Fluconazole has been associated with rare cases of serious hepatic toxicity including fatalities, primarily in patients with serious underlying medical conditions. In cases of fluconazole-associated hepatotoxicity, no obvious relationship to total daily dose, duration of therapy, sex or age of patients has been observed. Fluconazole hepatotoxicity has usually been reversible on discontinuation of therapy. Patients who develop abnormal liver function tests during fluconazole therapy should be monitored for the development of more serious hepatic injury. If clinical signs or symptoms consistent with liver disease develop, fluconazole should be discontinued.
Fluconazole should be administered with caution to patients with these potentially proarrhythmic conditions.
Patients have rarely developed exfoliative cutaneous reactions eg, Steven-Johnson syndrome and toxic epidermal necrolysis, during treatment with fluconazole. AIDS patients are more prone to the development of severe cutaneous reactions to many drugs. 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. If patients with invasive/systemic fungal infections develop rashes, they should be monitored closely and fluconazole discontinued if bullous lesions or erythema multiforme develop.
The co-administration of fluconazole at doses <400mg/day with terfenadine should be carefully monitored. In rare cases, anaphylaxis has been reported.
Some azoles, including fluconazole, have been associated with prolongation of the QT interval of the electrocardiograms. There have been very rare cases of QT prolongation and torsades de pointes in patients taking fluconazole. This is maybe caused by seriously ill patients with multiple confounding risk factors eg, structural heart disease, electrolyte abnormalities and concomitant medications.
Effects on ability to drive and use machines: No adverse effects on the ability to drive or operate machines have been reported.
Use in Pregnancy: There are no adequate and well controlled studies in pregnant women. Multiple congenital abnormalities have been reported in infants whose mothers were being treated for 3 or more months with high dose (400-800 mg/day) fluconazole therapy for coccidioidomycosis (an unindicated use). The relationship between fluconazole and these events is unclear. However, use of fluconazole in pregnancy is not recommended except in patients with severe or potentially life-threatening fungal infections in whom fluconazole may be used if the potential benefit justifies the possible risk to the fetus.
Use in lactation: Fluconazole is secreted in human breast milk at concentrations similar to plasma. Thus, its use in nursing mothers should be avoided.