3607?
    source=see_link&amp;anchor=H3#H3\">",
    " \"Clinical assessment and diagnosis of hypovolemia (dehydration) in
    children\", section on 'Clinical assessment'",
    " </a>",
    " .)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H13\">",
    " <span class=\"h3\">",
    " Low solute diet and thiazide diuretics",
    " </span>",
    " &nbsp;&mdash;&nbsp;A low solute diet (low salt and low protein [which is
    metabolized to urea]) and a thiazide diuretic can be used to reduce the urine
    output and therefore thirst in infants and toddlers with central DI who are not
    treated with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?source=see_link\">",
    " desmopressin",
    " </a>",
    " . When the urine osmolality is fixed, as in central DI without desmopressin
    therapy, the urine output is determined by the intake and subsequent excretion of
    solutes such as sodium salts and urea, which has been called the renal solute load.
    (See",
    " <a class=\"local\" href=\"#H144709921\">",
    " 'Choice of therapy'",
    " </a>",
    " above.)",
    " </p>",
    " <p>",
    " For infants who are dependent upon a milk diet, human milk is preferred
    because of its proven nutritional and immunologic benefits and a lower solute load
    compared with Similac PM",
    " <span class=\"nowrap\">",
    " 60/40",
    " </span>",
    " (low solute cow milk-based formula), regular cow milk-based formula, soy-based
    formula, and cow's milk (75, 92, 110, 126, and 235",
    " <span class=\"nowrap\">",
    " mosmol/L,",
    " </span>",
    " respectively). (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?31/47/32505?
    source=see_link\">",
    " \"Infant benefits of breastfeeding\"",
    " </a>",
    " .)",
    " </p>",
    " <p>",
    " The efficacy of a low solute diet can be illustrated by the following example.
    Suppose an infant with a daily intake of 750 mL of human milk has a maximum urine
    osmolality of 100",
    " <span class=\"nowrap\">",
    " mosmol/kg.",
    " </span>",
    " This quantity of human milk provides 56 milliosmoles of solute per day (0.75 L
    x 75",
    " <span class=\"nowrap\">",
    " milliosmoles/L)",
    " </span>",
    " so that the daily urine volume would be 0.56 L (56 milliosmoles per",
    " <span class=\"nowrap\">",
    " day/100",
    " </span>",
    " <span class=\"nowrap\">",
    " milliosmoles/L).",
    " </span>",
    " Changing to a regular cow milk-based formula would increase the renal solute
    load to 83",
    " <span class=\"nowrap\">",
    " mosmol/day",
    " </span>",
    " (0.75 L x 110",
    " <span class=\"nowrap\">",
    " milliosmoles/L)",
    " </span>",
    " and the daily urine volume would increase by 0.28 L to 0.84 L (ie, from 560 to
    840",
    " <span class=\"nowrap\">",
    " mL/day).",
    " </span>",
    " </p>",
    " <p>",
    " Thiazide therapy is typically given with the low solute diet to induce mild
    volume depletion, which will further reduce the urine volume. Oral",
    " <a class=\"drug drug_general\" href=\"UTD.htm?8/4/8263?source=see_link\">",
    " hydrochlorothiazide",
    " </a>",
    " is commonly used in infants up to six months of age at a dose of 2 to 3",
    " <span class=\"nowrap\">",
    " mg/kg",
    " </span>",
    " per day divided in two doses, maximum dose: 37.5",
    " <span class=\"nowrap\">",
    " mg/day.",
    " </span>",
    " The dose in older infants and small children is 2",
    " <span class=\"nowrap\">",
    " mg/kg",
    " </span>",
    " per day (divided in two doses).",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H14\">",
    " <span class=\"h3\">",
    " Subcutaneous desmopressin therapy",
    " </span>",
    " &nbsp;&mdash;&nbsp;Infants and small children treated with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?source=see_link\">",
    " desmopressin",
    " </a>",
    " therapy are at considerable risk for water intoxication and hyponatremia as
    they may not be able to eliminate the daily water load. This risk may be increased
    because accurate and consistent dosing of oral and intranasal desmopressin is
    difficult due to variable absorption and the challenge of administering these
    preparations to infants and small children.",
    " </p>",
    " <p>",
    " As a result, if",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?source=see_link\">",
    " desmopressin",
    " </a>",
    " is to be used, several experts prefer subcutaneous desmopressin, which is more
    reliably administered to infants and small children. The starting dose is 0.01",
    " <span class=\"nowrap\">",
    " microg/day,",
    " </span>",
    " which is titrated to a desired response (eg, reduction in urine output, while
    maintaining a normal serum sodium). The reported range of dosing is 0.02 to 0.08",
    " <span class=\"nowrap\">",
    " microg/day",
    " </span>",
    " [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/505/abstract/18,27\">",
    " 18,27",
    " </a>",
    " ].",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H45645699\">",
    " <span class=\"h3\">",
    " Monitoring of serum sodium",
    " </span>",
    " &nbsp;&mdash;&nbsp;Infants and small children differ from older children and
    adults since all or almost all of their calories are consumed as liquids, not as
    solids. As a result, monitoring of the serum sodium concentration and body weight
    is important to detect hypernatremia due to water loss with a low solute diet and
    thiazide diuretic and to detect hyponatremia due to water retention resulting
    from",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?source=see_link\">",
    " desmopressin",
    " </a>",
    " therapy.",
    " </p>",
    " <p>",
    " We suggest the following approach in infants and small children treated with
    a",
    " <strong>",
    " low solute diet and a thiazide diuretic",
    " </strong>",
    " :",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " The serum sodium should initially be measured at least daily.",
    " </li>",
    " <li>",
    " If the serum sodium is normal at one to two days, we suggest repeat
    measurement at three to four days and then at every patient visit. If the serum
    sodium is elevated, fluid intake should be increased and the serum sodium measured
    serially until it is stable in the normal range.",
    " </li>",
    " <li>",
    " The serum sodium should be measured immediately whenever there is an
    alteration in clinical status, particularly when an intercurrent illness impairs
    fluid intake",
    " <span class=\"nowrap\">",
    " and/or",
    " </span>",
    " increases fluid losses, both of which will tend to raise the serum sodium.",
    " </li>",
    " <li>",
    " Infants should be weighed frequently since weight loss or less than expected
    weight gain could be indicative of water loss and hypernatremia in between usual
    measurements of the serum sodium concentration. Normal healthy infants lose up to
    10 percent of their birth weight during the first week of life, a loss that is
    regained by two weeks of age. Thereafter, a healthy infant should gain weight at a
    rate of approximately 30",
    " <span class=\"nowrap\">",
    " g/day",
    " </span>",
    " in the first three months, 20",
    " <span class=\"nowrap\">",
    " g/day",
    " </span>",
    " from three to six months, 15",
    " <span class=\"nowrap\">",
    " g/day",
    " </span>",
    " from six to nine months, 12",
    " <span class=\"nowrap\">",
    " g/day",
    " </span>",
    " from nine to twelve months, and 8",
    " <span class=\"nowrap\">",
    " g/day",
    " </span>",
    " from one to three years. (See",
    " <a class=\"medical medical_review\" href=\"UTD.htm?41/40/42633?
    source=see_link&amp;anchor=H6#H6\">",
    " \"Normal growth patterns in infants and prepubertal children\", section on
    'Weight gain'",
    " </a>",
    " .)",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " We suggest the following approach in infants and small children treated with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?source=see_link\">",
    " desmopressin",
    " </a>",
    " :",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " The serum sodium should be measured at least daily after the initial dose
    of",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?
    source=see_link\">",
    " desmopressin",
    " </a>",
    " as well as after any dose adjustment [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/505/abstract/18,27\">",
    " 18,27",
    " </a>",
    " ].",
    " </li>",
    " <li>",
    " If the serum sodium is normal at one to two days, we suggest repeat
    measurement at three to four days since some young children have a later onset of
    hyponatremia.",
    " </li>",
    " <li>",
    " If any serum sodium measurement is below normal, the",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?
    source=see_link\">",
    " desmopressin",
    " </a>",
    " dose should be reduced and the serum sodium measured one to two days
    later.",
    " </li>",
    " <li>",
    " In children on a stable dose of",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?
    source=see_link\">",
    " desmopressin",
    " </a>",
    " , the serum sodium should be measured every one to two years.",
    " </li>",
    " <li>",
    " Infants should be weighed frequently since more than expected gains, as
    defined in the preceding paragraph, could reflect water retention and
    hyponatremia.",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " Hyponatremia is less likely to occur in older children and adults treated
    with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?source=see_link\">",
    " desmopressin",
    " </a>",
    " since, as noted above, the goal of therapy is only partial control of the
    polyuria during the day, which minimizes the risk of water retention. (See",
    " <a class=\"local\" href=\"#H216816726\">",
    " 'Dosing to prevent hyponatremia'",
    " </a>",
    " above.)",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H15\">",
    " <span class=\"h1\">",
    " PROBLEM WITH INTRAVENOUS FLUID REPLACEMENT",
    " </span>",
    " &nbsp;&mdash;&nbsp;When thirst is intact and there is free access to water,
    most patients with central DI can replace their water losses orally. Patients who
    are unable to drink water must be treated with intravenous dextrose and water
    (because intravenous sterile water without dextrose causes hemolysis).",
    " </p>",
    " <p>",
    " There is a potential complication if this is performed before the polyuria is
    corrected by the administration of",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?source=see_link\">",
    " desmopressin",
    " </a>",
    " . In adults, the intravenous administration of dextrose and water at more than
    1000",
    " <span class=\"nowrap\">",
    " mL/hour",
    " </span>",
    " delivers glucose at a rate that exceeds endogenous metabolic capacity for
    glucose even in patients without diabetes mellitus, possibly leading to severe and
    symptomatic hyperglycemia [",
    " <a class=\"abstract\" href=\"UTD.htm?0/31/505/abstract/28\">",
    " 28",
    " </a>",
    " ]. Thus, intravenous rates of fluid replacement with dextrose in water should
    be limited to a maximum of 500 to 750",
    " <span class=\"nowrap\">",
    " mL/h",
    " </span>",
    " and serum glucose levels should be monitored. Avoiding excess dextrose
    administration can be more readily achieved by administering desmopressin to reduce
    the urine flow rate.",
    " </p>",
    " <p>",
    " This sequence can also occur when patients with central DI and impaired
    consciousness present with polyuria and hypernatremia of unknown cause. One way to
    avoid this is to ensure that patients with central DI have a Medic Alert bracelet
    so that treating physicians will be aware of the need to administer",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?source=see_link\">",
    " desmopressin",
    " </a>",
    " in such instances.",
    " </p>",
    " <p>",
    " The development of hyperglycemia for any reason may have an additional effect
    that can be confusing clinically. Marked glucosuria can lead to an osmotic diuresis
    that is",
    " <strong>",
    " ADH-resistant",
    " </strong>",
    " . In this setting, the urine osmolality is typically similar to the plasma
    osmolality and polyuria is driven by the solute load. The administration of insulin
    to correct the hyperglycemia will restore responsiveness to ADH.",
    " </p>",
    " <p class=\"headingAnchor\" id=\"PATIENT_INFORMATION\">",
    " <span class=\"h1\">",
    " INFORMATION FOR PATIENTS",
    " </span>",
    " &nbsp;&mdash;&nbsp;UpToDate offers two types of patient education materials,
    &ldquo;The Basics&rdquo; and &ldquo;Beyond the Basics.&rdquo; The Basics patient
    education pieces are written in plain language, at the 5",
    " <sup>",
    " th",
    " </sup>",
    " to 6",
    " <sup>",
    " th",
    " </sup>",
    " grade reading level, and they answer the four or five key questions a patient
    might have about a given condition. These articles are best for patients who want a
    general overview and who prefer short, easy-to-read materials. Beyond the Basics
    patient education pieces are longer, more sophisticated, and more detailed. These
    articles are written at the 10",
    " <sup>",
    " th",
    " </sup>",
    " to 12",
    " <sup>",
    " th",
    " </sup>",
    " grade reading level and are best for patients who want in-depth information
    and are comfortable with some medical jargon.",
    " </p>",
    " <p>",
    " Here are the patient education articles that are relevant to this topic. We
    encourage you to print or e-mail these topics to your patients. (You can also
    locate patient education articles on a variety of subjects by searching on
    &ldquo;patient info&rdquo; and the keyword(s) of interest.)",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " Basics topics (see",
    " <a class=\"medical medical_basics\" href=\"UTD.htm?42/55/43889?
    source=see_link\">",
    " \"Patient information: Diabetes insipidus (The Basics)\"",
    " </a>",
    " )",
    " </li>",
    " </ul>",
    " </p>",
    " <p class=\"headingAnchor\" id=\"H27520276\">",
    " <span class=\"h1\">",
    " SUMMARY AND RECOMMENDATIONS",
    " </span>",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " The major symptoms of central diabetes insipidus (DI) are polyuria,
    nocturia, and polydipsia. Most patients have a normal or only mildly elevated
    plasma sodium concentration because concurrent stimulation of thirst minimizes the
    degree of net water loss. Treatment of this disorder is aimed at decreasing the
    urine output. (See",
    " <a class=\"local\" href=\"#H216816629\">",
    " 'Therapeutic goal'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " There are three major therapeutic options: a low solute (sodium and protein)
    diet;",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?
    source=see_link\">",
    " desmopressin",
    " </a>",
    " (dDAVP), an ADH analog; and other drugs, including thiazide diuretics. The
    choice of therapy varies with the severity of the polyuria. Patients with partial
    DI and mild to moderate polyuria and nocturia may be adequately controlled with a
    low solute diet (if acceptable to the patient) and, if necessary, a thiazide
    diuretic. Although these modalities also reduce the urine output in patients with
    marked polyuria and nocturia, desmopressin therapy is usually required for symptom
    control. Desmopressin can also be used in patients with less severe DI who do not
    want to comply with a low solute diet. (See",
    " <a class=\"local\" href=\"#H144709921\">",
    " 'Choice of therapy'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " The initial aim of therapy with",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?
    source=see_link\">",
    " desmopressin",
    " </a>",
    " is to reduce nocturia, thereby permitting adequate sleep; after this is
    achieved, one aims for control of the diuresis during the day. The size of and
    necessity for a daytime dose is determined by the effectiveness of the evening
    dose. (See",
    " <a class=\"local\" href=\"#H2\">",
    " 'Desmopressin'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?
    source=see_link\">",
    " Desmopressin",
    " </a>",
    " can be administered intranasally, orally, subcutaneously, or intravenously.
