Efavirenz use while Breastfeeding

Drugs containing Efavirenz: Atripla, Sustiva

Efavirenz Levels and Effects while Breastfeeding

Summary of Use during Lactation

In the United States and other developed countries, HIV-infected mothers should generally not breastfeed their infants. In countries in which no acceptable, feasible, sustainable and safe replacement feeding is available, exclusive breastfeeding for 6 months is recommended for HIV-infected mothers to reduce the risk of HIV transmission from the mother to the infant compared with mixed feeding.[1][2][3][4][5][6] In these settings, abrupt weaning at 4 months does not reduce the risk of HIV transmission or produce an overall health benefit compared to continued breastfeeding, and increases the risk of infant death in HIV-infected infants.[7] Extended antiretroviral prophylaxis in breastfed infants with antiretroviral drugs appears to reduce the rate of HIV transmission during breastfeeding by about half, but the optimal regimen and duration of prophylaxis has not yet been defined.[8][9][10][11] Efavirenz is recommended by the World Health Organization as one alternative drug in a 3-drug combination to all antiretroviral-naive women who are breastfeeding their infants.[12] Limited information in this setting indicates that efavirenz produces low levels in milk and no adverse reactions in breastfed infants.

Drug Levels

Maternal Levels. Thirteen mothers who averaged 15.8 weeks (range 6 to 25 weeks) postpartum were treated with efavirenz 600 mg daily plus zidovudine and lamivudine. Milk and plasma samples were taken 3 to 4 hours after the last dose. Skimmed breastmilk efavirenz concentrations averaged 3.5 mg/L (range 1.3 to 7.4 mg/L).[13]

Infant Levels. Thirteen mothers who averaged 15.8 weeks (range 6 to 25 weeks) postpartum were treated with efavirenz 600 mg daily plus lamivudine and zidovudine (n = 12) or stavudine (n = 1). Plasma samples were taken from their breastfed infants 3 to 4 hours after the last dose. Infant plasma concentrations averaged 0.86 mg/L (range 0.4 to 1.5 mg/L). Infant plasma concentrations averaged 13% of maternal plasma concentrations, but there was no statistically significant correlation between them. Average plasma levels were slightly below the plasma level considered effective for suppression of HIV in adults.[13]

Efavirenz was measured in 117 breastfed (90% exclusive) infants whose mothers were taking efavirenz for HIV infection during pregnancy and postpartum. All infants had detectable efavirenz in their plasma samples at 0 (mean 1.7 mg/L), 8 (mean 0.3 mg/L) and 12 (mean 0.3 mg/L) weeks postpartum. All infants had detectable efavirenz in their hair samples at 12 weeks postpartum at a mean concentration of 1.9 ng/mg of hair (range 0.34 to 11 ng/mg). The authors interpreted the results to mean that infants receive substantial exposure to efavirenz during breastfeeding.[14]

Effects in Breastfed Infants

Thirteen mothers nursed their infants while they were taking efavirenz 600 mg daily, lamivudine 150 mg and zidovudine 300 mg daily (n = 12) or stavudine 60 mg daily (n = 1) . No adverse reactions were reported in the infants after 6 months of breastfeeding, none had developed HIV infection and all were developing normally.[13]

Possible Effects on Lactation

Gynecomastia has been reported among men and at least one woman receiving efavirenz therapy.[15][16] Efavirenz appears to be much more likely to cause gynecomastia than other antiretroviral agents. Gynecomastia is unilateral initially, but can progress to bilateral. Spontaneous resolution usually occurred within one year, even with continuation of the regimen. The relevance of these findings to nursing mothers is not known. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.

