Drug interactions are changes in a drug's effects due to recent or concurrent use of another drug or drugs (drug-drug interactions) or due to ingestion of food (drug-nutrient interactions—see Nutrition: General Considerations: Nutrient-Drug Interactions).

A drug interaction may increase or decrease the effects of one or both drugs. Clinically significant interactions are often predictable and usually undesired (see Table 2: Concepts in Pharmacotherapy: Some Drugs With Potentially Serious Drug Interactions*). Adverse effects or therapeutic failure may result. Rarely, clinicians can use predictable drug-drug interactions to produce a desired therapeutic effect. For example, coadministration of lopinavir and ritonavirSome Trade Names
NORVIR
Click for Drug Monograph
to patients with HIV infection results in altered metabolism of lopinavir and increases serum lopinavir concentrations and effectiveness.

Table 2
PrintOpen table
Some Drugs With Potentially Serious Drug Interactions* Mechanism Examples Narrow margin of safety† Antiarrhythmic drugs (eg, quinidineSome Trade Names CARDIOQUIN QUINAGLUTE Click for Drug Monograph ) Antineoplastic drugs (eg, methotrexateSome Trade Names RHEUMATREX Click for Drug Monograph ) DigoxinSome Trade Names DIGITEK LANOXIN Click for Drug Monograph LithiumSome Trade Names ESKALITH LITHOBID LITHONATE Click for Drug Monograph TheophyllineSome Trade Names ELIXOPHYLLIN THEO-DUR Click for Drug Monograph WarfarinSome Trade Names COUMADIN Click for Drug Monograph Extensive metabolism by certain hepatic enzymes AlprazolamSome Trade Names XANAX Click for Drug Monograph AmitriptylineSome Trade Names ELAVIL ENDEP Click for Drug Monograph AtorvastatinSome Trade Names LIPITOR Click for Drug Monograph CarbamazepineSome Trade Names TEGRETOL Click for Drug Monograph ClozapineSome Trade Names CLOZARIL Click for Drug Monograph Corticosteroids CyclosporineSome Trade Names NEORAL SANDIMMUNE Click for Drug Monograph DiazepamSome Trade Names VALIUM Click for Drug Monograph ImipramineSome Trade Names TOFRANIL Click for Drug Monograph LovastatinSome Trade Names ALTOPREV MEVACOR Click for Drug Monograph MidazolamSome Trade Names No US trade name Click for Drug Monograph OlanzapineSome Trade Names ZYPREXA Click for Drug Monograph PhenytoinSome Trade Names DILANTIN Click for Drug Monograph Protease inhibitors SildenafilSome Trade Names VIAGRA Click for Drug Monograph SimvastatinSome Trade Names ZOCOR Click for Drug Monograph TacrolimusSome Trade Names PROGRAF Click for Drug Monograph TadalafilSome Trade Names CIALIS Click for Drug Monograph TheophyllineSome Trade Names ELIXOPHYLLIN THEO-DUR Click for Drug Monograph TriazolamSome Trade Names HALCION Click for Drug Monograph VardenafilSome Trade Names LEVITRA Click for Drug Monograph WarfarinSome Trade Names COUMADIN Click for Drug Monograph Inhibition of certain hepatic enzymes CimetidineSome Trade Names TAGAMET Click for Drug Monograph CiprofloxacinSome Trade Names CILOXAN CIPRO Click for Drug Monograph ClarithromycinSome Trade Names BIAXIN Click for Drug Monograph DiltiazemSome Trade Names CARDIZEM CARTIA DILACOR Click for Drug Monograph ErythromycinSome Trade Names ERY-TAB ERYTHROCIN Click for Drug Monograph FluconazoleSome Trade Names DIFLUCAN Click for Drug Monograph FluoxetineSome Trade Names PROZAC SARAFEM Click for Drug Monograph FluvoxamineSome Trade Names LUVOX Click for Drug Monograph ItraconazoleSome Trade Names SPORANOX Click for Drug Monograph KetoconazoleSome Trade Names NIZORAL Click for Drug Monograph ParoxetineSome Trade Names PAXIL Click for Drug Monograph RitonavirSome Trade Names NORVIR Click for Drug Monograph TelithromycinSome Trade Names KETEK Click for Drug Monograph Induction of certain hepatic enzymes Barbiturates (eg, phenobarbitalSome Trade Names LUMINAL Click for Drug Monograph ) CarbamazepineSome Trade Names TEGRETOL Click for Drug Monograph PhenytoinSome Trade Names DILANTIN Click for Drug Monograph RifabutinSome Trade Names MYCOBUTIN Click for Drug Monograph RifampinSome Trade Names RIFADIN RIMACTANE Click for Drug Monograph St. John's wort *Any drug to be used concurrently with one of these drugs should be thoroughly evaluated for possible drug interactions. †Even when used alone, these drugs may have serious adverse effects. Concurrent use of another drug that increases the action of these drugs further increases risk of adverse effects.

In therapeutic duplication, 2 drugs with similar properties are taken at the same time and have additive effects. For example, taking a benzodiazepine for anxiety and another benzodiazepine at bedtime for insomnia may have a cumulative effect, leading to toxicity.

Drug interactions involve

• Pharmacodynamics
• Pharmacokinetics

In pharmacodynamic interactions, one drug alters the sensitivity or responsiveness of tissues to another drug by having the same (agonistic) or a blocking (antagonistic) effect. These effects usually occur at the receptor level but may occur intracellularly.

In pharmacokinetic interactions, a drug usually alters absorption, distribution, protein binding, metabolism, or excretion of another drug. Thus, the amount and persistence of available drug at receptor sites change. Pharmacokinetic interactions alter magnitude and duration, not type, of effect. They are often predicted based on knowledge of the individual drugs or detected by monitoring drug concentrations or clinical signs.

Minimizing drug interactions: Clinicians should know all of their patients' current drugs, including drugs prescribed by other clinicians and all OTC drugs, herbal products, and nutritional supplements. Asking patients relevant questions about diet and alcohol consumption is recommended. The fewest drugs in the lowest doses for the shortest possible time should be prescribed. The effects, desired and undesired, of all drugs taken should be determined because these effects usually include the spectrum of drug interactions. If possible, drugs with a wide safety margin should be used so that any unforeseen interactions do not cause toxicity.

Patients should be observed and monitored for adverse effects, particularly after a change in treatment; some interactions (eg, effects that are influenced by enzyme induction) may take ≥ 1 wk to appear. Drug interactions should be considered as a possible cause of any unexpected problems. When unexpected clinical responses occur, prescribers should determine serum concentrations of selected drugs being taken, consult the literature or an expert in drug interactions, and adjust the dosage until the desired effect is produced. If dosage adjustment is ineffective, the drug should be replaced by one that does not interact with other drugs being taken.

Last full review/revision January 2010 by Daniel A. Hussar, PhD

Content last modified February 2012