What you eat and drink can affect the way your medicines work.

Use thisguide to alert you to possible food-druginteractions and to help you learn what you can do to prevent them. In this guide, a food-drug interaction is achange in how a medicine works caused by food, caffeine, or alcohol. A food-drug interaction can: prevent a medicine from working theway it should cause a side effect from a medicine to get worse or better cause a new side effect A medicine can also change the way your body uses a food. Any of these changes can be harmful. This guide covers interactions between some common prescription and over-thecounter medicines and food, caffeine, and alcohol. These interactions come from medicine labels that FDA has approved. This guide uses the generic names ofmedicines, never brand names.

What else can affect how my medicines work?

Your age, weight, and sex; medical conditions; the dose of the medicine; other medicines; and vitamins, herbals, and other dietary supplements can affect how your medicines work. Every time you usea medicine, carefully follow the information on the label and directions from yourdoctor or pharmacist.

Does it matter if I take a medicine on a full or emptystomach?

1

Yes, with some medicines. Some medicines can work faster, slower, better, or worse when you take them on a full orempty stomach. On the other hand, some medicines will upset your stomach, andif there is food in your stomach, that canhelp reduce the upset. If you dont see directions on your medicine labels, askyour doctor or pharmacist if it is best totake your medicines on an empty stomach(one hour before eating, or two hours after eating),with food, or after a meal (fullstomach).

Does it matter if I take my medicine with alcohol?

Yes, the way your medicine works can change when: you swallow your medicine withalcohol you drink alcohol after youve takenyour medicine you take your medicine after youve had alcohol to drink Alcohol can also add to the side effects caused by medicines. You should talk to your doctor about any alcohol you use or plan to use.
2

How do I know if caffeine is in my food or drinks?

Check the labels on your foods and drinksto see if they have caffeine. Some foods and drinks with caffeine are coffee, cola drinks, teas, chocolate, some high-

energydrinks,

and

other

soft

drinks.

For

more

about

caffeine

go

to:

www.fda.gov/downloads/UCM200805.pdf

Re

This guide should never take the place of the advice from your doctor, pharmacist, or other health careprofessionals. Always ask them if there are any problems you could have when you use your medicines with othermedicines; with vitamins, herbals and other dietary supplements; or with food, caffeine, or alcohol.

What isnt in this guide?

This guide wont include every medicineand every type of medicine thats used to treat a medical condition. And just because a medicine is listed here, doesnt mean you should or shouldnt use it. This guide only covers food-druginteractions with medicines you shouldswallow. It doesnt cover, for example, medicines that you put on the skin, injectthrough the skin, drop in your eyes andears, or spray into your mouth. This guide also doesnt cover drug-drug interactions, which are changes in theway your medicines work caused by othermedicines. Prescription medicines can interact with each other or with over-thecounter medicines, and over-the-counter medicines can interact with each other. 3 This guide usually doesnt coverinteractions between medicines and vitamins, herbals, and other dietary supplements. Find out what other interactions and side effects you could have with the medicines you use so you can try to avoid or preventthem. If you have any questions, talk toyour doctor or pharmacist. To find out more about how to use your medicines safely, visit the Web sites listed on the back panel of this guide.

How do I use this guide?

his guide arranges information by: active ingredients in medicines of this type

Types of medicines used to treat the medical condition Examples of

Interactions are listed by Food, Caffeine, and Alcohol.

Medical conditions If you see

A medical condition you have One of the types of medicines you use, or One of your medicines used as an example here, find out if food, caffeine, or alcohol might change the way your medicine works.
4

Allergies
Antihistamines
Antihistamines treat or relieve symptoms of colds and allergies, such as sneezing, runny nose, stuffy nose, and itchy eyes. They block the histamine your body releases when a substance (allergen) causes the symptoms of an allergic reaction. Some antihistamines you can buy over-thecounter and some you can buy only with a prescription from your doctor or other health care professional who can write a prescription. Some antihistamines can cause drowsiness. Examples brompheniramine cetirizine chlorpheniramine fexofenadine levocetirizine triprolidine I clemastine desloratadine diphenhydramine

Alcohol: Avoid alcohol because it can add to any drowsiness caused by these medicines.
5

Arthritis, Pain, and Fever

Analgesics/Antipyretics (Pain relievers/Fever reducers)
Analgesics/antipyretics relieve mild to moderate pain and lower fever. Example acetaminophen Acetaminophen relieves mild to moderate pain from headaches, muscle aches, toothaches, backaches, menstrual cramps, the common cold, pain of arthritis, and lowers fever. I Alcohol: If you drink three or more alcoholic drinks every day, ask your doctor if you should use medicines with acetaminophen or other pain reliever/fever reducers. Acetaminophen can cause liver damage. The chance for severe liver damage is higher if you drink three or more alcoholic drinks every day.

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

NSAIDs relieve pain, fever, and inflammation. Some NSAIDs you can buy over-thecounter and some you can buy only with a prescription. The over-the-counter NSAIDs give short term relief from minor aches and pains from headaches, muscle aches, toothaches, backaches, menstrual cramps, and minor aches and pain of
6 arthritis. NSAIDs may be prescribed for conditions such as osteoarthritis (arthritis

caused by the breakdown of the lining of the joints). NSAIDS can cause stomach bleeding. Examples aspirin celecoxib diclofenac ibuprofen ketoprofen naproxen I Food: Take these medicines with food or milk if they upset your stomach. Alcohol: If you drink three or more alcoholic drinks every day, ask your doctor if you should use medicines with NSAIDs or other pain relievers/ fever reducers. NSAIDs

can cause stomach bleeding and the chance is higher if you drink three or more alcoholic drinks every day.

