Pharmacotherapy Perspectives

by Sarah E. Bland, RPh

Column Editor: Lee Vermeulen, MS, RPh, Director, Center for Drug Policy, University of Wisconsin Hospital and Clinics

Drug-Food Interactions
he use of computerized drug interaction screens, built into community pharmacy computer systems and used by many on-line, point-of-sale prescription claim adjudication systems, have become an important tool for pharmacists in preventing negative outcomes associated with drugdrug interactions. Food-drug interactions are more challenging (since food consumption is not documented on patient profiles), but often pose equally substantial risk of negative outcome. Consider this brief case-in-point adapted from the records of the University of Wisconsin Hospital and Clinics (this describes an actual case, but many details have been modified). Case: A forty-nine year old male patient with a history of severe depression is placed on a monoamine oxidase inhibitor (MAOI) after failing on treatment with tricyclic antidepressants and selective serotonin re-uptake inhibitors. The patient was warned of possibly severe hypertensive reactions associated with the consumption of foods high in tyramine (a pressor amine) while on the MAOI. The patient remained adherent to a tyramine-free diet for several months, and was showing dramatic response to the new therapy. As the patients depression diminished, his appetite returned, and on one occasion he consumed a substantial quantity of chocolate (known to contain some tyramine, but generally considered safe for consumption in moderation in tyramine-free diets). Two hours later, the patient presented to the Emergency Department complaining of a severe headache. A diagnosis of hypertensive crisis was made and treatment with nitroprusside was begun. Unfortunately, the patient suffered a stroke and died within 20 minutes of treatment initiation. Despite the appropriate education and warnings provided by the patients physician and pharmacist, this food-drug interaction caused the death of a patient. In this issue, Sarah Bland provides a thorough reference tool that can be referred to as patients are counseled on diet considerations that affect their medication therapy. It is critical that pharmacists remain aware of potential food-drug interactions, recognize that they will not be warned of potential interactions by their standard drug-drug interaction software, and intervene with information and education when necessary. Lee Vermeulen

Summary
Interactions between foods and drugs can have profound influence on the success of drug treatment and on the side effect profiles of many drugs. The interactions are not always detrimental to therapy, but can in some cases be used to improve drug absorption or to minimize adverse effects. These interactions have received more attention recently, especially drug interactions with grapefruit juice. As new drug approvals occur with ever-increasing speed, there is less information available about their adverse effects and interactions when the drugs reach the market. A second area of concern is the use of herbal medicines and dietary supplements. These products are not rigorously monitored, and may contain little if any of the substance indicated on the label. Some of the herbs used can interact adversely with prescription drugs. Two notable examples are ma huang (ephedra) and feverfew. Ma huang is a stimulant that can cause hypertensive crises in patients taking monoamine oxidase inhibitors. Feverfew has anticoagulant properties that can augment the effects of warfarin. Most food-drug interactions occur through three mecha-

nisms: reduced rate or extent of absorption, increased rate or extent of absorption, or through chemical/pharmacologic effects. With some drugs, the presence of increased amounts of stomach acid results in the destruction of acid-labile drugs, such as penicillin G, ampicillin and dicloxacillin. In other cases, the components of the food, such as calcium or iron, may form complexes with the drug that are less easily absorbed. Examples include tetracycline, sodium fluoride and ciprofloxacin. The absorption of alendronate is impaired by food, calcium and almost everything, including orange juice and coffee. It should be taken with plain water and nothing else should be consumed for at least 30 minutes. In many cases, the actual mechanism by which food interferes with absorption is not known. Delayed absorption does not necessarily reduce the total overall exposure to the drug; the area under the curve (AUC) may be equivalent regardless of how the drug is taken.
Sarah Bland is a Clinical Pharmacist in the Center for Drug Policy and Clinical Economics, Department of Pharmacy, University of Wisconsin Hospital and Clinics, and is a Certified Specialist in Poison Information in the UW Hospital Poison Control Center.

The information given and views expressed herein do not necessarily reflect the opinions of PSW, its Board or members.