    The intranasal preparation should be used initially as not all patients respond to
    oral therapy. (See",
    " <a class=\"local\" href=\"#H144709866\">",
    " 'Preparations'",
    " </a>",
    " above.)",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " <ul class=\"hyphen-block\">",
    " <li>",
    " For the intranasal preparation, an initial dose of 5 microg at bedtime can
    be titrated upward in 5 microg increments depending upon the response of the
    nocturia. The usual daily maintenance dose is 5 to 20 microg once or twice a day.",
    " </li>",
    " <li>",
    " For the oral preparation, the initial dose is 0.05 mg (one-half a 0.1 mg
    tablet) at bedtime with subsequent titration as with the intranasal preparation.
    The usual daily maintenance dose ranges from 0.1 mg to 0.8 mg in divided doses but
    may be as high as 1.2",
    " <span class=\"nowrap\">",
    " mg/day.",
    " </span>",
    " </li>",
    " <li>",
    " For the subcutaneous preparation, the usual dose is 1 microg every 12
    hours.",
    " </li>",
    " <li>",
    " For intravenous administration (in patients who do not have an adequate
    response to the subcutaneous preparation), 2 microg of",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?
    source=see_link\">",
    " desmopressin",
    " </a>",
    " acetate may be given over two minutes; the duration of action is 12 hours or
    more.",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " <ul class=\"bullet-block\">",
    " <li>",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?
    source=see_link\">",
    " Desmopressin",
    " </a>",
    " can lead to water retention and hyponatremia if the urine is concentrated
    for most of the day. This can usually be avoided by giving the minimum required
    dose to control the polyuria and not administering another dose until the patient
    has had a period of brisk diuresis, indicating that the effect of the previous dose
    of desmopressin had waned. The serum sodium concentration should be checked at 24
    hours after the initiation of desmopressin therapy and patients educated about the
    symptoms that may be induced by hyponatremia. These include nausea, vomiting,
    headache, lethargy, and, if severe, seizures and coma. Patients should be
    instructed to call the physician if such manifestations occur. (See",
    " <a class=\"local\" href=\"#H216816636\">",
    " 'Risk of hyponatremia'",
    " </a>",
    " above and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?22/58/23464?
    source=see_link&amp;anchor=H2#H2\">",
    " \"Manifestations of hyponatremia and hypernatremia\", section on
    'Hyponatremia'",
    " </a>",
    " .)",
    " </li>",
    " <li>",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?
    source=see_link\">",
    " Desmopressin",
    " </a>",
    " therapy should be continued for as long as the patient has central DI. The
    duration of central DI varies: DI is permanent in idiopathic disease, improves in
    some elderly patients with familial disease, may be transient following
    neurosurgery (usually transsphenoidal), and may be reversible with appropriate
    therapy in patients with infiltrative diseases. (See",
    " <a class=\"local\" href=\"#H216816692\">",
    " 'Course of DI and duration of therapy'",
    " </a>",
    " above and",
    " <a class=\"medical medical_review\" href=\"UTD.htm?20/35/21048?
    source=see_link\">",
    " \"Clinical manifestations and causes of central diabetes insipidus\"",
    " </a>",
    " .)",
    " </li>",
    " <li>",
    " Other drugs that may decrease diuresis include",
    " <a class=\"drug drug_general\" href=\"UTD.htm?6/0/6151?source=see_link\">",
    " chlorpropamide",
    " </a>",
    " ,",
    " <a class=\"drug drug_general\" href=\"UTD.htm?25/10/25770?
    source=see_link\">",
    " carbamazepine",
    " </a>",
    " and clofibrate, nonsteroidal antiinflammatory drug (NSAID) and thiazide
    diuretics. (See",
    " <a class=\"local\" href=\"#H4\">",
    " 'Other drugs'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " The treatment of children with central DI varies with the age of the child.
    (See",
    " <a class=\"local\" href=\"#H10\">",
    " 'Children'",
    " </a>",
    " above.)",
    " </li>",
    " </ul>",
    " </p>",
    " <p>",
    " <ul class=\"hyphen-block\">",
    " <li>",
    " Older children (more than 12 years of age) can be treated in a similar
    manner as adults with oral or intranasal",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?
    source=see_link\">",
    " desmopressin",
    " </a>",
    " . (See",
    " <a class=\"local\" href=\"#H11\">",
    " 'Older children'",
    " </a>",
    " above.)",
    " </li>",
    " <li>",
    " Children younger than 12 years of age may be given the same initial",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?
    source=see_link\">",
    " desmopressin",
    " </a>",
    " dose, but the upper daily limit of the oral medication is 0.8 mg (divided
    two to three times a day), and the upper daily limit of the intranasal preparation
    is 30 microg (divided two times a day). (See",
    " <a class=\"local\" href=\"#H11\">",
    " 'Older children'",
    " </a>",
    " above.)",
    " <br/>",
    " <br/>",
    " Thiazide diuretic therapy and a low sodium diet are used to induce mild
    volume depletion, which will reduce the urine output. The dose of the thiazide is
    weight-based. Adolescents can be treated with same dose used in adults (",
    " <a class=\"drug drug_general\" href=\"UTD.htm?8/4/8263?source=see_link\">",
    " hydrochlorothiazide",
    " </a>",
    " , 25 mg once or twice daily or its equivalent). (See",
    " <a class=\"local\" href=\"#H11\">",
    " 'Older children'",
    " </a>",
    " above.).",
    " </li>",
    " <li>",
    " Infants and small children should be treated with a low solute diet (low
    salt and low protein) plus a thiazide diuretic. This will reduce the urine output
    and therefore thirst in infants and toddlers with central DI. For infants who are
    dependent upon a milk diet, human milk is preferred, if possible, because of its
    proven nutritional and immunologic benefits and lower solute load compared with
    formulae or cow&rsquo;s milk. (See",
    " <a class=\"local\" href=\"#H12\">",
    " 'Infants and small children'",
    " </a>",
    " above.)",
    " <br/>",
    " <br/>",
    " Thiazide therapy is typically given with the low solute diet to induce mild
    volume depletion. Oral",
    " <a class=\"drug drug_general\" href=\"UTD.htm?8/4/8263?source=see_link\">",
    " hydrochlorothiazide",
    " </a>",
    " is commonly used in infants up to six months of age at a dose of 2 to 3",
    " <span class=\"nowrap\">",
    " mg/kg",
    " </span>",
    " per day divided in two doses, maximum dose: 37.5",
    " <span class=\"nowrap\">",
    " mg/day.",
    " </span>",
    " The dose in older infants and small children is 2",
    " <span class=\"nowrap\">",
    " mg/kg",
    " </span>",
    " per day (divided in two doses). (See",
    " <a class=\"local\" href=\"#H13\">",
    " 'Low solute diet and thiazide diuretics'",
    " </a>",
    " above.)",
    " <br/>",
    " <br/>",
    " If",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?
    source=see_link\">",
    " desmopressin",
    " </a>",
    " is required in infants and small children, subcutaneous desmopressin is the
    preferred preparation, since it is more reliably administered and its effect is
    more predictable than oral and intranasal desmopressin. The starting dose is 0.01",
    " <span class=\"nowrap\">",
    " microg/day,",
    " </span>",
    " which is titrated to a desired response (eg, reduction in urine output,
    while maintaining a normal serum sodium). The reported range of dosing is 0.02 to
    0.08",
    " <span class=\"nowrap\">",
    " microg/day.",
    " </span>",
    " (See",
    " <a class=\"local\" href=\"#H14\">",
    " 'Subcutaneous desmopressin therapy'",
    " </a>",
    " above.)",
    " <br/>",
    " <br/>",
    " Infants and small children differ from older children and adults since all
    or almost all of their calories are consumed as liquids, not as solids. As a
    result, monitoring of the serum sodium concentration and body weight is important
    to detect hypernatremia due to water loss with a low solute diet and thiazide
    diuretic and to detect hyponatremia due to water retention resulting from
    desmopressin therapy. (See",
    " <a class=\"local\" href=\"#H45645699\">",
    " 'Monitoring of serum sodium'",
    " </a>",
    " above.)",
    " </li>",
    " </ul>",
    " </p>",
    " </div>",
    " <div id=\"topicAgreement\">",
    " Use of UpToDate is subject to the",
    " <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
    target=\"_blank\">",
    " Subscription and License Agreement",
    " </a>",
    " .",
    " </div>",
    " <div class=\"headingAnchor\" id=\"references\">",
    " <h1>",
    " REFERENCES",
    " </h1>",
    " <ol id=\"reference\">",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/505/abstract/1\">",
    " Mavrakis AN, Tritos NA. Diabetes insipidus with deficient thirst: report of
    a patient and review of the literature. Am J Kidney Dis 2008; 51:851.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/505/abstract/2\">",
    " Vokes TJ, Gaskill MB, Robertson GL. Antibodies to vasopressin in patients
    with diabetes insipidus. Implications for diagnosis and therapy. Ann Intern Med
    1988; 108:190.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/505/abstract/3\">",
    " Richardson DW, Robinson AG. Desmopressin. Ann Intern Med 1985; 103:228.",
    " </a>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/505/abstract/4\">",
    " Stenberg A, L&auml;ckgren G. Desmopressin tablets in the treatment of severe
    nocturnal enuresis in adolescents. Pediatrics 1994; 94:841.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/505/abstract/5\">",
    " Rittig S, Jensen AR, Jensen KT, Pedersen EB. Effect of food intake on the
    pharmacokinetics and antidiuretic activity of oral desmopressin (DDAVP) in hydrated
    normal subjects. Clin Endocrinol (Oxf) 1998; 48:235.",
    " </a>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/505/abstract/6\">",
    " Fjellestad-Paulsen A, Laborde K, Kindermans C, Czernichow P. Water-balance
    hormones during long-term follow-up of oral dDAVP treatment in diabetes insipidus.
