Nevirapine use while Breastfeeding
Drugs containing Nevirapine: Viramune, Viramune XR
Nevirapine 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 with triple antiretroviral therapy is recommended for HIV-infected mothers to reduce the risk of HIV transmission from the mother to the infant compared with mixed feeding. 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. Nevirapine is often used as part of a regimen that decreases mother-to-child transmission of HIV and is generally well tolerated by the breastfed infant. Nevirapine 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. 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. However, one study found that adding nevirapine to short-course zidovudine for prophylaxis appeared to delay, but not prevent the rebound in milk viral load after discontinuation of zidovudine. The infants who do become HIV infected during breastfeeding by mothers receiving a HAART regimen that includes nevirapine are often infected with multi-class resistant HIV. Because of the long half-life of nevirapine, subtherapeutic nevirapine concentrations can persist in breastmilk and infant serum for relatively long periods, potentially increasing the risk of development of nevirapine-resistant HIV infections when it is used alone for prophylaxis. Longer durations of nevirapine therapy have been used to improve efficacy and decrease resistance. Breastfed infants whose mothers receive highly active antiretroviral therapy (HAART) have higher rates of neutropenia during the first month and severe anemia during the first 6 months of life.
Maternal Levels. Four breastmilk samples were obtained from 3 mothers who were taking nevirapine either 100 mg or 200 mg daily. Milk concentrations averaged 76% (range 54 to 104%) of maternal serum concentrations.
Twenty-one women received a single 200 mg oral dose of nevirapine during labor. Milk samples were collected 48, 72 and 168 hours after the dose. Breastmilk concentration of nevirapine were 454 mcg/L (range 219 to 972 mcg/L) at 48 hours postpartum and declined to 103 mcg/L (range 25 to 309 mcg/L) at 7 days postpartum. Milk levels declined in parallel with the maternal serum concentration with a half-life averaging 61 hours.
Three women were receiving nevirapine 200 mg twice daily as part of a highly active antiretroviral combination regimen. During the first 5 days postpartum milk was collected just before and 2 hours after the dose of nevirapine. Breastmilk nevirapine concentrations from milk samples ranged between 68 and 90% of the maternal serum concentration. Further details on the timing, or actual breastmilk concentrations were not provided.
Twenty women who were receiving oral nevirapine 200 mg twice daily as part of a combination antiretroviral regimen had their milk analyzed at either 2 or 5 months postpartum. Milk samples were provided at a median of 4 hours (range 1 to 8.5 hours) after the last dose. The median nevirapine concentration in breastmilk was 6.8 mg/L.
Forty women were given postpartum prophylaxis with unstated dosages of lamivudine, nevirapine and zidovudine (or stavudine if the hemoglobin <8 g/dL). Blood and milk samples were collected once during the first 3 days postpartum and once at 7 days postpartum. The median times after a dose that samples were collected were 5.3 hours (range 0 to 99 hours) for the first sample and 6 hours (range 4.3 to 20 hours) for the 7-day sample. Average breastmilk nevirapine concentrations were calculated only for samples that had detectable (>50 mcg/L) concentrations of nevirapine. The mean breastmilk concentrations were 2.3 (n = 34) and 2.2 mg/L (n = 36), respectively, at the two sampling times, which was 60 to 80% of the simultaneous maternal serum concentrations.
Free and total breastmilk nevirapine concentrations were measured in one woman for 22 days after her last dose of nevirapine 200 mg which was given as part of a combination antiretroviral regimen to prevent mother-to-child transmission of HIV. The peak whole milk concentration was 2.7 mg/L. Nevirapine was detectable in whole breastmilk for up to 17 days after the dose with an average (of left and right breasts) concentration of 13 mcg/L at that time. The average half-life was 70.6 hours. The peak unbound milk concentration was 1.5 mg/L. Nevirapine was detectable in whole breastmilk for up to 13 days after the dose with an average (of left and right breasts) concentration of 15.5 mcg/L at that time. The average half-life was 58 hours.
