Brands, Medical Use, Clinical Data
- Powder for solution
Brands / Synonyms
Biocanol; Biozolene; Diflucan; Elazor; Flucazol; Fluconazole; Flucostat; Flukezol; Flunizol; Flusol; Pritenzol; Triflucan
For the treatment of fungal infections.
Fluconazole, a synthetic antifungal agent of the imidazole class, is used to treat vaginal candidiasis.
Mechanism of Action
Fluconazole interacts with 14-α demethylase, a cytochrome P-450 enzyme necessary to convert lanosterol to ergosterol. As ergosterol is an essential component of the fungal cell membrane, inhibition of its synthesis results in increased cellular permeability causing leakage of cellular contents. Fluconazole may also inhibit endogenous respiration, interact with membrane phospholipids, inhibit the transformation of yeasts to mycelial forms, inhibit purine uptake, and impair triglyceride and/or phospholipid biosynthesis.
Symptoms of overdose include hallucinations and paranoid behavior.
Biotrnasformation / Drug Metabolism
DIFLUCAN (fluconazole) is 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 DIFLUCAN to patients with hypersensitivity to other azoles.
Coadministration of terfenadine is contraindicated in patients receiving DIFLUCAN (fluconazole) at multiple doses of
400 mg or higher based upon results of a multiple dose interaction study.
Coadministration of cisapride is contraindicated in patients receiving DIFLUCAN (fluconazole).
Clinically or potentially significant drug interactions between DIFLUCAN and the following agents/classes have
been observed. These are described in greater detail below:
DIFLUCAN and the following agents/classes have been observed. These are described in greater detail below:
Oral hypoglycemics: Clinically significant hypoglycemia may be precipitated by the use of DIFLUCAN with
oral hypoglycemic agents; one fatality has been reported from hypoglycemia in association with combined DIFLUCAN and
glyburide use. DIFLUCAN reduces the metabolism of tolbutamide, glyburide, and glipizide and increases the plasma
concentration of these agents. When DIFLUCAN is used concomitantly with these or other sulfonylurea oral hypoglycemic
agents, blood glucose concentrations should be carefully monitored and the dose of the sulfonylurea should be
adjusted as necessary.
Coumarin-type anticoagulants: Prothrombin time may be increased in patients receiving concomitant
DIFLUCAN and coumarin-type anticoagulants. In post-marketing experience, as with other azole antifungals, bleeding
events (bruising, epistaxis, gastrointestinal bleeding, hematuria, and melena) have been reported in association with
increases in prothrombin time in patients receiving fluconazole concurrently with warfarin. Careful monitoring of
prothrombin time in patients receiving DIFLUCAN and coumarin-type anticoagulants is recommended. (See CLINICAL PHARMACOLOGY: Drug Interaction Studies.)
Phenytoin: DIFLUCAN increases the plasma concentrations of phenytoin. Careful monitoring of phenytoin
concentrations in patients receiving DIFLUCAN and phenytoin is recommended. (See CLINICAL PHARMACOLOGY: Drug Interaction Studies.)
Cyclosporine: DIFLUCAN may significantly increase cyclosporine levels in renal transplant
patients with or without renal impairment. Careful monitoring of cyclosporine concentrations and serum creatinine is
recommended in patients receiving DIFLUCAN and cyclosporine. (See CLINICAL
PHARMACOLOGY: Drug Interaction Studies.)
Rifampin: Rifampin enhances the metabolism of concurrently administered DIFLUCAN. Depending on clinical
circumstances, consideration should be given to increasing the dose of DIFLUCAN when it is administered with
Theophylline: DIFLUCAN increases the serum concentrations of theophylline. Careful monitoring of serum
theophylline concentrations in patients receiving DIFLUCAN and theophylline is recommended.
Terfenadine: Because of the occurrence of serious cardiac dysrhythmias secondary to prolongation of the
QTc interval in patients receiving azole antifungals in conjunction with terfenadine, interaction studies have been
performed. One study at a 200-mg daily dose of fluconazole failed to demonstrate a prolongation in QTc interval.
Another study at a 400-mg and 800-mg daily dose of fluconazole demonstrated that DIFLUCAN taken in doses of 400 mg
per day or greater significantly increases plasma levels of terfenadine when taken concomitantly. The combined use of
fluconazole at doses of 400 mg or greater with terfenadine is contraindicated. The coadministration of fluconazole at
doses lower than 400 mg/day with terfenadine should be carefully monitored.
Cisapride: There have been reports of cardiac events, including torsade de pointes in patients to whom
fluconazole and cisapride were coadministered. A controlled study found that concomitant fluconazole 200 mg once
daily and cisapride 20 mg four times a day yielded a significant increase in cisapride plasma levels and prolongation
of QTc interval.The combined use of fluconazole with cisapride is contraindicated.
Astemizole: The use of fluconazole in patients concurrently taking astemizole or other drugs metabolized
by the cytochrome P450 system may be associated with elevations in serum levels of these drugs. In the absence of
definitive information, caution should be used when coadministering fluconazole. Patients should be carefully
Rifabutin: There have been reports of uveitis in patients to whom fluconazole and rifabutin were
coadministered. Patients receiving rifabutin and fluconazole concomitantly should be carefully monitored.
Tacrolimus: There have been reports of nephrotoxicity in patients to whom fluconazole and tacrolimus were
coadministered. Patients receiving tacrolimus and fluconazole concomitantly should be carefully monitored.
Short-acting Benzodiazepines: Following oral administration of midazolam, fluconazole resulted in
substantial increases in midazolam concentrations and psychomotor effects. This effect on midazolam appears to be
more pronounced following oral administration of fluconazole than with fluconazole administered intravenously. If
short-acting benzodiazepines, which are metabolized by the cytochrome P450 system, are concomitantly administered
with fluconazole, consideration should be given to decreasing the benzodiazepine dosage, and the patients should be
Fluconazole tablets coadministered with ethinyl estradiol- and levonorgestrel-containing oral contraceptives
produced an overall mean increase in ethinyl estradiol and levonorgestrel levels; however, in some patients there
were decreases up to 47% and 33% of ethinyl estradiol and levonorgestrel levels. The data presently available
indicate that the decreases in some individual ethinyl estradiol and levonorgestrel AUC values with fluconazole
treatment are likely the result of random variation. While there is evidence that fluconazole can inhibit the
metabolism of ethinyl estradiol and levonorgestrel, there is no evidence that fluconazole is a net inducer of ethinyl
estradiol or levonorgestrel metabolism. The clinical significance of these effects is presently unknown.
Physicians should be aware that interaction studies with medications other than those listed in the CLINICAL PHARMACOLOGY section have not been conducted, but such interactions may