FDA warns fluconazole in early pregnancy may cause birth defects

August 12, 2011

FDA issued a warning this week that chronic high doses (400 mg/day to 800 mg/day) of fluconazole (Diflucan) during the first trimester of pregnancy may be associated with specific birth defects in infants. However, the risk does not appear to be associated with a single, low dose of fluconazole (150 mg), which is used to treat vaginal yeast infection (candidiasis), according to the Safety Alert released August 3.

FDA issued a warning last week that chronic high doses (400 mg/day to 800 mg/day) of fluconazole (Diflucan) during the first trimester of pregnancy may be associated with specific birth defects in infants. However, the risk does not appear to be associated with a single, low dose of fluconazole (150 mg), which is used to treat vaginal yeast infection (candidiasis), according to the safety alert released August 3.

The safety alert is based on several published case reports of birth defects in infants whose mothers were treated with high-dose fluconazole (400 mg/day to 800 mg/day) for serious and life-threatening fungal infections during most or all of the first trimester, the agency said.

“Four reports involved maternal use of chronic high-dose intravenous fluconazole for coccidioidal meningitis and one report involved a human immunodeficiency virus (HIV)-positive mother who received chronic high-dose oral fluconazole for vaginal candidiasis,” according to the data summary supplied by the agency. “Cases associated with high-dose fluconazole use all shared some characteristics with the autosomal recessive genetic disorder known as Antley-Bixler syndrome. This combination of congenital anomalies occurs rarely in the general population, and is similar to anomalies seen in animals following in utero fluconazole exposure.”

As a result of this data, the pregnancy category for fluconazole indications (other than vaginal candidiasis) has been changed from category C to category D based on this information; however, the pregnancy category for a single dose of fluconazole 150 mg to treat vaginal candidiasis has not changed and remains category C. 

FDA says healthcare professionals should be aware of the potential risks with long-term, high-dose use of fluconazole and counsel patients if the drug is used during pregnancy or if a patient becomes pregnant while taking the drug. Adverse events or side effects related to the use of fluconazole should be reported to FDA's MedWatch Safety Information and Adverse Event Reporting Program.