Fluconazole warnings and precautions

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Zaghw, M.D. [2]

Hepatic injury

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. DIFLUCAN hepatotoxicity has usually, but not always, been reversible on discontinuation of therapy. Patients who develop abnormal liver function tests during DIFLUCAN therapy should be monitored for the development of more severe hepatic injury. DIFLUCAN should be discontinued if clinical signs and symptoms consistent with liver disease develop that may be attributable to DIFLUCAN.

Anaphylaxis

In rare cases, anaphylaxis has been reported.

Dermatologic

Patients have rarely developed exfoliative skin disorders during treatment with DIFLUCAN. In patients with serious underlying diseases (predominantly AIDS and malignancy), these have rarely resulted in a fatal outcome. Patients who develop rashes during treatment with DIFLUCAN should be monitored closely and the drug discontinued if lesions progress. If a rash, which is considered attributable to fluconazole, develops in a patient treated for a superficial fungal infection, further therapy with this agent should be discontinued.

Pregnancy

There are no adequate and well-controlled studies of DIFLUCAN in pregnant women. Available human data do not suggest an increased risk of congenital anomalies following a single maternal dose of 150 mg. A few published case reports describe a rare 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 this drug 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 (See PRECAUTIONS, Pregnancy.)

• Some azoles, including fluconazole, have been associated with prolongation of the QT interval on the electrocardiogram. During post-marketing surveillance, there have been rare cases of QT prolongation and torsade de pointes in patients taking fluconazole. Most of these reports involved seriously ill patients with multiple confounding risk factors, such as structural heart disease, electrolyte abnormalities, and concomitant medications that may have been contributory.

• 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. This combination should be avoided.

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

• Fluconazole is a potent CYP2C9 inhibitor and a moderate CYP3A4 inhibitor. Fluconazole treated patients who are concomitantly treated with drugs with a narrow therapeutic window metabolized through CYP2C9 and CYP3A4 should be monitored.

• DIFLUCAN Powder for Oral Suspension contains sucrose and should not be used in patients with hereditary fructose, glucose/galactose malabsorption, and sucrase-isomaltase deficiency.

• When driving vehicles or operating machines, it should be taken into account that occasionally dizziness or seizures may occur.

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Adapted from the FDA Package Insert.