Birth Defects Linked to Fluconazole Prompt Change in Pregnancy Category

High Doses of Drug in First Trimester Pose Risk, Says FDA

August 08, 2011 04:15 pm News Staff

The antifungal medication fluconazole, which is marketed as Diflucan, has been linked to rare birth defects in infants whose mothers were treated with high doses of the drug -- 400 mg to 800 mg per day -- for long periods during the first trimester of pregnancy. The FDA has responded by changing the pregnancy category for most fluconazole indications from category C to category D.

[FDA News]

Pregnancy category D means there is evidence of fetal risk based on human data, but the potential benefits of the drug in pregnant women with serious or life-threatening conditions may outweigh its risks.

The FDA said in an Aug. 3 safety announcement(www.fda.gov) that those risks do not appear to be associated with the single 150-mg dose of fluconazole that is used to treat vaginal candidiasis. When used for that indication, the drug retains its category C designation, which means there are no adequate studies in humans, and, although studies of animals have shown an adverse effect on the fetus, potential benefits may warrant use of the drug in pregnant women despite potential risks.

In addition to vaginal candidiasis, fluconazole is used to treat yeast infections of the mouth, throat, esophagus, and other organs, as well as coccidioidal meningitis.

The FDA issued the following information for physicians:

  • Published case reports describe a rare pattern of distinct congenital anomalies in infants exposed in utero to high-dose fluconazole during the first trimester.
  • The features seen in affected infants include brachycephaly, abnormal facies, abnormal calvarial development, cleft palate, femoral bowing, thin ribs and long bones, arthrogryposis, and congenital heart disease.
  • If fluconazole is used during pregnancy, or if a patient becomes pregnant while taking fluconazole, the patient should be informed of the potential risks.
  • Adverse events involving fluconazole should be reported to the FDA's MedWatch program(www.accessdata.fda.gov).