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Press Release

Updates for Prezista (Darunavir) for Use in Pregnant Women

June 18, 2016

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On June 17, 2016, FDA approved updates to the Prezista (darunavir) for use in pregnant women. The major changes are outlined below.

Section 2: DOSAGE AND ADMINISTRATION is revised with addition of testing and dosing in pregnant women.


2.1 Testing Prior to Initiation of PREZISTA/Ritonavir

  • In treatment-experienced patients, treatment history genotypic and/or phenotypic testing is recommended prior to initiation of therapy with PREZISTA/ritonavir to assess drug susceptibility of the HIV-1 virus
  • Monitor serum liver chemistry tests before and during therapy with PREZISTA/ritonavir.


2.4 Recommended Dosage During Pregnancy

The recommended dosage in pregnant patients is PREZISTA 600 mg taken with ritonavir 100 mg twice daily with food.

PREZISTA 800 mg taken with ritonavir 100 mg once daily should only be considered in certain pregnant patients who are already on a stable PREZISTA 800 mg with ritonavir 100 mg once daily regimen prior to pregnancy, are virologically suppressed (HIV-1 RNA less than 50 copies per mL), and in whom a change to twice daily PREZISTA 600 mg with ritonavir 100 mg may compromise tolerability or compliance.

Section 8.1 Pregnancy and 8.2 Lactation was revised as follows


8.1 Pregnancy

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to PREZISTA during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) 1-800-258-4263.


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Risk Summary

Available limited data from the APR show no difference in rate of overall birth defects for darunavir (2.7%) compared with the background rate for major birth defects of 2.7% in a U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP) [see Data]. The rate of miscarriage is not reported in the APR. The estimated background rate of miscarriage in clinically recognized pregnancies in the U.S. general population is 15-20%. The background risk of major birth defects and miscarriage for the indicated population is unknown.

Studies in animals did not show evidence of developmental toxicity. Exposures (based on AUC) in rats were 3-fold higher, whereas in mice and rabbits, exposures were lower (less than 1-fold) than human exposures at the recommended daily dose [see Data].


Clinical Considerations

The recommended dosage in pregnant patients is PREZISTA 600 mg taken with ritonavir 100 mg twice daily with food.

PREZISTA 800 mg taken with ritonavir 100 mg once daily should only be considered in certain pregnant patients who are already on a stable PREZISTA 800 mg with ritonavir 100 mg once daily regimen prior to pregnancy, are virologically suppressed (HIV-1 RNA less than 50 copies per mL), and in whom a change to twice daily PREZISTA 600 mg with ritonavir 100 mg may compromise tolerability or compliance.


Human Data

PREZISTA/ritonavir (600/100 mg twice daily or 800/100 mg once daily) in combination with a background regimen was evaluated in a clinical trial of 34 pregnant women during the second and third trimesters, and postpartum. The pharmacokinetic data demonstrate that exposure to darunavir and ritonavir as part of an antiretroviral regimen was lower during pregnancy compared with postpartum (6-12 weeks). Virologic response was preserved throughout the trial period in both arms. No mother to child transmission occurred in the infants born to the 29 subjects who stayed on the antiretroviral treatment through delivery. PREZISTA/ritonavir was well tolerated during pregnancy and postpartum. There were no new clinically relevant safety findings compared with the known safety profile of PREZISTA/ritonavir in HIV-1 infected adults .

Based on prospective reports to the APR (through July 2015) of 532 live births following exposure to darunavir-containing regimens during pregnancy (including 333 exposed in the first trimester and 199 exposed in the second/third trimester), there was no difference in rate of overall birth defects for darunavir compared with the background rate for major birth defects in a U.S. reference population of the MACDP.

The prevalence of birth defects in live births was 2.7% (95% CI: 1.2% to 5.1%) with first trimester exposure to darunavir containing regimens and 1.5% (95% CI: 0.3% to 4.4%) with second/third trimester exposure to darunavir containing regimens.


Animal Data

Reproduction studies conducted with darunavir showed no embryotoxicity or teratogenicity in mice (doses up to 1000 mg/kg from gestation day (GD) 6-15 with darunavir alone) and rats (doses up to 1000 mg/kg from GD 7-19 in the presence or absence of ritonavir) as well as in rabbits (doses up to 1000 mg/kg/day from GD 8-20 with darunavir alone). In these studies, darunavir exposures (based on AUC) were higher in rats (3-fold), whereas in mice and rabbits, exposures were lower (less than 1-fold) compared to those obtained in humans at the recommended clinical dose of darunavir boosted with ritonavir.

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This article was provided by U.S. Food and Drug Administration. Visit the FDA's website to find out more about their activities and publications.
 

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