Narcotic Analgesics
Narcotic analgesics treat moderate to severe pain. Codeine can also help you cough less. Some of these medicines are mixed with other medicines that arent narcotics, such as acetaminophen, aspirin, or cough syrups. You can only buy narcotic analgesics with a prescription. Follow your doctors or pharmacists advice carefully because these medicines can be habit forming and can cause serious side effects if not used correctly. 7 Examples codeine + acetaminophen hydrocodone + acetaminophen meperidine morphine oxycodone + acetaminophen nteractions Alcohol: Dont drink alcohol while using narcotics. Alcohol can increase the chance of dangerous side effects, coma, or death.

Asthma
Bronchodilators
Bronchodilators treat and prevent breathing problems from bronchial asthma, chronic bronchitis, emphysema, and chronic obstructive pulmonary disease (COPD). These medicines relax and open the air passages to the lungs to relieve wheezing, shortness of breath, troubled breathing, and chest tightness. Take these medicines only as directed. If your symptoms get worse or you need to take the medicine more often than usual, you should talk to your doctor right away. Examples albuterol theophylline I Food: Food can have different effects on different forms of 8 theophylline (some forms are regular release, sustained release, and sprinkles). Check with your pharmacist to be sure you know which form of the medicine you use and if food can affect your medicine. Follow directions for sprinkle forms of the medicine. You can swallow sprinkle capsules whole or open them and sprinkle them on soft foods, such as applesauce or pudding. Swallow the mixture without chewing, as soon as it is mixed. Follow with a full glass of cool water or juice. Caffeine: Using bronchodilators with foods and drinks that have caffeine can increase the chance of side effects, such as excitability, nervousness, and rapid heart beat. Alcohol: Avoid alcohol if youre using theophylline medicines because alcohol can increase the chance of side effects, such as nausea, vomiting, headache, and irritability.

Cardiovascular Disorders
These medicines prevent or treat disorders of the cardiovascular system, such as high blood pressure, angina (chest pain), irregular heart beat, heart failure, blood clots, and high cholesterol. Some types of medicines can treat many conditions. For example, beta blockers can treat high blood pressure, angina (chest pain), and irregular heart beats.
9 ACE

Inhibitors (Angiotensin Converting Enzyme Inhibitors)

ACE inhibitors alone or with other medicines lower blood pressure or treat heart failure. They relax blood vessels so blood flows more smoothly and the heart can pump blood better. Examples captopril enalapril lisinopril moexipril quinapril ramipril Interactions Food: Take captopril and moexipril one hour before meals. ACE inhibitors can increase the amount of potassium in your body. Too much potassium can be harmful and can cause an irregular heartbeat and heart palpitations (rapid heart beats). Avoid eating large amounts of foods high in potassium, such as bananas, oranges, green leafy vegetables, and salt substitutes that contain potassium. They can raise the level of potassium even higher. Tell your doctor if you are taking salt substitutes with potassium, potassium supplements, or diuretics (water pills) because these can add to the amount of potassium in your body.

Beta Blockers
Beta blockers can be used alone or with other medicines to treat high blood
10pressure. They are also used to prevent angina (chest pain) and treat heart attacks.

They work by slowing the heart rate and relaxing the blood vessels so the heart doesnt have to work as hard to pump blood. Dont suddenly stop taking a beta blocker without talking to your doctor. If you stop a beta blocker suddenly, you can get chest pain, an irregular heartbeat, or a heart attack. Your doctor might tell you to decrease your dose gradually. Examples carvedilol metoprolol Interactions Food: Take carvedilol with food to decrease the chance it will lower your blood pressure too much. Take carvedilol extended release capsules in the morning with food; dont crush, chew, or divide the capsule. Take metoprolol with a meal or right after a meal.

Diuretics

Sometimes called water pills, diuretics help remove water, sodium, and chloride from the body. Diuretics reduce sodium and the swelling and excess fluid caused by some medical problems such as heart or liver disease. Diuretics can also treat high blood pressure. Examplesbumetanide furosemide hydrochlorothiazide 11metolazone triamterene triamterene + hydrochlorothiazide Interactions Food: Take your diuretic with food if it upsets your stomach. Some diuretics cause loss of the minerals potassium, calcium, and magnesium from the body. Other diuretics, like triamterene (not with hydrochlorothiazide), lower the kidneys ability to remove potassium, which can cause high levels of potassium in the blood stream (hyperkalemia). Too much potassium can be harmful and can cause an irregular or rapid beating of the heart. When you use diuretics that can increase potassium in your body, avoid eating large amounts of foods high in potassium, such as bananas, oranges, and green leafy vegetables, and salt substitutes that contain potassium. They can raise the level of potassium even higher. Tell your doctor if you are taking salt substitutes with potassium or potassium supplements because they can add to the amount of potassium in your body.

Glycosides
Glycosides treat heart failure and abnormal heart rhythms. They help control the heart rate and help the heart work better. Example digoxin
12Interactions

Food: Take digoxin one hour before or two hours after eating food. Try to take it at the same time(s) every day and carefully follow the label and directions from your doctor. Foods high in fiber may decrease the digoxin in your body, so take digoxin at least two hours before or two hours after eating foods high in fiber (such as bran). Avoid taking digoxin with senna and St. Johns wort since they may decrease the amount and action of digoxin in your body. Avoid taking digoxin with black licorice (which contains the glycyrrhizin used in some candies, cakes and other sweets). Digoxin with glycyrrhizin can cause irregular heart beat and heart attack.

