FDA: High doses of fluconazole may be linked to birth defects

High doses of fluconazole taken during the first trimester of pregnancy may be associated with a rare and distinct array of birth defects known as Antley-Bixler syndrome, according to a safety announcement released today from the FDA.

High doses of fluconazole (Diflucan, Pfizer) are defined as 400 mg/day to 800 mg/day. A single 150 mg dose to treat vaginal candidiasis does not carry the same risk, FDA officials said in a press release.

In addition to brachycephaly and congenital heart disease, risks include abnormal facies, abnormal calvarial development, arthrogryposis, cleft palate, femoral bowing and thin ribs and long bones, according to the FDA.

The agency has changed the pregnancy category for fluconazole indications other than vaginal candidiasis from category C to category D. The single 150-mg dose remains in category C.

The decision came in the wake of several published case reports that indicated the presence of symptoms of Antley-Bixler syndrome. The FDA stressed that although the syndrome is often associated with animals, the case studies in question occurred in humans. The officials also suggested that chronic high-dose fluconazole may be teratogenic in humans when used in the first trimester of pregnancy, but the extent of this risk is still unknown. However, they did note that a possible drug threshold effect for a fluconazole embryopathy may have occurred in the five case studies.

Patients should notify a health care provider if they are pregnant or become pregnant while taking the drug. Health care providers should inform patients of the potential adverse events. Adverse events should be reported to the FDA’s MedWatch program.

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