Alternate Drugs to Consider

Lamivudine, Nelfinavir, Nevirapine, Zidovudine

References

1. World Health Organization. HIV and infant feeding: update. 2007. http://whqlibdoc.who.int/publications/2007/9789241595964_eng.pdf

2. Dao H, Mofenson LM, Ekpini R et al. International recommendations on antiretroviral drugs for treatment of HIV-infected women and prevention of mother-to-child HIV transmission in resource-limited settings: 2006 update. Am J Obstet Gynecol. 2007;197 (3 Suppl):S42-55. PMID: 17825650

3. Branson BM, Handsfield HH, Lampe MA et al. Revised recommendations for HIV testing of adults, adolescents, and pregnant women in health-care settings. MMWR Recomm Rep. 2006;55 (RR-14):1-17. PMID: 16988643

4. McIntyre J, Dabis F, Mofenson LM et al. Rapid advice: Use of antiretroviral drugs for treating pregnant women and preventing HIV infection in infants. World Health Organization. Geneva. 2009;1-23.

5. Chasela CS, Hudgens MG, Jamieson DJ et al. Maternal or infant antiretroviral drugs to reduce HIV-1 transmission. N Engl J Med. 2010;362:2271-81. PMID: 20554982

6. Shapiro RL, Hughes MD, Ogwu A et al. Antiretroviral regimens in pregnancy and breast-feeding in Botswana. N Engl J Med. 2010;362:2282-94. PMID: 20554983

7. Kuhn L, Aldrovandi GM, Sinkala M et al. Effects of early, abrupt weaning on HIV-free survival of children in Zambia. N Engl J Med. 2008;359:130-41. PMID: 18525036

8. Kumwenda NI, Hoover DR, Mofenson LM et al. Extended antiretroviral prophylaxis to reduce breast-milk HIV-1 transmission. N Engl J Med. 2008;359:119-29. PMID: 18525035

9. Mofenson LM. Antiretroviral prophylaxis to reduce breast milk transmission of HIV type 1: new data but still questions. J Acquir Immune Defic Syndr. 2008;48:237-40. PMID: 18545160

10. Bedri A, Gudetta B, Isehak A et al. Extended-dose nevirapine to 6 weeks of age for infants to prevent HIV transmission via breastfeeding in Ethiopia, India, and Uganda: an analysis of three randomised controlled trials. Lancet. 2008;372:300-13. PMID: 18657709

11. Chigwedere P, Seage GR, Lee TH, Essex M. Efficacy of antiretroviral drugs in reducing mother-to-child transmission of HIV in Africa: a meta-analysis of published clinical trials. AIDS Res Hum Retroviruses. 2008;24:827-37. PMID: 18544018

12. Hirnschall G, Harries AD, Easterbrook PJ. The next generation of the World Health Organization's global antiretroviral guidance. J Int AIDS Soc. 2013;16:18757. PMID: 23819908

13. Schneider S, Peltier A, Gras A et al. Efavirenz in human breast milk, mothers', and newborns' plasma. J Acquir Immune Defic Syndr. 2008;48:450-4. PMID: 18614925

14. Gandhi M, Mwesigwa J, Aweeka F et al. Hair and plasma data show that lopinavir, ritonavir, and efavirenz all transfer from mother to infant in utero, but only efavirenz transfers via breastfeeding. J Acquir Immune Defic Syndr. 2013;63:578-84. PMID: 24135775

15. Jover F, Cuadrado JM, Roig P et al. Efavirenz-associated gynecomastia: report of five cases and review of the literature. Breast J. 2004;10:244-6. PMID: 15125753

16. Rahim S, Ortiz O, Maslow M, Holzman R. A case-control study of gynecomastia in HIV-1-infected patients receiving HAART. AIDS Read. 2004;14:23-4, 29-32, 35-40. PMID: 14959701

Efavirenz Identification

Substance Name

Efavirenz

CAS Registry Number

154635-17-3

Drug Class

  • Antiinfective Agents
  • Anti-HIV Agents
  • Antiviral Agents
  • Anti-Retroviral Agents
  • Reverse Transcriptase Inhibitors

Administrative Information

LactMed Record Number

644

Information from the National Library of Medicine's LactMed Database.

Last Revision Date

2013-12-06

Disclaimer

Information presented in this database is not meant as a substitute for professional judgment. You should consult your healthcare provider for breastfeeding advice related to your particular situation. The U.S. government does not warrant or assume any liability or responsibility for the accuracy or completeness of the information on this Site.

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