    Acta Paediatr 1993; 82:752.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/505/abstract/7\">",
    " Lam KS, Wat MS, Choi KL, et al. Pharmacokinetics, pharmacodynamics, long-
    term efficacy and safety of oral 1-deamino-8-D-arginine vasopressin in adult
    patients with central diabetes insipidus. Br J Clin Pharmacol 1996; 42:379.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/505/abstract/8\">",
    " Rembratt A, Graugaard-Jensen C, Senderovitz T, et al. Pharmacokinetics and
    pharmacodynamics of desmopressin administered orally versus intravenously at
    daytime versus night-time in healthy men aged 55-70 years. Eur J Clin Pharmacol
    2004; 60:397.",
    " </a>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/505/abstract/9\">",
    " Vande Walle J, Stockner M, Raes A, N&oslash;rgaard JP. Desmopressin 30 years
    in clinical use: a safety review. Curr Drug Saf 2007; 2:232.",
    " </a>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/505/abstract/10\">",
    " Ray JG. DDAVP use during pregnancy: an analysis of its safety for mother and
    child. Obstet Gynecol Surv 1998; 53:450.",
    " </a>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/505/abstract/11\">",
    " Webster B, Bain J. Antidiuretic effect and complications of chlorpropamide
    therapy in diabetes insipidus. J Clin Endocrinol Metab 1970; 30:215.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/505/abstract/12\">",
    " Rad&oacute; JP. Combination of carbamazepine and chlorpropamide in the
    treatment of \"hyporesponder\" pituitary diabetes insipidus. J Clin Endocrinol
    Metab 1974; 38:1.",
    " </a>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/505/abstract/13\">",
    " Welch WJ, Ott CE, Lorenz JN, Kotchen TA. Effects of chlorpropamide on loop
    of Henle function and plasma renin. Kidney Int 1986; 30:712.",
    " </a>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/505/abstract/14\">",
    " Rocha AS, Ping WC, Kudo LH. Effect of chlorpropamide on water and urea
    transport in the inner medullary collecting duct. Kidney Int 1991; 39:79.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/505/abstract/15\">",
    " Wales JK. Treatment of diabetes insipidus with carbamazepine. Lancet 1975;
    2:948.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/505/abstract/16\">",
    " Moses AM, Howanitz J, van Gemert M, Miller M. Clofibrate-induced
    antidiuresis. J Clin Invest 1973; 52:535.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/505/abstract/17\">",
    " Gold PW, Robertson GL, Ballenger JC, et al. Carbamazepine diminishes the
    sensitivity of the plasma arginine vasopressin response to osmotic stimulation. J
    Clin Endocrinol Metab 1983; 57:952.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/505/abstract/18\">",
    " Rivkees SA, Dunbar N, Wilson TA. The management of central diabetes
    insipidus in infancy: desmopressin, low renal solute load formula, thiazide
    diuretics. J Pediatr Endocrinol Metab 2007; 20:459.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/505/abstract/19\">",
    " CRAWFORD JD, KENNEDY GC, HILL LE. Clinical results of treatment of diabetes
    insipidus with drugs of the chlorothiazide series. N Engl J Med 1960; 262:737.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/505/abstract/20\">",
    " Earley LE, Orloff J. THE MECHANISM OF ANTIDIURESIS ASSOCIATED WITH THE
    ADMINISTRATION OF HYDROCHLOROTHIAZIDE TO PATIENTS WITH VASOPRESSIN-RESISTANT
    DIABETES INSIPIDUS. J Clin Invest 1962; 41:1988.",
    " </a>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/505/abstract/21\">",
    " Stokes JB. Integrated actions of renal medullary prostaglandins in the
    control of water excretion. Am J Physiol 1981; 240:F471.",
    " </a>",
    " </li>",
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    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/505/abstract/22\">",
    " Berl T, Raz A, Wald H, et al. Prostaglandin synthesis inhibition and the
    action of vasopressin: studies in man and rat. Am J Physiol 1977; 232:F529.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/505/abstract/23\">",
    " Libber S, Harrison H, Spector D. Treatment of nephrogenic diabetes insipidus
    with prostaglandin synthesis inhibitors. J Pediatr 1986; 108:305.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/505/abstract/24\">",
    " Monnens L, Jonkman A, Thomas C. Response to indomethacin and
    hydrochlorothiazide in nephrogenic diabetes insipidus. Clin Sci (Lond) 1984;
    66:709.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/505/abstract/25\">",
    " Allen HM, Jackson RL, Winchester MD, et al. Indomethacin in the treatment of
    lithium-induced nephrogenic diabetes insipidus. Arch Intern Med 1989; 149:1123.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/505/abstract/26\">",
    " Becker DJ, Foley TP Jr. 1-deamino-8-D-arginine vasopressin in the treatment
    of central diabetes insipidus in childhood. J Pediatr 1978; 92:1011.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/505/abstract/27\">",
    " Blanco EJ, Lane AH, Aijaz N, et al. Use of subcutaneous DDAVP in infants
    with central diabetes insipidus. J Pediatr Endocrinol Metab 2006; 19:919.",
    " </a>",
    " </li>",
    " <li>",
    " <a class=\"nounderline abstract\" href=\"UTD.htm?0/31/505/abstract/28\">",
    " Freidenberg GR, Kosnik EJ, Sotos JF. Hyperglycemic coma after suprasellar
    surgery. N Engl J Med 1980; 303:863.",
    " </a>",
    " </li>",
    " </ol>",
    " </div>",
    " <div id=\"topicVersionRevision\">",
    " Topic 2313 Version 10.0",
    " </div>",
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    var outline_f0_31_505=[" <div id=\"toggleOutline\">",
    " <a href=\"#\" title=\"Collapse Topic Outline\">",
    " <img alt=\"\" src=\"./../images/orange_arrow_left.myextg\"/>",
    " </a>",
    " </div>",
    " <div id=\"innerOutline\">",
    " <h1>",
    " TOPIC OUTLINE",
    " </h1>",
    " <div id=\"outline\">",
    " <ul>",
    " <li>",
    " <a class=\"sr_button\" href=\"#H27520276\" id=\"summRecButton\">",
    " <span>",
    " SUMMARY &amp; RECOMMENDATIONS",
    " </span>",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H1\">",
    " INTRODUCTION",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H144709921\">",
    " CHOICE OF THERAPY",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H216816629\">",
    " THERAPEUTIC GOAL",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H216816636\">",
    " Risk of hyponatremia",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H216816726\">",
    " - Dosing to prevent hyponatremia",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H216816692\">",
    " Course of DI and duration of therapy",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H2\">",
    " DESMOPRESSIN",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H144709866\">",
    " Preparations",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H4\">",
    " OTHER DRUGS",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H5\">",
    " Chlorpropamide",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H6\">",
    " Carbamazepine or clofibrate",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H8\">",
    " Thiazide diuretics",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H9\">",
    " NSAIDs",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H10\">",
    " CHILDREN",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H11\">",
    " Older children",
    " </a>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"outlineLink\" href=\"#H12\">",
    " Infants and small children",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H13\">",
    " - Low solute diet and thiazide diuretics",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H14\">",
    " - Subcutaneous desmopressin therapy",
    " </a>",
    " </li>",
    " <li class=\"dashItem\">",
    " <a class=\"outlineLink\" href=\"#H45645699\">",
    " - Monitoring of serum sodium",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H15\">",
    " PROBLEM WITH INTRAVENOUS FLUID REPLACEMENT",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#PATIENT_INFORMATION\">",
    " INFORMATION FOR PATIENTS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#H27520276\">",
    " SUMMARY AND RECOMMENDATIONS",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#references\">",
    " REFERENCES",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " RELATED TOPICS",
    " </h1>",
    " <div id=\"relatedTopics\">",
    " <ul>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?3/33/3607?
    source=related_link\">",
    " Clinical assessment and diagnosis of hypovolemia (dehydration) in children",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?20/35/21048?
    source=related_link\">",
    " Clinical manifestations and causes of central diabetes insipidus",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"drug drug_general\" href=\"UTD.htm?9/60/10184?
    source=related_link\">",
    " Desmopressin: Drug information",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?23/47/24312?
    source=related_link\">",
    " Diagnosis of polyuria and diabetes insipidus",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?35/63/36857?
    source=related_link\">",
    " Etiology and evaluation of hypernatremia",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?31/47/32505?
    source=related_link\">",
    " Infant benefits of breastfeeding",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?22/58/23464?
    source=related_link\">",
    " Manifestations of hyponatremia and hypernatremia",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?41/40/42633?
    source=related_link\">",
    " Normal growth patterns in infants and prepubertal children",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?7/46/7913?
    source=related_link\">",
    " Pathophysiology and etiology of the syndrome of inappropriate antidiuretic
    hormone secretion (SIADH)",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_basics\" href=\"UTD.htm?42/55/43889?
    source=related_link\">",
    " Patient information: Diabetes insipidus (The Basics)",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?23/52/24393?
    source=related_link\">",
    " Treatment of hypernatremia",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"medical medical_review\" href=\"UTD.htm?23/32/24071?
    source=related_link\">",
    " Treatment of nephrogenic diabetes insipidus",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " </div>"].join("\n");
    var title_f0_31_506="Atazanavir: Drug information";
    var content_f0_31_506=[" <noscript>",
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    " <!-- TC:TOPIC_PAGE -->",
    " <div id=\"topicContent\">",
    " <div id=\"drugTitle\">",
    " Atazanavir: Drug information",
    " </div>",
    " <div id=\"lexiTitleImg\">",
    " <img height=\"17\" src=\"./../images/lexiComp/Lexicomp_2012_71x17.myextg\"
    width=\"71\"/>",
    " </div>",
    " <div class=\"clear\">",
    " </div>",
    " <div id=\"drugCopy\">",
    " Copyright 1978-2013 Lexicomp, Inc. All rights reserved.",
    " </div>",
    " <div id=\"topicText\">",
    " (For additional information",
    " <a class=\"drug drug_patient\" href=\"UTD.htm?8/51/9013?source=see_link\">",
    " see \"Atazanavir: Patient drug information\"",
    " </a>",
    " and",
    " <a class=\"drug drug_pediatric\" href=\"UTD.htm?7/7/7290?source=see_link\">",
    " see \"Atazanavir: Pediatric drug information\"",
    " </a>",
    " )",
    " <br/>",
    " For abbreviations and symbols that may be used in Lexicomp (",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?23/39/24183\">",
    " show table",
    " </a>",
    " )",
    " <div class=\"list ubnlist drugH1Div drugBrandNames\" id=\"F137353\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Brand Names: U.S.",
    " </span>",
    " <ul>",
    " <li>",
    " Reyataz&reg;",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"list cbnlist drugH1Div drugBrandNames\" id=\"F855135\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Brand Names: Canada",
    " </span>",
    " <ul>",
    " <li>",
    " Reyataz&reg;",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"ex_sect_xr thclist drugH1Div drugBrandNames\" id=\"F137372\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pharmacologic Category",
    " </span>",
    " <ul>",
    " <li>",
    " Antiretroviral Agent, Protease Inhibitor",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"block doa drugH1Div\" id=\"F137356\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Adult",
    " </span>",
    " <p style=\"text-indent:0em;margin-left:0em;display:inline\">",
    " <b>",
    " Treatment of HIV-1 infection:",
    " </b>",
    " Oral:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Antiretroviral-naive patients:",
    " </b>",
    " Atazanavir 300 mg once daily",
    " <b>",
    " plus",
    " </b>",
    " ritonavir 100 mg once daily",
    " <b>",
    " or",
    " </b>",
    " atazanavir 400 mg once daily in patients unable to tolerate ritonavir.",
    " <b>",
    " Note:",
    " </b>",
    " Recommended (with ritonavir) as a first-line therapy with
    tenofovir/emtricitabine in nonpregnant antiretroviral-naive patients (DHHS, 2013).
    Acceptable alternative regimens would be atazanavir plus lamivudine/zidovudine",
    " <b>",
    " or",
    " </b>",
    " atazanavir plus abacavir/lamivudine. Do not use tenofovir with unboosted
    atazanavir (DHHS, 2013).",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Antiretroviral-experienced patients:",
    " </b>",
    " Atazanavir 300 mg once daily",
    " <b>",
    " plus",
    " </b>",
    " ritonavir 100 mg once daily.",
    " <b>",
    " Note:",
    " </b>",
    " Atazanavir without ritonavir is not recommended in antiretroviral-experienced
    patients with prior virologic failure.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Pregnant patients:",
    " </b>",
    " Atazanavir 300 mg once daily",
    " <b>",
    " plus",
    " </b>",
    " ritonavir 100 mg once daily.",
    " <b>",
    " Note:",
    " </b>",
    " Preferred regimen for pregnant patients who are antiretroviral-naive.
    Postpartum dosage adjustment not needed. Observe patient for adverse events,
    especially within 2 months after delivery. Dose adjustments required for
    concomitant tenofovir",
    " <i>",
    " or",
    " </i>",
    " H",
    " <sub>",
    " 2",
    " </sub>",
    " antagonist use (insufficient information for dose adjustment if",
    " <i>",
    " both",
    " </i>",
    " tenofovir and an H",
    " <sub>",
    " 2",
    " </sub>",
    " antagonist are used). Some experts recommend atazanavir 400 mg plus ritonavir
    100 mg in all pregnant women during the second and third trimesters due to
    decreased plasma concentrations (DHHS [perinatal], 2012).",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;margin-top:2em;text-
    align:justify;\">",
    " <b>",
    " Dosage adjustments for concomitant therapy:",
    " </b>",
    " Oral:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;margin-top:0em;text-
    align:justify;\">",
    " <b>",
    " Coadministration with efavirenz:",
    " </b>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " <i>",
    " Antiretroviral-naive patients:",
    " </i>",
    " Atazanavir 400 mg plus ritonavir 100 mg given with efavirenz 600 mg (all once
    daily but administered at different times; atazanavir and ritonavir with food and
    efavirenz on an empty stomach).",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " <i>",
    " Antiretroviral-experienced patients:",
    " </i>",
    " Concurrent use not recommended due to decreased atazanavir exposure.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Coadministration with didanosine buffered or enteric-coated formulations:",
    " </b>",
    " Administer atazanavir 2 hours before or 1 hour after didanosine buffered or
    enteric coated formulations",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Coadministration with H",
    " <sub>",
    " 2",
    " </sub>",
    " antagonists:",
    " </b>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " <i>",
    " Antiretroviral-naive patients:",
    " </i>",
    " Atazanavir 300 mg plus ritonavir 100 mg given simultaneously with, or at
    least 10 hours after an H",
    " <sub>",
    " 2",
    " </sub>",
    " antagonist equivalent dose of &le;80 mg famotidine/day",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " <i>",
    " Patients unable to tolerate ritonavir:",
    " </i>",
    " Atazanavir 400 mg once daily given at least 2 hours before or at least 10
    hours after an H",
    " <sub>",
    " 2",
    " </sub>",
    " antagonist equivalent daily dose of &le;40 mg famotidine (single dose &le;20
    mg)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " <i>",
    " Antiretroviral-experienced patients:",
    " </i>",
    " Atazanavir 300 mg plus ritonavir 100 mg given simultaneously with, or at
    least 10 hours after an H",
    " <sub>",
    " 2",
    " </sub>",
    " antagonist equivalent dose of &le;40 mg famotidine/day",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " <i>",
    " Antiretroviral-experienced pregnant patients in the second or third
    trimester:",
    " </i>",
    " Atazanavir 400 mg plus ritonavir 100 mg simultaneously with, or at least 10
    hours after an H",
    " <sub>",
    " 2",
    " </sub>",
    " antagonist.",
    " <b>",
    " Note:",
    " </b>",
    " Insufficient information for dose adjustment if tenofovir",
    " <b>",
    " and",
    " </b>",
    " an H",
    " <sub>",
    " 2",
    " </sub>",
    " antagonist are used.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Coadministration with proton pump inhibitors:",
    " </b>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " <i>",
    " U.S. labeling:",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " <i>",
    " Antiretroviral-naive patients:",
    " </i>",
    " Atazanavir 300 mg plus ritonavir 100 mg given 12 hours after a proton pump
    inhibitor equivalent dose of &le;20 mg omeprazole/day",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " <i>",
    " Antiretroviral-experienced patients:",
    " </i>",
    " Concurrent use not recommended. (",
    " <b>",
    " Note:",
    " </b>",
    " One study noted adequate serum concentrations when atazanavir 400 mg plus
    ritonavir 100 mg was given at the same time or 12 hours after omeprazole 20 mg.)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " <i>",
    " Canadian labeling:",
    " </i>",
    " Concurrent use is not recommended; however, if unavoidable, administer
    atazanavir 400 mg plus ritonavir 100 mg once daily with proton pump inhibitor
    equivalent dose of &le;20 mg omeprazole/day.",
    " <b>",
    " Note:",
    " </b>",
    " Manufacturer labeling does not specify patient population (antiretroviral-
    na&iuml;ve and/or experienced) to which dosing recommendation applies.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Coadministration with tenofovir:",
    " </b>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " <i>",
    " Antiretroviral-naive patients:",
    " </i>",
    " Atazanavir 300 mg plus ritonavir 100 mg given with tenofovir 300 mg (all as a
    single daily dose)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " <i>",
