Overview
DESCRIPTION Fluconazole, the first of a new subclass of synthetic triazole antifungal agents, is available as tablets for oral administration. Fluconazole is designated chemically as 2,4-difluoro-α,α 1 -bis(1H-1,2,4-triazol-1-ylmethyl) benzyl alcohol with a molecular formula of C 13 H 12 F 2 N 6 O and molecular weight of 306.3.
Mechanism of Action
CLINICAL PHARMACOLOGY Pharmacokinetics and Metabolism The pharmacokinetic properties of fluconazole are similar following administration by the intravenous or oral routes. In normal volunteers, the bioavailability of orally administered fluconazole is over 90% compared with intravenous administration. Bioequivalence was established between the 100 mg tablet and both suspension strengths when administered as a single 200 mg dose. Peak plasma concentrations (C max ) in fasted normal volunteers occur between 1 and 2 hours with a terminal plasma elimination half-life of approximately 30 hours (range: 20 to 50 hours) after oral administration. In fasted normal volunteers, administration of a single oral 400 mg dose of fluconazole leads to a mean C max of 6.72 mcg/mL (range: 4.12 to 8.
Indications
- INDICATIONS AND USAGE Fluconazole tablets are indicated for the treatment of: Vaginal candidiasis (vaginal yeast infections due to Candida ). Oropharyngeal and esophageal candidiasis. In open noncomparative studies of relatively small numbers of patients, fluconazole tablets were also effective for the treatment of Candida urinary tract infections, peritonitis, and systemic Candida infections including candidemia, disseminated candidiasis, and pneumonia. Cryptococcal meningitis .
Common Doses
- 150 mg
- 200 mg
- 100 mg
- 400 mg
Dosage
DOSAGE AND ADMINISTRATION Dosage and Administration in Adults: Single Dose Vaginal candidiasis: The recommended dosage of fluconazole for vaginal candidiasis is 150 mg as a single oral dose. Multiple Dose SINCE ORAL ABSORPTION IS RAPID AND ALMOST COMPLETE, THE DAILY DOSE OF FLUCONAZOLE IS THE SAME FOR ORAL AND INTRAVENOUS ADMINISTRATION. In general, a loading dose of twice the daily dose is recommended on the first day of therapy to result in plasma concentrations close to steady-state by the second day of therapy.
Contraindications
- CONTRAINDICATIONS Fluconazole tablets are contraindicated in patients who have shown hypersensitivity to fluconazole or to any of its excipients. There is no information regarding cross-hypersensitivity between fluconazole and other azole antifungal agents. Caution should be used in prescribing fluconazole tablets to patients with hypersensitivity to other azoles. Coadministration of other drugs known to prolong the QT interval and which are metabolized via the enzyme CYP3A4 such as erythromycin, pimozide, and quinidine are contraindicated in patients receiving fluconazole.
Side Effects
- ADVERSE REACTIONS Fluconazole is generally well tolerated. In some patients, particularly those with serious underlying diseases such as AIDS and cancer, changes in renal and hematological function test results and hepatic abnormalities have been observed during treatment with fluconazole and comparative agents, but the clinical significance and relationship to treatment is uncertain. In Patients Receiving a Single Dose for Vaginal Candidiasis: During comparative clinical studies conducted in the United States, 448 patients with vaginal candidiasis were treated with fluconazole, 150 mg single...
Interactions
- Drug Interaction Studies (See PRECAUTIONS, Drug Interactions) Oral contraceptives: Oral contraceptives were administered as a single dose both before and after the oral administration of fluconazole 50 mg once daily for 10 days in 10 healthy women. There was no significant difference in ethinyl estradiol or levonorgestrel AUC after the administration of 50 mg of fluconazole. The mean increase in ethinyl estradiol AUC was 6% (range: –47 to 108%) and levonorgestrel AUC increased 17% (range: –33 to 141%).