Animal studies have revealed evidence of embryotoxicity with oral doses of 20 to 40 mg/kg/day in rabbits (percentage of pregnancies reduced, increased resorptions, reduced pup weight) and rats (decreased litter size and number of viable young, reduced fetal weight, delayed ossification, increased rate of skeletal variants); no evidence of teratogenicity observed with oral doses up to 40 mg/kg/day in rats (25, 50, and 100 times the recommended intravaginal human dose of the suppository, 0.8% vaginal cream, and 0.4% vaginal cream formulations, respectively) or 20 mg/kg/day in rabbits or with subcutaneous doses up to 20 mg/kg/day in rats. Cmax averaged 0.176 mcg/mL in pregnant rats administered 10 mg/kg/day (the no-effect dose) which exceeded by 44, 30, and 17 times the average Cmax in normal subjects after intravaginal use of 0.4% vaginal cream, 0.8% vaginal cream, and 80 mg vaginal suppository, respectively; this assessment did not account for possible fetal exposure via direct transfer of drug from irritated vagina by diffusion across amniotic membranes. This drug is absorbed from the human vagina. There are no controlled data in human pregnancy.

In studies, over 600 patients used this drug during the second and third trimesters without apparent adverse effects on their pregnancies. No increased risk of abnormalities observed during these studies.

In a review of 229,101 deliveries to Michigan Medicaid patients, 1167 first-trimester exposures to this drug and 7551 exposures any time during pregnancy were recorded. A total of 34 birth defects were reported with first trimester exposure (48 expected) and included (observed/expected) 14/12 cardiovascular defects, 3/2 polydactyly, 1 limb reduction, and 1 hypospadias. These data do not support an association between use of this drug and birth defects. (written communication, Franz Rosa, MD, US FDA, 1994)

US FDA pregnancy category C: Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Use is not recommended during the first trimester of pregnancy unless considered essential to patient welfare; this drug may be used during the second and third trimester if the benefit outweighs the risk to the fetus.

US FDA pregnancy category: C

See references

A decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother.

Excreted into human milk: Unknown
Excreted into animal milk: Yes

Comments:
-The effects in the nursing infant are unknown.
-According to some experts, other antifungal agents may be preferred, particularly while breastfeeding newborn or preterm infants.

See references