    " Antiretroviral-experienced patients:",
    " </i>",
    " Atazanavir 300 mg plus ritonavir 100 mg given with tenofovir 300 mg (all as a
    single daily dose); if H",
    " <sub>",
    " 2",
    " </sub>",
    " antagonist coadministered (not to exceed equivalent daily dose of &le;40 mg
    famotidine), increase atazanavir to 400 mg (plus ritonavir 100 mg) once daily",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " <i>",
    " Antiretroviral-experienced pregnant patients in the second or third
    trimester:",
    " </i>",
    " Atazanavir 400 mg plus ritonavir 100 mg.",
    " <b>",
    " Note:",
    " </b>",
    " Insufficient information for dose adjustment if tenofovir",
    " <b>",
    " and",
    " </b>",
    " an H",
    " <sub>",
    " 2",
    " </sub>",
    " antagonist are used",
    " </p>",
    " </div>",
    " <div class=\"block dop drugH1Div\" id=\"F554147\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Pediatric",
    " </span>",
    " <p>",
    " (For additional information",
    " <a class=\"drug drug_pediatric\" href=\"UTD.htm?7/7/7290?source=see_link\">",
    " see \"Atazanavir: Pediatric drug information\"",
    " </a>",
    " )",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " <b>",
    " Treatment of HIV-1 infection:",
    " </b>",
    " Oral: Children 6 to &lt;18 years:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;\">",
    " <b>",
    " Antiretroviral-naive patients:",
    " </b>",
    " <b>",
    " Note:",
    " </b>",
    " Ritonavir-boosted atazanavir dosing regimen is preferred:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;\">",
    " Ritonavir-unboosted regimen:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:8em;\">",
    " Children 6 years to &lt;13 years: Dose not established; use not recommended",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:8em;\">",
    " Children &ge;13 years and &lt;40 kg",
    " <b>",
    " who are not able to tolerate ritonavir",
    " </b>",
    " : No dosage recommendations provided in the manufacturer&rsquo;s labeling.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:8em;\">",
    " Children &ge;13 years and &ge;40 kg",
    " <b>",
    " who are not able to tolerate ritonavir",
    " </b>",
    " : Atazanavir 400 mg once daily (without ritonavir)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;\">",
    " Ritonavir-boosted regimen:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:8em;\">",
    " 15 to &lt;20 kg: Atazanavir 150 mg once daily",
    " <b>",
    " plus",
    " </b>",
    " ritonavir 100 mg once daily",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:8em;\">",
    " 20 to &lt;40 kg: Atazanavir 200 mg once daily",
    " <b>",
    " plus",
    " </b>",
    " ritonavir 100 mg once daily",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:8em;\">",
    " &ge;40 kg: Atazanavir 300 mg once daily",
    " <b>",
    " plus",
    " </b>",
    " 100 mg ritonavir once daily",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " <i>",
    " Alternate recommendations (DHHS [pediatric], 2011):",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " 15-24 kg: Atazanavir 150 mg once daily",
    " <b>",
    " plus",
    " </b>",
    " ritonavir 80 mg once daily",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " 25-31 kg: Atazanavir 200 mg once daily",
    " <b>",
    " plus",
    " </b>",
    " ritonavir 100 mg once daily",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " 32-38 kg: Atazanavir 250 mg once daily",
    " <b>",
    " plus",
    " </b>",
    " ritonavir 100 mg once daily",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " &ge;39 kg: Atazanavir 300 mg once daily",
    " <b>",
    " plus",
    " </b>",
    " 100 mg ritonavir once daily.",
    " <b>",
    " Note:",
    " </b>",
    " Treatment-naive patients &ge;39 kg and &ge;13 years of age who are unable to
    tolerate ritonavir, refer to adult dosing.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Antiretroviral-experienced patients:",
    " </b>",
    " <b>",
    " Note:",
    " </b>",
    " Atazanavir without ritonavir is not recommended in antiretroviral-experienced
    patients with prior virologic failure:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Ritonavir-unboosted regimen: Use not recommended",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;\">",
    " Ritonavir-boosted regimen:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:8em;text-align:justify;\">",
    " 15 to &lt;20 kg: Atazanavir 150 mg once daily",
    " <b>",
    " plus",
    " </b>",
    " ritonavir 100 mg once daily",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:8em;text-align:justify;\">",
    " 20 to &lt;40 kg: Atazanavir 200 mg once daily",
    " <b>",
    " plus",
    " </b>",
    " ritonavir 100 mg once daily",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:8em;text-align:justify;\">",
    " &ge;40 kg: Atazanavir 300 mg once daily",
    " <b>",
    " plus",
    " </b>",
    " 100 mg ritonavir once daily",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " <i>",
    " Alternate recommendations (DHHS [pediatric], 2011):",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " 25-31 kg: Atazanavir 200 mg once daily",
    " <b>",
    " plus",
    " </b>",
    " ritonavir 100 mg once daily",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " 32-38 kg: Atazanavir 250 mg once daily",
    " <b>",
    " plus",
    " </b>",
    " ritonavir 100 mg once daily",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " &ge;39 kg: Atazanavir 300 mg once daily",
    " <b>",
    " plus",
    " </b>",
    " 100 mg ritonavir once daily",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;margin-top:2em;text-
    align:justify;\">",
    " <b>",
    " Dosing adjustment for concomitant therapy:",
    " </b>",
    " Children (antiretroviral-experienced or antiretroviral-naive patients):",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Coadministration with H",
    " <sub>",
    " 2",
    " </sub>",
    " antagonists, proton pump inhibitors, or tenofovir:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Children 6 to &lt;13 years: Use not recommended.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Children &ge;13 years and &lt;40 kg: Use not recommended.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:6em;text-align:justify;\">",
    " Children &ge;13 years and &ge;40 kg:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:8em;text-align:justify;\">",
    " Ritonavir-unboosted regimen: Use not recommended.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:8em;text-align:justify;\">",
    " Ritonavir-boosted regimen: Refer to adult dosing.",
    " </p>",
    " </div>",
    " <div class=\"block doe drugH1Div\" id=\"F2533373\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Geriatric",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Refer to adult dosing.",
    " </p>",
    " </div>",
    " <div class=\"block dor drugH1Div\" id=\"F137357\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Renal Impairment",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Not on hemodialysis: No dosage adjustment necessary",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Hemodialysis:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;margin-top:0em;text-
    align:justify;\">",
    " <i>",
    " Antiretroviral-naive patients:",
    " </i>",
    " Use boosted therapy of atazanavir 300 mg with ritonavir 100 mg once daily",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;margin-top:0em;text-
    align:justify;\">",
    " <i>",
    " Antiretroviral-experienced patients:",
    " </i>",
    " Not recommended.",
    " </p>",
    " </div>",
    " <div class=\"block doh drugH1Div\" id=\"F137358\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosing: Hepatic Impairment",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Atazanavir:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Mild-to-moderate hepatic insufficiency: Use with caution; if moderate
    insufficiency (Child-Pugh class B) and no prior virologic failure, reduce dose to
    300 mg once daily.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Severe hepatic insufficiency (Child-Pugh class C): Not recommended",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " <b>",
    " Note:",
    " </b>",
    " Patients with underlying hepatitis B or C may be at increased risk of hepatic
    decompensation.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Atazanavir/ritonavir: Use not recommended in hepatic impairment (has not been
    studied).",
    " </p>",
    " </div>",
    " <div class=\"block foc drugH1Div\" id=\"F137329\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dosage Forms: U.S.",
    " </span>",
    " <p style=\"text-indent:0em;text-align:justify;display:inline\">",
    " Excipient information presented when available (limited, particularly for
    generics); consult specific product labeling.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Capsule, oral, as sulfate:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Reyataz&reg;: 100 mg, 150 mg, 200 mg, 300 mg",
    " </p>",
    " </div>",
    " <div class=\"block geq drugH1Div\" id=\"F137315\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Generic Equivalent Available: U.S.",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " No",
    " </p>",
    " </div>",
    " <div class=\"block adm drugH1Div\" id=\"F137332\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Administration",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Administer with food. Swallow capsules whole with water; do not open
    capsules.",
    " </p>",
    " </div>",
    " <div class=\"block use drugH1Div\" id=\"F137330\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Use",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Treatment of HIV-1 infections in combination with at least two other
    antiretroviral agents",
    " </p>",
    " </div>",
    " <div class=\"block ars drugH1Div\" id=\"F137370\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Adverse Reactions Significant",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Includes data from both treatment-naive and treatment-experienced patients.
    Percentages listed for adults unless otherwise specified.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;margin-top:0em;text-
    align:justify;\">",
    " &gt;10%:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Dermatologic: Rash (3% to 21%; median onset 7 weeks)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Endocrine &amp; metabolic: Cholesterol increased (&ge;240 mg/dL: 6% to 25%)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Gastrointestinal: Nausea (3% to 14%), amylase increased (&le;14%)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Hepatic: Bilirubin increased (&ge;2.6 times ULN: 35% to 49%)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Neuromuscular &amp; skeletal: CPK increased (6% to 11%)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Respiratory: Cough (children 21%)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " 2% to 10%:",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Cardiovascular: AV block (first degree: 6%; second degree [children] 2%)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Central nervous system: Headache (1% to 6%; children 7%), peripheral
    neuropathy (&lt;1% to 4%), insomnia (&lt;1% to 3%), depression (2%), fever (2%;
    children 19%), dizziness (&lt;1% to 2%)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Endocrine &amp; metabolic: Triglycerides increased (&lt;1% to 8%),
    hyperglycemia (&ge;251 mg/dL: 5%)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Gastrointestinal: Lipase increased (&lt;1% to 5%), abdominal pain (4%),
    vomiting (3% to 4%; children 8%), diarrhea (1% to 3%; children 8%)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Hematologic: Neutropenia (3% to 7%), hemoglobin decreased (&lt;1% to 5%),
    thrombocytopenia (2%)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Hepatic: Jaundice (5% to 9%; children 13%), ALT increased (&gt;5 times ULN:
    3% to 9%; 10% to 25% in patients seropositive for hepatitis B and/or C), AST
    increased (&gt;5 times ULN: 2% to 7%; 9% to 10% in patients seropositive for
    hepatitis B and/or C)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Neuromuscular &amp; skeletal: Myalgia (4%)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " Respiratory: Rhinorrhea (children 6%)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " &lt;2%, postmarketing, and/or case reports: Alopecia, arthralgia, AV block
    (second- and third-degree, rare), cholecystitis, cholelithiasis, cholestasis,
    diabetes mellitus, DRESS syndrome, edema, erythema multiforme, immune
    reconstitution syndrome, left bundle branch block, macropapular rash,
    nephrolithiasis, pancreatitis, PR prolongation, pruritus, QT",
    " <sub>",
    " c",
    " </sub>",
    " prolongation, Stevens-Johnson syndrome, torsade de pointes",
    " </p>",
    " </div>",
    " <div class=\"block coi drugH1Div\" id=\"F137335\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Contraindications",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Hypersensitivity (eg, Stevens-Johnson syndrome, erythema multiforme, or toxic
    skin eruptions) to atazanavir or any component of the formulation; concurrent
    therapy with alfuzosin, cisapride, ergot derivatives (dihydroergotamine,
    ergonovine, ergotamine, methylergonovine), indinavir, irinotecan, lovastatin,
    midazolam (oral), pimozide, rifampin, sildenafil (when used for pulmonary artery
    hypertension [eg, Revatio&reg;]), simvastatin, St John&rsquo;s wort, or triazolam",
    " </p>",
    " <p style=\"text-indent:0em;margin-top:2em;\">",
    " Canadian labeling: Additional contraindications (not in U.S. labeling):
    Concomitant use of quinidine or bepridil (currently not marketed in Canada)",
    " </p>",
    " </div>",
    " <div class=\"block war drugH1Div\" id=\"F137319\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Warnings/Precautions",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " <i>",
    " Concerns related to adverse effects:",
    " </i>",
    " </b>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Elevated bilirubin: Asymptomatic elevations in bilirubin
    (unconjugated) occur commonly during therapy; consider alternative therapy if
    bilirubin is &gt;5 times ULN. Evaluate alternative etiologies if transaminase
    elevations also occur.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Fat redistribution: May cause redistribution of fat (eg, buffalo hump,
    peripheral wasting with increased abdominal girth, cushingoid appearance).",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Hypersensitivity reactions: Protease inhibitors have been associated
    with a variety of hypersensitivity events (some severe), including rash,
    anaphylaxis (rare), angioedema, bronchospasm, erythema multiforme, Stevens-Johnson
    syndrome (rare), and/or toxic skin eruptions (including DRESS [drug rash,
    eosinophilia and systemic symptoms] syndrome). It is generally recommended to
    discontinue treatment if severe rash or moderate symptoms accompanied by other
    systemic symptoms occur.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Immune reconstitution syndrome: Patients may develop immune
    reconstitution syndrome resulting in the occurrence of an inflammatory response to
    an indolent or residual opportunistic infection during initial HIV treatment or
    activation of autoimmune disorders (eg, Graves&rsquo; disease, polymyositis,
    Guillain-Barr&eacute; syndrome) later in therapy; further evaluation and treatment
    may be required.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Nephrolithiasis: Cases have been reported in postmarketing
    surveillance; temporary or permanent discontinuation of therapy should be
    considered if symptoms develop.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " <i>",
    " Disease-related concerns:",
    " </i>",
    " </b>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Conduction abnormalities: May prolong PR interval, use with caution in
    patients with pre-existing conduction abnormalities or with medications which
    prolong AV conduction (dosage adjustment required with some agents); rare cases of
    second-degree AV block have been reported.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Diabetes: Changes in glucose tolerance, hyperglycemia, exacerbation of
    diabetes, DKA, and new-onset diabetes mellitus have been reported in patients
    receiving protease inhibitors.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Hemophilia A or B: Use with caution in patients with hemophilia A or
    B; increased bleeding during protease inhibitor therapy has been reported.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Hepatic impairment: Protease inhibitors may cause hepatitis and/or
    exacerbate pre-existing hepatic dysfunction; use with caution in patients with
    underlying hepatic disease, such as hepatitis B or C or cirrhosis; monitor
    closely.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " <i>",
    " Concurrent drug therapy issues:",
    " </i>",
    " </b>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; High potential for interactions: Concomitant use of atazanavir with
    some drugs may require cautious use, may not be recommended, may require dosage
    adjustments, or may be contraindicated.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " <i>",
    " Special populations:",
    " </i>",
    " </b>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " &bull; Pediatrics: Do not use in children &lt;3 months of age due to
    potential for kernicterus.",
    " </p>",
    " </div>",
    " <div class=\"block cyt drugH1Div\" id=\"F137366\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Metabolism/Transport Effects",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " <b>",
    " Substrate",
    " </b>",
    " of CYP3A4 (major);",
    " <b>",
    " Note:",
    " </b>",
    " Assignment of Major/Minor substrate status based on clinically relevant drug
    interaction potential;",
    " <b>",
    " Inhibits",
    " </b>",
    " CYP1A2 (weak), CYP2C8 (weak), CYP2C9 (weak), CYP3A4 (strong), UGT1A1",
    " </p>",
    " </div>",
    " <div class=\"block dri drugH1Div\" id=\"F137323\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Drug Interactions",
    " </span>",
    " <br/>",
    " <br/>",
    " <div class=\"lexi\" id=\"lexiInteractAddInfo\">",
    " (For additional information:",
    " <a class=\"dip\" href=\"./drug-interaction\" target=\"_blank\">",
    " Launch Lexi-Interact&trade; Drug Interactions Program",
    " </a>",
    " )",
    " </div>",
    " <div class=\"lexi\" id=\"lexiInteractImgB\">",
    " <img border=\"0\" height=\"17\"
    src=\"./../images/lexiComp/Lexicomp_2012_71x17.myextg\" width=\"71\"/>",
    " </div>",
    " <div class=\"clear\">",
    " </div>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Abacavir: Protease Inhibitors may decrease the serum concentration of
    Abacavir.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Ado-Trastuzumab Emtansine: CYP3A4 Inhibitors (Strong) may increase serum
    concentrations of the active metabolite(s) of Ado-Trastuzumab Emtansine.
