Stavudine use while Breastfeeding
Drugs containing Stavudine: Zerit, Zerit XR
Stavudine 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. 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. 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. Because there is little published experience with stavudine during breastfeeding, an alternate drug may be preferred, especially while nursing a newborn or preterm infant.
Maternal Levels. One study measured stavudine in breastmilk samples from nursing mothers who had been randomized to receive the drug as part of a clinical trial to evaluate maternal to child transmission of HIV infection. The dosages, dosage regimens and time of breastmilk sample collection times were not reported. The stavudine milk to plasma ratio was found to be 1.73 in 2 patients.
Fifty-two mothers who were taking stavudine either 30 mg (<60 kg) or 40 mg (>60 kg) twice daily had milk samples analyzed for stavudine. Exact timing of the previous dose was not available. Stavudine was detectable in 44 samples of whole milk and 45 samples of skim milk. The median stavudine concentrations were 151 mcg/L in whole milk and 190 mcg/L in skim milk. The average infant intake of stavudine via breastmilk was estimated to be 22.7 mcg/kg daily.
Twenty-eight mothers who were receiving stavudine 30 mg twice daily as part of a combination antiretroviral regimen provided a total of 93 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 stavudine concentration was 105 mcg/L (range 34 to 117 mcg/L).
Infant Levels. Four mothers received prophylaxis with stavudine, nevirapine and lamivudine (doses not specified) beginning at week 25 of gestation until 6 months postpartum. Blood samples taken at unspecified times failed to detect (<5 mcg/L) stavudine in 8 infant blood samples.
Fifty-two infants whose mothers who were taking stavudine either 30 mg (<60 kg) or 40 mg (>60 kg) twice daily had blood samples analyzed for stavudine. Exact timing of the mothers' previous dose was not available. Stavudine was undetectable (<5 mcg/L) in all but 7 of the infants with an estimated stavudine intake from milk of 22.7 mcg/kg daily. In the 7 infants who had detectable serum concentrations, all had serum concentrations less than 10 mcg/L and their median serum concentration was 5% (range 1 to 15%) of their mothers' serum concentration.
Breastfed infants of 28 mothers who were receiving stavudine 30 mg twice daily as part of a combination antiretroviral regimen had a total of 30 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' stavudine plasma concentrations ranged from 0 to 2.5 mcg/L, which was a median of 4% (range 0 to 8%) of the maternal serum concentration.
Effects in Breastfed Infants
Relevant published information was not found as of the revision date.
Possible Effects on Lactation
Some case reports and in vitro studies have suggested that protease inhibitors might cause hyperprolactinemia and galactorrhea in some male patients, although this has been disputed. One case series found an incidence of gynecomastia of 2.4 cases per person annually among men receiving highly active antiretroviral therapy; 70% of the affected patients were taking stavudine. Gynecomastia was unilateral initially, but progressed to bilateral in 53% of cases. No alterations in serum prolactin were noted and 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
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. 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
13. Fogel JM, Taha TE, Sun J et al. Stavudine (d4T) concentrations in women receiving post-partum antiretroviral treatment and their breastfeeding infants. J Acquir Immune Defic Syndr. 2012;60:462-5. PMID: 22614899
14. 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
15. Liotta G, PirilloM, Andreotti M, Sagno JB, Doro Altan A, Marchei E et al. Drug concentrations in breastfeeding infants of women receiving ARV for the prevention of postnatal transmission in Malawi. 18th Conference on Retroviruses and Opportunistic Infections. Boston, MA. 2011;Paper # 757. Abstract.
16. Hutchinson J, Murphy M, Harries R, Skinner CJ. Galactorrhoea and hyperprolactinaemia associated with protease-inhibitors. Lancet. 2000;356:1003-4. PMID: 11041407
17. Orlando G, Brunetti L, Vacca M. Ritonavir and saquinavir directly stimulate anterior pituitary prolactin secretion, in vitro. Int J Immunopathol Pharmacol. 2002;15:65-8. PMID: 12593790
18. Montero A, Bottasso OA, Luraghi MR et al. Galactorrhoea, hyperprolactinaemia, and protease inhibitors. Lancet. 2001;357:473-4; author reply 475. PMID: 11273087
19. Garcia-Benayas T, Blanco F, Martin-Carbonero L et al. Gynecomastia in HIV-infected patients receiving antiretroviral therapy. AIDS Res Hum Retroviruses. 2003;19:739-41. PMID: 14585204
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.
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