Effect of fluconazole dose on the extent of fluconazole‐triazolam interaction

Abstract

1Azole antimycotics interact with the short acting hypnotic triazolam. The effect of fluconazole dose on the extent of fluconazole‐triazolam interaction was investigated in a double‐blind, randomized cross‐over study of four phases. 2Eight healthy volunteers received either 50 mg, 100 mg or 200 mg (400 mg on day 1) of fluconazole or placebo orally once a day for 4 days. On day 4, they took a 0.25 mg oral dose of triazolam, after which plasma samples were collected and pharmacodynamic effects measured for 18 h. 3The mean area under the triazolam concentration‐time curve (AUC) was increased 1.6‐, 2.1‐ and 4.4‐fold (P<0.001) by fluconazole 50 mg, 100 mg and 200 mg, respectively. The increase in the elimination half‐life of triazolam (t½,z) varied from 1.3‐fold (fluconazole 50 mg, P<0.05) to 2.3‐fold (fluconazole 200 mg, P<0.001). The peak concentration of triazolam was also increased significantly during all fluconazole phases; more than twofold by fluconazole 200 mg (P<0.001). 4The pharmacodynamic effects of triazolam were increased significantly (P<0.05) by fluconazole 100 mg and 200 mg. 5Even a small 50 mg daily dose of fluconazole can interact with triazolam and the extent of the interaction increases with increasing fluconazole dose. When triazolam is used concomitantly with fluconazole 50–200 mg, the dose of triazolam should be reduced, accordingly. Simultaneous use of triazolam with higher fluconazole doses should be avoided.