Drug interactions are changes in a drug’s effects due to recent or concurrent use of another drug(s) (drug-drug interactions), ingestion of food (drug-nutrient interactions), or ingestion of dietary supplements (dietary supplement-drug interactions).
Topic Resources
A drug-drug interaction may increase or decrease the effects of one or both drugs. Clinically significant interactions are often predictable and usually undesired (see table Some Medications With Potentially Serious Drug-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 ritonavir to patients with HIV infection results in altered metabolism of lopinavir and increases serum lopinavir concentrations and effectiveness.). 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 ritonavir to patients with HIV infection results in altered metabolism of lopinavir and increases serum lopinavir concentrations and effectiveness.
Some Medications With Potentially Serious Drug-Drug Interactions*
Mechanism | Examples |
|---|---|
Narrow margin of safety† | Antiarrhythmic drugs (eg, quinidine)Antiarrhythmic drugs (eg, quinidine) Antineoplastic drugs (eg, methotrexate)Antineoplastic drugs (eg, methotrexate) DigoxinDigoxin LithiumLithium TheophyllineTheophylline WarfarinWarfarin |
Extensive metabolism by certain hepatic enzymes | AlprazolamAlprazolam AmitriptylineAmitriptyline AtorvastatinAtorvastatin CarbamazepineCarbamazepine ClozapineClozapine Corticosteroids CyclosporineCyclosporine DiazepamDiazepam HIV protease inhibitors ImipramineImipramine LovastatinLovastatin MidazolamMidazolam OlanzapineOlanzapine PhenytoinPhenytoin SildenafilSildenafil SimvastatinSimvastatin TacrolimusTacrolimus TadalafilTadalafil TheophyllineTheophylline TriazolamTriazolam VardenafilVardenafil WarfarinWarfarin |
Inhibition of certain hepatic enzymes‡ | AprepitantAprepitant Boceprevir CimetidineCimetidine CiprofloxacinCiprofloxacin ClarithromycinClarithromycin CobicistatCobicistat ConivaptanConivaptan DiltiazemDiltiazem ErythromycinErythromycin FluconazoleFluconazole FluoxetineFluoxetine FluvoxamineFluvoxamine ItraconazoleItraconazole KetoconazoleKetoconazole ParoxetineParoxetine PosaconazolePosaconazole RitonavirRitonavir Telaprevir Telithromycin VerapamilVerapamil VoriconazoleVoriconazole |
Induction of certain hepatic enzymes | Barbiturates (eg, phenobarbital)Barbiturates (eg, phenobarbital) BosentanBosentan CarbamazepineCarbamazepine EfavirenzEfavirenz PhenytoinPhenytoin RifabutinRifabutin RifampinRifampin St. John’s wort |
* Any medication to be used concurrently with one of these medications should be thoroughly evaluated for possible interactions. † Even when used alone, these medications may have serious adverse effects. Concurrent use of another medication that increases the action of these medications further increases risk of adverse effects. For additional research on potential drug-drug interactions, consult a reliable source, such as the Drugs.com Drug Interaction Checker. ‡ Inhibition also can occur after ingestion of grapefruit products. | |
In therapeutic duplication, 2 medications 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
In pharmacodynamic interactions, one medication alters the sensitivity or responsiveness of tissues to another medication 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 medication alters absorption, distribution, protein binding, metabolism, or excretion of another medication. Thus, the amount and persistence of available medication at receptor sites is changed. Pharmacokinetic interactions alter magnitude and duration, not type, of effect. They can often be predicted based on knowledge of the individual medications or detected by monitoring medication concentrations or clinical signs.
Minimizing drug interactions
Clinicians should know all of their patients’ current medications, including medications prescribed by other clinicians and all over-the-counter medications, herbal products, and nutritional supplements. Asking patients relevant questions about diet and alcohol consumption is recommended. The fewest medications in the lowest doses for the shortest possible time should be prescribed. The effects, desired and undesired, of all medications taken should be determined because these effects usually include the spectrum of medication interactions. If possible, medications 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 week 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 medications 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 medication should be replaced by one that does not interact with other medications being taken.
