Clinically significant pharmacokinetic drug interactions with benzodiazepines.

The reports of interactions between benzodiazepines (BZPs) and other drugs (e.g., antidepressants, selective serotonin reuptake inhibitors, antiulcer drugs, antiepileptic drugs, macrolide antibiotics) during their combined use are reviewed. In general, metabolism of BZPs is delayed when combined with a number of other drugs but some reports have suggested otherwise. In recent years, the cytochrome P450 (P450 or CYP) isoenzyme that catalyses the metabolism of BZPs has also been identified. BZPs are mainly catalysed by CYP3A4. When published reports are studied, it appears necessary to be exceptionally careful about interactions mainly between BZPs and selective serotonin reuptake inhibitors, cimetidine, antiepileptic drugs, macrolide antibiotics and antimycotics. More information is necessary to identify individuals at greatest risk of drug interactions and adverse events.