misoprostol - oral, Cytotec

GENERIC NAME: MISOPROSTOL - ORAL (my-so-PROST-ohl)

BRAND NAME(S): Cytotec WARNING: Do not take this medication if you think that you may be pregnant. It may cause abortion, premature birth, or birth defects. In rare cases, serious complications (e.g., uterine rupture) have occurred when misoprostol was used to start labor or when used in combination with another drug to cause abortion after the eighth week of pregnancy. These complications have resulted in harm to the unborn baby and mother. Avoid pregnancy while taking misoprostol and for at least one month or one completed menstrual cycle after you have stopped treatment. If you become pregnant while taking misoprostol, contact your doctor immediately. If you are pregnant, do not take this medication to reduce the risk of stomach ulcers due to aspirin or other related drugs (non-steroidal anti-inflammatory drugs-NSAIDs such as ibuprofen). Also, if you are of childbearing age, do not use this drug to reduce the risk of ulcers from NSAIDs unless you are at high risk of having an ulcer or ulcer complications. Female patients must meet the following four requirements in order to use this drug: 1) test negative for pregnancy within two weeks before starting treatment; 2) use effective birth control to prevent pregnancy; 3) receive oral and written warnings on the dangers of using misoprostol while of childbearing age and the risks of possible birth control failure; 4) start taking misoprostol only on the second or third day of the next normal menstrual period. This medication must not be shared with others. USES: This medication is used to prevent stomach ulcers while you take NSAIDs (e.g., aspirin, ibuprofen, naproxen), especially if you are at risk for developing ulcers or have a history of ulcers. Misoprostol helps to decrease your risk of serious ulcer complications such as bleeding. This medication protects your stomach lining by lowering the amount of acid that comes in contact with it.This medication is also used in combination with another drug (mifepristone) to end a pregnancy (abortion).OTHER This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.This medication may also be used to assist with childbirth only at the time of delivery (e.g., cervical ripening, induction of labor) and for the treatment of severe bleeding after delivery. When misoprostol is used vaginally for these purposes, it works by causing the womb muscles to contract. HOW TO USE: This medicine comes with a patient information leaflet. Read it carefully. If you have any questions about this drug, ask your doctor, nurse, or pharmacist.Dosage is based on your medical condition and response to therapy.If you are taking this drug to prevent stomach ulcers, take it by mouth usually four times a day, after meals and at bedtime to minimize diarrhea, or as directed by your doctor.If you are taking this medication for abortion, take it by mouth exactly as directed by your doctor.If you are using this medication to start labor, your healthcare professional will insert it into your vagina.Avoid taking

antacids that contain magnesium while using misoprostol because they may make the diarrhea it causes worse. If you need an antacid, consult your doctor or pharmacist to help you choose a product.For ulcer prevention, continue to take this drug for as long as you take NSAIDs. Use this medication regularly in order to get the most benefit from it. Remember to use it at the same times each day.Inform your doctor if your condition persists or worsens. SIDE EFFECTS: Nausea or stomach cramps may occur. If any of these effects persist or worsen, notify your doctor or pharmacist promptly.Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.Diarrhea is common with misoprostol and usually occurs about two weeks after you start taking it, and lasts for about a week. Be sure to keep up your intake of fluids and minerals/electrolytes to prevent dehydration. Persistent diarrhea may sometimes lead to a large loss of your body's water and minerals. Tell your doctor immediately if you develop any of these serious signs of dehydration and mineral imbalance: severe dizziness, decreased amount of urine, mental/mood changes, muscle weakness, slow/irregular heartbeat.Tell your doctor immediately if any of these unlikely but serious side effects occur: menstrual problems or irregularities, unusual/heavy vaginal bleeding.A very serious allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of a serious allergic reaction may include: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.In the US -Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA1088.In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345. PRECAUTIONS: Before taking misoprostol, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies.Before using this medication, tell your doctor or pharmacist your medical history, especially of: stomach/intestinal disease (e.g., inflammatory bowel disease), risk factors for uterine rupture when this drug is used vaginally (e.g., prior Cesarean delivery, uterine surgery, five or more previous pregnancies).Daily use of alcohol and tobacco may increase your risk for stomach bleeding. Limit alcohol beverages and stop smoking. Consult your doctor or pharmacist for more information.If you are taking this medication in combination with mifepristone to end a pregnancy, an incomplete abortion may rarely occur. It is very important for you to be closely monitored by your doctor and to keep your scheduled appointments to follow your progress. Be sure to have clear instructions from your doctor about who to call and what to do in case of an emergency. Expect vaginal bleeding after you take the combined medicine, however tell your doctor immediately if you develop any unlikely symptoms such as severe/prolonged vaginal bleeding, signs of infection (e.g., fever, chills), or fainting.This drug must not be used during pregnancy to prevent stomach ulcers because of possible harm to an unborn baby (see also Warnings). If you are of childbearing age, use effective birth control methods while taking misoprostol and for at least one month or one completed menstrual cycle after you stop taking it. If you become pregnant or think you may be pregnant, inform your doctor immediately.This medication passes into breast milk. However, this drug is unlikely to harm a nursing infant. Consult your doctor before breast-feeding.