    Specifically, strong CYP3A4 inhibitors may increase concentrations of the cytotoxic
    DM1 component.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Alfuzosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of
    Alfuzosin.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Alfuzosin: Protease Inhibitors may increase the serum concentration of
    Alfuzosin.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Almotriptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Almotriptan. Management: Limit initial almotriptan adult dose to 6.25 mg and
    maximum adult dose to 12.5 mg/24-hrs when used with a strong CYP3A4 inhibitor.
    Avoid concurrent use in patients with impaired hepatic or renal function.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Alosetron: CYP3A4 Inhibitors (Strong) may increase the serum concentration of
    Alosetron.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " ALPRAZolam: Protease Inhibitors may increase the serum concentration of
    ALPRAZolam. Management: Concurrent use of alprazolam with indinavir is
    contraindicated. All patients receiving such a combination should be monitored
    closely for excessive response to alprazolam.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Amiodarone: Protease Inhibitors may decrease the metabolism of Amiodarone.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Antacids: May decrease the absorption of Atazanavir.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Antacids: May decrease the absorption of Protease Inhibitors.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Apixaban: CYP3A4 Inhibitors (Strong) may increase the serum concentration of
    Apixaban. Management: Apixaban U.S. prescribing information states dose reduction
    criteria that may be applied under some circumstances. The apixaban Canadian
    product monograph suggests that any combined use is contraindicated. See full
    interaction monograph for details.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " ARIPiprazole: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of ARIPiprazole. Management: See full interaction monograph for details.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " AtorvaSTATin: Protease Inhibitors may increase the serum concentration of
    AtorvaSTATin. Management: Maximum adult atorvastatin doses: 20 mg/day with
    darunavir/ritonavir, fosamprenavir, fosamprenavir/ritonavir, saquinavir/ritonavir;
    40 mg/day with nelfinavir; lowest necessary dose with lopinavir/ritonavir. Avoid
    atorvastatin with tipranavir/ritonavir.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Avanafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of
    Avanafil.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Axitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of
    Axitinib. Management: Avoid concurrent use of axitinib with any strong CYP3A
    inhibitor whenever possible. If a strong CYP3A inhibitor must be used with
    axitinib, a 50% axitinib dose reduction is recommended.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Bedaquiline: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Bedaquiline. Management: Limit the duration of concomitant administration of
    bedaquiline with CYP3A4 inhibitors to no more than 14 days, unless the benefit of
    continued administration is judged to outweigh the possible risks. Monitor for
    toxic effects of bedaquiline.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Boceprevir: May decrease the serum concentration of Protease Inhibitors.
    Protease Inhibitors may decrease the serum concentration of Boceprevir. Management:
    Avoid initiating coadministration of boceprevir with ritonavir-boosted atazanavir,
    darunavir, or lopinavir. Monitor for reduced HIV and HCV infection responses when
    boceprevir is combined with any ritonavir-boosted HIV protease inhibitor regimen.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Bortezomib: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Bortezomib.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Bosentan: Atazanavir may increase the serum concentration of Bosentan.
    Bosentan may decrease the serum concentration of Atazanavir. Management:
    Concurrent use of atazanavir (without ritonavir) and bosentan is not recommended.
    Bosentan dose adjustments are required when used together with
    atazanavir/ritonavir.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Bosutinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of
    Bosutinib.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Brentuximab Vedotin: CYP3A4 Inhibitors (Strong) may increase the serum
    concentration of Brentuximab Vedotin. Specifically, concentrations of the active
    monomethyl auristatin E (MMAE) component may be increased.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Brinzolamide: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Brinzolamide.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Budesonide (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum
    concentration of Budesonide (Nasal).",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Budesonide (Systemic, Oral Inhalation): CYP3A4 Inhibitors (Strong) may
    increase the serum concentration of Budesonide (Systemic, Oral Inhalation).
    Management: Consider reducing the oral budesonide dose when used together with a
    CYP3A4 inhibitor. This interaction is likely less severe with orally inhaled
    budesonide. Monitor patients closely for signs/symptoms of corticosteroid
    excess.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Buprenorphine: Atazanavir may increase the serum concentration of
    Buprenorphine. Buprenorphine may decrease the serum concentration of Atazanavir.
    Management: Avoid this combination in patients un-boosted atazanavir due to
    possible decreased atazanavir concentrations. This combination is not
    contraindicated in patients also receiving ritonavir, but monitoring for
    buprenorphine toxicity is recommended.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Cabozantinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Cabozantinib.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Calcium Channel Blockers (Dihydropyridine): Protease Inhibitors may decrease
    the metabolism of Calcium Channel Blockers (Dihydropyridine).",
    " <b>",
    " Exceptions:",
    " </b>",
    " Clevidipine.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Calcium Channel Blockers (Nondihydropyridine): Protease Inhibitors may
    decrease the metabolism of Calcium Channel Blockers (Nondihydropyridine). Increased
    serum concentrations of the calcium channel blocker may increase risk of AV nodal
    blockade. Management: Avoid concurrent use when possible. If this combination is
    used, monitor for evidence of toxicity. The manufacturer of atazanavir recommends a
    50% dose reduction for diltiazem be considered. Saquinavir or tipranavir use with
    bepridil is contraindicated.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " CarBAMazepine: May increase the metabolism of Protease Inhibitors. Protease
    Inhibitors may decrease the metabolism of CarBAMazepine.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Cisapride: Protease Inhibitors may increase the serum concentration of
    Cisapride. This may result in QTc prolongation and malignant cardiac arrhythmias.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Clarithromycin: Protease Inhibitors may diminish the therapeutic effect of
    Clarithromycin. Specifically, certain protease inhibitors may decrease formation of
    the active 14-hydroxy-clarithromycin metabolite, which may negatively impact
    clarithromycin effectiveness vs. H. influenzae and other non-MAC infections.
    Clarithromycin may increase the serum concentration of Protease Inhibitors.
    Protease Inhibitors may increase the serum concentration of Clarithromycin.
    Clarithromycin dose adjustment in renally impaired patients may be needed.
    Management: Avoid clarithromycin doses greater than 1000 mg/day when used with a
    protease inhibitor. Further dose reductions may be needed in patients with impaired
    renal function. Consider alternative antimicrobial for any non-MAC infection.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Colchicine: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Colchicine. Management: Colchicine is contraindicated in patients with impaired
    renal or hepatic function who are also receiving a strong CYP3A4 inhibitor. In
    those with normal renal and hepatic function, reduce colchicine dose as directed.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Conivaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Conivaptan.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Contraceptives (Estrogens): Protease Inhibitors may decrease the serum
    concentration of Contraceptives (Estrogens). Management: Use oral contraceptives
    containing at least 35mcg ethinyl estradiol with atazanavir/ritonavir, or no more
    than 30mcg in patients receiving atazanavir alone. Use of an alternative, non-
    hormonal contraceptive is recommended with other protease inhibitors.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Contraceptives (Progestins): Atazanavir may increase the serum concentration
    of Contraceptives (Progestins).",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Corticosteroids (Orally Inhaled): CYP3A4 Inhibitors (Strong) may increase the
    serum concentration of Corticosteroids (Orally Inhaled). Management: Monitor for
    signs and symptoms of adrenal suppression if inhaled budesonide or mometasone are
    coadministered with a strong CYP3A4 inhibitor. Avoid combining inhaled fluticasone
    with any strong CYP3A4 inhibitor.",
    " <b>",
    " Exceptions:",
    " </b>",
    " Beclomethasone (Oral Inhalation); Triamcinolone (Systemic).",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Crizotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Crizotinib.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " CycloSPORINE (Systemic): May increase the serum concentration of Protease
    Inhibitors. Protease Inhibitors may increase the serum concentration of
    CycloSPORINE (Systemic).",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " CYP3A4 Inducers (Strong): May increase the metabolism of CYP3A4 Substrates.
    Management: Consider an alternative for one of the interacting drugs. Some
    combinations may be specifically contraindicated. Consult appropriate manufacturer
    labeling.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " CYP3A4 Inhibitors (Moderate): May decrease the metabolism of CYP3A4
    Substrates.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " CYP3A4 Inhibitors (Strong): May decrease the metabolism of CYP3A4
    Substrates.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " CYP3A4 Substrates: CYP3A4 Inhibitors (Strong) may decrease the metabolism of
    CYP3A4 Substrates.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Dasatinib: May increase the serum concentration of CYP3A4 Substrates.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Deferasirox: May decrease the serum concentration of CYP3A4 Substrates.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Delavirdine: May increase the serum concentration of Protease Inhibitors.
    Protease Inhibitors may decrease the serum concentration of Delavirdine.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Didanosine: Atazanavir may decrease the serum concentration of Didanosine.
    Reported with enteric coated didanosine capsules. Didanosine may decrease the serum
    concentration of Atazanavir. Specifically, the buffered formulation of didanosine
    may decrease atazanavir absorption. Management: To avoid therapeutic failure of
    atazanavir the drug should be administered 2 hours before or 1 hour after
    didanosine. This recommendation applies to both buffered didanosine products and
    enteric coated didanosine products.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Dienogest: CYP3A4 Inhibitors (Strong) may increase the serum concentration of
    Dienogest.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Digoxin: Protease Inhibitors may increase the serum concentration of Digoxin.
    Increased serum concentrations of digoxin may increase risk of AV nodal blockade.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Divalproex: Protease Inhibitors may decrease the serum concentration of
    Divalproex.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Dronedarone: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Dronedarone.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Dutasteride: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Dutasteride.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Efavirenz: May decrease the serum concentration of Atazanavir. Management:
    When used with efavirenz, the atazanavir regimen should be atazanavir 400
    mg/ritonavir 100 mg daily for treatment-naive patients; treatment-experienced
    patients should not use atazanavir together with efavirenz.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Enfuvirtide: May increase the serum concentration of Protease Inhibitors.
    Protease Inhibitors may increase the serum concentration of Enfuvirtide.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Enzalutamide: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Enzalutamide.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Eplerenone: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Eplerenone.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Eplerenone: Protease Inhibitors may decrease the metabolism of Eplerenone.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Ergot Derivatives: Protease Inhibitors may increase the serum concentration
    of Ergot Derivatives.",
    " <b>",
    " Exceptions:",
    " </b>",
    " Cabergoline.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Etravirine: Atazanavir may increase the serum concentration of Etravirine.
    Etravirine may decrease the serum concentration of Atazanavir.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Everolimus: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Everolimus.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " FentaNYL: CYP3A4 Inhibitors (Strong) may increase the serum concentration of
    FentaNYL. Management: Monitor patients extra closely for several days following
    initiation of the combination, and fentanyl dosage reductions should be made as
    appropriate.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Fesoterodine: CYP3A4 Inhibitors (Strong) may increase serum concentrations of
    the active metabolite(s) of Fesoterodine. Management: Avoid fesoterodine doses
    greater than 4 mg daily in adult patients who are also receiving strong CYP3A4
    inhibitors.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Fluticasone (Nasal): CYP3A4 Inhibitors (Strong) may increase the serum
    concentration of Fluticasone (Nasal).",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Fluticasone (Oral Inhalation): CYP3A4 Inhibitors (Strong) may increase the
    serum concentration of Fluticasone (Oral Inhalation).",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Fusidic Acid: May decrease the metabolism of Protease Inhibitors. Protease
    Inhibitors may decrease the metabolism of Fusidic Acid.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Garlic: May decrease the serum concentration of Protease Inhibitors.
    Management: Concurrent use of garlic supplements with protease inhibitors is not
    recommended. If this combination is used, monitor closely for altered serum
    concentrations/effects of protease inhibitors, and particularly for signs/symptoms
    of therapeutic failure.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " GuanFACINE: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of GuanFACINE.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " H2-Antagonists: May decrease the serum concentration of Atazanavir.