Lipid-Altering Agents (also called Statins)

Statins lower cholesterol by lowering the rate of production of LDL (lowdensity lipoproteins, or sometimes called bad cholesterol). Some of these medicines also lower triglycerides. Some statins can raise HDL-C (highdensity lipoproteins, or sometimes called good cholesterol), and lower the chance of heart attack, stroke, or small strokes. Examples atorvastatin fluvastatin lovastatin 13 I

pravastatin simvastatin rosuvastatin nteractions Food: You can take most statins on a full or empty stomach. Some statins will work better if you take them with an evening meal. Dont drink more than one quart of grapefruit juice a day if you are taking atorvastatin, lovastatin, or simvastatin. Large amounts of grapefruit juice can raise the levels of those statins in your body and increase the chance of side effects. Some statins dont interact with grapefruit juice. Ask your doctor or pharmacist if you have any questions. Alcohol: Avoid alcohol because it can increase the chance of liver damage.

Vasodilators-Nitrates
Nitrates prevent or treat chest pain (angina). They work by relaxing the blood vessels to the heart, which improves the blood and oxygen flow to the heart. Examples isosorbide dinitrate or mononitrate nitroglycerin Interactions Food: You can take all forms of nitrates on a full or empty stomach. Alcohol: Avoid alcohol. Alcohol may
14add to the blood vessel-relaxing effect of nitrates and lead to a dangerously low blood

pressure.

Vitamin K Agonists/ Anticoagulants

Anticoagulants are also called blood thinners. They lower the chance of blood clots forming or growing larger in your blood or blood vessels. Anticoagulants are used to treat people with certain types of irregular heartbeat, people with prosthetic (replacement or mechanical) heart valves, and people who have had a heart attack. Anticoagulants also treat blood clots that have formed in the veins of the legs or lungs. Example warfarin Interactions Food: You can take warfarin on a full or empty stomach. Vitamin K in food can make the medicine less effective. Eat a normal balanced diet with a steady amount of leafy green vegetables, and talk to your doctor before making changes in your diet. Foods high in vitamin K include broccoli, cabbage, collard greens, spinach, kale, turnip greens, and brussel sprouts. Avoid cranberry juice or cranberry products while using anticoagulants because they can change the effects of warfarin. Many dietary supplements and vitamins can interact with anticoagulants and can
15reduce the benefit or increase the risk of warfarin. Avoid garlic, ginger, glucosamine,

ginseng, and ginkgo because they can increase the chance of bleeding. Alcohol: Tell your doctor and pharmacist if you drink alcohol or have problems with alcohol abuse. Avoid alcohol because it can affect your dose of warfarin.

Gastroesophageal andUlcers
Proton Pump Inhibitors

Reflux

Disease

(GERD)

Proton Pump Inhibitors (PPIs) work by decreasing the amount of acid made in the stomach. They treat conditions when the stomach produces too much acid. Some of these medicines you can buy over-the-counter to treat frequent heartburn, such as omeprazole and lansoprazole. Some of these medicines you can only buy with a prescription to treat conditions such as ulcers, gastroesophageal reflux disease, and to reduce the risk of stomach ulcers in people taking nonsteroidal antiinflammatory drugs (NSAIDs). (See Arthritis, Pain and Fever-Nonsteroidal Anti-inflammatory Drugs above.) Proton pump inhibitors are also used along with antibiotics to stop infections in the stomach that cause ulcers. Proton pump inhibitors come in different forms (such as delayed-release tablets, delayed-release disintegrating tablets,
16 immediate release). Dont change your dose or stop using these without talking to

your doctor first. Examplesdexlansoprazole pantoprazole rabeprazole Interactions

esomeprazole

lansoprazole

omeprazole

Food: You can take dexlansoprazole and pantoprazole on a full or empty stomach. Esomeprazole should be taken at least one hour before a meal. Lansoprazole and omeprazole should be taken before eating. Ask your doctor or pharmacist how you should take rabeprazole. Tell your doctor if you cannot swallow delayed-release medicines whole because you shouldnt split, crush, or chew them. Some of these medicines can be mixed with food but you must carefully follow the label and directions from your doctor or pharmacist.

hypothyroidism is a condition where the thyroid gland doesnt produce enough thyroid hormone. Without this hormone, the body cannot function properly, so there is poor growth, slow speech, lack of energy, weight gain, hair loss, dry thick skin, and increased sensitivity to cold. Thyroid Medicines Thyroid medicines control hypothyroidism but they dont cure it. They reverse the symptoms of hypothyroidism. Thyroid medicine is also used to treat congenital hypothyroidism (cretinism), autoimmune hypothyroidism, other causes of hypothyroidism (such as after thyroid surgery), and goiter (enlarged thyroid gland). It may take several weeks before you notice a change in your symptoms. Dont stop taking the medicine without talking to your doctor.
17

Hypothyroidism

Examplelevothyroxine

Nteractions Foods: Tell your doctor if you are allergic to any foods. Take levothyroxine once a day in the morning on an empty stomach, at least one-half hour to one hour before eating any food. Tell your doctor if you eat soybean flour (also found in soybean infant formula), cotton seed meal, walnuts, I
18

and dietary fiber; the dose of the medicine may need to be changed.

Infections
Be sure to finish all of your medicine for an infection, even if you are feeling better. All of the medicine is needed to kill the cause of infection. If you stop the medicine early, the infection may come back; the next time, the medicine may not work for the infection. Ask your doctor if you should drink more fluids than usual when you take medicine for an infection.

Antibacterials
Medicines known as antibiotics or antibacterials are used to treat infections caused by bacteria. None of these medicines will work for infections that are caused by viruses (such as colds and flu).

