Diflucan Clinical Pharmacology

Drug Library
Diflucan - Clinical Pharmacology [Fluconazole]

Oral hypoglycemics

The effects of fluconazole on the pharmacokinetics of the sulfonylurea oral hypoglycemic agents tolbutamide, glipizide, and glyburide were evaluated in three placebo-controlled studies in normal volunteers. All subjects received the sulfonylurea alone as a single dose and again as a single dose following the administration of DIFLUCAN 100 mg daily for 7 days. In these three studies 22/ 46 (47.8%) of DIFLUCAN treated patients and 9/ 22 (40.1%) of placebo treated patients experienced symptoms consistent with hypoglycemia. (See PRECAUTIONS.)

Tolbutamide:

In 13 normal male volunteers, there was significant increase in tolbutamide (500 mg single dose) AUC and Cmax following the administration of fluconazole. There was a mean ą SD increase in tolbutamide AUC of 26% ą 9% (range: 12 to 39%). Tolbutamide Cmax increased 11% ą 9% (range: ?6 to 27%). (See PRECAUTIONS.)

Glipizide

The AUC and Cmax of glipizide (2.5 mg single dose) were significantly increased following the administration of fluconazole in 13 normal male volunteers. There was a mean ą SD increase in AUC of 49% ą 13% (range: 27 to 73%) and an increase in Cmax of 19% ą 23% (range: ?11 to 79%). (See PRECAUTIONS.)

Glyburide

The AUC and Cmax of glyburide (5 mg single dose) were significantly increased following the administration of fluconazole in 20 normal male volunteers. There was a mean ą SD increase in AUC of 44% ą 29% (range: ?13 to 115%) and Cmax increased 19% ą 19% (range: ?23 to 62%). Five subjects required oral glucose following the ingestion of glyburide after 7 days of fluconazole administration. (See PRECAUTIONS.)

Rifabutin:

There have been published reports that an interaction exists when fluconazole is administered concomitantly with rifabutin, leading to increased serum levels of rifabutin. (See PRECAUTIONS.)

Tacrolimus:

There have been published reports that an interaction exists when fluconazole is administered concomitantly with tacrolimus, leading to increased serum levels of tacrolimus.
(See PRECAUTIONS.)

Cisapride

A preliminary report from a placebo-controlled, randomized multiple-dose study in subjects given fluconazole 200 mg daily and cisapride 20 mg four times daily starting after 7 days of fluconazole dosing found that fluconazole significantly increased the AUC and Cmax of cisapride both after single (AUC 102% and Cmax 92% increases) and multiple (AUC 192% and Cmax 153% increases) dosing of cisapride. Fluconazole significantly increased the QTc interval in subjects receiving cisapride 20 mg four times daily for 5 days. (See CONTRAINDICATIONS and PRECAUTIONS.)

Microbiology

Fluconazole exhibits in vitro activity against Cryptococcus neoformans and Candida spp. Fungistatic activity has also been demonstrated in normal and immunocompromised animal models for systemic and intracranial fungal infections due to Cryptococcus neoformans and for systemic infections due to Candida albicans.

In common with other azole antifungal agents, most fungi show a higher apparent sensitivity to fluconazole in vivo than in vitro. Fluconazole administered orally and/ or intravenously was active in a variety of animal models of fungal infection using standard laboratory strains of fungi. Activity has been demonstrated against fungal infections caused by Aspergillus flavus and Aspergillus fumigatus in normal mice. Fluconazole has also been shown to be active in animal models of endemic mycoses, including one model of Blastomyces dermatitidis pulmonary infections in normal mice; one model of Coccidioides immitis intracranial infections in normal mice; and several models of Histoplasma capsulatum pulmonary infection in normal and immunosuppressed mice. The clinical significance of results obtained in these studies is unknown.

Oral fluconazole has been shown to be active in an animal model of vaginal candidiasis. Concurrent administration of fluconazole and amphotericin B in infected normal and immunosuppressed mice showed the following results: a small additive antifungal effect in systemic infection with C. albicans, no interaction in intracranial infection with Cr. neoformans, and antagonism of the two drugs in systemic infection with Asp. fumigatus. The clinical significance of results obtained in these studies is unknown.

There have been reports of cases of superinfection with Candida species other than C. albicans, which are often inherently not susceptible to DIFLUCAN (e. g., Candida krusei). Such cases may require alternative antifungal therapy.