December 27, 2004 The Clinical Pharmacology section of the Crixivan (indinavir)
label has been revised to include pharmacokinetic data from a study (PACTG 358)
in HIV-ifected pregnant women. Results from this study show substantially
reduced indinavir concentrations in women at weeks 30-32 weeks gestation
compared to postpartum. Based on these data, the Precautions Sections now
states that indinavir is not recommended in HIV-infected pregnant patients.
Revisions to the Package Insert
1. The following was added to the CLINICAL PHARMACOLOGY:
Pharmacokinetics: Pregnant Patients section:
"Pregnant Patients: The optimal dosing regimen for use of
indinavir in pregnant patients has not been established. A CRIXIVAN dose of
800 mg every 8 hours (with zidovudine 200 mg every 8 hours and lamivudine
150 mg twice a day) has been studied in 16 HIV-infected pregnant patients at
14 to 28 weeks of gestation at enrollment (study PACTG 358). The mean
indinavir plasma AUC0-8hr at weeks 30-32 of gestation (n=11) was 9231 nM*hr,
which is 74% (95% CI: 50%, 86%) lower than that observed 6 weeks postpartum.
Six of these 11 (55%) patients had mean indinavir plasma concentrations 8
hours post-dose (Cmin) below assay threshold of reliable quantification. The
pharmacokinetics of indinavir in these 11 patients at 6 weeks postpartum
were generally similar to those observed in non-pregnant patients in another
study (see PRECAUTIONS, Pregnancy)."
2. The following was added to the PRECAUTIONS: Pregnancy:
Pregnancy Category C section:
"A CRIXIVAN dose of 800 mg every 8 hours (with zidovudine
200 mg every 8 hours and lamivudine 150 mg twice a day) has been studied in
16 HIV-infected pregnant patients at 14 to 28 weeks of gestation at
enrollment (study PACTG 358). Given the substantially lower antepartum
exposures observed and the limited data in this patient population,
indinavir use is not recommended in HIV-infected pregnant patients (see
CLINICAL PHARMACOLOGY, Pregnant Patients)."
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Jeffrey Murray
Division of Antiviral Drug Products
Food and Drug Administration
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