Quinolone Antibacterials
Examples ciprofloxacin levofloxacin moxifloxacin Interactions Food: You can take ciprofloxacin and moxifloxacin on a full or empty stomach. Take levofloxacin tablets on a full or empty stomach. Take levofloxacin oral solution one hour before eating or two hours after eating.
19Dont take ciprofloxacin with dairy products (like milk and yogurt) or calcium-fortified

juices alone, but you can take ciprofloxacin with a meal that has these products in it. Caffeine: Tell your doctor if you take foods or drinks with caffeine when you take ciprofloxacin, because caffeine may build up in your body.

Tetracycline Antibacterials
Examplesdoxycycline minocycline tetracycline I Food: Take these medicines one hour before a meal or two hours after a meal, with a full glass of water. You can take tetracycline with food if it upsets your stomach, but avoid dairy products (such as milk, cheese, yogurt, ice cream) one hour before or two hours after. You can take minocycline and some forms of doxycycline with milk if the medicine upsets your stomach.

Oxazolidinone Antibacterials
Example linezolid I Food: Avoid large amounts of foods and drinks high in tyramine while using linezolid. High levels of tyramine can cause a sudden, dangerous increase in your blood pressure. Follow your doctors directions very carefully.
20

Foods with Tyramine Foods that are spoiled or not refrigerated, handled, or stored properly, and aged, pickled, fermented, or smoked foods may contain tyramine. Some of these are: cheeses, especially strong, aged, or processed cheese, such as American processed, cheddar, colby, blue, brie, mozzarella, and parmesan cheese; yogurt; sour cream (you can eat cream and cottage cheese) beef or chicken liver, dry sausage (including Genoa salami, hard salami, pepperoni, and Lebanon bologna), caviar, dried or pickled herring, anchovies, meat extracts, meat tenderizers and meats prepared with tenderizers avocados, bananas, canned figs, dried fruits (raisins, prunes), raspberries, overripe fruit, sauerkraut, soy beans and soy sauce, yeast extract (including brewers yeast in large quantities) broad beans (fava) excessive amounts of chocolate Caffeine: Many foods and drinks with caffeine also contain tyramine. Ask your doctor if you should avoid or limit caffeine. Alcohol: Avoid alcohol while using linezolid. Many alcoholic drinks contain tyramine, including tap beer, red wine, sherry, and liqueurs. Tyramine can also be in alcohol-free and reduced alcohol beer.
21Metronidazole

Antibacterials

Example metronidazole nteractions Alcohol: Dont drink alcohol while taking metronidazole and for at least one full day after finishing the medicine; together alcohol and metronidazole can cause nausea, stomach cramps, vomiting, flushing, and headaches.

Antifungals
Antifungals are medicines that treat or prevent fungal infections. Antifungals work by slowing or stopping the growth of fungi that cause infection. Examples fluconazole itraconazole posaconazole voriconazole

griseofulvin terbinafine

Interactions Food: Itraconazole capsules will work better if you take it during or right after a full meal. Itraconazole solution should be taken on an empty stomach. Posaconazole will work better if you take it with a meal, within 20 minutes of eating a full meal, or with a liquid nutritional supplement. Dont mix voriconazole suspension with any other medicines, water, or any other liquid.

22

Griseofulvin works better when taken with fatty food. You can take the rest of the antifungals listed here on a full or empty stomach. Alcohol: Avoid alcohol while you are taking griseofulvin because griseofulvin can make the side effects of alcohol worse. For example, together they can cause the heart to beat faster and can cause flushing.

Antimycobacterials
Antimycobacterials treat infections caused by mycobacteria, a type of bacteria that causes tuberculosis (TB), and other kinds of infections. Examplesethambutol isoniazid rifampin rifampin + isoniazid rifampin + isoniazid + pyrazinamide Interactions Food: Ethambutol can be taken with or without food. Take the rest of these medicines one hour before a meal or two hours after a meal, with a full glass of water. Avoid foods and drinks with tyramine and foods with histamine if you take isoniazid alone or combined with other antimycobacterials. High levels of tyramine can cause a sudden, dangerous increase in your blood pressure. Foods with histamine
23

can cause headache, sweating, palpitations (rapid heart beats), flushing, and hypotension (low blood pressure). Follow your doctors directions very carefully. Foods that contain tyramine are listed on page 21, under Foods with Tyramine. Foods with histamine include skipjack, tuna, and other tropical fish. Caffeine: Many foods and drinks with caffeine also contain tyramine. Ask your doctor if you should avoid or limit caffeine. Alcohol: Avoid alcohol. Many alcoholic drinks contain tyramine, including tap beer, red wine, sherry, and liqueurs. Tyramine can also be in alcohol-free and reduced alcohol beer. If you drink alcohol every day while using isoniazid you may have an increased risk of isoniazid hepatitis.

Antiprotozoals
Antiprotozoals treat infections caused by certain protozoa (parasites that can live in your body and can cause diarrhea). Examples metronidazole tinidazole
24

Interactions Alcohol: Together alcohol and these medicines can cause nausea, stomach cramps, vomiting, flushing, and headaches. Avoid drinking alcohol while taking metronidazole and for at least one full day after finishing the medicine. Avoid drinking alcohol while taking tinidazole and for three days after finishing the medicine.

Psychiatric Disorders
Depression, bipolar disorder, general anxiety disorder, social phobia, panic disorder, and schizophrenia are a few examples of common psychiatric (mental) disorders. Use the amount of medicine that your doctor tells you to use, even if you are feeling better. In some cases it can take several weeks before you see your symptoms get better. Dont stop these medicines until you talk to your doctor. You may need to stop your medicine gradually to avoid getting side effects. Some of these medicines can affect your thinking, judgment, or physical skills. Some may cause drowsiness and can affect how alert you are and how you respond. Dont do activities like operating machinery or driving a car, until you know how your medicine affects you.

