[Interaction studies with fluconazole, a new triazole antifungal drug]

Fluconazole is a new systemic antifungal agent from the class of triazoles. Its efficacy was documented in clinical studies of patients with candidosis and cryptococcosis. Due to the influence on human cytochrome-P-450-dependent enzymes, special attention should be paid, in the development of new antifungal agents, to the inhibition of the metabolization of other simultaneously given substances and to the inhibition of steroid hormone synthesis in the gonads and adrenal glands. The interaction studies carried out with frequently administered drugs such as oral contraceptives, cimetidine, warfarin, tolbutamide, and cyclosporin (transplantation patients) allow the concomitant intake of these substances with fluconazole. Concomitant anti-coagulant treatment requires a precautionary monitoring of prothrombin time; it may be necessary in individual cases to reduce the anticoagulant dosage. The intake of oral hypoglycemics of the tolbutamide type requires monitoring of blood glucose, although blood glucose lowering effects were not found. One interaction study carried out with phenazone showed the low metabolization tendency of fluconazole. Approximately 80% of the administered fluconazole dose appeared in the urine unchanged. Studies in male and female subjects with multiple doses of fluconazole (4 weeks) did not show any significant effects on the endocrinology and steroid synthesis in man.