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A reduced rate of absorption may sometimes be useful in reducing the side effects of a drug, as in the case of ibuprofen, without reducing bioavailability. The bioavailability of some drugs may be enhanced by food. For example, an acid environment is necessary for the absorption of ketoconazole. The absorption of griseofulvin is increased by fat in a meal. Fenofibrate, mebendazole, isotretinoin, tamsulosin, carbamazepine and labetalol are examples of drugs that will be better absorbed when taken with food. Improved absorption of a drug may or may not have a significant effect on the drugs efficacy. Chemical or pharmacologic interactions occur through a wide variety of mechanisms. A very common interaction is that between beverage alcohol and drugs that have sedative effects. The effects of sedative drugs will usually be potentiated by the consumption of alcohol. Opiates, benzodiazepines and antihistamines are well-known examples of this phenomenon. Another alcohol-related interaction is the competitive inhibition of the enzyme aldehyde dehydrogenase, often called the Antabuse reaction. Nausea, vomiting, flushing, dizziness and tachycardia may occur with exposure to alcohol in patients taking some cephalosporins, ketoconazole, metronidazole and sulfonylureas. In addition, chronic alcohol overuse can increase the toxicity of some drugs, as with acetaminophen and methotrexate, or reduce the drugs efficacy, as with phenytoin. Components of food may antagonize the desired effect of the drug, as in the case of warfarin. Foods which are high in vitamin K, or which enhance vitamin K production by intestinal microorganisms, can reduce the effectiveness of warfarin in diminishing the bodys supply of vitamin K, which is needed to activate clotting factors. Changing to a diet with increased consumption of leafy and/or dark green vegetables, such as spinach and turnip greens, could lessen the degree of anticoagulation made possible by warfarin by supplying additional vitamin K. Perhaps the most feared food-drug interaction is that between monoamine oxidase inhibitors (MAOIs) and the amino acid tyramine, which is found in a variety of aged, fermented, overripe or pickled foods and beverages and, to a lesser extent, chocolate and yeast-containing foods. Tyramine is indirectly sympathomimetic. When its metabolism is suppressed, as it is by MAOIs, it can cause a significant release of norepinephrine, resulting in markedly increased blood pressure, cardiac arrhythmias, hyperthermia and cerebral hemorrhage. The interaction between grapefruit juice and a variety of drugs has been widely reported. It appears that one or more flavonoids found in grapefruit juice inhibit some of the enzymes in the cytochrome P450 system. This results in reduced metabolism of drugs that are cleared by the same system; bioavailability may increase by as much as 200%. Patients

should avoid drinking grapefruit juice for two hours before and four hours after taking drugs in this category. If the drug is in an extended-release dosage form, patients should wait until six hours have passed before drinking grapefruit juice. Additional information about drug-food interactions can be found in these references:

1. Lieber CS. Mechanisms of ethanol-drug-nutrition interactions. J Toxicol Clin Toxicol 1994;32:631-81. 2. Bailey DG, Malcom J, Arnold A, Spence JD. Grapefruit juice-drug interactions. Br J Clin Pharmacol 1988;46:101-10. 3. Walker SE, Shulman KI, Tailor SAN, Gardner D. Tyramine content of previously restricted foods in monoamine oxidase inhibitor diets. J Clin Psychopharmacol 1996;16:383-88. 4. Booth SL, Charnley JM, Sadowski JA, Saltzman E, Bovill EG, Cushman M. Dietary vitamin K1 and stability of oral anticoagulation: proposal of a diet with constant vitamin K1 content. Thromb Haemost 1997;77:503-9 5. Bieck PR, Antonin K-H, Schmidt E. Clinical pharmacology of reversible monoamine oxidase-A inhibitors. Clin Neuropharmacol 1993;16suppl.2:s34s41. 6. Williams L, Hill DP, Davis JA, Lowenthal DT. The influence of food on the absorption and metabolism of drugs: an update. Eur J Drug Metab Pharmacokinet 1996;21:201-11. 7. DArcy PF. Nutrient-drug interactions. Adverse Drug React Toxicol Rev 1995;14:233-54. 8. Ameer B, Weintraub RA. Drug interactions with grapefruit juice. Clin Pharmacokinet 1997;3:103-21. 9. Fuhr U. Drug interactions with grapefruit juice: extent, probable mechanism and clinical relevance, Drug Safety 1998;18:251-72. 10. Livingston MG, Livingston HM. Monoamine oxidase inhibitors: an update on drug interactions. Drug Safety 1996;14;219-27. 11. Brown C, Taniguchi G, Yip K. The monoamine oxidase inhibitortyramine interaction. J Clin Pharmacol 1989;29:529-32. 12. Lippman SB, Nash K. Monoamine oxidase inhibitor update: potential adverse food and drug interactions. Drug Safety 1990;5:195-204. 13. Muller JL, Clauson KA. Pharmaceutical considerations of common herbal medicine. Am J Managed Care 1997;3:1753-70. 14. Ernst E. Harmless herbs? A review of the recent literature. Am J Med 1998;104:170-8.

