(Last updated: March 28, 2014; last reviewed: March 28, 2014)
Animal Carcinogenicity StudiesMaraviroc was neither mutagenic nor clastogenic in a series of in vitro and animal in vivo screening tests. Long-term animal carcinogenicity studies of maraviroc showed no drug-related increases in tumor incidence.
Reproduction/Fertility Animal StudiesReproductive toxicity has been evaluated in rats and rabbits. Maraviroc produced no adverse effects on fertility of male or female rats at doses with exposures (area under the curve [AUC]) up to 20-fold higher than in humans given the recommended 300-mg twice-daily dose.
Teratogenicity/Developmental Toxicity Animal StudiesThe incidence of fetal variations and malformations was not increased in embryo-fetal toxicity studies in rats at AUC approximately 20-fold higher (and in rabbits at approximately 5-fold higher) than human exposures at the recommended 300 mg, twice-daily dose (up to 1000 mg/kg/day in rats and 75 mg/kg/day in rabbits).
Placental and Breast Milk PassageAn ex vivo human placental cotyledon perfusion model demonstrated minimal placental passage of maraviroc.1 This was also demonstrated in a study of single-dose maraviroc in rhesus macaques that showed poor placental transfer and rapid clearance from infant monkeys’ blood.2 In a study in humans of six mother/infant pairs, the median ratio of cord blood to maternal plasma drug concentrations was 0.33 (0.03–0.56).3 Studies in lactating rats indicate that maraviroc is extensively secreted into rat milk. Whether maraviroc is secreted into human milk is unknown.
Human Studies in PregnancySafety and efficacy of maraviroc have not been established in pregnancy. Data on the use of maraviroc in human pregnancy are limited to a small pharmacokinetic study that found exposure to maraviroc was 21% lower during the third trimester than postpartum.3 The Antiretroviral Pregnancy Registry lists only 13 pregnancies with first-trimester exposure to entry inhibitors, with no malformations noted.4