Triazolam CYP3A4/5/7 substrate

Aprepitant may be affected by paroxetine, CYP2C9 substrates (eg, phenytoin, tolbutamide, warfarin), CYP3A4 substrates (eg, alprazolam, cisapride, dexamethasone, docetaxel, etoposide, ifosfamide, imatinib, irinotecan, methylprednisolone, midazolam, paclitaxel, pimozide, triazolam, vinblastine, vincristine, vinorelbine), and oral contraceptives. 

Delavirdine should not be used in combination with drugs that are CYP3A4 substrates such as pimozide, midazolam, triazolam, amiodarone, propafenone and ergot derivatives. Inducers of the hepatic P-450 system, rifampin, rifabutin, pheno-barbital, phenytoin or carbamazepine, should not be used in combination with delaviridine. It also increases the plasma levels of HIV protease inhibitors. 

Meanwhile, the currently marketed CYP3A4 inducers can profoundly affect the pharmacokinetics of coadministered CYP3A4 substrates, e.g., rifampin on midazolam (139) or triazolam (140). Clearly, the most frequent outcome is a loss of efficacy, which is perhaps less serious than inhibition interactions, although the consequences of coadministering rifampin with the oral contraceptive pill can lead to contraceptive failure (141-143). 

In a double-blind, crossover, pharmacokinetic and pharmacodynamic study of the interaction of ketoconazole with alprazolam and triazolam, two CYP3A4 substrate drugs with different kinetic profiles, impaired clearance by ketoconazole had more profound clinical consequences for triazolam than for alprazolam (39). 

Of aU the HIV protease inhibitors, saquinavir is the least potent inhibitor of CYP3A4. Nonetheless, it is recommended that the drug not be coadministered with ergot derivatives, triazolam, midazolam, or other CYP3A4 substrates with a low therapeutic index. Saquinavir clearance is increased with CYP3A4 induction thus coadministration of rifampin, nevirapine, or efavirenz lowers saquinavir concentrations and should be avoided. The effect of nevirapine or efavirenz on saquinavir may be partially or completely reversed with ritonavir. 

Backman JT, Wang J-S, WenX, Kivisto KT, Neuvonen PJ. Mibefradil but not isradipine substantially elevates tiie plasma concentrations of the CYP3A4 substrate triazolam. CUn Pharmacol Ther( 999) 66, 401-7. 

Schrag, M.L. and Wienkers, L.C. (2001) Triazolam substrate inhibition evidence of competition for heme-bound reactive oxygen within the CYP3A4 active site. Drug Metabolism and Disposition, 29 (1), 70-75. 

Nefazodone is a weak inhibitor of CYP2D6 but a potent inhibitor of CYP3A4 and it increases plasma concentrations of drugs that are substrates of CYP3A4, such as alprazolam, astemizole, carbamazepine, ciclosporin, cisapride, terfenadine, and triazolam. 

A general study in psychiatric patients found that when data on benzodiazepines was pooled, they caused a modest 23% increase in serum citalopram levels, which is almost certainly too small to be clinically relevant. Alprazolam was the only benzodiazepine to cause an elevation of citalopram levels (by 13%) when analysed alone. In another study, citalopram was found to have no effect on alprazolam plasma levels, although the time to maximum alprazolam concentration was increased by 30 minutes. Similarly, a study in 17 healthy subjects found no pharmacokinetic interaction between triazolam and citalopram, and it was suggested that triazolam and other substrates of the cytochrome P450 isoenzyme CYP3A4 are unlikely to have pharmacokinetic interactions with citalopram. ... 

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