drug interaction

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 ritonavir

to patients with HIV infection results in altered metabolism of lopinavir and increases serum lopinavir concentrations and effectiveness.
Table 2

Some Drugs With Potentially Serious Drug Interactions*

Mechanism
Examples

Narrow margin of safety†
Antiarrhythmic drugs (eg, quinidine

)

Antineoplastic drugs (eg, methotrexate

)

Digoxin

Lithium

Theophylline

Warfarin

Extensive metabolism by certain hepatic enzymes
Alprazolam

Amitriptyline

Atorvastatin

Carbamazepine

Clozapine

Corticosteroids

Cyclosporine

Diazepam

Imipramine

Lovastatin

Midazolam

Olanzapine

Phenytoin

Protease inhibitors

Sildenafil

Simvastatin

Tacrolimus

Tadalafil

Theophylline

Triazolam

Vardenafil

Warfarin

Inhibition of certain hepatic enzymes
Cimetidine

Ciprofloxacin

Clarithromycin

Diltiazem

Erythromycin

Fluconazole

Fluoxetine

Fluvoxamine

Itraconazole

Ketoconazole

Paroxetine

Ritonavir

Telithromycin

Induction of certain hepatic enzymes
Barbiturates (eg, phenobarbital

)

Carbamazepine

Phenytoin

Rifabutin

Rifampin

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.

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