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Alprazolam is primarily metabolized via CYP3A4.[48] Combining CYP3A4 inhibitors such as cimetidine, erythromycin, norfluoxetine, fluvoxamine, itraconazole, ketoconazole, nefazodone, propoxyphene, and ritonavir delay the hepatic clearance of alprazolam, which may result in its accumulation[49] and increased severity of its side effects

Imipramine and desipramine have been reported to increase an average of 31% and 20% respectively by the concomitant administration of alprazolam tablets.[6] Combined oral contraceptive pills reduce the clearance of alprazolam, which may lead to increased plasma levels of alprazolam and accumulation.

Alcohol is one of the most common interactions; alcohol and alprazolam taken in combination have a synergistic effect on one another, which can cause severe sedation, behavioral changes, and intoxication. The more alcohol and alprazolam taken, the worse the interaction.[34] Combination of alprazolam with the herb kava can result in the development of a semi-comatose state.[53] Plants in the genus Hypericum, including St. John’s wort, conversely can lower the plasma levels of alprazolam and reduce its therapeutic effect.

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