Pregnancy: No adequate human data are available to establish whether or not PREVYMIS poses a risk to pregnancy outcomes. Embryofetal toxicity was observed in rats and rabbits at maternally toxic systemic AUC exposures of approximately 11- and 2-fold, respectively, the AUC at the recommended human dose (RHD). In the rat pre-and post-natal development study, no developmental toxicity was observed up to the highest maternal systemic AUC exposure (approximately 2-fold the AUC at the RHD). For the purpose of calculating safety margins, the AUC at the RHD is defined as the mean AUC in HSCT recipients receiving 480 mg IV.
The background risk of major birth defects and miscarriage for the indicated population is unknown. The potential risk for humans is unknown. PREVYMIS should be used in pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nursing Mothers: It is not known whether letermovir is present in human breast milk, affects human milk production, or has effects on the breastfed child.
When administered to lactating rats, letermovir was present in milk, without effects on growth and development in nursing pups.
The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for PREVYMIS and any potential adverse effects on the breastfed child from PREVYMIS or from the underlying maternal condition.
Fertility: There were no effects on female fertility in rats. Impairment of fertility was observed in male rats, but not in male mice or male monkeys. Testicular toxicity in rats appears to be species-specific, and the relevance to humans is unknown. In the Phase 3 trial in HSCT recipients, there was no evidence of letermovir-related testicular toxicity [see Clinical Trials Experience under ADVERSE REACTIONS].