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Atazanavir / cobicistat Pregnancy and Breastfeeding Warnings

Atazanavir / cobicistat is also known as: Evotaz

Medically reviewed on July 12, 2017

Atazanavir / cobicistat Pregnancy Warnings

Animal studies have failed to reveal evidence of teratogenicity with atazanavir at maternal doses producing systemic drug exposure levels 0.7 (rabbits) or 1.2 (rats) times those at the human clinical dose (atazanavir 300 mg/day boosted with ritonavir 100 mg/day); at an exposure level causing maternal toxicity, body weight loss or weight gain suppression was observed in rat offspring. Animal studies have failed to reveal evidence of teratogenicity, embryofetal toxicity, or an effect on reproductive function with cobicistat. Atazanavir/ritonavir has been evaluated in a limited number of women during pregnancy. Available data suggest atazanavir does not increase risk of major birth defects overall (compared with background rate). For cobicistat and atazanavir-cobicistat, there are no controlled data in human pregnancy.

Placental transfer of atazanavir to the fetus has been reported as low (cord blood/maternal delivery plasma drug ratio less than 0.3). In studies of patients using atazanavir (plus ritonavir) during therapy, cord blood atazanavir level averaged 13% to 21% of maternal serum levels at delivery.

Symptomatic hyperlactatemia and lactic acidosis syndrome (some cases fatal) have been reported in pregnant women using atazanavir in combination with nucleoside analogs, which are known to have greater risk of lactic acidosis; patients should be apprised of the potential risks of lactic acidosis and hyperbilirubinemia. Hyperbilirubinemia has been reported frequently during atazanavir therapy; it is not known whether maternal use would lead to neonatal kernicterus. All infants (including newborns exposed to atazanavir in utero) should be monitored for the development of severe hyperbilirubinemia during the first few days of life.

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 1800 exposures to atazanavir-containing regimens (over 1200 exposed in the first trimester; over 600 exposed in the second/third trimester) resulting in live births; there was no difference between atazanavir 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 2.2% and 2.4%, respectively.

The APR has not received enough reports of exposures to cobicistat-containing regimens during pregnancy to estimate the birth defect rate.

AU TGA pregnancy category B2: 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 are inadequate or may be lacking, but available data show no evidence of an increased occurrence of fetal damage.

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: B2
US FDA pregnancy category: Not assigned.

Risk summary: No data available on use of this drug in pregnant women to inform a drug-related risk.

Comments:
-A pregnancy exposure registry is available.
-No dosing recommendations can be provided as the pharmacokinetics, safety, and efficacy of this drug cannot be predicted from studies of other atazanavir-containing products in pregnant women.
-According to some authorities: This drug should not be used in therapy-experienced patients taking an H2-receptor antagonist and/or tenofovir disoproxil fumarate during the second or third trimester.
-The manufacturer product information for atazanavir should be consulted regarding its use during pregnancy.

See references

Atazanavir / cobicistat Breastfeeding Warnings

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

Excreted into human milk: Yes (atazanavir); Unknown (cobicistat)
Excreted into animal milk: Yes (cobicistat)

Comments:
-The effects in the nursing infant are unknown.
-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.

On postpartum days 5 and 14, samples of breast milk and plasma were obtained at 0, 2, 5, 8, and 24 hours postdose from 3 women taking atazanavir (dose not stated; 300 mg/day likely) as part of highly active antiretroviral therapy. Breast milk levels over 24 hours averaged 212 mcg/L on day 5 and 265 mcg/L on day 14. Peak breast milk levels averaged 419 mcg/L at 5 hours postdose. The breast milk to plasma ratio averaged 13% for atazanavir.

See references

References for pregnancy information

  1. "Product Information. Reyataz (atazanavir)." Bristol-Myers Squibb, Princeton, NJ.
  2. Panel on Treatment of Pregnant Women with HIV Infection and Prevention of Perinatal Transmission "Recommendations for the Use of Antiretroviral Drugs in Pregnant Women with HIV Infection and Interventions to Reduce Perinatal HIV Transmission in the United States Available from: URL: https://aidsinfo.nih.gov/contentfiles/lvguidelines/perinatalgl.pdf." ([2018, Mar 27]):
  3. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  4. "Product Information. Evotaz (atazanavir-cobicistat)." Bristol-Myers Squibb, Princeton, NJ.
  5. Cerner Multum, Inc. "Australian Product Information." O 0

References for breastfeeding information

  1. "Product Information. Evotaz (atazanavir-cobicistat)." Bristol-Myers Squibb, Princeton, NJ.
  2. Cerner Multum, Inc. "Australian Product Information." O 0
  3. Panel on Treatment of Pregnant Women with HIV Infection and Prevention of Perinatal Transmission "Recommendations for the Use of Antiretroviral Drugs in Pregnant Women with HIV Infection and Interventions to Reduce Perinatal HIV Transmission in the United States Available from: URL: https://aidsinfo.nih.gov/contentfiles/lvguidelines/perinatalgl.pdf." ([2018, Mar 27]):
  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 -]):
  6. "Infant feeding and transmission of human immunodeficiency virus in the United States." Pediatrics 131 (2013): 391-6

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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