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FDA. Valium® prescribing information (2013)
“Metabolism: **Diazepam** is N-demethylated by **CYP3A4** and 2C19 to the active metabolite N-desmethyldiazepam, and is hydroxylated by **CYP3A4** to the active metabolite temazepam. N-desmethyldiazepam and temazepam are both further metabolized to oxazepam. Temazepam and oxazepam are largely eliminated by glucuronidation. […]
- Drug Interactions
Centrally Acting Agents: If **Valium** is to be combined with other centrally acting agents, careful consideration should be given to the pharmacology of the agents employed particularly with compounds that may
potentiate or be potentiated by the action of **Valium**, such as phenothiazines, antipsychotics, anxiolytics/sedatives, hypnotics, anticonvulsants, narcotic analgesics, anesthetics, sedative antihistamines, narcotics, barbiturates,
**MAO inhibitors**† and other antidepressants. […]
Compounds Which Inhibit Certain Hepatic Enzymes:
There is a potentially relevant interaction between **diazepam** and compounds which inhibit certain hepatic enzymes (particularly **cytochrome P450 3A**† and 2C19). 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.”
†Zhao T, He YQ, Wang J, Ding KM, Wang CH, Wang ZT.
Inhibition of human **cytochrome P450 enzymes 3A4** and 2D6 by **β-carboline alkaloids**, harmine derivatives. Phytother Res. 2011 Nov;25(11):1671-7. doi: 10.1002/ptr.3458. Epub 2011 Mar 24. PMID: 21433154.
“Abstract: **β-Carboline alkaloids** are the main chemical constituents of the plant **Peganum harmala**, while they also could be formed endogenously and found in coffee, alcoholic beverages and tobacco. Considering the fact that the possibility of herb-drug interactions has recently received great attention worldwide, the aim of the current study was to assess the potential for the metabolism-based drug-drug interactions arising from five **β-carboline alkaloids** (harmine, harmaline, harmalol, harmol and harmane) from **P. harmala** in vitro. With microsome incubation assays and UPLC/HPLC methods, the inhibitions on human liver **CYP3A4** and CYP2D6 enzymes by those **β-carboline alkaloids** were studied kinetically. Harmine, harmol and harmane exhibited noncompetitive inhibition on the activity of CYP3A4 with K(i) values of 16.76, 5.13 and 1.66 μM, respectively. These **β-carboline alkaloids** were also found to be both substrates and inhibitors for CYP2D6. Harmaline, harmine and harmol showed typical competitive inhibition on the activity of CYP2D6 with K(i) values of 20.69, 36.48 and 47.11 μM, respectively.
The inhibition of the two major CYP enzymes by those β-carboline alkaloids suggested that changes in the pharmacokinetics of co-administered drugs were likely to have occurred. Therefore, caution should be exercised for possible drug interactions of medicinal plants containing those β-carboline alkaloids and CYP substrates.”