25 I

Anti-Anxiety and Panic Disorder Medicines

Examples alprazolam clonazepam diazepam lorazepam nteractions Alcohol: Avoid alcohol. Alcohol can add to the side effects caused by these medicines, such as drowsiness.

Antidepressants
Antidepressants treat depression, general anxiety disorder, social phobia, obsessivecompulsive disorder, some eating disorders, and panic attacks. The medicines below work by increasing the amount of serotonin, a natural substance in the brain that helps maintain mental balance. Never stop an antidepressant medicine without first talking to a doctor. You may need to stop your medicine gradually to avoid getting side effects. Examples citalopram escitalopram fluoxetine paroxetine sertraline Interactions Food: You can take these medicines on a full or empty stomach. Swallow
26

paroxetine whole; dont chew or crush it. Alcohol: Avoid alcohol. Alcohol can add to the side effects caused by these medicines, such as drowsiness.

Antidepressants-Monoamine Oxidase Inhibitors (MAOIs)

MAOIs treat depression in people who havent been helped by other medicines. They work by increasing the amounts of certain natural substances that are needed for mental balance. Examples phenelzine tranylcypromine Interactions Food: Avoid foods and drinks that contain tyramine when you use MAOIs. High levels of tyramine can cause a sudden, dangerous increase in your blood pressure. Follow your doctors directions very carefully. Foods that contain tyramine are listed on page 21, under Foods with Tyramine. Caffeine: Many foods and drinks with caffeine also contain tyramine. Ask your doctor if you should avoid or limit caffeine.

27 Alcohol: Dont drink alcohol while using these medicines. Many alcoholic drinks

contain tyramine, including tap beer, red wine, sherry, and liqueurs. Tyramine also can be in alcohol-free and reduced alcohol beer. Alcohol also can add to the side effects caused by these medicines.

Antipsychotics
Antipsychotics treat the symptoms of schizophrenia and acute manic or mixed episodes from bipolar disorder. People with schizophrenia may believe things that are not real (delusions) or see, hear, feel, or smell things that are not real (hallucinations). They can also have disturbed or unusual thinking and strong or inappropriate emotions. These medicines work by changing the activity of certain natural substances in the brain.

Examples aripiprazole clozapine olanzapine quetiapine risperidone ziprasidone Interactions Food: Take ziprasidone capsules with food.You can take the rest of these medicines on a full or empty stomach. Caffeine: Avoid caffeine when using clozapine because caffeine can increase the amount of medicine in your blood and cause side effects.
28 I Alcohol: Avoid alcohol. Alcohol can add to the side effects caused by these

medicines, such as drowsiness.

Sedatives and Hypnotics (Sleep Medicines)

Sedative and hypnotic medicines treat people who have problems falling asleep or staying asleep. They work by slowing activity in the brain to allow sleep. Some of these medicines you can buy over-the-counter and some you can only buy with a prescription. Tell your doctor if you have ever abused or have been dependent on alcohol, prescription medicines, or street drugs before starting any sleep medicine. You could have a greater chance of becoming addicted to sleep medicines. Examples eszopiclone zolpidem nteractions Food: To get to sleep faster, dont take these medicines with a meal or right after a meal. Alcohol: Dont drink alcohol while using these medicines. Alcohol can add to the side effects caused by these medicines.

Bipolar Disorder Medicines

People with bipolar disorder experience mania (abnormally excited mood, racing thoughts, more talkative than usual, and decreased need for sleep)
29 and depression at different times during their lives. Bipolar disorder medicines help

people who have mood swings by helping to balance their moods. Examples carbamazepine divalproex sodium lamotrigine lithium Interactions Food: Take divalproex with food if it upsets your stomach. Take lithium immediately after meal or with food or milk to avoid stomach upset. Lithium can cause you to lose sodium, so maintain a normal diet, including salt; drink plenty of fluids (eight to 12 glasses a day) while on the medicine. Alcohol: Avoid alcohol. Alcohol can add to the side effects caused by these medicines, such as drowsiness.

Osteoporosis
Bisphosphonates (bone calcium phosphorus metabolism)
Bisphosphonates prevent and treat osteoporosis, a condition in which the bones become thin and weak and break easily. They work by preventing bone breakdown and increasing bone thickness.
30

Examples alendronate sodium alendronate sodium + cholecalciferol ibandronate sodium risedronate sodium risedronate sodium + calcium carbonate Food: These medicines work only when you take them on an empty stomach. Take the medicine first thing in the morning with a full glass (six to eight ounces) of plain water while you are sitting or standing up. Dont take with mineral water. Dont take antacids or any other medicine, food, drink, calcium, or any vitamins or other dietary supplements for at least 30 minutes after taking alendronate or risedronate, and for at least 60 minutes after taking ibandronate. Dont lie down for at least 30 minutes after taking alendronate or risedronate and for at least 60 minutes after taking ibandronate. Dont lie down until you eat your first food of the day.