Twenty-one samples of breastmilk and maternal serum were obtained at 6, 12 and 24 weeks postpartum from mothers taking nevirapine as part of a combination of antiretrovirals. The nevirapine dosage the mothers were taking was not stated in the abstract. The median breastmilk concentrations of nevirapine were 1.3 mg/L at a median of 15 hours after the last dose at 6 weeks postpartum (8 samples), 3.4 mg/L at a median of 13 hours after the last dose at 12 weeks postpartum (7 samples), and 1.2 mg/L at a median of 12 hours after the last dose at 24 weeks postpartum (6 samples). Median milk concentrations were 12% (interquartile range 0 to 30%) of maternal plasma concentrations. In a related study by the same authors, the nevirapine milk to plasma ratio was found to be 0.82 in 39 patients.
Fifty-eight mothers who were taking a combination regimen of lamivudine, nevirapine and zidovudine had their serum and breastmilk analyzed for the presence of these drugs. Mothers took nevirapine 200 mg daily for 14 days, then 200 mg twice daily starting at 34 to 36 weeks postpartum and continuing until 6 months postpartum. Breastmilk was collected within 24 hours after delivery and at 2, 6, 14 and 24 weeks postpartum at variable times after the previous dose. The median breastmilk lamivudine concentration across all visits was 4546 mcg/L. The authors estimated that a fully breastfed infant would receive a daily dosage of 682 mcg/kg of nevirapine.
Sixty-two women received a single 200 mg dose of nevirapine at a median time of 5.2 hours before delivery. Breastmilk was obtained from each breast at delivery and 1, 2, and 6 weeks after the dose. A total of 116 breastmilk samples were obtained and analyzed. At delivery, the median breastmilk nevirapine concentration was 1012 mcg/L (interquartile range [IQR] 657 to 1364 mcg/L). At 1 week postpartum, breastmilk nevirapine had a median concentration of 164 mcg/L (IQR 75 to 213 mcg/L); breastmilk obtained 13 to 16 days postpartum had a median nevirapine concentration of 17 mcg/L (IQR 15 to 35 mcg/L). Nevirapine was undetectable (<15 mcg/L) in breastmilk at 6 weeks postpartum. Maternal plasma and breastmilk nevirapine concentrations fell with a half-life of 50.3 hours. A pharmacokinetic simulation indicated that breastmilk nevirapine concentrations fell below the IC50 for HIV at a median of 17 days (range 11.25 to 25.8 days) postpartum.
Ten women received a single oral dose of nevirapine 200 mg at delivery, followed by either 1 week of zidovudine pus lamivudine (Combivir) or a single dose of emtricitabine and tenofovir (Truvada). At one week postpartum, their median milk concentration of nevirapine was 290 mg/L (range 110 to 900 mg/L).
Milk samples were analyzed for nevirapine after mothers took a single 200 mg dose of nevirapine at the onset of labor. Of 51 mothers' milk samples, 47 had detectable nevirapine one week after taking the dose, with a median concentration of 112 mcg/L. At 2 weeks after the dose, the median concentration was 15 mcg/L in 40 milk samples assayed. At 4 weeks, nevirapine was undetectable (<10 mcg/L) in all 43 samples assayed.
Fifty-seven mothers who were receiving nevirapine 200 mg twice daily as part of a combination antiretroviral regimen provided a total of 181 milk samples at birth, 1 month, 3 months and/or 6 months postpartum. Milk samples were collected at a median of 4.5 hours (range 3.5 to 6 hours) after the previous dose. The median breastmilk nevirapine concentration was 2901 mcg/L (range 2097 to 4684 mcg/L).
Fifteen women had been taking nevirapine 200 mg twice daily as part of one of three drug combinations. Breastmilk samples were collected at just before a dose at a median of 1 month postpartum. Whole breastmilk levels contained a median of 1.83 mg/L of nevirapine, which was a median of 27% of maternal blood levels.
Infant Levels. Twenty nursing mothers were receiving oral nevirapine 200 mg twice daily as part of a combination antiretroviral regimen. Their infants had serum concentrations determined at either 2 or 5 months postpartum. Serum samples were provided at a median of 4 hours (range 1 to 8.5 hours) after the last dose. The median infant serum nevirapine concentration was 971 mcg/L (range <16 to 2191 mcg/L). The average value was 40 times the IC50 for HIV.