Note: The list of drugs on the following pages includes only drugs that have been or are currently on the UW Hospital & Clinics formulary. The absense of a drug on this list does not necessarily mean that it has no drug-food interactions.

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Pharmacotherapy Perspectives

DRUG-FOOD INTERACTIONS
DRUG Acetaminophen EFFECT reduced rate of absorption; chronic alcohol ingestion increases hepatotoxicity increased sedation with alcohol reduced side effects with food; increased sedation with alcohol reduced side effects with food; increased sedation with alcohol reduced side effects with food; increased sedation with alcohol altered glycemic control with alcohol reduced absorption chronic alcohol use reduces sensitivity to alfentanil reduced side effects; reduced clearance of active metabolite with protein-poor diet increased sedation with alcohol; clearance may be inhibited by grapefruit juice see theophylline increased sedation with alcohol grapefruit juice inhibits metabolism slightly increased sedation with alcohol increased sedation with alcohol reduced side effects reduced absorption reduced effectiveness with high-protein meals reduced side effects with food; increased GI blood loss with alcohol reduced side effects with food; increased sedation with alcohol reduced absorption; metabolism may be inhibited by grapefruit juice reduced absorption NOTE DRUG Azathioprine N* * Azithromycin Baclofen Bethanechol Bisacodyl Bromocriptine Bumetanide Buspirone F* * E * Butalbital Calcium carbonate Captopril Carbamazepine Carbidopa/levodopa EFFECT reduced side effects reduced absorption reduced side effects increased side effects dissolves enteric coating reduced side effects with food; increased side effects with alcohol delayed onset; reduced efficacy delayed rate but increased total absorption increased sedation with alcohol increased absorption except with phytates and oxalates reduced absorption increased absorption slows rate of absorption; reduced side effects; dietary fiber increases absorption slows rate of absorption slows rate of absorption; peak levels reduced; AUC unchanged disulfiram reaction with alcohol slows rate of absorption; decreased side effects disulfiram reaction with alcohol disulfiram reaction with alcohol increased absorption increased absorption slows rate of absorption slows rate of absorption; reduces side effects slows rate of absorption; increased sedation with alcohol reduced efficacy when mixed with dairy foods, marmalade, simple syrup or cocoa increased sedation with alcohol decreases bioavailability by 10 to 20 percent increased sedation with alcohol NOTE F E F E E F* C N * N C F

Acetaminophen/ butalbital +/- caffeine Acetaminophen/ codeine Acetaminophen/ Hydrocodone Acetaminophen/ oxycodone Acetohexamide Alendronate Alfentanil Allopurinol

F*

F*

F*

Alprazolam

C N E * N * * F F N N *

* * * * * * F E N F*

Carvedilol Cefaclor Cefamandole Cefixime Cefoperazone Cefotetan Cefpodoxime Cefuroxime Cephalexin Cephradine Cetirizine Charcoal, activated

Aminophylline Amitriptyline Amlodipine Amobarbital Amoxapine Amoxicillin/ clavulanic acid Ampicillin Antacids (aluminum) Aspirin Aspirin/caffeine/ butalbital Astemizole Atenolol Atovaquone

F* E* N Chloral hydrate Chlorambucil Chlordiazepoxide

* * N *

greatly increased absorption, especially with fatty food F

ACTION KEY:

Ctake with or without food, but be consistent; Etake on an empty stomach; Nno specific action necessary, but consistency may be advised; Ftake with food; *specific action/precaution as in food effects column

