(Last updated: October 26, 2016; last reviewed: October 26, 2016)
Maraviroc is classified as Food and Drug Administration Pregnancy Category B.1
Maraviroc 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.
Reproductive 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.
The 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 Passage
Minimal placental passage was demonstrated in a study of single-dose maraviroc in rhesus macaques that showed poor placental transfer and rapid clearance from infant monkeys’ blood.2 Studies in lactating rats indicate that maraviroc is extensively secreted into rat milk.1
Human Studies in Pregnancy
A U.S./European study of intensive, steady-state 12-hour pharmacokinetic profiles in the third trimester and at least 2 weeks postpartum included 18 women taking maraviroc as part of clinical care.3 Sixty-seven percent were taking 150 mg BID with a protease inhibitor; 11% took 300 mg BID and 22% took an alternative regimen. The geometric mean ratios for third-trimester versus postpartum AUC were 0.72 and 0.70 for maximum maraviroc concentration. Despite the overall 30% decrease in maraviroc exposure during pregnancy and 15% decrease in Ctrough, Ctrough exceeded the minimum target concentration of 50 ng/mL, and only one woman had a Ctrough below that level both during pregnancy and post-partum. These data suggest that the standard adult dose adjusted for concomitant antiretroviral (ARV) drugs seems appropriate in pregnancy. A review of drug interactions between ARV drugs and oral contraceptives found that it is safe to coadminister oral contraceptives with maraviroc.4
Other Safety Issues
A retrospective study from an English-Irish cohort of 857 pregnant women showed an increased rate of hepatotoxicity among the 492 who started antiretroviral therapy during pregnancy.5 Maraviroc was one of three drugs that was associated with an increased risk of liver enzyme elevation during pregnancy with an aHR of 4.19 [1.34–13.1, P = 0.01], along with efavirenz and nevirapine. In a model using human placental BeWo cells, maraviroc inhibited transplacental passage of two fluorescent organic cations, suggesting that it might influence placental drug transfer and cause drug-drug interactions.6
Placental and Breast Milk Passage
An ex vivo human placental cotyledon perfusion model demonstrated minimal placental passage of maraviroc.7 In a study in humans of 6 mother/infant pairs, the median ratio of cord blood-to-maternal-plasma drug concentrations was 0.33 (0.03–0.56).3,8 Whether maraviroc is secreted into human milk is unknown.
In the Antiretroviral Pregnancy Registry, insufficient numbers of first-trimester exposures to maraviroc in humans have been monitored to be able to make a risk determination.9,10
|Formulation||Dosing Recommendations||Use in Pregnancy|
||Standard Adult Dose:
||No evidence of teratogenicity in rats or rabbits; insufficient data to assess for teratogenicity in humans.
MVC placental passage category should be moderate.b
a Individual antiretroviral drug dosages may need to be adjusted in renal or hepatic insufficiency (for details, see Adult Guidelines, Appendix B, Table 7).
b Placental transfer categories—Mean or median cord blood/maternal delivery plasma drug ratio:
Key to Abbreviations: ARV = antiretroviral; AUC = area under the curve; BID = twice daily; EFV = efavirenz; ETR = etravirine; MVC = maraviroc; PI = protease inhibitor; PK = pharmacokinetic