    Management: Specific dose limitations and administration guidelines exist; consult
    full interaction monograph or atazanavir prescribing information.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Halofantrine: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Halofantrine.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk
    and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-
    Prolonging Agents. Management: Avoid such combinations when possible. Use should
    be accompanied by close monitoring for evidence of QT prolongation or other
    alterations of cardiac rhythm.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Ifosfamide: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of
    the active metabolite(s) of Ifosfamide.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Iloperidone: CYP3A4 Inhibitors (Strong) may increase serum concentrations of
    the active metabolite(s) of Iloperidone. Specifically, concentrations of the
    metabolites P88 and P95 may be increased. CYP3A4 Inhibitors (Strong) may increase
    the serum concentration of Iloperidone. Management: Reduce iloperidone dose by
    half when administered with a strong CYP3A4 inhibitor.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Indinavir: Atazanavir may enhance the adverse/toxic effect of Indinavir.
    Indinavir may enhance the adverse/toxic effect of Atazanavir.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Irinotecan: Atazanavir may increase the serum concentration of Irinotecan.
    The metabolism (via glucuronidation) of the active SN-38 metabolite may be
    primarily impacted by this interaction.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Ivabradine: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Ivabradine.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Ivacaftor: CYP3A4 Inhibitors (Strong) may increase the serum concentration of
    Ivacaftor. Management: Decrease ivacaftor dose to 150 mg twice a week in patients
    also receiving strong CYP3A4 inhibitors.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Ixabepilone: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Ixabepilone.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Lapatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of
    Lapatinib. Management: If an overlap in therapy cannot be avoided, consider
    reducing lapatinib dose to 500 mg/day during, and within 1 week of completing,
    treatment with the strong CYP3A4 inhibitor.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Lomitapide: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Lomitapide.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Lovastatin: Protease Inhibitors may increase the serum concentration of
    Lovastatin.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Lovastatin: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Lovastatin.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Lumefantrine: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Lumefantrine.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Lurasidone: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Lurasidone.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Maraviroc: CYP3A4 Inhibitors (Strong) may increase the serum concentration of
    Maraviroc. Management: Reduce the adult dose of maraviroc to 150 mg twice daily
    when used with a strong CYP3A4 inhibitor. Do not use maraviroc with strong CYP3A4
    inhibitors in patients with Clcr less than 30 mL/min.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Meperidine: Protease Inhibitors may enhance the adverse/toxic effect of
    Meperidine. Protease Inhibitors may decrease the serum concentration of Meperidine.
    Concentrations of the toxic Normeperidine metabolite may be increased.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " MethylPREDNISolone: CYP3A4 Inhibitors (Strong) may increase the serum
    concentration of MethylPREDNISolone. Management: Consider methylprednisolone dose
    titration and/or adjustments in patients receiving strong CYP3A4 inhibitors (eg,
    azole antifungals, protease inhibitors) and monitor for increased steroid related
    adverse effects.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Midazolam: Protease Inhibitors may increase the serum concentration of
    Midazolam. Management: Oral midazolam contraindicated with all protease
    inhibitors. IV midazolam contraindicated with fosamprenavir and nelfinavir; other
    protease inhibitors recommend caution, close monitoring, and consideration of lower
    IV midazolam doses with concurrent use.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Mifepristone: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Mifepristone. Management: Limit mifepristone adult dose, when used for
    treatment of hyperglycemia in Cushing's syndrome, to a maximum of 300 mg/day when
    combined with a strong CYP3A4 inhibitor. Monitor for increased mifepristone
    toxicity regardless of dose or indication.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Minocycline: May decrease the serum concentration of Atazanavir.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate
    Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk
    QTc-Prolonging Agents.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Nefazodone: Protease Inhibitors may increase the serum concentration of
    Nefazodone.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Nevirapine: Atazanavir may increase the serum concentration of Nevirapine.
    Nevirapine may decrease the serum concentration of Atazanavir.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Nilotinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of
    Nilotinib.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Nisoldipine: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Nisoldipine.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Paricalcitol: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Paricalcitol.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Pazopanib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of
    Pazopanib. Management: Avoid concurrent use of pazopanib with strong inhibitors of
    CYP3A4 whenever possible. If it is not possible to avoid such a combination,
    reduce pazopanib adult dose to 400 mg. Further dose reductions may also be
    required.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Pimecrolimus: CYP3A4 Inhibitors (Strong) may decrease the metabolism of
    Pimecrolimus.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Pimozide: Protease Inhibitors may decrease the metabolism of Pimozide.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Pimozide: CYP3A4 Inhibitors (Strong) may increase the serum concentration of
    Pimozide.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Pitavastatin: Atazanavir may increase the serum concentration of
    Pitavastatin.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Pomalidomide: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Pomalidomide.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Ponatinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of
    Ponatinib. Management: Per ponatinib U.S. prescribing information, the starting
    dose of ponatinib should be reduced to 30 mg daily during treatment with any strong
    CYP3A4 inhibitor.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Posaconazole: May increase the serum concentration of Atazanavir.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Prasugrel: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of
    the active metabolite(s) of Prasugrel.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Propafenone: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Propafenone.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Protease Inhibitors: May increase the serum concentration of other Protease
    Inhibitors. Management: Atazanavir--indinavir combination contraindicated.
    Tipranavir/ritonavir or atazanavir/ritonavir not recommended with other protease
    inhibitors. Other combos may require dose changes.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Proton Pump Inhibitors: May decrease the serum concentration of Atazanavir.
    Management: Avoid concurrent PPI in HIV treatment-experienced patients. For
    treatment-naive patients, atazanavir/ritonavir dose should be given approximately
    12 hours after the PPI, and the PPI should not exceed the equivalent of 20 mg
    omeprazole.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " QuiNIDine: Protease Inhibitors may decrease the metabolism of QuiNIDine.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Ranolazine: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Ranolazine.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Red Yeast Rice: CYP3A4 Inhibitors (Strong) may increase the serum
    concentration of Red Yeast Rice. Specifically, concentrations of lovastatin and
    related compounds found in Red Yeast Rice may be increased.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Regorafenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Regorafenib.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Rifabutin: Atazanavir may increase serum concentrations of the active
    metabolite(s) of Rifabutin. Atazanavir may increase the serum concentration of
    Rifabutin.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Rifampin: May decrease the serum concentration of Atazanavir.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Rivaroxaban: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Rivaroxaban.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " RomiDEPsin: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of RomiDEPsin.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Rosuvastatin: Protease Inhibitors may increase the serum concentration of
    Rosuvastatin. Management: Start with the lowest possible rosuvastatin dose and
    monitor for signs/symptoms of toxicity. In adult patients receiving
    atazanavir/ritonavir or lopinavir/ritonavir, initiate rosuvastatin at a 5 mg/day
    and do not exceed a dose of 10 mg/day.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Ruxolitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Ruxolitinib. Management: Reduce ruxolitinib initial adult dose to 10 mg twice
    daily in patients receiving strong CYP3A4 inhibitors whose platelet count is
    100*10^9/L or greater. Avoid in patients with lower platelet count.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Salmeterol: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Salmeterol.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Saxagliptin: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Saxagliptin. Management: Saxagliptin U.S. product labeling recommends limiting
    saxagliptin adult dose to 2.5 mg/day when used with a strong CYP3A4 inhibitor.
    Monitor for increased saxagliptin levels/effects. A similar recommendation is not
    made in the Canadian product labeling.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Sildenafil: Protease Inhibitors may increase the serum concentration of
    Sildenafil. Management: Erectile dysfunction: sildenafil max = 25 mg/48 hrs with
    ritonavir, atazanavir, or darunavir; starting dose = 25 mg with other protease
    inhibitors (adult doses). Contraindicated if sildenafil being used for pulmonary
    arterial hypertension.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Sildenafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Sildenafil. Management: When used for treatment of pulmonary arterial
    hypertension, use of sildenafil with strong CYP3A4 inhibitors should be avoided.
    When used for erectile dysfunction, starting dose should be reduced to 25 mg. Max
    dose with ritonavir is 25 mg per 48 hours.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Silodosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration of
    Silodosin.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Simvastatin: Protease Inhibitors may increase the serum concentration of
    Simvastatin.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Simvastatin: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Simvastatin.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Sirolimus: Protease Inhibitors may increase the serum concentration of
    Sirolimus.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " SORAfenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration of
    SORAfenib.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " St Johns Wort: May increase the metabolism of Protease Inhibitors.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Tacrolimus (Systemic): Protease Inhibitors may decrease the metabolism of
    Tacrolimus (Systemic).",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Tacrolimus (Topical): Protease Inhibitors may decrease the metabolism of
    Tacrolimus (Topical).",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Tadalafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration of
    Tadalafil. Management: Recommendations regarding use of tadalafil in patients also
    receiving strong CYP3A4 inhibitors may vary based on indication and/or
    international labeling. Consult appropriate product labeling.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Tamsulosin: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Tamsulosin.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Telaprevir: Atazanavir may decrease the serum concentration of Telaprevir.
    Telaprevir may increase the serum concentration of Atazanavir.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Temsirolimus: Protease Inhibitors may enhance the adverse/toxic effect of
    Temsirolimus. Levels of sirolimus, the active metabolite, may be increased, likely
    due to inhibition of CYP-mediated metabolism.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Tenofovir: Atazanavir may increase the serum concentration of Tenofovir.
    Tenofovir may decrease the serum concentration of Atazanavir. Management: When
    combined use required, tenofovir 300 mg and atazanavir 300 mg should be used with
    ritonavir 100 mg (adult doses), all given in single daily dose with food.
    Atazanavir without ritonavir should not be used with tenofovir.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Theophylline Derivatives: Protease Inhibitors may decrease the serum
    concentration of Theophylline Derivatives.",
    " <b>",
    " Exceptions:",
    " </b>",
    " Dyphylline.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Ticagrelor: CYP3A4 Inhibitors (Strong) may decrease serum concentrations of
    the active metabolite(s) of Ticagrelor. CYP3A4 Inhibitors (Strong) may increase the
    serum concentration of Ticagrelor.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Tofacitinib: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Tofacitinib. Management: Reduce the adult dose of tofacitinib to 5 mg daily in
    patients receiving strong CYP3A4 inhibitors.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Tolterodine: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Tolterodine. Management: The maximum recommended dose of long-acting
    tolterodine is 2 mg/day when used together with a strong CYP3A4 inhibitor.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Tolvaptan: CYP3A4 Inhibitors (Strong) may increase the serum concentration of
    Tolvaptan.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Toremifene: CYP3A4 Inhibitors (Strong) may enhance the adverse/toxic effect
    of Toremifene. CYP3A4 Inhibitors (Strong) may increase the serum concentration of
    Toremifene.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " TraZODone: Atazanavir may increase the serum concentration of TraZODone.
    Management: Consider using a lower dose of trazodone when used in combination with
    atazanavir.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Triazolam: Protease Inhibitors may increase the serum concentration of
    Triazolam.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Tricyclic Antidepressants: Protease Inhibitors may increase the serum
    concentration of Tricyclic Antidepressants.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Valproic Acid: Protease Inhibitors may decrease the serum concentration of
    Valproic Acid.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Vardenafil: Protease Inhibitors may increase the serum concentration of
    Vardenafil. Management: Limit vardenafil adult dose to max of 2.5 mg/72 hrs with
    ritonavir, atazanavir, or darunavir; limit to max adult dose of 2.5 mg/24 hrs with
    other protease inhibitors.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Vardenafil: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Vardenafil. Management: Recommendations regarding concomitant use of vardenafil
    with strong CYP3A4 inhibitors may vary depending on brand name (e.g., Levitra,
    Staxyn) or by international labeling. Consult appropriate product labeling for
    specific recommendations.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Vemurafenib: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Vemurafenib.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Vilazodone: CYP3A4 Inhibitors (Strong) may increase the serum concentration
    of Vilazodone. Management: Limit maximum adult vilazodone dose to 20 mg/day in
    patients receiving strong CYP3A4 inhibitors.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " VinCRIStine (Liposomal): CYP3A4 Inhibitors (Strong) may increase the serum
    concentration of VinCRIStine (Liposomal).",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Voriconazole: Atazanavir may decrease the serum concentration of
    Voriconazole. Atazanavir may increase the serum concentration of Voriconazole.
    Voriconazole may decrease the serum concentration of Atazanavir. Management:
    Voriconazole should not be used in a patient who is being treated with ritonavir-
    boosted atazanavir unless the benefits of the combination outweigh the potential
    risks. Extra monitoring for both loss of effectivness and toxicity is warranted.",
    " <i>",
    " Risk X: Avoid combination",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Warfarin: Atazanavir may increase the serum concentration of Warfarin.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Zidovudine: Protease Inhibitors may decrease the serum concentration of
    Zidovudine.",
    " <i>",
    " Risk C: Monitor therapy",
    " </i>",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;\">",
    " Zuclopenthixol: CYP3A4 Inhibitors (Strong) may increase the serum
    concentration of Zuclopenthixol. Management: Consider zuclopenthixol dosage
    reduction with concomitant use of a strong CYP3A4 inhibitor (eg, ketoconazole) in
    poor CYP2D6 metabolizers or with strong CYP2D6 inhibitors (eg, paroxetine). Monitor
    for increased zuclopenthixol levels/toxicity.",
    " <i>",
    " Risk D: Consider therapy modification",
    " </i>",
    " </p>",
    " </div>",
    " <div class=\"block foi drugH1Div\" id=\"F137349\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Ethanol/Nutrition/Herb Interactions",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Food: Bioavailability of atazanavir increased when taken with food.