31

More About Using Medicines Safely

Read the label before you use anymedicine. Over-the-counter Medicines Over-the-counter medicine has a label called Drug Facts on the medicine container or packaging. The label is there to help you choose the right medicine for you and your problem and use the medicine safely. Some overthe-counter medicines also come with a consumer information leaflet which gives more information. Prescription Medicines Medication Guide (also called Med Guide): This is one kind of information written for consumers about prescription medicines. The pharmacist must give you a Medication Guide each time you fill your prescription when there is one written for your medicine. Medication Guides are made for certain medicines that have serious risks. The information tells about the risks and how to avoid them. Read the information carefully before you use the medicine. If you have any questions, ask a doctor or pharmacist. For more information on Medication Guides, visit: www.fda.gov/drugs

32

Patient Package Insert(also called PPI or patientinformation): This is another kind of information written for consumers about prescription medicines. Your pharmacist might give this to you with your medicine. It gives you information about the medicine and how to use it. The pharmacist must give you a PPI with birth control pills or any medicine with estrogen.

Resources
http://www.fda.gov/usemedicinesafely Consumer education on how to choose and use medicine, from the FDA. http://www.medlineplus.gov Health information for consumers, from the governments National Library of Medicine (NLM). http://dailymed.nlm.nih.gov FDA-approved drug labeling written for healthcare professionals, from thegovernments National Institutes of Health (NIH); sometimes this labeling will also have a Patient Package Insertor PPI or a Medication Guide, written for patients. http://www.accessdata.fda.gov/scripts/cder/drugsatfda/index.cfm Drugs@FDA website with FDA-approved labeling written for healthcareprofessionals; sometimes this labelingwill also have a Patient Package Insert or PPI, or a Medication Guide, written for patients. The site may have a Drug
33

Safety Communication, or OtherImportant Information from FDA, ifthere has been new information about the medicine that has not made it to the label yet. http://www.fda.gov/drugs/ucm079489.htm A personal medicine record can help you keep track of your prescriptionand overthe-counter medicines and vitamins, herbals, and other dietary supplements you use. If you keep awritten record, it can make it easy toshare this information with all yourhealthcare professionalsat office, clinic and hospital visits, and inemergencies.

34National Consumers League

A 501(c)(3) nonprofit membership organization Phone: 202-835-3323 Fax: 202-835-0747 Email: info@nclnet.org Web: www.nclnet.org

U.S. Department of Health and Human Services

Food and Drug Administration Phone: 1-888-INFO-FDA Email questions: druginfo@fda.hhs.gov Web: www.fda.gov/drugs

For an online version of this guide, visit: www.nclnet.org or www.fda.gov/drugs Publication no. (FDA) CDER 10-1933

hats the best time to take your pills? From heartburn to heart disease, swallow your medicine at the wrong time of day and it may not work

By David Hurst UPDATED: 22:25 GMT, 27 February 2012

Comments (8) Share

o o o

While millions of us take medicine daily, few pay much attention to the time of day we take it. Yet a growing number of health experts say this is much more important than patients think indeed when it comes to conditions such as arthritis, osteoporosis and heartburn, the time you have your medication can have a significant impact on its effectiveness and how well it protects you. New U.S. research, published last week, seems to support this. A study of mice, published in the journal Nature, identified why heart rhythm problems are more common in the morning.

A growing number of health experts believe the time you have your medication can have a significant impact

Experts believe this understanding means patients who are on anticoagulants to prevent heart attacks and strokes could maximise the effect by taking the pills when they wake up. Its thought the key is the circadian rhythm, our 24-hour internal body clock driven by the brains hypothalamus gland. This controls not only the immune system but also blood pressure, body temperature, hormone production, bowel movements and tiredness. So whats the best time to take your medication? We asked the experts...

OSTEOPOROSIS
The most commonly prescribed drugs for osteoporosis are bisphosphonates, which prevent the loss of bone mass.

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The key thing with bisphosphonates is that they are poorly absorbed, says Sarah Leyland, senior nurse at the National Osteoporosis Society. This is because they do not dissolve well, especially in oils and fats. So you need to take your pill first thing in the morning with water on an empty stomach after a night of not eating. Then patients must wait up to hour to eat or drink. Many osteoporosis patients have to take calcium and vitamin D but these too can disrupt absorption, so patients should also wait at least an hour after taking their bisphosphonates, she adds. If you eat or drink something other than water, or take another medication, it could mean you wont get any benefit from it, so it could be a total waste of time taking it.

HIGH BLOOD PRESSURE

Taking blood-pressure tablets at night may better control hypertension and greatly reduce the risk of heart attack and stroke, research published last year suggests.

While millions of us take medicine daily, few pay much attention to the time of day we take it

The results of the five-year Spanish study highlighted the importance of reducing blood pressure at night. In healthy people blood pressure dips at night between 10 to 20 per cent those whose blood pressure doesnt fall as it should are more likely to suffer from heart attack and stroke, the researchers said. In the study of 2,156 men and women with high blood pressure, those who routinely took at least one of their blood-pressure medicines at night had a 33 per cent lower risk of angina, stroke and heart attack than those who took all their blood-pressure pills in the morning. This study confirms sleep-time blood pressure as the most relevant predictor of cardiovascular risk, says lead researcher Ramon Hermida of the University of Vigo. Sleep-time blood pressure is best reduced when medication is taken at bedtime.

However, those who now take their pills in the morning should not begin taking them at night without speaking with their doctor, says Hermida. Theres a risk for nocturnal hypotension (abnormally low blood pressure) which could increase the risk of stroke, he adds.

ARTHRITIS
Osteoarthritis patients are likely to find their joint pain is worst in the afternoon, according to a recent Texas Tech University study. The researchers concluded that the optimal time for taking a non-steroidal antiinflammatory drug such as ibuprofen would be around noon to midafternoon, so that it takes effect as symptoms begin to build up. They also found that rheumatoid arthritis patients generally experience the greatest pain in the mornings, so taking painkillers just after their evening meal may be the most effective way to prevent pain developing overnight.

