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Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States

Entry Inhibitors

Maraviroc (Selzentry, MVC)

(Last updated: August 6, 2015; last reviewed: August 6, 2015)

Maraviroc is classified as Food and Drug Administration Pregnancy Category B.

Animal Studies 

Carcinogenicity
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.

Reproduction/Fertility
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. 

Teratogenicity/Developmental Toxicity
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. 

Human Studies in Pregnancy 

Pharmacokinetics
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.

Placental and Breast Milk Passage
An ex vivo human placental cotyledon perfusion model demonstrated minimal placental passage of maraviroc.4 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 Whether maraviroc is secreted into human milk is unknown.

Teratogenicity/Developmental Toxicity
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.5,6

 

References

  1. Maraviron (Selzentry [package insert]. Food and Drug Administration. 2014. Available at http://www.fda.gov/downloads/Drugs/DrugSafety/ucm089122.pdf. Accessed July 10, 2015. 
  2. Winters MA, Van Rompay KK, Kashuba AD, Shulman NS, Holodniy M. Maternal-fetal pharmacokinetics and dynamics of a single intrapartum dose of maraviroc in rhesus macaques. Antimicrob Agents Chemother. 2010;54(10):4059-4063. Available at http://www.ncbi.nlm.nih.gov/pubmed/20696881.
  3. Colbers A, Best B, et al. A comparison of the pharmacokinetics of maraviroc during pregnancy and postpartum. Abstract 931. Presented at: 20th Conference on Retroviruses and Opportunistic Infections. 2013. Atlanta, GA.
  4. Vinot C, Gavard L, Treluyer JM, et al. Placental transfer of maraviroc in an ex vivo human cotyledon perfusion model and influence of ABC transporter expression. Antimicrob Agents Chemother. 2013;57(3):1415-1420. Available at http://www.ncbi.nlm.nih.gov/pubmed/23295922.
  5. Antiretroviral Pregnancy Registry Steering Committee. Antiretroviral Pregnancy Registry international interim report for 1 Jan 1989–31 July 2014. Wilmington, NC: Registry Coordinating Center. 2014. Available at http://www.APRegistry.com.
  6. Floridia M, Mastroiacovo P, Tamburrini E, et al. Birth defects in a national cohort of pregnant women with HIV infection in Italy, 2001-2011. BJOG. 2013;120(12):1466-1475. Available at http://www.ncbi.nlm.nih.gov/pubmed/23721372.
     

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