The Basics
What is Nevirapine?
Used along with other medications to treat HIV infection in adults and children 15 days of age and older.
Brand names for Nevirapine
Viramune
How Nevirapine is classified
Anti-Infective Agents, Anti-HIV Agents, Antiviral Agents, Anti-Retroviral Agents, Reverse Transcriptase Inhibitors
Nevirapine During Pregnancy
Nevirapine pregnancy category
Category BNote that the FDA has deprecated the use of pregnancy categories, so for some medications, this information isn’t available. We still think it’s useful to list historical info, however, given what a common proxy this has been in the past.
What we know about taking Nevirapine while pregnant
Available data from the APR show no difference in the risk of overall major birth defects for nevirapine compared with the background rate for major birth defects of 2.7% in the U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP) . The rate of miscarriage is not reported in the APR. The estimated background rate of miscarriage in clinically recognized pregnancies in the U.S. general population is 15-20%. The background risk of birth defects and miscarriage for the indicated population is unknown. Methodological limitations of the APR include the use of MACDP as the external comparator group. The MACDP population is not disease-specific, evaluates women and infants from a limited geographic area, and does not include outcomes for births that occurred at <20 weeks gestation. In literature reports, immediate-release nevirapine exposure (Cmin) can be up to 29% lower during pregnancy. However, as this reduction was not found to be clinically meaningful, dose adjustment is not necessary . There is a risk for severe hepatic events in pregnant women exposed to VIRAMUNE [see Clinical Considerations]. In animal reproduction studies, no evidence of adverse developmental outcomes were observed following oral administration of nevirapine during organogenesis in the rat and rabbit, at systemic exposures (AUC) to nevirapine approximately equal (rats) and 50% higher (rabbits) than the exposure in humans at the recommended 400 mg daily dose .
Taking Nevirapine While Breastfeeding
What are recommendations for lactation if you're taking Nevirapine?
In the United States and other developed countries, HIV-infected mothers should generally not breastfeed their infants. Nevirapine has been well studied in nursing mothers. In countries in which no acceptable, feasible, sustainable and safe replacement feeding is available, World Health Organization guidelines recommend that all women with an HIV infection who are pregnant or breastfeeding should be maintained on antiretroviral therapy for at least the duration of risk for mother-to-child transmission. Mothers should exclusively breastfeed their infants for the first 6 months of life; breastfeeding with complementary feeding should continue through 12 months of life. The first choice regimen for nursing mothers is tenofovir, efavirenz and either lamivudine or emtricitabine. If these drugs are unavailable, alternative regimens include: 1) zidovudine, lamivudine and efavirenz; 2) zidovudine, lamivudine and nevirapine; or 3) tenofovir, nevirapine and either lamivudine or emtricitabine. Exclusively breastfed infants should also receive 6 weeks of prophylaxis with nevirapine.[1][2] 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 in the mother.[3][4][5][6][7][8]
Maternal / infant drug levels
In the United States and other developed countries, HIV-infected mothers should generally not breastfeed their infants. Nevirapine has been well studied in nursing mothers. In countries in which no acceptable, feasible, sustainable and safe replacement feeding is available, World Health Organization guidelines recommend that all women with an HIV infection who are pregnant or breastfeeding should be maintained on antiretroviral therapy for at least the duration of risk for mother-to-child transmission. Mothers should exclusively breastfeed their infants for the first 6 months of life; breastfeeding with complementary feeding should continue through 12 months of life. The first choice regimen for nursing mothers is tenofovir, efavirenz and either lamivudine or emtricitabine. If these drugs are unavailable, alternative regimens include: 1) zidovudine, lamivudine and efavirenz; 2) zidovudine, lamivudine and nevirapine; or 3) tenofovir, nevirapine and either lamivudine or emtricitabine. Exclusively breastfed infants should also receive 6 weeks of prophylaxis with nevirapine.[1][2] 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 in the mother.[3][4][5][6][7][8]
Possible effects of Nevirapine on milk supply
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.[27] The prolactin level in a mother with established lactation may not affect her ability to breastfeed.
Possible alternatives to Nevirapine
None listed
List of References
Lactation sources: Drugs and Lactation Database (LactMed) [Internet]. Bethesda (MD): National Library of Medicine (US); 2006-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK501922/1. World Health Organization. HIV and infant feeding: update. 2007. http://whqlibdoc.who.int/publications/2007/9789241595964_eng.pdf
2. World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection. Geneva: World Health Organization. 2013. http://www.who.int/hiv/pub/guidelines/arv2013/en/
3. 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
4. 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
5. 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
6. 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
7. 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
8. Micek MA, Dross S, Blanco AJ et al. Transmission of nevirapine-resistant HIV Type 1 via breast milk to infants after single-dose nevirapine in Beira, Mozambique. J Infect Dis. 2014;210:641-5. PMID: 24596282
9. 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
10. 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
11. 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
12. 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
13. 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
14. 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
15. 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.
16. 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
17. 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
18. 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
19. 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
20. 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
21. 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
22. Olagunju A, Amara A, Waitt C et al. Validation and clinical application of a method to quantify nevirapine in dried blood spots and dried breast-milk spots. J Antimicrob Chemother. 2015;70:2816-22. PMID: 26108608
23. Olagunju A, Khoo S, Owen A. Pharmacogenetics of nevirapine excretion into breast milk and infants’ exposure through breast milk versus postexposure prophylaxis. Pharmacogenomics. 2016;17:891-906. PMID: 27268507
24. 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
25. 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.
26. 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
27. Duval X, Larger E, Longuet P et al. Galactorrhoea, hyperprolactinaemia, and protease inhibitors. Lancet. 2001;357:475. PMID: 11273090
Disclaimer: This material is provided for educational purposes only and is not intended for medical advice, diagnosis, or treatment. Consult your healthcare provider with any questions.