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DRUG Chloroquine Chlorpheniramine

EFFECT reduced side effects slows rate of absorption; GI side effects decreased; increased sedation with alcohol increased sedation with alcohol disulfiram reaction with alcohol increased absorption reduced side effects; excretion de termined by urine pH

NOTE F

DRUG Dextroamphetamine Diazepam Diclofenac

EFFECT acidic juices reduce absorption; foods which acidify urine increase clearance may increase absorption; increased sedation with alcohol reduced peak concentration but not extent of absorption; reduced side effects decreased absorption decreased absorption reduced side effects increased sedation with alcohol caffeine reduces effect of drug slows rate of absorption; decreased absorption with high-fiber foods increased absorption increased sedation with alcohol increased sedation with alcohol alcohol intolerance delayed absorption; reduced side effects with food; increased sedation with alcohol increased sedation with alcohol reduced side effects; reduced absorption with milk; reduced efficacy with alcohol increased sedation with alcohol reduced rate of metabolism with alcohol increased bioavailability with fats and grapefruit juice increased/decreased absorption depending on form; avoid high fat meals with P.C.E. reduced side effects reduced side effects reduced side effects reduced absorption increased absorption with high-fat foods reduced side effects bioavailability markedly increased by grapefruit juice and fatty meals

NOTE C C

* * * C

Chlorpromazine Chlorpropamide Chlorothiazide Choline magnesium salicylate Cimetidine Ciprofloxacin Cisapride

F E E F * * N* C * * *

Dicloxacillin Didanosine

Diethylstilbestrol Diphenoxylate/ atropine Dipyridamole

increased blood alcohol levels; reduced caffeine clearance * dairy products decrease absorption; food delays rate of absorption; AUC unchanged increased absorption; take 30 minutes ac for best effect; increases blood alcohol levels slows rate of absorption; may reduce GI side effects

* N* N

Digoxin Diltiazem Dimenhydrinate Diphenhydramine Disulfiram Divalproex sodium

Clarithromycin Clomipramine Clonazepam Clonidine Clorazepate Cocaine Codeine

increased sedation with alcohol; metabolism reduced by grapefruit juice * increased sedation with alcohol increased sedation with alcohol; reduces side effects increased sedation with alcohol alcohol increases cardiac toxicity of cocaine reduced side effects with food; increased sedation with alcohol * N * * * F *

F* *

Doxepin Doxycycline

F* * * C

Doxylamine Dronabinol Enalapril Erythromycin

Conjugated estrogens reduced side effects Cyclobenzaprine Cyclosporine increased sedation with alcohol may increase or delay absorption; fruit juice reduces absorption; grapefruit juice increases AUC increased sedation with alcohol interference with test outcome; fast overnight & 5 hrs post-test increased absorption increased sedation with alcohol increased absorption when taken with acidic juices reduced absorption increased sedation with alcohol

C* * E C * C E *

Cyproheptadine D-xylose Danazol Dantrolene Delavirdine Demeclocycline Desipramine

* F F F E C F *

Erythromycin/ sulfisoxazole Ethinyl estradiol Ethionamide Etidronate Etretinate Felbamate Felodipine

ACTION KEY:

Ctake with or without food, but be consistent; Etake on an empty stomach; Nno specific action necessary, but consistency may be advised; Ftake with food; *specific action/precaution as in food effects column

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Pharmacotherapy Perspectives

DRUG Ferrous sulfate

EFFECT

NOTE

DRUG Indinavir

EFFECT reduced absorption with fat, proteins; slightly decreased AUC with grape fruit juice slows rate of absorption; reduced side effects prolonged hypoglycemia with alcohol see ferrous sulfate tyramine precautions; increased sedation with alcohol

NOTE

maximal absorption on empty stomach; reduced side effects; ascorbic acid increases absorption; tea, coffee and cocoa reduce absorption * reduced side effects reduced side effects reduces rate of absorption increased sedation with alcohol increased sedation with alcohol F F N * *

E* F * F *

Flecainide Fludrocortisone Fluoxetine Fluphenazine Flurazepam Fluvastatin Furazolidone Furosemide Gabapentin Ganciclovir Glipizide