The infants of postpartum mothers taking nevirapine as part of a combination of antiretrovirals had undetectable serum nevirapine concentrations by HPLC/MS analysis. The nevirapine dosage the mothers were taking and times of infant plasma sampling were not stated in the abstract. Infant serum concentrations were measured at 6 (8 samples), 12 (7 samples), and 24 (6 samples) weeks of age at averages of 15, 13 and 12 hours after the last maternal dose. Median infant serum nevirapine concentrations were 584, 607 and 233 mcg/L, respectively, which was 12% of the maternal serum concentration.
Fifty-eight infants whose mothers were taking a combination regimen of lamivudine, nevirapine and zidovudine had their serum analyzed for the presence of these drugs. Mothers took nevirapine 150 mg twice daily starting at 34 to 36 weeks postpartum and continuing until 6 months postpartum and were instructed to exclusively breastfeed for 5.5 months. Serum samples were collected within 24 hours after delivery and at 2, 6, 14 and 24 weeks postpartum. The median infant dried blood spot nevirapine concentrations were 2967 mcg/L at delivery, 987 mcg/L at week 2, 1032 mcg/L at week 6, 734 mcg/L at week 14 and 303 mcg/L at week 24 postpartum.
Breastfed infants of 58 mothers who were receiving nevirapine 200 mg twice daily as part of a combination antiretroviral regimen had a total of 58 blood samples analyzed at 1 month, 3 months and/or 6 months postpartum. Samples were collected at a median of 4.5 hours (range 3.5 to 6 hours) after the previous maternal dose and a median of 30 minutes (range 20 to 60 minutes) after the previous nursing. The infants' median nevirapine plasma concentration was 809 mcg/L (range 535 to 1061 mcg/L, which was a median of 18% (range 14 to 24%) of the maternal serum concentration.
Nine infants were breastfed either partially or exclusively by their mothers who had been taking nevirapine 200 mg twice daily as part of a drug combination that included zidovudine and lamivudine. Infant blood was collected at a median of 1 month postpartum at 12 to 17 hours after the last dose and a median of 1 hour (range 6 minutes to 35 hours) after the last breastfeeding. All nine infants had detectable nevirapine levels in their serum, with a median concentration of 0.37 mg/L (range 0.24 to 1.2 mg/L).
Effects in Breastfed Infants
A study assigned pregnant women to zidovudine alone or highly-active antiretroviral therapy (HAART: zidovudine, lamivudine and nevirapine) to prevent maternal-to-child transmission of HIV infection. After delivery, All infants received one month of zidovudine prophylaxis; some infants were breastfed and others were formula fed. A higher percentage of infants in the HAART-exposed group had neutropenia than those in the unexposed group at 1 month of age (15.9 and 3.7%, respectively). Hematologic toxicity was transient and asymptomatic. From 2 to 6 months postpartum, no differences in hematologic toxicity were seen between breastfed and formula-fed infants. No statistical difference in hepatic toxicity was seen between the breastfed and formula-fed infants.
A study compared the breastfed infants of women who received a HAART regimen with nevirapine (n = 270) to one that contained nelfinavir (n = 206) as an alternative. Both regimens also contained zidovudine and lamivudine. Moderate rash was slightly more prevalent in infants who received nevirapine than nelfinavir via breastmilk. No differences were found in the rates of severe rash, liver toxicity or hyperbilirubinemia.
A study compared the frequency of rash, hepatotoxicity, and hyperbilirubinemia among 464 breastfed infants whose mothers were taking either nevirapine (n = 258) or nelfinavir (n = 206) along with zidovudine and lamivudine for HIV infection during pregnancy and postpartum. Infants were examined during the first, second and sixth weeks postpartum. Moderate rash occurred in 7 (2.7%) of the infant exposed to nevirapine and one (0.5%) infant exposed to nelfinavir. Rash occurred at a median of 2 weeks postpartum. Four infants (1.9%) exposed to nelfinavir developed hepatotoxicity (3 moderate and 1 severe) and none exposed to nevirapine. Twenty-one infants (4.5%) developed high-risk hyperbilirubinemia, all prior to 48 hours of age, but there was no difference in exposure between the two drugs.
Possible Effects on Lactation
Hyperprolactinemia and galactorrhea occurred in a woman on a combination antiretroviral regimen after nevirapine was substituted for nelfinavir. Galactorrhea ceased rapidly after nevirapine was discontinued. The prolactin level in a mother with established lactation may not affect her ability to breastfeed.
