From the FDA Drug Label
Drug-Drug Interactions Alprazolam is primarily eliminated by metabolism via cytochrome P450 3A (CYP3A) Most of the interactions that have been documented with alprazolam are with drugs that inhibit or induce CYP3A4. Compounds that are potent inhibitors of CYP3A would be expected to increase plasma alprazolam concentrations. Fluconazole is a moderate CYP2C9 and CYP3A4 inhibitor.
The interaction between fluconazole (Diflucan) and alprazolam is that fluconazole, being a moderate CYP3A4 inhibitor, would be expected to increase plasma alprazolam concentrations. This is because alprazolam is primarily eliminated by metabolism via cytochrome P450 3A (CYP3A), and inhibitors of this enzyme can lead to increased levels of alprazolam in the body. 1 2
From the Research
Interaction between Fluconazole and Alprazolam
- The interaction between fluconazole (Diflucan) and alprazolam is primarily due to fluconazole's inhibition of the cytochrome P450 (CYP) 3A4 enzyme, which is responsible for metabolizing alprazolam 3.
- Fluconazole is a potent inhibitor of CYP3A4, although its potency is much lower than that of other azole antifungals like ketoconazole and itraconazole 3.
- Coadministration of fluconazole with alprazolam can result in increased alprazolam plasma concentrations, potentially leading to enhanced sedative effects or other adverse reactions 3, 4.
- However, the clinical significance of this interaction is generally observed only with fluconazole dosages of 200 mg/day or higher 3.
- A study found that coadministration of cimetidine, fluoxetine, fluvoxamine, or propoxyphene with alprazolam significantly impairs alprazolam clearance, but it did not specifically investigate the interaction with fluconazole 5.
Clinical Relevance
- The frequency of potential azole-drug interactions, including those with fluconazole, is high in hospitalized patients, but the clinical consequences of these interactions are often minimal 6.
- A retrospective cohort study found that among patients exposed to potential fluconazole drug interactions, few adverse drug events were attributed to these interactions 6.
- Physicians should be aware of the potential for interactions between fluconazole and other medications, including alprazolam, to prevent or reduce the burden of adverse events 4.