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, DIFLUCAN was also effective for the treatment of Candida urinary tract infections, peritonitis, and systemic Candida infections including candidemia, disseminated candidiasis, and pneumonia.

Cryptococcal Meningitis:

• Before prescribing DIFLUCAN (fluconazole) for AIDS patients with cryptococcal meningitis, please see CLINICAL STUDIES section. Studies comparing DIFLUCAN to amphotericin B in non-HIV infected patients have not been conducted.

Prophylaxis:

• DIFLUCAN is also indicated to decrease the incidence of candidiasis in patients undergoing bone marrow transplantation who receive cytotoxic chemotherapy and/or radiation therapy.

DIFLUCAN should be administered with caution to patients with liver dysfunction. DIFLUCAN has been associated with rare cases of serious hepatic toxicity, including fatalities primarily in patients with serious underlying medical conditions. In cases of DIFLUCAN-associated hepatotoxicity, no obvious relationship to total daily dose, duration of therapy, sex, or age of the patient has been observed.

Fluconazole should be administered with caution to patients with renal dysfunction.

Exfoliative skin disorders during treatment with DIFLUCAN have been reported. Fatal outcomes have been reported in patients with serious underlying diseases.

Some azoles, including fluconazole, have been associated with prolongation of the QT interval on the electrocardiogram.

Co-administration 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. Fluconazole should be administered with caution to patients with these potentially proarrhythmic conditions.

Concomitant use of fluconazole and erythromycin has the potential to increase the risk of cardiotoxicity (prolonged QT interval, torsade de pointes) and consequently sudden heart death.

Co-administration of fluconazole and pimozide is contraindicated.

Concomitant administration of fluconazole with amiodarone may increase QT prolongation.

Concomitant administration of voriconazole and fluconazole at any dose is not recommended.

Avoid concomitant use of DIFLUCAN with lemborexant.

DIFLUCAN is a potent inhibitor of cytochrome P450 (CYP) isoenzyme 2C9 and 2C19, and a moderate inhibitor of CYP3A4.

Clinically significant hypoglycemia may be precipitated by the use of DIFLUCAN with oral hypoglycemic agents.

Prothrombin time may be increased in patients receiving concomitant DIFLUCAN and coumarin-type anticoagulants.

DIFLUCAN increases the plasma concentrations of phenytoin.

DIFLUCAN significantly increases cyclosporine levels in renal transplant patients with or without renal impairment.

Rifampin enhances the metabolism of concurrently administered DIFLUCAN.

DIFLUCAN increases the serum concentrations of theophylline.

There have been reports that an interaction exists when fluconazole is administered concomitantly with rifabutin, leading to increased serum levels of rifabutin up to 80%.

Fluconazole may increase the serum concentrations of orally administered tacrolimus up to 5 times due to inhibition of tacrolimus metabolism through CYP3A4 in the intestines.

Following oral administration of midazolam, fluconazole resulted in substantial increases in midazolam concentrations and psychomotor effects.

Systemic exposure to tofacitinib is increased when tofacitinib is coadministered with fluconazole.

Fluconazole increases the AUC of triazolam (single dose) by approximately 50%.

Fluconazole increases the effect of amitriptyline and nortriptyline.

Fluconazole inhibits the metabolism of carbamazepine and an increase in serum carbamazepine of 30% has been observed.

Fluconazole has the potential to increase the systemic exposure of the calcium channel antagonists.

Fluconazole increases the effect of Celecoxib.

Fluconazole significantly delays the elimination of fentanyl. Elevated fentanyl concentration may lead to respiratory depression.

Fluconazole can increase halofantrine plasma concentration.

The risk of myopathy and rhabdomyolysis increases when fluconazole is co-administered with HMG-CoA reductase inhibitors metabolized through CYP3A4, such as atorvastatin and simvastatin, or through CYP2C9, such as fluvastatin.

Fluconazole may enhance the serum concentration of methadone.

Fluconazole increases Cmax and AUC of zidovudine by 84% and 74%.

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.

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 inpatients receiving fluconazole concurrently with warfarin.

Although not studied, fluconazole may increase the plasma levels of the vinca alkaloids (e.g., vincristine and vinblastine) and lead to neurotoxicity, which is possibly due to an inhibitory effect on CYP3A4.

There are no adequate and well-controlled studies of DIFLUCAN in pregnant women. Case reports describe a pattern of distinct congenital anomalies in infants exposed in utero to high dose maternal fluconazole (400-800 mg/day) during most or all of the first trimester. These reported anomalies are similar to those seen in animal studies. If DIFLUCAN is used during pregnancy or if the patient becomes pregnant while taking the drug, the patient should be informed of the potential hazard to the fetus.

Effective contraceptive measures should be considered in women of childbearing potential who are being treated with DIFLUCAN 400 to 800 mg/day and should continue throughout the treatment period and for approximately 1 week (5 to 6 half-lives) after the final dose.

Fluconazole is secreted in human milk at concentrations similar to maternal plasma concentrations.

GoToSource

• Prevention of neonatal invasive fungal infections in very low birth weight infants. GoToSource 

• Newly diagnosed acute myeloid leukemia. GoToSource 

• Chronic pulmonary or non meningeal disseminated coccidioidomycosis. GoToSource

• Plaque psoriasis of the lips. GoToSource

Agranulocytosis (low white blood cell count) and thrombocytopenia (low blood platelet count). GoToSource

Stevens-johnson syndrome and toxic epidermal necrolysis (life-threatening skin disorder). GoToSource

Hair loss. GoToSource

Liver failure. GoToSource

Prolongation of the QT interval. GoToSource 

Increased cyclosporine levels in renal transplant patients with or without renal impairment. GoToSource

Lawsuits filed for birth defects.