Table 1.

The FDA Diazepam Statements on Metabolism and Drug Interactions (2020, 2017)

Drug (formulation)Metabolism and pharmacogenetic interactions
Diazepam (tablet, oral solution)aDiazepam is N-demethylated by CYP3A4 and 2C19 to the active metabolite N-desmethyldiazepam, and is hydroxylated by CYP3A4 to the active metabolite temazepam.
[…]
There is a potentially relevant interaction between diazepam and compounds that inhibit certain hepatic enzymes (particularly CYP3A and CYP2C19). Data indicate that these compounds influence the pharmacokinetics of diazepam and may lead to increased and prolonged sedation. At present, this reaction is known to occur with cimetidine, ketoconazole, fluvoxamine, fluoxetine, and omeprazole.
Diazepam (gel)bThe marked inter-individual variability in the clearance of diazepam reported in the literature is probably attributable to variability of CYP2C19 (which is known to exhibit genetic polymorphism; approximately 3–5% of Caucasians have little or no activity and are “poor metabolizers”) and CYP3A4.
[…]
… Potential interactions may occur when diazepam is given concurrently with agents that affect CYP2C19 and CYP3A4 activity. Potential inhibitors of CYP2C19 and CYP3A4 could decrease the rate of diazepam elimination, while inducers of CYP2C19 and CYP3A4 could increase the rate of elimination of diazepam.
Effect of diazepam on the metabolism of other drugs: There are no reports as to which isozymes could be inhibited or induced by diazepam. But, based on the fact that diazepam is a substrate for CYP2C19 and CYP3A4, it is possible that diazepam may interfere with the metabolism of drugs that are substrates for CYP2C19, (for example, omeprazole, propranolol, and imipramine) and CYP3A4 (for example, cyclosporine, paclitaxel, terfenadine, theophylline, and warfarin) leading to a potential drug-drug interaction.
a

Information adapted from (1, 5).

b

Information adapted from (3).

From: Diazepam Therapy and CYP2C19 Genotype

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