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Bictegravir / emtricitabine / tenofovir alafenamide Pregnancy and Breastfeeding Warnings

Bictegravir / emtricitabine / tenofovir alafenamide is also known as: Biktarvy

Medically reviewed by Drugs.com. Last updated on Mar 27, 2018.

Bictegravir / emtricitabine / tenofovir alafenamide Pregnancy Warnings

Animal studies of the components of this drug have failed to reveal evidence of adverse developmental outcomes; exposures were either not maternally toxic (rabbits) or greater than (rats and mice) those in humans at recommended human dose (RHD). For bictegravir, no embryofetal toxicity observed in rats and rabbits at exposures up to about 36 (rats) and 0.6 (rabbits) times the exposure in humans at RHD; spontaneous abortion, increased clinical signs (fecal changes, thin body, cold-to-touch), and decreased body weight observed at maternotoxic dose in rabbits (about 1.4 times higher than human exposure at RHD). For emtricitabine, no significant embryofetal toxicity observed in mice at exposures about 60 times higher and rabbits at about 108 times higher than human exposures at RHD. For tenofovir alafenamide, no adverse embryofetal effects observed in rats at exposures about 2 times higher and rabbits at about 78 times higher than human exposures at RHD. There are no controlled data in human pregnancy; however, emtricitabine has been evaluated in a limited number of women during pregnancy. Available data showed no difference in the overall risk of major birth defects for emtricitabine compared to the background rate in the US reference population.

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 3950 exposures to emtricitabine-containing regimens (over 2750 exposed in the first trimester; over 1200 exposed in the second/third trimester) resulting in live births; there was no difference between emtricitabine and overall birth defects compared with the background birth defect rate of 2.7% in the US reference population. Enough first trimester exposures have been monitored to detect at least a 1.5-fold increased risk of overall birth defects and a 2-fold increase in cardiovascular and genitourinary defects (the more common classes); no such increases detected. The prevalence of birth defects with first trimester and second/third trimester exposures was 2.4% and 2.3%, respectively.

The APR has not received sufficient numbers of reports regarding exposures to tenofovir alafenamide-containing regimens to estimate rate of birth defects.

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 Not Assigned: The US FDA has amended the pregnancy labeling rule for prescription drug products to require labeling that includes a summary of risk, a discussion of the data supporting that summary, and relevant information to help health care providers make prescribing decisions and counsel women about the use of drugs during pregnancy. Pregnancy categories A, B, C, D, and X are being phased out.

This drug should be used during pregnancy only if the benefit outweighs the risk to the fetus.

AU TGA pregnancy category: B3
US FDA pregnancy category: Not assigned.

Risk summary: Insufficient data available on use of this drug in pregnant women to inform a drug-related risk.

Comments:
-A pregnancy exposure registry is available.

See references

Bictegravir / emtricitabine / tenofovir alafenamide Breastfeeding Warnings

Breastfeeding is not recommended during use of this drug; if replacement feeding is not an option, a different drug is recommended.

Excreted into human milk: Yes (emtricitabine); Unknown (bictegravir, tenofovir alafenamide)
Excreted into animal milk: Yes (bictegravir); Unknown (tenofovir alafenamide)

Comments:
-Tenofovir is present in human breast milk after administration of tenofovir disoproxil fumarate.
-The effects in the nursing infant are unknown; potential for HIV-infected infants developing viral resistance and breastfed infants developing side effects
-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.

EMTRICITABINE:
Samples of breast milk obtained from 5 HIV-1-infected women show that emtricitabine is secreted in human milk. Average peak and trough drug levels in breast milk were 679 and 177 mcg/L, respectively. According to author estimation, an exclusively breastfed infant would receive about 2% of the proposed emtricitabine dose for infants and achieve serum levels that may lead to emergence of viral resistance to emtricitabine. Breastfeeding infants whose mothers are treated with emtricitabine may be at risk for developing viral resistance to emtricitabine; other emtricitabine-related risks in such infants are unknown.

Preexposure prophylaxis, using emtricitabine (200 mg/day) and tenofovir disoproxil fumarate, was administered by directly observed therapy for 10 days to 50 women without HIV infection who were breastfeeding their infants. On days 7 and 10 of therapy, peak and trough milk samples were collected 1 to 2 hours after dosing and 23 to 24 hours after the previous dose, respectively; a single infant blood sample was collected after the mother's 7th dose. Median peak and trough milk emtricitabine levels were 212.5 and 183 mcg/L, respectively; these levels correspond to a daily dose of 27.5 to 31.5 mcg/kg (estimated), which is about 0.5% of the proposed therapeutic dose for infants. Of 49 infant blood samples collected, 47 had detectable emtricitabine levels (median plasma level: 13.2 mcg/L); plasma levels were 16.6 mcg/L in infants younger than 13 weeks and 10.5 mcg/L in infants at least 13 weeks of age. Diarrhea lasting 2 to 3 days was reported in 2 of the 50 breastfed infants; no other side effects were reported.

During ongoing therapy, emtricitabine was measured after a 300-mg dose to 6 nursing mothers with HIV infection. Peak breast milk level was 872 mcg/L (range: 696 to 1063 mcg/L) at about 3 hours; 1 breastfed infant had detectable emtricitabine serum level of 17.5 mcg/L.

Emtricitabine (200 mg once a day) was part of a combination regimen for HIV in 16 Nigerian women exclusively breastfeeding their infants (on demand). Expressed milk samples were collected before dosing and at 0.5, 1, 2, 4, 8, and 12 hours after dosing; peak breast milk level from dried breast milk spots was 843 mcg/L (interquartile range [IQR]: 702 to 1132 mcg/L) at 4 hours (IQR: 2 to 8 hours) after dosing. Infant blood samples were collected at 2 and 8 hours after maternal dosing; analysis of the dried blood spots showed only 3 samples with quantifiable (greater than 16.6 mcg/L) emtricitabine blood levels of 17.5, 18.8, and 19.4 mcg/L.

See references

References for pregnancy information

  1. "Product Information. Biktarvy (bictegravir/emtricitabine/tenofovir)." Gilead Sciences, Foster City, CA.
  2. Cerner Multum, Inc. "Australian Product Information." O 0
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0

References for breastfeeding information

  1. Cerner Multum, Inc. "Australian Product Information." O 0
  2. "Product Information. Biktarvy (bictegravir/emtricitabine/tenofovir)." Gilead Sciences, Foster City, CA.
  3. "Infant feeding and transmission of human immunodeficiency virus in the United States." Pediatrics 131 (2013): 391-6
  4. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  5. 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 -]):

Further information

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