Nelfinavir use while Breastfeeding
Drugs containing Nelfinavir: Viracept, AccessPak for HIV PEP Expanded with Viracept
Nelfinavir 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. Nelfinavir 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. 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. The infants who do become HIV infected during breastfeeding by mothers receiving a highly active antiretroviral therapy (HAART) regimen that includes nelfinavir are often infected with multi-class resistant HIV; however, levels of nelfinavir in the infant are very low and resistance to nelfinavir usually does not develop. Breastfed infants whose mothers receive HAART have higher rates of neutropenia during the first month and severe anemia during the first 6 months of life.
Maternal Levels. Five women were receiving nelfinavir 1250 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 nelfinavir. Breastmilk nelfinavir concentrations ranged between 6 and 24% of the maternal serum concentration. The M8 metabolite was not detectable in milk. Further details on the timing, or actual breastmilk concentrations were not provided.
Twenty-six samples of breastmilk and maternal serum were obtained at 6, 12 and 24 weeks postpartum from mothers taking nelfinavir as part of a combination of antiretrovirals. The nelfinavir dosage the mothers were taking was not stated in the abstract. The median breastmilk concentrations of nelfinavir were 49 mcg/L at a median of 14 hours after the last dose at 6 weeks postpartum (10 samples), 51 mcg/L at a median of 14 hours after the last dose at 12 weeks postpartum (7 samples), and 184 mcg/L at a median of 16 hours after the last dose at 24 weeks postpartum (9 samples). Median milk concentrations were 8% (interquartile range 4 to 14%) of maternal plasma concentrations. In a related study by the same authors, the nelfinavir milk to plasma ratio was found to be 0.21 in 29 patients.
Twenty-six breastfeeding Kenyan mothers were receiving oral nelfinavir 1.25 grams twice daily in addition to zidovudine and lamivudine for HIV infection. Blood and breastmilk samples were collected at delivery, and at 2, 6, 14, and 24 weeks postpartum at various times after the previous dose of nelfinavir. The 104 breastmilk samples were analyzed for nelfinavir and its active metabolite, hydroxyl-t-butylamidenelfinavir (M8). Median breastmilk nelfinavir concentrations were 83 mcg/L at birth, 358 mcg/L at 2 weeks, 286 mcg/L at 6 weeks, 233 mcg/L at 14 weeks and 180 mcg/L at 24 weeks postpartum. The M8 metabolite was undetectable (<10 mcg/L) in most samples; the highest concentrations found at any time was 32 mcg/L. Nelfinavir levels in breastmilk tended to drop during the dosing interval but M8 levels were relatively stable.
Infant Levels. The infants of postpartum mothers taking nelfinavir as part of a combination of antiretrovirals had undetectable serum nelfinavir concentrations by HPLC/MS analysis. The nelfinavir dosage the mothers were taking and times of infant plasma sampling were not stated in the abstract. Nelfinavir was not detectable in infant plasma at 6, 12 or 24 weeks of age.
Twenty-six breastfeeding Kenyan mothers were receiving oral nelfinavir 1.25 grams twice daily in addition to zidovudine and lamivudine for HIV infection. Infant blood samples were obtained at various times between 2 and 24 weeks postpartum. Nelfinavir and M8 concentration were undetectable (<10 mcg/L) for 20 of the 28 infant blood samples. The highest concentrations detected were 30 mcg/L for nelfinavir and 32 mcg/L for M8 which are less than the MIC for the HIV virus.
Effects in Breastfed Infants
A study compared the frequency of rash, hepatotoxicity, and hyperbilirubinemia among 464 breastfed infants whose mothers were taking either nelfinavir (n = 206) or nevirapine (n = 258) 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
Gynecomastia has been reported among men receiving highly active antiretroviral therapy. Gynecomastia is unilateral initially, but progresses to bilateral in about half of cases. No alterations in serum prolactin were noted and spontaneous resolution usually occurred within one year, even with continuation of the regimen. 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.
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. 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
5. 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
6. 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
7. 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
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. Weidle PJ, Zeh C, Martin A, Lando R et al. Nelfinavir and its active metabolite, hydroxyl-t-butylamidenelfinavir (M8), are transferred in low quantities to breast milk and do not result in biologically significant concentrations in breast-feeding infants whose mothers are taking nelfinavir. Antimicrob Agents Chemother. 2011;55:5168-71. PMID: 21876052
13. 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
14. 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.
15. 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
16. 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
17. 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
18. Pantanowitz L, Evans D, Gross PD, Dezube BJ. HIV-related gynecomastia. Breast J. 2003;9:131-2. PMID: 12603389
19. Evans DL, Pantanowitz L, Dezube BJ, Aboulafia DM. Breast enlargement in 13 men who were seropositive for human immunodeficiency virus. Clin Infect Dis. 2002;35:1113-9. PMID: 12384846
20. Hutchinson J, Murphy M, Harries R, Skinner CJ. Galactorrhoea and hyperprolactinaemia associated with protease-inhibitors. Lancet. 2000;356:1003-4. PMID: 11041407
21. 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
22. Montero A, Bottasso OA, Luraghi MR et al. Galactorrhoea, hyperprolactinaemia, and protease inhibitors. Lancet. 2001;357:473-4; author reply 475. PMID: 11273087
CAS Registry Number
- Antiinfective Agents
- Anti-HIV Agents
- Antiviral Agents
- Anti-Retroviral Agents
- HIV Protease Inhibitors
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Information from the National Library of Medicine's LactMed Database.
Last Revision Date
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