    Management: Administer with food.",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Herb/Nutraceutical: St John's wort decreases serum concentrations of protease
    inhibitors and may lead to treatment failures. Garlic may decrease the serum
    concentration of protease inhibitors. Management: Concurrent use of St John's wort
    is contraindicated. Use of garlic supplements while taking protease inhibitors is
    not recommended.",
    " </p>",
    " </div>",
    " <div class=\"block prf drugH1Div\" id=\"F137325\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pregnancy Risk Factor",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " B (",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?16/42/17068\">",
    " show table",
    " </a>",
    " )",
    " </p>",
    " </div>",
    " <div class=\"block pri drugH1Div\" id=\"F137339\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pregnancy Implications",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Teratogenic effects have not been observed in animal reproduction studies.
    Atazanavir crosses the placenta with cord blood concentrations reported as 13% to
    21% of maternal serum concentrations at delivery. An increased risk of teratogenic
    effects has not been observed based on information collected by the antiretroviral
    pregnancy registry. A small increased risk of preterm birth has been associated
    with maternal use of protease inhibitor-based combination antiretroviral (ARV)
    therapy during pregnancy; however, the benefits of use generally outweigh this risk
    and protease inhibitors (PIs) should not be withheld if otherwise recommended.
    Hyperglycemia, new onset of diabetes mellitus, or diabetic ketoacidosis have been
    reported with PIs; it is not clear if pregnancy increases this risk.
    Hyperbilirubinemia or hypoglycemia may occur in neonates following",
    " <i>",
    " in utero",
    " </i>",
    " exposure to atazanavir, although data are conflicting.",
    " </p>",
    " <p style=\"text-indent:0em;margin-top:2em;\">",
    " The DHHS Perinatal HIV Guidelines recommend atazanavir as a preferred PI when
    combined with low-dose ritonavir boosting. Pharmacokinetic studies suggest that
    standard dosing during pregnancy may provide decreased plasma concentrations and
    some experts recommend increased doses during the second and third trimesters.
    However, the manufacturer notes that dose adjustment is not required unless using
    concomitant H",
    " <sub>",
    " 2",
    " </sub>",
    " -receptor blockers or tenofovir or for ARV-naive pregnant women taking
    efavirenz. May give as once-daily dosing.",
    " </p>",
    " <p style=\"text-indent:0em;margin-top:2em;\">",
    " Regardless of CD4 count or HIV RNA copy number, all HIV-infected pregnant
    women should receive a combination antepartum ARV drug regimen; this includes women
    who require therapy for their own health, as well as women who do not yet require
    therapy for their own health. ARV therapy should be started as soon as possible if
    required for the woman&rsquo;s health Although earlier initiation may be more
    effective in reducing the perinatal transmission of HIV), also consider maternal
    conditions (eg, nausea and vomiting) and the potential risks of first trimester
    fetal exposure for specific agents. Plasma HIV RNA levels should be assessed at
    ~34-36 weeks gestation in order to help determine mode of delivery. If ARV therapy
    must be interrupted for &lt;24 hours during the peripartum period, stop then
    restart all medications simultaneously in order to decrease the chance of
    developing resistance. Long-term follow-up is recommended for all infants exposed
    to ARV medications.",
    " </p>",
    " <p style=\"text-indent:0em;margin-top:2em;\">",
    " Healthcare providers are encouraged to enroll pregnant women exposed to
    antiretroviral medications in the Antiretroviral Pregnancy Registry (1-800-258-4263
    or www.APRegistry.com). Healthcare providers caring for HIV-infected women and
    their infants may contact the National Perinatal HIV Hotline (888-448-8765) for
    clinical consultation (DHHS [perinatal], 2012).",
    " </p>",
    " </div>",
    " <div class=\"block lac drugH1Div\" id=\"F137361\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Lactation",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Enters breast milk/contraindicated",
    " </p>",
    " </div>",
    " <div class=\"block brc drugH1Div\" id=\"F137340\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Breast-Feeding Considerations",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Maternal or infant antiretroviral therapy does not completely eliminate the
    risk of postnatal HIV transmission. In addition, multiclass-resistant virus has
    been detected in breast-feeding infants despite maternal therapy. Therefore, in the
    United States, where formula is accessible, affordable, safe, and sustainable, and
    the risk of infant mortality due to diarrhea and respiratory infections is low,
    complete avoidance of breast-feeding by HIV-infected women is recommended to
    decrease potential transmission of HIV (DHHS [perinatal], 2012).",
    " </p>",
    " </div>",
    " <div class=\"block dic drugH1Div\" id=\"F137341\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Dietary Considerations",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Must be taken with food; enhances absorption.",
    " </p>",
    " </div>",
    " <div class=\"block fee drugH1Div\" id=\"F137338\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pricing: U.S. (Medi-Span&reg;)",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " <b>",
    " Capsules",
    " </b>",
    " (Reyataz Oral)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " 100 mg (60): $1318.66",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " 150 mg (60): $1318.66",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " 200 mg (60): $1318.66",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:4em;text-align:justify;\">",
    " 300 mg (30): $1306.20",
    " </p>",
    " </div>",
    " <div class=\"block mop drugH1Div\" id=\"F137327\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Monitoring Parameters",
    " </span>",
    " <p style=\"text-indent:0em;display:inline\">",
    " Viral load, CD4, serum glucose; liver function tests, bilirubin, drug levels
    (with certain concomitant medications), ECG monitoring in patients with prolonged
    PR interval or with concurrent AV nodal blocking drugs",
    " </p>",
    " </div>",
    " <div class=\"list fbnlist drugH1Div drugBrandNames\" id=\"F137342\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " International Brand Names",
    " </span>",
    " <ul>",
    " <li>",
    " Atazor (IN);",
    " </li>",
    " <li>",
    " Reyataz (AR, AT, AU, BE, BG, CH, CL, CN, CO, CZ, DE, DK, EE, ES, FI, FR, GB,
    GR, HK, HN, ID, IE, IL, IT, KP, MT, MX, MY, NL, NO, NZ, PE, PL, PT, RU, SE, SG, SK,
    TH, TR, TW, UY)",
    " </li>",
    " </ul>",
    " </div>",
    " <div class=\"block pha drugH1Div\" id=\"F137318\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Mechanism of Action",
    " </span>",
    " <p style=\"text-indent:0em;text-align:justify;display:inline\">",
    " Binds to the site of HIV-1 protease activity and inhibits cleavage of viral
    Gag-Pol polyprotein precursors into individual functional proteins required for
    infectious HIV. This results in the formation of immature, noninfectious viral
    particles.",
    " </p>",
    " </div>",
    " <div class=\"block phk drugH1Div\" id=\"F137334\"
    xmlns=\"file://www.w3.org/1999/xhtml\">",
    " <span class=\"drugH1\">",
    " Pharmacodynamics/Kinetics",
    " </span>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Absorption: Rapid; enhanced with food",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Protein binding: 86%",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Metabolism: Hepatic, via multiple pathways including CYP3A4; forms two
    metabolites (inactive)",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Half-life elimination: Unboosted therapy: 7-8 hours; Boosted therapy (with
    ritonavir): 9-18 hours",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Time to peak, plasma: 2-3 hours",
    " </p>",
    " <p style=\"text-indent:-2em;margin-left:2em;text-align:justify;\">",
    " Excretion: Feces (79%, 20% of total dose as unchanged drug); urine (13%, 7%
    of total dose as unchanged drug)",
    " </p>",
    " </div>",
    " </div>",
    " <div id=\"topicAgreement\">",
    " Use of UpToDate is subject to the",
    " <a class=\"licenseLink\" href=\"./license\" id=\"sla_in_page\"
    target=\"_blank\">",
    " Subscription and License Agreement",
    " </a>",
    " .",
    " </div>",
    " <div class=\"headingAnchor\" id=\"references\">",
    " <h1>",
    " REFERENCES",
    " </h1>",
    " <ol id=\"reference\">",
    " <li>",
    " <div class=\"reference\">",
    " DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents,
    &ldquo;Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and
    Adolescents, Department of Health and Human Services,&rdquo; February 12, 2013;1-
    267. Available at",
    " <a href=\"file://aidsinfo.nih.gov/Guidelines/GuidelineDetail.aspx?
    GuidelineID=7&amp;ClassID=1\" target=\"_blank\">",
    " file://www.aidsinfo.nih.gov",
    " </a>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " DHHS Panel on Treatment of HIV-Infected Pregnant Women and Prevention of
    Perinatal Transmission, \"Recommendations for Use of Antiretroviral Drugs in
    Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce
    Perinatal HIV Transmission in the United States,\" July 31, 2012. Available at",
    " <a
    href=\"file://aidsinfo.nih.gov/contentfiles/lvguidelines/perinatalgl.pdf\"
    target=\"_blank\">",
    " file://aidsinfo.nih.gov/contentfiles/lvguidelines/perinatalgl.pdf",
    " </a>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Molina JM, Andrade-Villanueva J, Echevarria J, et al, &ldquo;Once-Daily
    Atazanavir/Ritonavir Compared With Twice-Daily Lopinavir/Ritonavir, Each in
    Combination With Tenofovir and Emtricitabine, for Management of Antiretroviral-
    Naive HIV-1-Infected Patients: 96-Week Efficacy and Safety Results of the CASTLE
    Study,&rdquo;",
    " <i>",
    " J Acquir Immune Defic Syndr",
    " </i>",
    " , 2010, 53(3):323-32.",
    " <span class=\"pubmed-id\">",
    " [PubMed",
    " <a href=\"UTD.htm?0/31/506/abstract-text/20032785/pubmed\" id=\"20032785\"
    target=\"_blank\">",
    " 20032785",
    " </a>",
    " ]",
    " </span>",
    " </div>",
    " </li>",
    " <li>",
    " <div class=\"reference\">",
    " Working Group on Antiretroviral Therapy and Medical Management of HIV-
    Infected Children, &ldquo;Guidelines for the Use of Antiretroviral Agents in
    Pediatric HIV Infection,&rdquo; August 16, 2010. Available at",
    " <a href=\"file://www.aidsinfo.nih.gov\" target=\"_blank\">",
    " file://www.aidsinfo.nih.gov",
    " </a>",
    " </div>",
    " </li>",
    " </ol>",
    " </div>",
    " <div id=\"topicVersionRevision\">",
    " Topic 9353 Version 51.0",
    " </div>",
    " </div>",
    " <div id=\"footer\">",
    " <div id=\"supportFooter\">",
    " <span class=\"sfInfo\">",
    " &copy; 2013 UpToDate, Inc. All rights reserved.",
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    " |",
    " </span>",
    " <a class=\"licenseLink\" href=\"./license\" id=\"sla_footer\">",
    " Subscription and License Agreement",
    " </a>",
    " <span class=\"sfInfo\">",
    " <span class=\"pipeSpace\">",
    " |",
    " </span>",
    " Release: 21.3 - C21.34",
    " </span>",
    " <br/>",
    " <span class=\"sfInfo\">",
    " Licensed to:",
    " <span class=\"emphasis\">",
    " Morehouse School of Medicine",
    " </span>",
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    " |",
    " </span>",
    " Support Tag: [1104-118.195.65.244-FC54B750F8-S473950.14]",
    " <br/>",
    " </span>",
    " </div>",
    " </div>",
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    " </a>",
    " </div>",
    " <div id=\"innerOutline\">",
    " <h1>",
    " TOPIC OUTLINE",
    " </h1>",
    " <div id=\"outline\">",
    " <ul>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F137353\">",
    " Brand Names: U.S.",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F855135\">",
    " Brand Names: Canada",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F137372\">",
    " Pharmacologic Category",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F137356\">",
    " Dosing: Adult",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F554147\">",
    " Dosing: Pediatric",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F2533373\">",
    " Dosing: Geriatric",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F137357\">",
    " Dosing: Renal Impairment",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F137358\">",
    " Dosing: Hepatic Impairment",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F137329\">",
    " Dosage Forms: U.S.",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F137315\">",
    " Generic Equivalent Available: U.S.",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F137332\">",
    " Administration",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F137330\">",
    " Use",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F137370\">",
    " Adverse Reactions Significant",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F137335\">",
    " Contraindications",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F137319\">",
    " Warnings/Precautions",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F137366\">",
    " Metabolism/Transport Effects",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F137323\">",
    " Drug Interactions",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F137349\">",
    " Ethanol/Nutrition/Herb Interactions",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F137325\">",
    " Pregnancy Risk Factor",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F137339\">",
    " Pregnancy Implications",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F137361\">",
    " Lactation",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F137340\">",
    " Breast-Feeding Considerations",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F137341\">",
    " Dietary Considerations",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F137338\">",
    " Pricing: U.S. (Medi-Span&reg;)",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F137327\">",
    " Monitoring Parameters",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F137342\">",
    " International Brand Names",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F137318\">",
    " Mechanism of Action",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"outlineLink\" href=\"#F137334\">",
    " Pharmacodynamics/Kinetics",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a href=\"#references\">",
    " REFERENCES",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " <div class=\"openRelatedGraphics\" id=\"DRUG_GEN/9353\" rel=\"outline_link\">",
    " GRAPHICS",
    " <a class=\"graphics_icon\" href=\"#\" title=\"View All Related Graphics\">",
    " View All",
    " </a>",
    " </div>",
    " </h1>",
    " <div id=\"relatedGraphics\">",
    " <ul>",
    " <li class=\"plainItem\">",
    " <div class=\"openRelatedGraphics\" id=\"DRUG_GEN/9353|TAB\">",
    " <a href=\"#\" title=\"TABLES\">",
    " TABLES",
    " </a>",
    " </div>",
    " </li>",
    " <li class=\"bulletItem\">",
    " <a class=\"graphic graphic_table\" href=\"UTD.htm?23/39/24183\"
    title=\"Lexicomp clinical abbreviations\">",
    " Lexicomp clinical abbreviations",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " <h1>",
    " RELATED TOPICS",
    " </h1>",
    " <div id=\"relatedTopics\">",
    " <ul>",
    " <li class=\"plainItem\">",
    " <a class=\"drug drug_patient\" href=\"UTD.htm?8/51/9013?