Alternate Drugs to Consider
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 AP 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. Farr SL, Nelson JA, Ng'ombe TJ et al. Addition of 7 days of zidovudine plus lamivudine to peripartum single-dose nevirapine effectively reduces nevirapine resistance postpartum in HIV-infected mothers in Malawi. J Acquir Immune Defic Syndr. 2010;54:515-23. PMID: 20672451
9. Meda N, Fao P, Ky-Zerbo O et al. Triple antiretroviral compared with zidovudine and single-nose nevirapine prophylaxis during pregnancy and breastfeeding for prevention of mother-to-child transmission of HIV-1 (Kesho Bora Study): a randomised controlled trial. Lancet Infect Dis. 2011;11:171-80. PMID: 21237718
10. Hirnschall G, Harries AD, Easterbrook PJ etr al. The next generation of the World Health Organization's global antiretroviral guidance. J Int AIDS Soc. 2013;16:18757. PMID: 23819908
11. 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
12. 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
13. 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
14. 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
15. Thomas TK, Masaba R, Borkowf CB et al. Triple-antiretroviral prophylaxis to prevent mother-to-child HIV transmission through breastfeeding-the Kisumu Breastfeeding Study, Kenya: a clinical trial. PLoS Med. 2011;8:e1001015. PMID: 21468300
16. Rossenkhan R, Ndung'u T, Sebunya TK et al. Temporal reduction of HIV type 1 viral load in breast milk by single-dose nevirapine during prevention of MTCT. AIDS Res Hum Retroviruses. 2009;25:1261-4. PMID: 20001515
17. Zeh C, Weidle PJ, Nafisa L et al. HIV-1 drug resistance emergence among breastfeeding infants born to HIV-infected mothers during a single-arm trial of triple-antiretroviral prophylaxis for prevention of mother-to-child transmission: a secondary analysis. PLoS Med. 2011;8:e1000430. PMID: 21468304
18. Fogel J, Li Q, Taha TE et al. Initiation of antiretroviral treatment in women after delivery can induce multiclass drug resistance in breastfeeding HIV-infected infants. Clin Infect Dis. 2011;52:1069-76. PMID: 21460326
19. Fogel JM, Mwatha A, Richardson P et al. Impact of maternal and infant antiretroviral drug regimens on drug resistance in HIV-infected breastfeeding infants. Pediatr Infect Dis J. 2012. PMID: 23249916
20. Arrive E, Newell ML, Ekouevi DK et al. Prevalence of resistance to nevirapine in mothers and children after single-dose exposure to prevent vertical transmission of HIV-1: a meta-analysis. Int J Epidemiol. 2007;36:1009-21. PMID: 17533166
21. Kunz A, Frank M, Mugenyi K et al. Persistence of nevirapine in breast milk and plasma of mothers and their children after single-dose administration. J Antimicrob Chemother. 2009;63:170-7. PMID: 18974161
22. Moorthy A, Gupta A, Bhosale R et al. Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants. PLoS ONE. 2009;4:e4096. PMID: 19119321
23. Hudelson SE, McConnell MS, Bagenda D et al. Emergence and persistence of nevirapine resistance in breast milk after single-dose nevirapine administration. AIDS. 2010;24:557-61. PMID: 20057308
24. Gantt S, Payant R, Carlsson J et al. Nevirapine-resistant HIV-1 DNA in breast milk after single-dose nevirapine with or without zidovudine for prevention of mother-to-child transmission. J Pediatric Infect Dis Soc. 2012;1:244-9. PMID: 23687579
25. Omer SB. Twelve-month follow-up of Six Week Extended Dose Nevirapine randomized controlled trials: differential impact of extended-dose nevirapine on mother-to-child transmission and infant death by maternal CD4 cell count. AIDS. 2011;25:767-76. PMID: 21330912
26. Mirochnick M, Fenton T, Gagnier P et al. Pharmacokinetics of nevirapine in human immunodeficiency virus type 1-infected pregnant women and their neonates. Pediatric AIDS clinical trials group protocol 250 team. J Infect Dis. 1998;178: 368-74. PMID: 9697716