Prostaglandin Analogs: Misoprostol Chemistry; Mechanism of Action; Pharmacology. Prostaglandin E2 (PGE2) and prostacyclin (PGI2) are the major prostaglandins synthesized by the gastric mucosa. They bind to the EP3 receptor on parietal cells (see Chapter 26) and stimulate the Gi pathway, thereby decreasing intracellular cyclic AMP and gastric acid secretion. PGE2 also can prevent gastric injury by cytoprotective effects that include stimulation of mucin and bicarbonate secretion and increased mucosal blood flow. Although smaller doses than those required for acid suppression can protect the gastric mucosa in laboratory animals, this has not been convincingly demonstrated in humans; acid suppression appears to be the most important effect clinically (Wolfe and Sachs, 2000). Since NSAIDs diminish prostaglandin formation by inhibiting cyclooxygenase, synthetic prostaglandin analogs offer a logical approach to reducing NSAID-induced mucosal damage (see below). Misoprostol (15-deoxy-16-hydroxy-16methyl-PGE1; CYTOTEC) is a synthetic analog of prostaglandin E1. Structural modifications include an additional methyl ester group at C1 that increases potency and duration of antisecretory effect, and transfer of a hydroxyl group from C15 to C16 and addition of a methyl group that increases oral bioactivity, duration of antisecretory action, and safety. The degree of inhibition of gastric acid secretion by misoprostol is directly related to dose; oral doses of 100 to 200 g significantly inhibit basal acid secretion (up to 85% to 95% inhibition) or food-stimulated acid secretion (up to 75% to 85% inhibition). The usual recommended dose for ulcer prophylaxis is 200 g four times a day.

Pharmacodynamics
Misoprostol has both acid inhibitory and mucosal protective properties. It is believed to stimulate mucus and bicarbonate secretion and enhance mucosal blood flow. In addition, it binds to a prostaglandin receptor on parietal cells, reducing histamine-stimulated cAMP production and causing modest acid inhibition. Prostaglandins have a variety of other actions, including stimulation of intestinal electrolyte and fluid secretion, intestinal motility, and uterine contractions.

Pharmacokinetics. Misoprostol is rapidly absorbed after oral administration and then is rapidly and extensively de-esterified to form misoprostol acid, the principal and active metabolite of the drug. Some of this conversion may occur in the parietal cells. A single dose inhibits acid production within 30 minutes; the therapeutic effect peaks at 60 to 90 minutes and lasts for up to 3 hours. Food and antacids decrease the rate of misoprostol absorption, resulting in delayed and decreased peak plasma concentrations of the active metabolite. The free acid is excreted mainly in the urine, with an elimination half-life of about 20 to 40 minutes. Adverse Effects. Diarrhea, with or without abdominal pain and cramps, occurs in up to 30% of patients who take misoprostol. Apparently dose-related, it typically begins within the first 2 weeks after therapy is initiated and often resolves spontaneously within a week; more severe or protracted cases may necessitate drug discontinuation. Misoprostol can cause clinical exacerbations of inflammatory bowel disease (see Chapter 38) and should be avoided in patients with this disorder. Misoprostol is contraindicated during pregnancy because it can increase uterine contractility. Therapeutic Use. Misoprostol is FDA approved to prevent NSAID-induced mucosal injury. However, it rarely is used because of its adverse effects and the inconvenience of four-times-daily dosing. The proton pump inhibitors and H2-receptor antagonists also are used to diminish the gastrointestinal side effects of NSAIDs, but only lansoprazole holds an FDA approved indication for this purpose.