On January 27, 2010, FDA approved revisions to the Prezista (darunavir) product labeling to include the 96 week data from two trials; one trial in treatment-experienced patients (TMC114-C214) and one trial in treatment-naïve patients (TMC114-C211).
Section 6: Adverse Reactions and Section 14 Clinical Studies were updated to reflect the updated 96 week efficacy and safety data. The 96 week efficacy results are summarized briefly below.
Study TMC114-C211 is a randomized, controlled, open-label Phase 3 trial comparing PREZISTA/ritonavir 800/100 mg once daily versus lopinavir/ritonavir 800/200 mg per day (given as a twice daily or as a once daily regimen) in antiretroviral treatment-naïve HIV-1 infected adult subjects. All patients received a fixed background regimen consisting of tenofovir disoproxil fumarate (TDF) 300 mg once daily and emtricitabine 200 mg once daily (FTC). At Week 96, 78% of patients randomized to PREZISTA/ritonavir were virologic successes (HIV RNA < 50 copies/mL) compared to 74% of patients randomized to lopinavir/ritonavir.
Study TMC114-C214 is a randomized, controlled, open-label Phase 3 trial comparing PREZISTA/ritonavir 600/100 mg twice daily versus lopinavir/ritonavir 400/100 mg twice daily in antiretroviral treatment-experienced, lopinavir/ritonavir-naïve HIV-1 infected adult subjects. Both arms used an optimized background regimen consisting of at least 2 antiretrovirals (nucleoside reverse transcriptase inhibitors with or without non-nucleoside reverse transcriptase inhibitors). At Week 96, 58% of patients randomized to PREZISTA/ritonavir were virologic successes (HIV RNA < 50 copies/mL) compared to 52% of patients randomized to lopinavir/ritonavir.
Additional revisions were made to the label and include the following:
The Contraindications section (Section 4) is updated for alfuzosin (Table 2) in order to maintain consistency with the list of contraindicated medications in the ritonavir label:
In Section 6.1 Clinical Trials Experience: Treatment-Naïve Adults, under Less Common Adverse Reactions: drug hypersensitivity, angioedema and urticaria were added.
In Section 6.2 Clinical Trials Experience: Treatment-Experienced Adults, under Less Common Adverse Reactions: urticaria was added.
A new section was added to identify osteonecrosis as an Adverse Drug Reaction (ADR).
Section 6.4 Additional ADRs to PREZISTA/ritonavir identified in adult subjects in other clinical trials
The additional ADR of interest identified from other clinical trials was osteonecrosis.
The Postmarketing Experience Section (Section 6.7) was updated to include: redistribution of body fat and toxic epidermal necrolysis.
Drug Interactions (Section 7), Table 7 was updated with the maraviroc drug interaction data. In summary maraviroc concentrations are increased when co-administered with PREZISTA/ritonavir. When used in combination with PREXISTA/ritonavir, the dose of maraviroc should be 150 mg twice daily.
The Microbiology section (Section 12.4) is updated with additional resistance data and baseline genotype and phenotype virologic analyses and cross-resistance data.
The updated labeling will be posted soon at Drugs@FDA.
PREZISTA, is a protease inhibitor made by Tibotec, Inc.
Richard Klein
Office of Special Health Issues
Food and Drug Administration
Kimberly Struble
Division of Antiviral Drug Products
Food and Drug Administration
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