Tenofovir

Drug Levels and Effects:




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] Limited published experience with tenofovir during breastfeeding in HIV-positive mothers and HIV negative mothers treated for hepatitis B infection indicates that the exposure of the infant to the drug is trivial and unlikely to have any adverse consequences.

Tenofovirhas not been studied in HIV-negative nursing mothers being treated for hepatitis B infection, but the low doses used would not be expected to cause any serious adverse effects in breastfed infants. Some sources recommend not breastfeeding during lamivudine therapy for hepatitis B.[12] In a survey, 226 physicians with a practice interest in liver disease in the United States responded. Of these, 31% stated that they recommend breastfeeding for their patients with hepatitis B who are taking antiviral therapy, 44% stated that they do not recommend breastfeeding during antiviral therapy and 25% stated that they were unsure.[13]


Drug Levels:


Maternal Levels.

Five exclusively breastfeeding mothers received oral tenofovir 300 mg plusemtricitabine200 mg and nevirapine 200 mg at the start of labor, then oral tenofovir 300 mg daily andemtricitabine200 mg for 7 days postpartum. A total of 16 concurrent maternal blood and milk samples were collected on days 1, 2, 3, and 7 postpartum between 10 minutes and 21 hours after the mothers' doses. Median peak and trough tenofovir concentrations in breastmilk were 14.1 mcg/L and 6.8 mcg/L, respectively. The authors estimated that an exclusively breastfed infant would receive about 0.03% of the proposed infant dose for tenofovir and achieve trivial infant serum concentrations that would likely have no adverse consequences.[14]

Infant Levels.

Five infants were exclusively breastfed by 4 mothers who took tenofovir 245 mg (presumably 300 mg oftenofovirdisoproxilfumarate) daily. At an average of 1.8 months of age, infant serum tenofovir concentrations were measured.Tenofovirwas undetectable (<0.005 mg/L) in the serum of 4 of the infants, and 0.0055 mg/L in the serum of one infant.[15]


Effects in Breastfed Infants:


Five women with hepatitis B infection were treated withtenofovirdisoproxilfumarate300 mg daily beginning in the third trimester of pregnancy and continuing postpartum. Although instructed not to breastfeed, 5 mothers breastfed (extent not stated) their newborn infants and no short-term adverse reactions were seen.[16]

Two newborn infants whose mothers were treated with tenofovir 245 mg (presumably 300 mg oftenofovirdisoproxilfumarate) daily were exclusively breastfed for 3 months. At 4 months of age, neither showed any adverse outcomes on standard developmental parameters.[15]


Possible Effects on Lactation:


Relevant published information was not found as of the revision date.


Alternate Drugs to Consider:


Lamivudine,Nelfinavir,Nevirapine,Zidovudine


References:


1. World Health Organization. HIV and infant feeding: update. 2007.
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. Bzowej NH. Optimal management of the hepatitis B patient who desires pregnancy or is pregnant. Curr Hepat Rep. 2012;11:82-9. PMID:22707918
13. Ahn J, Salem SB, Cohen SM. Evaluation and management of hepatitis B in pregnancy: a survey of current practices. Gastroenterol Hepatol (N Y). 2010;6:570-8. PMID:21088746
14. Benaboud S, Pruvost A, Coffie PA et al. Concentrations of tenofovir andemtricitabinein breast milk of HIV-1-infected women in Abidjan, Cote d'Ivoire, in the ANRS 12109 TEMAA Study, step 2. Antimicrob Agents Chemother. 2011;55:1315-7. PMID:21173182
15. Gouraud A, Millaret A, Bernard N, Bruel M, Paret N, Descotes J et al.Tenofovirexposure through breast feeding: Serum concentrations in neonates and clinical follow-up. Fundam Clin Pharmacol. 2012;26:9. Abstract.
16. Pan CQ, Mi LJ, Bunchorntavakul C et al.Tenofovirdisoproxilfumaratefor prevention of vertical transmission of hepatitis B virus infection by highly viremic pregnant women: A case series. Dig Dis Sci. 57:2423-9. PMID:22543886



Substance Identification:




Substance Name:

Tenofovir

CAS Registry Number:

147127-20-6

Drug Class:


  • Antiinfective Agents

  • Anti-HIV Agents

  • Antiviral Agents

  • Anti-Retroviral Agents

  • Reverse Transcriptase Inhibitors


  • Administrative Information:




    LactMed Record Number:


    658


    Last Revision Date:


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