Indomethacin Insulin Iron preparations Isocarboxazid Isoniazid

delayed absorption, reduced peak levels (not clinically significant) N disulfiram reaction with alcohol; tyramine precautions reduced absorption enhanced absorption with protein increased absorption delayed absorption; take 1/2 hour before meal; disulfiram reaction, prolonged hypoglycemia with alcohol increased sedation with alcohol disulfiram reaction, prolonged hypoglycemia control with alcohol increased peak levels, lower total systemic exposure increased rate or extent of absorption with fats; reduced side effects with food; disulfiram reaction with alcohol increased vasodilation with alcohol * C C F

reduced absorption with food; disulfiram reaction, increased hepatotoxicity, and reduced INH levels with alcohol E* delayed absorption increased absorption with food; disulfiram reaction with alcohol delayed absorption increased absorption reduced bioavailability delayed absorption with food; disulfiram reaction with alcohol delayed absorption; reduced side effects increased absorption slows rate of absorption disulfiram reaction with alcohol see carbidopa/levodopa di- and trivalent cations reduce absorption increased sedation with alcohol reduced absorption; anionic exchange resins reduce absorption (Product information-Synthroid(R)) reduced side effects with food slows rate of absorption delayed absorption, increased peak levels increased sedation with alcohol delayed absorption, AUC decreased somewhat increased absorption (except reduced absorption with high-fiber foods) increased sedation with alcohol E F* N F E N* F C E * C * *

Isosorbide dinitrate Isotretinoin Isradipine Itraconazole capsules Itraconazole solution Ketoconazole Ketorolac (oral) Labetalol Lansoprazole Levamisole Levodopa Levofloxacin Levorphanol Levothyroxine

* * * N

Glutethimide Glyburide Granisetron Griseofulvin

F* *

Guanethidine Haloperidol Hydralazine

reduced side effects; increased sedation with alcohol N* variable effects on absorption; reduced hypotensive effects with food in some patients reduced peak levels and AUC increased sedation with alcohol slows rate of absorption; reduced peak levels; reduced side effects increased sedation with alcohol reduced side effects increased sedation with alcohol reduced side effects increased sedation with alcohol

C* C * F * F * F *

Hydrochlorothiazide Hydrocodone Hydrocortisone Hydromorphone Hydroxychloroquine Hydroxyzine Ibuprofen Imipramine

E* F N C * N N* *

Lithium Loracarbef Loratadine Lorazepam Losartan Lovastatin Loxapine

ACTION KEY:

Ctake with or without food, but be consistent; Etake on an empty stomach; Nno specific action necessary, but consistency may be advised; Ftake with food; *specific action/precaution as in food effects column

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DRUG Mag/Al/simethicone Magnesium/ aluminum hydroxide Mebendazole Mecamylamine Meclizine Meclofenamate Mefloquine Melphalan Meperidine Meprobamate Mercaptopurine Mesalamine Mesoridazine Metformin

EFFECT high-protein foods decrease efficacy high-protein foods decrease efficacy increased absorption delayed absorption with food (may permit more gradual onset of effects) increased sedation with alcohol

NOTE * * F F* *

DRUG Minocycline Mirtazepine Misoprostol Moexipril Molindone Morphine solution Morphine sulfate Moxalactam Mycophenolate Nabumetone Nafcillin (oral) Naproxen Nefazodone Nelfinavir Niacin Nicardipine Nicotine polacrilex Nifedipine capsules

EFFECT dairy products decrease absorption increased sedation with alcohol delayed absorption; reduced side effects reduced absorption increased sedation with alcohol increased absorption; increased sedation with alcohol increased sedation with alcohol disulfiram reaction with alcohol slows rate of absorption increased absorption; reduced side effects reduced absorption reduced side effects reduced bioavailability, slows rate of absorption; may potentiate alcohol greatly increases absorption and AUC reduced absorption; decreases side effects reduced absorption

