Animal studies have not been reported with this drug; however, levoketoconazole constituted about 70% of the exposure in humans and animals after racemic ketoconazole administration. Levoketoconazole is the 2S, 4R enantiomer of ketoconazole. Animal reproduction studies reported embryotoxic effects in pregnant mice, rats, and rabbits, and fetal malformations were observed in rats, following oral dosing of racemic ketoconazole during the period of organogenesis at doses equal and less than the maximum recommended human dose (MRHD), respectively. Additionally, dystocia (difficult labor) was reported in mice and rats administered oral ketoconazole during the period of organogenesis at exposures below the MRHD of levoketoconazole. There are no controlled data in human pregnancy.

This drug may lower testosterone levels and impair male and female fertility. Clinical manifestations of low testosterone may include gynecomastia, impotence and oligospermia. Animal studies with ketoconazole showed impaired fertility in male and female rats. Dog fertility studies showed that levoketoconazole targeted the reproductive male tissues in a dose-dependent manner, affecting spermatogenesis and maturation of spermatozoa. These effects were reversible upon discontinuation of treatment.

US FDA pregnancy category Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

Benefit should outweigh risk.

US FDA pregnancy category: Not assigned.

Risk summary: There are insufficient data available on use of this drug in pregnant women to inform a drug-related risk. There are risks to the mother and fetus from active Cushing's syndrome during pregnancy, including gestational diabetes, gestational hypertension, pre-eclampsia, maternal death, miscarriage, intrauterine fetal demise, preterm birth and neonatal death.

Comments:
-The patient should be apprised of the potential harm to the fetus.

See references

Breastfeeding is not recommended during use of this drug and for 1 day after the last dose.

Excreted into human milk: Yes (ketoconazole)

Comments:
-Limited data are insufficient to inform the risk to a breastfed infant with exposure to ketoconazole through breast milk.
-There are no data on the effects of ketoconazole on milk production.
-The effects in the nursing infant are unknown; there is the potential for serious adverse reactions, including liver toxicity.

Published data from 1 lactating woman show that ketoconazole is present in human milk in low amounts, with no reported effects on the breastfed infant.

See references