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  • Title: Fluconazole, but not terbinafine, enhances the effects of triazolam by inhibiting its metabolism.
    Author: Varhe A, Olkkola KT, Neuvonen PJ.
    Journal: Br J Clin Pharmacol; 1996 Apr; 41(4):319-23. PubMed ID: 8730978.
    Abstract:
    1. The interaction between triazolam and two antifungal agents, fluconazole and terbinafine, was investigated in a double-blind, randomized crossover study of three phases. 2. Twelve healthy young volunteers received 100 mg fluconazole, 250 mg terbinafine or placebo orally once a day for 4 days. On day 4 they took a single 0.25 mg dose of triazolam. Plasma samples were collected and pharmacodynamic effects were measured up to 17 h after the intake of triazolam. 3. Fluconazole increased the area under the triazolam concentration time-curve more than twofold (P < 0.001) and prolonged the elimination half-life of triazolam nearly twofold (P < 0.001). The peak concentration of triazolam was also increased significantly (P < 0.05) by fluconazole. 4. During the fluconazole phase pharmacodynamic effects of triazolam (e.g. digit symbol substitution test, body sway and drowsiness) were enhanced significantly (P < 0.05) when compared with the placebo phase. 5. Terbinafine did not change significantly the pharmacokinetics or pharmacodynamics of triazolam. 6. Care should be taken when triazolam is prescribed to patients using fluconazole. Although the interaction is not as strong as that of triazolam with ketoconazole or itraconazole, it is clinically significant. Triazolam and probably other drugs metabolized by CYP3A4 can be used in normal doses with terbinafine.
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