27. Musoke P, Guay LA, Bagenda D et al. A phase I/II study of the safety and pharmacokinetics of nevirapine in HIV-1-infected pregnant Ugandan women and their neonates (HIVNET 006). AIDS. 1999;13:479-86. PMID: 10197376
28. Colebunders R, Hodossy B, Burger D et al. The effect of highly active antiretroviral treatment on viral load and antiretroviral drug levels in breast milk . AIDS. 2005;19 :1912-5 . PMID: 16227801
29. Shapiro RL, Holland DT, Capparelli E et al. Antiretroviral concentrations in breast-feeding infants of women in Botswana receiving antiretroviral treatment. J Infect Dis. 2005;192:720-7. PMID: 16088821
30. Giuliano M, Guidotti G, Andreotti M et al. Triple antiretroviral prophylaxis administered during pregnancy and after delivery significantly reduces breast milk viral load study within the Drug Resource Enhancement Against AIDS and Malnutrition Program. J Acquir Immune Defic Syndr. 2006 ;14:459-60. PMID: 17146372
31. Bennetto-Hood C, Aldrovandi GM, King JR et al. Persistence of nevirapine in breast milk after discontinuation of treatment. Clin Infect Dis. 2007;45:391-4. PMID: 17599320
32. Corbett A, Kashuba A, Rezk N et al. Antiretroviral drug concentrations in breast milk and breastfeeding infants. 15th Annual Conference on Retroviruses and Opportunistic Infections (CROI) 2/3/2008 to 2/6/2008; Boston, MA. Poster # 648. 2008.
33. Rezk NL, White N, Bridges AS et al. Studies on antiretroviral drug concentrations in breast milk: validation of a liquid chromatography-tandem mass spectrometric method for the determination of 7 anti-human immunodeficiency virus medications. Ther Drug Monit. 2008;30:611-9. PMID: 18758393
34. Mirochnick M, Thomas T, Capparelli E et al. Antiretroviral concentrations in breast-feeding infants of mothers receiving highly active antiretroviral therapy. Antimicrob Agents Chemother. 2009;53:1170-6. PMID: 19114673
35. Salado-Rasmussen K, Theilgaard ZP, Chiduo M et al. Good performance of an immunoassay based method for nevirapine measurements in human breast milk. Clin Chem Lab Med. 2011;49:1171-5. PMID: 21504374
36. Aizire J, McConnell MS, Mudiope P et al. Kinetics of nevirapine and its impact on HIV-1 RNA levels in maternal plasma and breast milk over time after perinatal single-dose nevirapine. J Acquir Immune Defic Syndr. 2012;60:483-8. PMID: 22217678
37. Palombi L, Pirillo MF, Andreotti M et al. Antiretroviral prophylaxis for breastfeeding transmission in Malawi: drug concentrations, virological efficacy and safety. Antivir Ther. 2012;17:1511-9. PMID: 22910456
38. Shapiro RL , Rossi S, Ogwu A et al. Therapeutic levels of lopinavir in late pregnancy and abacavir passage into breast milk, in the Mma Bana Study, Botswana. Antivir Ther. 2013;18:585-90. PMID: 23183881
39. Bae WH, Wester C, Smeaton LM et al. Hematologic and hepatic toxicities associated with antenatal and postnatal exposure to maternal highly active antiretroviral therapy among infants. AIDS. 2008;22:1633-40. PMID: 18670224
40. Minniear TD, Zeh C, Polle N et al. Adverse events in infants born to HIV-infected mothers receiving triple antiretroviral regimens for prevention of mother-to-child HIV transmission in Kenya, 2003-2006. Presented at the 6th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention.Rome, Italy. July 18, 2011:MOPE251. Abstract.
41. Minniear TD, Zeh C, Polle N et al. Rash, hepatotoxicity and hyperbilirubinemia among Kenyan infants born to HIV-infected women receiving triple-antiretroviral drugs for the prevention of mother-to-child HIV transmission. Pediatr Infect Dis J. 2012;31:1155-7. PMID: 22772167
42. Duval X, Larger E, Longuet P et al. Galactorrhoea, hyperprolactinaemia, and protease inhibitors. Lancet. 2001;357:475. PMID: 11273090
CAS Registry Number
- Antiinfective Agents
- Anti-HIV Agents
- Antiviral Agents
- Anti-Retroviral Agents
- Reverse Transcriptase Inhibitors
LactMed Record Number
Information from the National Library of Medicine's LactMed Database.
Last Revision Date
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.