    source=related_link\">",
    " Atazanavir: Patient drug information",
    " </a>",
    " </li>",
    " <li class=\"plainItem\">",
    " <a class=\"drug drug_pediatric\" href=\"UTD.htm?7/7/7290?
    source=related_link\">",
    " Atazanavir: Pediatric drug information",
    " </a>",
    " </li>",
    " </ul>",
    " </div>",
    " </div>"].join("\n");
    var title_f0_31_507="Poisons causing nystagmus";
    var content_f0_31_507=[" <div id=\"graphicsToolbar\">",
    " <div id=\"graphicsCopy\">",
    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
    " </div>",
    " <div id=\"graphicsLinks\">",
    " <a href=\"?imageKey=EM
    %2F74834&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\">",
    " <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
    title=\"Print this page\"/>",
    " </a>",
    " <a class=\"icontxt textLink\" href=\"?imageKey=EM
    %2F74834&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\"
    title=\"Print this page\">",
    " Print",
    " </a>",
    " <a class=\"etacLink\" href=\"#\">",
    " <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
    title=\"Email graphic(s)\"/>",
    " </a>",
    " <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
    " Email",
    " </a>",
    " </div>",
    " </div>",
    " <div class=\"graphic\">",
    " <div class=\"figure\">",
    " <div class=\"ttl\">",
    " Common poisonings that can cause nystagmus",
    " </div>",
    " <div class=\"cntnt\">",
    " <table cellspacing=\"0\">",
    " <tbody>",
    " <tr>",
    " <td>",
    " Anticonvulsants: carbamazepine, phenytoin",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Barbiturates",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Dextromethorphan",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Ethanol",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Ketamine",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Lithium",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Phencyclidine",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Scorpion sting",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Serotonin syndrome",
    " </td>",
    " </tr>",
    " </tbody>",
    " </table>",
    " </div>",
    " <div class=\"lgnd\">",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f0_31_507=[""].join("\n");
    var outline_f0_31_507=null;
    var title_f0_31_508="Causes of hemolytic anemia in children";
    var content_f0_31_508=[" <div id=\"graphicsToolbar\">",
    " <div id=\"graphicsCopy\">",
    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
    " </div>",
    " <div id=\"graphicsLinks\">",
    " <a href=\"?imageKey=PEDS
    %2F64454&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\">",
    " <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
    title=\"Print this page\"/>",
    " </a>",
    " <a class=\"icontxt textLink\" href=\"?imageKey=PEDS
    %2F64454&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\"
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    " Print",
    " </a>",
    " <a class=\"etacLink\" href=\"#\">",
    " <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
    title=\"Email graphic(s)\"/>",
    " </a>",
    " <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
    " Email",
    " </a>",
    " </div>",
    " </div>",
    " <div class=\"graphic\">",
    " <div class=\"figure\">",
    " <div class=\"ttl\">",
    " Causes of hemolytic anemia in children",
    " </div>",
    " <div class=\"cntnt\">",
    " <table cellspacing=\"0\">",
    " <tbody>",
    " <tr>",
    " <td class=\"subtitle1_single\">",
    " Intrinsic red blood cell defects",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Enzyme deficiencies (eg, G6PD or pyruvate kinase deficiencies)",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Hemoglobinopathies (eg, sickle cell disease, thalassemias, unstable
    hemoglobins)",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Membrane defects (eg, hereditary spherocytosis, elliptocytosis)",
    " </td>",
    " </tr>",
    " <tr>",
    " <td class=\"subtitle1_single\">",
    " Extrinsic red blood cell defects",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Auto-immune hemolytic anemia (AIHA)",
    " <ul>",
    " <li>",
    " Warm-reactive",
    " </li>",
    " <li>",
    " Cold-reactive (paroxysmal cold hemoglobinuria or cold agglutinin
    disease)",
    " </li>",
    " </ul>",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Liver disease (eg, cirrhosis, hypersplenism, acquired disorders of the red
    cell membrane [see topic review, \"Extrinsic nonimmune hemolytic anemia due to
    systemic disease\"])",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Hypersplenism",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Oxidant agents (eg, dapsone, nitrites, aniline dyes)",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Microangiopathies",
    " <ul>",
    " <li>",
    " Hemolytic-uremic syndrome (HUS)",
    " </li>",
    " <li>",
    " Disseminated intravascular coagulation (DIC)",
    " </li>",
    " <li>",
    " Artificial heart valves",
    " </li>",
    " <li>",
    " Kasabach-Merritt phenomena (destruction of platelets and red blood cells
    within a vascular tumor)",
    " </li>",
    " </ul>",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Paroxysmal cold hemoglobinuria (PCH)",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Paroxysmal nocturnal hemoglobinuria (PNH)",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Use of anti-D immune globulin",
    " </td>",
    " </tr>",
    " </tbody>",
    " </table>",
    " </div>",
    " <div class=\"lgnd\">",
    " <div class=\"footnotes\">",
    " G6PD: glucose-6-phosphate deficiency.",
    " </div>",
    " <div class=\"reference\">",
    " Courtesy of Dr. Michael Recht.",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f0_31_508=[""].join("\n");
    var outline_f0_31_508=null;
    var title_f0_31_509="Pleural effusions in HIV II";
    var content_f0_31_509=[" <div id=\"graphicsToolbar\">",
    " <div id=\"graphicsCopy\">",
    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
    " </div>",
    " <div id=\"graphicsLinks\">",
    " <a href=\"?imageKey=PULM
    %2F71626&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\">",
    " <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
    title=\"Print this page\"/>",
    " </a>",
    " <a class=\"icontxt textLink\" href=\"?imageKey=PULM
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    " </a>",
    " <a class=\"etacLink\" href=\"#\">",
    " <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
    title=\"Email graphic(s)\"/>",
    " </a>",
    " <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
    " Email",
    " </a>",
    " </div>",
    " </div>",
    " <div class=\"graphic\">",
    " <div class=\"figure\">",
    " <div class=\"ttl\">",
    " Pleural effusions in HIV: Differential diagnosis and diagnostic testing
    (continued)",
    " </div>",
    " <div class=\"cntnt\">",
    " <table cellspacing=\"0\">",
    " <tr>",
    " <td class=\"subtitle1\">",
    " Etiology",
    " </td>",
    " <td class=\"subtitle1\">",
    " History/physical exam/lab findings",
    " </td>",
    " <td class=\"subtitle1\">",
    " Pleural fluid characteristics",
    " </td>",
    " <td class=\"subtitle1\">",
    " Additional tests of pleural fluid",
    " </td>",
    " <td class=\"subtitle1\">",
    " Other helpful tests",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Kaposi sarcoma (KS) associated effusion",
    " </td>",
    " <td>",
    " <p>",
    " Skin lesions of KS",
    " </p>",
    " <p>",
    " No pleuritic pain",
    " </p>",
    " </td>",
    " <td>",
    " <p>",
    " Large to massive, bilateral effusion(s)",
    " </p>",
    " <p>",
    " Hemorrhagic fluid",
    " </p>",
    " </td>",
    " <td>",
    " Cytology is negative",
    " </td>",
    " <td>",
    " <p>",
    " Chest radiograph: diffuse pulmonary opacities",
    " </p>",
    " <p>",
    " Endobronchial lesions of KS",
    " </p>",
    " <p>",
    " Pleural biopsy is negative",
    " </p>",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Multicentric Castleman disease",
    " </td>",
    " <td>",
    " <p>",
    " Fever",
    " </p>",
    " <p>",
    " Cough, dyspnea in 60 percent",
    " </p>",
    " <p>",
    " Peripheral lymphadenopathy",
    " </p>",
    " <p>",
    " Anemia",
    " </p>",
    " </td>",
    " <td>",
    " &nbsp;",
    " </td>",
    " <td>",
    " &nbsp;",
    " </td>",
    " <td>",
    " <p>",
    " Chest radiograph: reticular or nodular opacities",
    " </p>",
    " <p>",
    " Chest CT: mediastinal adenopathy as disease progresses",
    " </p>",
    " <p>",
    " Lymph node biopsy",
    " </p>",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Systemic lymphoma",
    " </td>",
    " <td>",
    " <p>",
    " Low CD4 level",
    " </p>",
    " <p>",
    " Serum LDH high",
    " </p>",
    " </td>",
    " <td>",
    " <p>",
    " Large, serosanguinous exudative effusion (may have mass effect)",
    " </p>",
    " <p>",
    " Pleural LDH high",
    " </p>",
    " <p>",
    " Cytology positive (60 percent)",
    " </p>",
    " </td>",
    " <td>",
    " Flow cytometry",
    " </td>",
    " <td>",
    " Pleural biopsy",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Primary effusion lymphoma",
    " </td>",
    " <td>",
    " <p>",
    " Low CD 4 count",
    " </p>",
    " <p>",
    " Preexisting KS in 30 percent",
    " </p>",
    " </td>",
    " <td>",
    " Pleural fluid cytology usually diagnostic",
    " </td>",
    " <td>",
    " <p>",
    " LANA-1 (HHV8) +",
    " </p>",
    " <p>",
    " Lymphocytes often:",
    " </p>",
    " <p>",
    " CD45 +/CD30 +/EMA -/T cell antigen -/LMP1 usually -",
    " </p>",
    " <p>",
    " Monoclonal B cell population by Southern blot",
    " </p>",
    " </td>",
    " <td>",
    " <p>",
    " Chest CT: adjacent parietal pleural thickening and absent
    lymphadenopathy",
    " </p>",
    " <p>",
    " Pericardial effusion and ascites (common)",
    " </p>",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Thromboembolism",
    " </td>",
    " <td>",
    " Risk factor(s) for thromboembolism",
    " </td>",
    " <td>",
    " Exudative, may be serous or serosanguinous",
    " </td>",
    " <td>",
    " &nbsp;",
    " </td>",
    " <td>",
    " <p>",
    " d-Dimer (positive)",
    " </p>",
    " <p>",
    " CT pulmonary angiogram",
    " </p>",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Hypoalbuminemia",
    " </td>",
    " <td>",
    " Bilateral peripheral edema",
    " </td>",
    " <td>",
    " Transudative",
    " </td>",
    " <td>",
    " &nbsp;",
    " </td>",
    " <td>",
    " Serum albumin (low)",
    " </td>",
    " </tr>",
    " <tr>",
    " <td>",
    " Heart failure",
    " </td>",
    " <td>",
    " <p>",
    " Chronic dyspnea",
    " </p>",
    " <p>",
    " Bilateral peripheral edema",
    " </p>",
    " </td>",
    " <td>",
    " Transudative",
    " </td>",
    " <td>",
    " &nbsp;",
    " </td>",
    " <td>",
    " <p>",
    " Serum BNP (elevated)",
    " </p>",
    " <p>",
    " Echocardiogram",
    " </p>",
    " </td>",
    " </tr>",
    " </table>",
    " </div>",
    " <div class=\"lgnd\">",
    " <div class=\"footnotes\">",
    " EMA: epithelial membrane antigen; LANA-1: as latency-associated nuclear
    antigen, a latent HHV8 gene product; LMP1: latent membrane protein 1 of Epstein
    Barr virus.",
    " </div>",
    " <div class=\"reference\">",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
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    var title_f0_31_510="Structure of selectins";
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    " Structure of selectins",
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    " </div>",
    " <div class=\"lgnd\">",
    " The protein structure of selectins is characterized by variable numbers of
    short consensus repeats (related to complement regulatory proteins), an epithelial
    growth factor-like domain, and a C-type (calcium-dependent) lectin domain. Three
    selectins are known to exist: P-selectin, E-selectin, and L-selectin.",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f0_31_510=[""].join("\n");
    var outline_f0_31_510=null;
    var title_f0_31_511="Fusarium toe cellulitis";
    var content_f0_31_511=[" <div id=\"graphicsToolbar\">",
    " <div id=\"graphicsCopy\">",
    " &copy;2013 UpToDate",
    " <sup>",
    " &reg;",
    " </sup>",
    " </div>",
    " <div id=\"graphicsLinks\">",
    " <a href=\"?imageKey=ID
    %2F50045&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\">",
    " <img alt=\"Print this page\" src=\"./../images/icn_print.myextg\"
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    " </a>",
    " <a class=\"icontxt textLink\" href=\"?imageKey=ID
    %2F50045&amp;source=image_view&amp;view=print&amp;elapsedTimeMs=1\" onclick=\"\"
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    " Print",
    " </a>",
    " <a class=\"etacLink\" href=\"#\">",
    " <img alt=\"Email graphic(s)\" src=\"./../images/icn_email.myextg\"
    title=\"Email graphic(s)\"/>",
    " </a>",
    " <a class=\"icontxt textLink etacLink\" href=\"#\" title=\"Email graphic(s)\">",
    " Email",
    " </a>",
    " </div>",
    " </div>",
    " <div class=\"graphic\">",
    " <div class=\"figure\" style=\"width: 470px\">",
    " <div class=\"ttl\">",
    " Fusarium toe cellulitis",
    " </div>",
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    " </div>",
    " <div class=\"lgnd\">",
    " Fusarium toe cellulitis developing at the site of onychomycosis after
    cytotoxic chemotherapy in a 45-year-old woman with lymphoma who underwent
    allogeneic hematopoietic cell transplantation.",
    " <div class=\"footnotes\">",
    " </div>",
    " <div class=\"reference\">",
    " This research was originally published in Blood. Boutati EI, Anaissie EJ.
    Fusarium, a significant emerging pathogen in patients with hematologic malignancy:
    ten years' experience at a cancer center and implications for management. Blood
    1997; 90:999. Copyright &copy; 1997 American Society of Hematology.",
    " </div>",
    " </div>",
    " </div>",
    " </div>",
    "</div>"].join("\n");
    var script_f0_31_511=[""].join("\n");
    var outline_f0_31_511=null;

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