NOTE * * F E * F* * * C F E F C F F E

reduced absorption; reduced side effects F reduced side effects reduced absorption F E

reduced side effects; increased sedation with alcohol F* increased sedation with alcohol *

reduced absorption; reduced side effects C slows rate of absorption N

reduced side effects; increased sedation with alcohol F* decreases rate and extent of absorption; alcohol potentiates its effects on lactate metabolism; reduced side effect C* reduced side effects; increased sedation with alcohol F foods which alkalize urine may reduce efficacy increased sedation with alcohol increased sedation with alcohol * * *

Methadone Methenamine Methocarbamol Methohexital Methotrexate Methoxsalen Methylprednisolone Methysergide Metoclopramide Metoprolol Metronidazole Mexiletine

reduced absorption in presence of acidic substances such as coffee or cola * reduces rate of absorption reduced side effects; grapefruit juice increases AUC depends on brand *delayed absorption **minimal effects; grapefruit juice increases AUC reduced rate of absorption grapefruit juice inhibits metabolism grapefruit juice greatly enhances bioavailability increased absorption with food dairy products decrease absorption increased sedation with alcohol increased sedation and orthostatic hypotension with alcohol increased efficiency of drug delayed absorption increased absorption

C*

reduced absorption with food; increased hepatotoxicity with chronic alcohol use E * increased absorption; reduced side effects reduced side effects reduced side effects take 30 minutes ac for best effect; increases rate of absorption of alcohol increased absorption reduced side effects with food; disulfiram reaction with alcohol reduced side effects; slows rate of absorption; reduces rate of caffeine clearance increased sedation with alcohol; bioavailability increased by grapefruit juice F F F * C F*

Nifedipine ERT *Adalat CC **Procardia XL Nisoldipine Nitrendipine Nitrofurantoin Norfloxacin Nortriptyline Olanzapine Olsalazine Omeprazole

**C * * * F* * * * F E N

*E

Midazolam

Ondansetron

ACTION KEY:

Ctake with or without food, but be consistent; Etake on an empty stomach; Nno specific action necessary, but consistency may be advised; Ftake with food; *specific action/precaution as in food effects column

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Pharmacotherapy Perspectives

DRUG Opium tincture Oxacillin Oxazepam Oxybutynin Oxycodone Oxytocin Pancreatin Penicillamine Penicillin G Penicillin VK Pentazocine Pentobarbital Pentoxifylline Pergolide Perphenazine Phenelzine Phenobarbital Phenytoin

EFFECT increased sedation with alcohol reduced absorption increased sedation with alcohol; low calorie diet may decrease metabolism increased peak serum levels

NOTE * E * C

DRUG Propranolol Propylthiouracil Protriptyline Pseudoephedrine Pyridostigmine Quazepam Quetiapine Quinacrine Quinapril Quinidine

EFFECT

NOTE

slows rate but increases extent of absorption; efficacy reduced by alcohol F * variable effects increased sedation with alcohol delayed absorption delays time to peak plasma level increased sedation with alcohol C * N N *

reduced side effects; increased sedation with alcohol * reduced efficacy with alcohol alkaline foods dissolve enteric coating reduced absorption reduced absorption * * E E

increased peak concentration and AUC; potentiates the effects of alcohol C * reduced side effects; disulfiram reaction with alcohol delayed absorption variable effects; grapefruit juice reduces both absorption and metabolism; clinical significance unknown reduced side effects increased absorption reduced side effects reduced side effects high-fat meal delays absorption; food reduces side effects delayed absorption increased absorption slightly reduced absorption delayed absorption; reduced side effects increased absorption; grapefruit juice increases bioavailability increased sedation with alcohol tyramine precautions increased absorption; reduced side effects absorption may be reduced by high-fiber meal reduced side effects foods, especially dairy foods, reduce bioavailability reduced absorption increased absorption; reduced side effects reduced efficacy F* N

reduces and prolongs peak serum level; extent of absorption unchanged N increased sedation with alcohol increased sedation with alcohol * *

C* F N F F N E F N F F* * * N * F * C F E

delayed absorption; reduced side effects F reduced side effects reduced GI side effects; increased sedation with alcohol tyramine precautions increased sedation with alcohol increased absorption with food; increased phenytoin metabolism with chronic alcohol use slows rate of absorption; reduced side effects reduced side effects variable effects reduced side effects reduced side effects increased sedation with alcohol reduced side effects; increased absorption with fat tyramine precautions; disulfiram reaction and increased sedation with alcohol increased sedation with alcohol increased sedation with alcohol increased absorption slows rate of absorption; increased toxicity of propoxyphene with alcohol F F * *

