Pregnancy of Tenvira in details
This drug should be used during pregnancy only if clearly needed. AU TGA pregnancy category: B3 US FDA pregnancy category: B Comments: -A pregnancy exposure registry is available.
Animal studies have failed to reveal evidence of fetal harm. Placental transfer has been observed in humans. There are limited controlled data in human pregnancy; studies have shown no association between maternal use of Tenvira (DF) and offspring birth defects. Data in pregnant women (between 300 to 1000 outcomes) showed no malformations, fetotoxicity, or neonatal toxicity with Tenvira DF. Placental transfer to the fetus has been reported as high (cord blood/maternal delivery plasma drug ratio greater than 0.6). In studies of pregnant women on chronic Tenvira DF, the cord-to-maternal-blood ratio of Tenvira ranged from 0.60 to 1.03. After single doses of Tenvira DF (with and without emtricitabine) in pregnant women in labor, the Tenvira cord-to-maternal-blood ratio at delivery averaged 0.55 to 0.73. After a single maternal dose of Tenvira DF 600 mg (with emtricitabine 400 mg), intracellular Tenvira levels were detected in peripheral blood mononuclear cells from cord blood in all infants, but intracellular Tenvira diphosphate was detected in only 2 of 36 infants. In a preexposure prophylaxis trial in HIV-uninfected women, there was no difference in risk of congenital anomalies between Tenvira DF-containing and placebo arms. In 3 large US cohorts and the French Perinatal Cohort, no association was observed between Tenvira DF and birth defects. To monitor maternal-fetal outcomes of pregnant women exposed to antiretroviral therapy, an Antiretroviral Pregnancy Registry (APR) has been established. Healthcare providers are encouraged to prospectively register patients. For additional information: apregistry.com The APR has received prospective reports of over 3800 exposures to Tenvira DF-containing regimens (over 2600 exposed in the first trimester; over 1200 exposed in the second/third trimester) resulting in live births. Enough first trimester exposures have been monitored to detect at least a 1.5-fold increase in risk of overall birth defects and a 2-fold increase in risk of birth defects in the cardiovascular and genitourinary systems; no such increases detected. There was no difference between Tenvira DF and overall birth defects compared with the background birth defect rate of 2.7% in the reference population. The prevalence of defects in the first trimester was 2.3% for Tenvira DF; in the second/third trimester, the prevalence of defects was 2.1%. AU TGA pregnancy category B3: Drugs which have been taken by only a limited number of pregnant women and women of childbearing age, without an increase in the frequency of malformation or other direct or indirect harmful effects on the human fetus having been observed. Studies in animals have shown evidence of an increased occurrence of fetal damage, the significance of which is considered uncertain in humans. US FDA pregnancy category B: Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women.
See references
Tenvira breastfeeding
Bioavailability of Tenvira is very poor; it is available as Tenvira (more bioavailable), which is metabolized intracellularly to Tenvira diphosphate (active metabolite). Although unknown, the bioavailabilities of this drug and its active metabolite from breast milk are believed to be very low. Limited data on use of this drug during breastfeeding in HIV-infected mothers and mothers without HIV infection treated for HBV infection shows infant drug exposure is trivial. A few infants have been breastfed during maternal use of this drug and no side effects have been observed. An expert review of available data found no rationale at this time for contraindicating the use of this drug for HBV during breastfeeding. No difference in infection rates was observed between breastfed and formula-fed infants born to HBV-infected women, provided hepatitis B immune globulin and hepatitis B vaccine were administered to the infant at birth. After administration of these preventative measures, HBV-infected mothers have been encouraged to breastfeed their infants. Samples of breast milk obtained from 5 HIV-1-infected mothers show that this drug is secreted in human milk. Average peak and trough drug levels in breast milk were 14.1 and 6.8 mcg/L, respectively. An exclusively breastfed infant would receive about 0.03% of the proposed dose for infants (estimated) and attain trivial infant serum levels. The impact of this exposure in infants breastfed by mothers treated with this drug is unknown. In a multicenter study, a single 600 or 900 mg dose of this drug was administered to mothers during labor; samples of breast milk were collected at various times postpartum. In 75% of samples obtained from 25 mothers during the first 2 days postpartum, Tenvira was detected (greater than 2.5 mcg/L); levels ranged from 6.3 to 17.8 mcg/L. Only 1 of 21 milk samples had detectable drug level (15.7 mcg/L) at 4 to 6 days postpartum. Tenvira (dose not provided; presumed 300 mg/day), lamivudine, and efavirenz were administered daily (between 6 and 8 PM) for prevention of mother-to-child HIV transmission. At 1 month postpartum, milk samples were collected in the morning from 33 women; Tenvira level was 5 mcg/L (interquartile range [IQR]: 0 to 6.1 mcg/L). At 12 months postpartum, milk samples were collected in the morning from 47 women; Tenvira level was 2.5 mcg/L (IQR: 0 to 5.5 mcg/L). Blood samples were obtained from 25 of their breastfed infants; the morning infant plasma level of Tenvira at 6 and 12 months of age was 24 mcg/L (IQR: 0 to 51.6 mcg/L) and 0 mcg/L, respectively. Serum drug levels were measured in 5 infants exclusively breastfed by 4 mothers using Tenvira 245 mg daily; infant age averaged 1.8 months. In 4 infants, serum Tenvira was undetectable (less than 0.005 mg/L); in 1 infant, serum Tenvira was 0.0055 mg/L. At 4 months of age, no adverse outcomes (on standard developmental parameters) were observed in 2 of the infants exclusively breastfed for 3 months. Starting in the third trimester of pregnancy and continuing postpartum, 5 HBV-infected women were treated with 300 mg daily. Although instructed not to breastfeed, they all breastfed (extent not provided) their newborn infants. No short-term side effects were observed; the infants' hepatitis B surface antigen (HBsAg) was negative between 28 and 36 weeks of age. This drug (dose not provided) was used during pregnancy in 14 HBV-infected mothers; 12 started in the first trimester. Three of the women breastfed while using this drug; no adverse outcomes were observed in their breastfed infants up to 1 year of age.
