Advertisement
Advertisement


Press Release

Updates for Prezista (Darunavir) for Use in Pregnant Women

June 18, 2016

 < Prev  |  1  |  2 

8.2 Lactation

Risk Summary

The Centers for Disease Control and Prevention recommend that HIV-infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV.

There are no data on the presence of darunavir in human milk, the effects on the breastfed infant, or the effects on milk production. Darunavir is present in the milk of lactating rats [see Data]. Because of the potential for (1) HIV transmission (in HIV-negative infants), (2) developing viral resistance (in HIV-positive infants) and (3) serious adverse reactions in a breastfed infant, instruct mothers not to breastfeed if they are receiving PREZISTA [see Use in Specific Populations (8.4)].


Animal Data

Studies in rats (with darunavir alone or with ritonavir) have demonstrated that darunavir is secreted in the milk. In the rat pre- and postnatal development study, a reduction in pup body weight gain was observed due to exposure of pups to drug substances via milk. The maximal maternal plasma exposures achieved with darunavir (up to 1000 mg/kg with ritonavir) were approximately 50% of those obtained in humans at the recommended clinical dose with ritonavir.

Section 12 Clinical Pharmacology was updated as follows:

Pregnancy and Postpartum

The exposure to total darunavir and ritonavir after intake of PREZISTA/ritonavir 600/100 mg twice daily and PREZISTA/ritonavir 800/100 mg once daily as part of an antiretroviral regimen was generally lower during pregnancy compared with postpartum (see Tables 14, Table 15 and Figure 1).


Table 14: Pharmacokinetic Results of Total Darunavir After Administration of PREZISTA/ritonavir at 600/100 mg Twice Daily as Part of an Antiretroviral Regimen, During the 2nd Trimester of Pregnancy, the 3rd Trimester of Pregnancy and Postpartum

Pharmacokinetics of total darunavir
(mean ±SD)

2nd Trimester of pregnancy (n=11)*

3rd Trimester of pregnancy (n=11)

Postpartum (6-12 Weeks) (n=11)

Cmax, ng/mL

4601 ± 1125

5111 ± 1517

6499 ± 2411

AUC24h, ng.h/mL

77900 ± 20020

87400 ± 32800

110600 ± 54040

Cmin, ng/mL

1980 ± 839.9

2498 ± 1193

2711 ± 2268

* n=10 for AUC24h

† excluding Cmin value below LLOQ, n=10 for reference

‡ AUC24h is calculated as AUC12h*2


Pharmacokinetics of Total Darunavir (Mean ±SD)


Table 15: Pharmacokinetic Results of Total Darunavir After Administration of PREZISTA/ritonavir at 800/100 mg Once Daily as Part of an Antiretroviral Regimen, During the 2nd Trimester of Pregnancy, the 3rd Trimester of Pregnancy and Postpartum
Pharmacokinetics of total darunavir (mean ±SD) 2nd Trimester of pregnancy (n=16) 3rd Trimester of pregnancy (n=14)

Postpartum (6-12 Weeks) (n=15)

Cmax, ng/mL

4988 ± 1551

5138 ± 1243

7445 ± 1674

AUC24h, ng.h/mL

61303 ± 16232

60439 ± 14052

94529 ± 28572

Cmin, ng/mL*

1193 ± 509

1098 ± 609

1572 ± 1108

* N=12 for postmartum, N=15 for 2nd trimester and N=14 for 3rd trimester


Due to an increase in the unbound fraction of darunavir during pregnancy compared to postpartum, unbound darunavir exposures were less reduced during pregnancy as compared to postpartum. Exposure reductions during pregnancy were greater for the once daily regimen as compared to the twice daily regimen (see Figure 1).


Figure 1: Pharmacokinetic Results (Within-Subject Comparison) of Total and Unbound Darunavir After Administration of Prezista/Ritonavir at 600/100 mg Twice Daily or 800/100 mg Once Daily as Part of an Antiretroviral Regimen, During the 2nd and 3rd Trimester of Pregnancy Compared to Postpartum

Figure 1

Credit: U.S. Food and Drug Administration


Prezista is a product of Janssen Therapeutics.

Complete labeling will be available at Drugs@FDA.

 < Prev  |  1  |  2 



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.
 

No comments have been made.
 

Add Your Comment:
(Please note: Your name and comment will be public, and may even show up in
Internet search results. Be careful when providing personal information! Before
adding your comment, please read TheBody.com's Comment Policy.)

Your Name:


Your Location:

(ex: San Francisco, CA)

Your Comment:

Characters remaining:

Advertisement

The content on this page is free of advertiser influence and was produced by our editorial team. See our content and advertising policies.