Drug-food interactions in clinical practice

Drug--food interactions are a significant problem in clinical practice. Foods may alter the effects of drugs by interfering with pharmacokinetic processes, such as absorption and elimination. For example, absorption of tetracyclines is decreased when taken with milk or other dairy products. Pharmacologic and pharmacodynamic mechanisms also play an important role in drug--food interactions by altering drug effects. An example is the interaction of warfarin sodium with leafy green vegetables, whereby the hypoprothrombinemic effect of warfarin may be decreased and thromboembolic complications may develop. Similarly, certain drugs may have an effect on food intake, absorption, metabolism, and utilization. Numerous drugs, such as antineoplastic agents, have been shown to suppress appetite, resulting in decreased food intake and nutritional deficiency.

It is important that health care providers, such as physicians, pharmacists, and dietitians, recognize and work as a team to prevent significant drug--food interactions. Minimizing adverse drug--food interactions would improve patient care by optimizing therapeutic effects and maintaining proper nutritional status.

Key words. Food--drug interactions; drugs; food; pharmacology; drug toxicity; therapeutic failure; nutritional deficiency. (J Fam Pract 1995; 40:376-384)

As with drug--drug interactions, drug--food interactions represent a substantial clinical problem that may result in adverse drug effects or toxicity. In some cases, the interacting effects may cause therapeutic failure(1) or nutritional deficiency.(2) Recent guidelines of the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) have encouraged hospital pharmacists and dietitians to monitor interactions between drugs and foods in patients.(3) This article reviews and updates the database for clinicians regarding drug--food interactions, focusing on those of clinical significance.

Mechanisms of Drug--Food Interactions

The interactions of foods with drugs can be classified in two major categories: pharmacokinetic and pharmacodynamic interactions.

Pharmacokinetics

The absorption, distribution, metabolism, and excretion of a drug is known as pharmacokinetics.(4) Foods may affect the rate or extent, or both, of drug absorption by altering gastric pH, secretion, and gastrointestinal motility and transit time. Alterations in the rate of a drug's absorption caused by the ingestion of certain foods generally is not considered as clinically important as changes in the extent of its absorption. However, a delay in time to peak plasma concentration or time to achieve steady-state therapeutic concentrations may occur if the rate of absorption is decreased. The types of food and the amount or size of a meal also can affect the absorption of a drug. Certain constituents in foods may chelate or adsorb the drug, resulting in a decrease in the extent and rate of its absorption.(5)

Food may interact with a drug by interfering with its metabolism. For example, charcoal-broiled meat can activate hepatic microsomal enzymes, causing an increase in theophylline metabolism or clearance.(6) Likewise, certain drugs may interfere with the metabolism of food or food additives, as in the case of metronidazole and alcohol.(7)

Pharmacodynamics

The study of drug effects is known as pharmacodynamics. Foods may interact with drugs by influencing their effects or pharmacologic actions, as in the case of diets high in vitamin K, which decrease the effects of warfarin sodium,(8)(9)(10)(11) or alcoholic beverages,...