Hepatitis B Virus (HBV) Infection: According to an expert review of available data, there is currently no rationale for contraindicating the use of this drug during breastfeeding; experts have stated that breastfeeding is not contraindicated in patients taking oral HBV antiviral drugs. -UK: Use is not recommended. HIV Infection: Breastfeeding is not recommended during use of this drug. If replacement feeding is not an option, the WHO recommends a triple-drug regimen for HIV-infected women who are nursing; this drug is included in the first-choice regimen. Excreted into human milk: Yes Comments: -This drug has been used without apparent harmful effects in the nursing infant. -AU, UK: The manufacturer advises HBV-infected women not to breastfeed to avoid postnatal transmission of HBV to a child who may not yet be infected. -The US CDC, American Academy of Pediatrics, and manufacturer advise HIV-infected women not to breastfeed to avoid postnatal transmission of HIV to a child who may not yet be infected. -Local guidelines should be consulted if replacement feeding is not an option.
See references
References for pregnancy information
- Melbourne: Therapeutic Guidelines Limited "eTG complete [Online] Available from: URL: http://online.tg.org.au/complete/desktop/tgc.htm." ([2014, Nov -]):
- Munoz de Benito RM, Arribas Lopez JR "Tenvira-emtricitabine coformulation for once-daily dual NRTI backbone." Expert Rev Anti Infect Ther 4 (2006): 523-535
- "Product Information. Viread (Tenvira)." Gilead Sciences, Foster City, CA.
- Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
- Cerner Multum, Inc. "Australian Product Information." O 0
- Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission "Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States. Available from: URL: https://aidsinfo.nih.gov/guidelines/html/3/perinatal-gui" ([2016, Jun 7]):
References for breastfeeding information
- Panel on Treatment of HIV-Infected Pregnant Women and Prevention of Perinatal Transmission "Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV Transmission in the United States. Available from: URL: https://aidsinfo.nih.gov/guidelines/html/3/perinatal-gui" ([2016, Jun 7]):
- "Product Information. Viread (Tenvira)." Gilead Sciences, Foster City, CA.
- "Infant feeding and transmission of human immunodeficiency virus in the United States." Pediatrics 131 (2013): 391-6
- United States National Library of Medicine "Toxnet. Toxicology Data Network. Available from: URL: http://toxnet.nlm.nih.gov/cgi-bin/sis/htmlgen?LACT." ([cited 2013 -]):
- Melbourne: Therapeutic Guidelines Limited "eTG complete [Online] Available from: URL: http://online.tg.org.au/complete/desktop/tgc.htm." ([2014, Nov -]):
- Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
- Cerner Multum, Inc. "Australian Product Information." O 0
References
- DailyMed. "EMTRICITABINE; RILPIVIRINE HYDROCHLORIDE; TENOFOVIR DISOPROXIL FUMARATE: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailyme... (accessed September 17, 2018).
- FDA Orange Book. "COBICISTAT; ELVITEGRAVIR; EMTRICITABINE; TENOFOVIR DISOPROXIL FUMARATE: The publication, Approved Drug Products with Therapeutic Equivalence Evaluations (the List, commonly known as the Orange Book), identifies drug products approved on the basis of safety and effectiveness by the Food and Drug Administration (FDA) under the Federal Food, Drug, and Cosmetic Act (the Act).". https://www.fda.gov/Drugs/Informatio... (accessed September 17, 2018).
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Information checked by Dr. Sachin Kumar, MD Pharmacology