HIGH CHOLESTEROL
It is now recommended that cholesterol medicines be taken at bedtime instead of first thing in the morning. Studies at the University of Sunderland found that when patients taking simvastatin, one of the most commonly prescribed statins, switched from evening to morning, there was a significant increase in bad LDL cholesterol. Another study published in the International Journal of Clinical Practice in 2008 revealed that taking another commonly prescribed statin, atorvastatin (brand name Lipitor), in the evening was better than taking it in the morning it was associated with fewer heart attacks, blockage of the arteries as well as greater improvements in total good cholesterol and better blood vessel function. Experts think this may be because most cholesterol is produced at night, while we are not eating.

UNDERACTIVE THYROID
As many as three million people in Britain are said to suffer from an underactive thyroid the majority of them women. Most thyroid medicines contain levothyroxine, a synthetic version of the thyroid hormone T4. The T4 hormone needs to be first converted to the active form of thyroid hormone T3 for it to be effective. This takes a long time to occur inside the body.

Traditionally, many doctors suggest that taking thyroid medication first thing in the morning is best. But two recent Dutch studies have found that taking medication at bedtime rather than the morning results in higher thyroid hormone concentrations. The researchers suggested that as the bowel is slower at night, it takes longer for the levothyroxine tablet to move through the intestinal system. This results in longer exposure to the intestinal wall, and so better absorption of the medication. Other studies have shown that the key is taking thyroid medication consistently at the same time each day. To ensure quick absorption, doctors also advise avoiding calcium and iron supplements, high fibre foods, antacids and antidepressants for at least two hours after taking a thyroid pill.

HEART MEDICATION
For some time its been known that heart attacks and strokes are three times more likely to happen in the morning than any other time, but until now its not been clear why. But research published last week by Case Western Reserve University School of Medicine in Ohio has identified a protein called KLF15 that is crucial in regulating the hearts rhythm. The researchers found levels of the protein rise and fall in a 24-hour cycle. The hearts electrical impulses are slowest from 6am to noon. As the duration between impulses slow down, this makes the heart more likely to go out of rhythm, to short circuit or for electrical storms to occur, says Professor Mukesh Jain, who led the research. This increases the risk of a heart attack which means that the best time to take heart medication is first thing in the morning. This realisation will be one of the most important innovations in medicine in the next 20 years, says Professor Russell Foster, a circadian rhythms specialist at the University of Oxford. Certainly, if I was taking anti-stroke medication I know at what time of the day Id take it. It should be delivered before you properly wake up. You should lie there calmly and take it, then get up.

HEARTBURN
The general advice is to take proton-pump inhibitors (PPIs, drugs which suppress acid production) 30 minutes before the first meal of the day.

However, a recent study by the University of Kansas found the drugs were more effective against acid reflux when taken in the evening. More than 70 per cent of patients with gastro-oesophageal reflux disease who took a commonly prescribed PPI, rabeprazole, in the afternoon or evening found their symptoms were eased, compared with 42 per cent who took it in the morning. They suggested this could be because the drug will act throughout the night, when heartburn can be exacerbated by lying down. They concluded that before the evening meal would be the preferred time for patients to take their medication, particularly those who suffer at night. However, Marcus Harbord, gastroenterologist at the Chelsea and Westminster Hospital, suggests splitting the daily dose, providing half in the morning then half in the evening, to keep symptoms at bay at all times.
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Introduction Understanding the possible clinical implications of taking medicines with or without a meal is important for achieving quality use of medicines. Although the effect of food is not clinically important for many drugs, there are food-drug interactions which may have adverse consequences. Often these interactions can be avoided by advising the patient to take their medicines at the same time with respect to meals. The effect of food on absorption The formulation of a drug influences its absorption. Food can affect both the rate and extent of absorption (Table 1). Rate of absorption Meals slow down gastric emptying and this can delay drug absorption. The composition of the meal influences the rate of gastric emptying - high fat meals lead to delayed gastric emptying. A delay in the drug reaching the small intestine can delay its subsequent absorption into the systemic circulation. Based on these observations, oral administration of a medicine under fasting conditions is

often recommended when rapid absorption (and hence rapid onset of therapeutic effect) is needed. For most medicines, especially those used for chronic conditions, a delay in the onset of absorption is of no clinical consequence as long as the amount of drug absorbed is unaffected. Extent of absorption Food has the potential to either increase or decrease the extent of drug absorption. Understanding food-drug interaction mechanisms enables the clinician to provide appropriate advice to patients about taking medicines with respect to the timing and composition of meals. The effect of food depends on the physicochemical and pharmacokinetic characteristics of the drugs.1 The clinical significance of the effect will in turn depend on the pharmacodynamic characteristics of the drug. For example, the poorly water soluble antiretroviral drug saquinavir should be taken with food to allow bile enhancement of its dissolution which then facilitates absorption. The extent of absorption is more than doubled by taking saquinavir after a full cooked breakfast. Taking saquinavir on an empty stomach reduces its bioavailability and could lead to therapeutic failure.1 Delayed gastric emptying after a meal and the associated gastric acid secretions can reduce the bioavailability of some medicines that are acid labile. The constituents of a meal may also specifically interact with drugs (Table 2). Calcium and other cations in food can form insoluble chelates with some medicines preventing their optimal absorption. Bisphosphonates are therefore recommended to be taken with plain water to prevent the formation of chelates which significantly reduce bioavailability. Grapefruit juice: an important example Co-ingestion of grapefruit juice and certain drugs (Table 3) significantly increases their bioavailability because the constituents of the juice inhibit pre-systemic drug metabolism or transport. This increase in bioavailability can lead to excessive beneficial or adverse effects.2 The effects of grapefruit juice are complex and have been widely studied.3,4 A single glass of grapefruit juice is enough to increase the bioavailability of some drugs. If the juice is drunk over several days the effects are long-lasting3,4, so simply separating the dose of medicine and the ingestion of grapefruit juice does not prevent the interaction. For this reason grapefruit juice ingestion should be avoided completely with certain drugs, for example cyclosporin. Could grapefruit juice be routinely used to enhance the bioavailability of some medicines? The answer would appear to be no because the effect of grapefruit juice on drug absorption is highly

