In human therapy, is the drug-drug interaction or the adverse drug reaction the issue?

In recent years, many publications in scientific journals have reported, in healthy volunteers, potential food-drug or drug-drug interactions. The lay press has frequently emphasized such interactions and extrapolated on the dangers of food-drug or drug-drug interactions. However, the clinical relevancy of these interactions has not always been substantiated in patients. The aim of the present review was to assess the clinical relevancy of drug-drug interactions occurring at the level of the biotransformation of the drug. For this purpose, the incidence of serious, life-threatening adverse drug reactions (ADRs) of drugs metabolized by different enzymes of cytochrome P450 found in the safety reports issued in megatrials were compared with those from placebo trials. It was concluded that serious ADRs secondary to drug-drug interactions are infrequent; drug-drug interactions including selected drugs with a narrow therapeutic index and eliciting life-threatening undesired effects occur; and serious ADRs secondary to drug-drug interactions are most frequent in elderly patients, in the presence of polypharmacy, in the psychiatric patient population, and in the presence of inappropriate prescriptions and of multiple prescriptors.