Quinine Raloxifene Rescinnamine Reserpine Rifabutin Rifampin Ritonavir capsules Ritonavir liquid Salsalate Saquinavir Secobarbital Selegilene Sertraline Simvastatin Sodium chloride Sodium fluoride Sotalol Spironolactone Sucralfate

C* F F C F F * F

Piroxicam Potassium salts Prazosin Prednisolone Prednisone Primidone Procainamide Procarbazine

* * * C *

Prochlorperazine Promethazine Propafenone Propoxyphene

ACTION KEY:

Ctake with or without food, but be consistent; Etake on an empty stomach; Nno specific action necessary, but consistency may be advised; Ftake with food; *specific action/precaution as in food effects column

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DRUG Sulfasalazine Sulfinpyrazone Sulfisoxazole Sulindac Tacrolimus Temazepam Terbinafine Tetracycline Theophylline

EFFECT reduced side effects reduced side effects reduced side effects

NOTE F F F

DRUG Troglitazone Typhoid vaccine (oral) Ursodiol Valproate sodium Valproic acid Venlafaxine Verapamil

EFFECT increased absorption reduced absorption may reduce side effects

NOTE F E F

reduced absorption; reduced side effects F reduced absorption; grapefruit juice reduces metabolism increased sedation with alcohol potentiates caffeine by reducing its clearance reduced absorption, especially when taken with antacids or dairy products E* * * E

reduced side effects; increased sedation with alcohol F* delayed absorption, reduced side effects; increased sedation with alcohol F * reduced side effects; may potentiate effects of alcohol grapefruit juice increases AUC; blood alcohol levels may be increased; prolongs half-life of caffeine large amounts of vitamin K-containing foods may reduce efficacy; alcohol consumption may increase anticoagulation; garlic may increase anticoagulation reduced absorption reduced peak concentration and bioavailability reduced absorption when taken with high-fat foods reduced absorption, reduced side effects reduced absorption; reduced side effects F*

reduced absorption (increased absorption from SR products in children is possible);reduced side effects; high fat meal increases absorption; high carbohydrate diet reduces absorption; high caffeine intake inhibits metabolism C increased sedation with alcohol increased sedation with alcohol reduced absorption increased absorption; reduced side effects disulfiram reaction, prolonged hypoglycemia with alcohol disulfiram reaction with alcohol disulfiram reaction, prolonged hypoglycemia with alcohol * * E F * * *

Warfarin

* E E * N C

Thiopental Thioridazine Thyroid Ticlopidine Tolazamide Tolazoline Tolbutamide Tolmetin Topiramate Tranylcypromine Trazodone Triamterene Triazolam

Zafirlukast Zalcitabine Zidovudine Zinc salts Zolpidem

Sources:

Gelman CR, Rumack BH & Hess AJ (eds): DRUGDEX System. MICROMEDEX, Inc., Englewood, Colorado (Edition expires 11/30/98). Anonymous. Grapefruit juice interactions with drugs. Med Lett Drugs Ther August 18, 1995;37(955):73-4. Tatro DS, Olin BR, Hebel SK (eds): Drug Interaction Facts. Facts and Comparisons, St. Louis, Missouri, 1996. Updated 10/19/98

reduced absorption; reduced side effects F reduces rate of absorption; increased sedation with alcohol tyramine precautions N* *

delayed absorption; reduced side effects; increased sedation with alcohol F * high-potassium foods or salt substitutes may cause hyperkalemia * reduced rate of absorption with food; increased sedation with alcohol; AUC increased by 50% by grapefruit juice increased sedation with alcohol increased sedation with alcohol reduced absorption; reduced side effects increased sedation with alcohol

E* * * N *

Trifluoperazine Trihexyphenidyl Trimethoprim Trimipramine

ACTION KEY:

Ctake with or without food, but be consistent; Etake on an empty stomach; Nno specific action necessary, but consistency may be advised; Ftake with food; *specific action/precaution as in food effects column

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