variable. It depends on the constituents of the juice, how it is prepared and varies with brands and batches. Grapefruit juice is not 'pharmaceutical grade' or consistently of the same 'quality', so coadministration with a drug would lead to a variable response.

Table 1

Mechanisms of food-drug interactions1

Mechanism Medicines or class Implication Actions *

Poor acid stability azithromycin

ampicillin

erythromycin (some salts)

isoniazid

phenoxymethylpenicillin

Exposure to acid and prolonged gastric residence leads to chemical degradation and reduced bioavailability with risk of therapeutic failure Take on an empty stomach

( or at a consistent time with respect to meals)

Chelation bisphosphonates

ciprofloxacin

norfloxacin

penicillamine

Reduced therapeutic effect Take on an empty stomach

( or at a consistent time with respect to meals)

Acid dependency amprenavir

itraconazole (capsules)

ketoconazole

Reliable absorption depends on acid environment Take with meals or at a consistent time with respect to meals

Bile acid or fat enhanced drug dissolution acitretin

carbamazepine

griseofulvin

isotretinoin

halofantrine

mefloquine

saquinavir

tacrolimus

Enhanced bioavailability Take with meals or at a consistent time with respect to meals

Physical binding/adsorption digoxin Digoxin may bind to fibre reducing its bioavailability Avoid concurrent ingestion with fibre or take digoxin at consistent time with respect to meals

Reduced gastric emptying most medicines Reduced rate of absorption Take at a consistent time with respect to meals

* Note: Taking a medicine with a meal implies taking the dose within 30 minutes of a meal. Taking a medicine on an empty stomach implies taking the dose one hour before or two hours after a meal.

Table 2

The effect of specific dietary components on selected drugs1

Specific foods Medicines (class) Advice on meals and implications

Vitamin K rich foods

warfarin Dietary intake of vitamin K rich foods should be consistent to avoid fluctuation in INR. Abstinence is not required.

Potassium rich foods

and supplements ACE inhibitors, potassium sparing diuretics, and angiotensin receptor antagonists Foods and accompaniments high in potassium should be ingested in moderation to avoid the risk of hyperkalaemia

High protein meal levodopa Reduce the cerebral uptake (not bioavailability) of levodopa and potentially reduce clinical efficacy

Tyramine rich foods monoamine oxidase inhibitors Significant risk of hypertensive crisis

Calcium rich foods tetracycline

quinolones Co-administration of calcium rich foods and supplements results in chelation and reduced drug absorption with a risk of therapeutic failure

Table 3

Drugs affected by oral co-ingestion of grapefruit juice 3,4

Advice to patients Drug

Avoid co-ingestion of grapefruit juice amiodarone due to risk of unwanted effects atorvastatin

cyclosporin

diazepam

felodipine

midazolam

nifedipine

saquinavir

sildenafil

simvastatin

verapamil

Co-ingestion of grapefruit juice may be acceptable with appropriate monitoring and awareness amlodipine

diltiazem

ethinyloestradiol

pravastatin

prednisolone/prednisone

theophylline

Studying the effect of food The product information approved by the Therapeutic Goods Administration is the main source of information about the possible effects of food on drug absorption. This information is generally derived from a 'food effect study' that is conducted during drug development. Typically, this involves a randomised cross-over single dose pharmacokinetic study in healthy people. They take the drug of interest after an overnight fast and also after a standard high fat breakfast. This design is meant to examine the effect of food under 'extreme' conditions. Unfortunately, a volunteer eating a high fat meal does not necessarily reflect the circumstances of the patients who will take the drug. Dosing recommendations with respect to food derived from these studies may therefore not provide the best guide to the actual impact of food on drug absorption. Taking medicines with meals to help adherence, tolerability and efficacy Prescribing a drug regimen that fits in with the patient's daily routine (which is usually centred around mealtimes) can enhance the patient's adherence to treatment. This leads to the general recommendation that patients should take their medicines at prescribed and consistent times relative to their meals. This is despite the fact that the absorption of some medicines may be

significantly reduced when taken with food, for example atorvastatin and thyroxine. Patients should also be informed if particular foods can interfere with their treatment (Table 2). Some medicines (for example non-steroidal anti-inflammatory drugs and metformin) are taken with food to minimise the risk of gastrointestinal adverse effects. Repaglinide and the sulfonylureas should be taken before a meal to avoid the risk of significant hypoglycaemia. In the case of repaglinide, if a meal is skipped then the drug dose should also be skipped. Similarly, taking acarbose with meals is essential to ensure its maximum efficacy in delaying the intestinal absorption of carbohydrates. Conclusion Meals may have variable and often unpredictable effects on drugs via a range of mechanisms. By understanding and appreciating the clinical consequences of these effects health professionals can provide advice about the appropriateness of ingesting medicines with respect to the times and the composition of meals. The provision of timely and appropriate advice about the possible effects of meals on medicines and the importance (or lack) of the timing of meals and medicines is an important issue impacting on the quality use of medicines.