Drug Interactions

Definition & scope

• Drug interaction (DDI) — occurs when the effect of one drug is changed by the presence of another drug, herbal medicine, food, drink or environmental chemical. Change is mostly quantitative (response increased/decreased) but sometimes qualitative (a new response, e.g. serotonin syndrome from two serotonergic drugs).
• Object vs precipitant — every interaction is analysed as a precipitant (perpetrator) drug that causes the change acting on an object (victim) drug whose effect/concentration is altered — the central analytic device of Hansten & Horn and Stockley's. A perpetrator is regulatorily significant when it produces a ≥5-fold change in victim AUC (FDA "sensitive substrate").
• Pharmaceutical incompatibility is EXCLUDED — in-vitro/IV-admixture precipitation or inactivation (penicillin + gentamicin, or thiopentone + suxamethonium in one syringe) occurs outside the body — an incompatibility, not a true pharmacological interaction (covered separately).
• Polypharmacy gradient — risk rises non-linearly with number of drugs — clinically relevant interaction rate ~7% on 6–10 drugs but ~40% on 16–20 drugs. A loss of efficacy (rifampicin abolishing warfarin; antacids blocking tetracycline) can be as harmful as added toxicity.