Prezista (Darunavir Ethanolate) - Summary

PREZISTA SUMMARY

PREZISTA™ (darunavir) is an inhibitor of the human immunodeficiency virus (HIV) protease. PREZISTA™ (darunavir), in the form of darunavir ethanolate, has the following chemical name: [(1 S,2 R)-3-[[(4-aminophenyl)sulfonyl](2-methylpropyl)amino]-2-hydroxy-1- (phenylmethyl)propyl]-carbamic acid (3 R,3a S,6a R)-hexahydrofuro[2,3- b ]furan-3-yl ester monoethanolate.

PREZISTA, co-administered with 100 mg ritonavir (PREZISTA/rtv), and with other antiretroviral agents, is indicated for the treatment of human immunodeficiency virus (HIV) infection in antiretroviral treatment-experienced adult patients, such as those with HIV-1 strains resistant to more than one protease inhibitor.

This indication is based on Week 24 analyses of plasma HIV RNA levels and CD4+ cell counts from 2 controlled trials of PREZISTA/rtv in combination with other antiretroviral drugs. Both studies were conducted in clinically advanced, treatment-experienced (NRTIs, NNRTIs, and PIs) adult patients with evidence of HIV-1 replication despite ongoing antiretroviral therapy.

The following points should be considered when initiating therapy with PREZISTA/rtv:

• Treatment history and, when available, genotypic or phenotypic testing, should guide the use of PREZISTA/rtv (see MICROBIOLOGY).
• The use of other active agents with PREZISTA/rtv is associated with a greater likelihood of treatment response (see MICROBIOLOGY and INDICATIONS AND USAGE, Description of Clinical Studies).
• The risks and benefits of PREZISTA/rtv have not been established in treatment-naïve adult patients or pediatric patients.

NEWS HIGHLIGHTS

Published Studies Related to Prezista (Darunavir)

Characterization of virologic failure patients on darunavir/ritonavir in treatment-experienced patients. [2009.09.10]
OBJECTIVE: Characterization of resistance development in virologic failure patients on the protease inhibitor darunavir administered with low-dose ritonavir (DRV/r) in the 48-week analysis of TMC114/r In Treatment-experienced pAtients Naive to lopinavir (TITAN). DESIGN: TITAN is a randomized, controlled, open-label, phase III, noninferiority trial comparing the efficacy and safety of DRV/r with that of lopinavir/ritonavir (LPV/r) in HIV-1-infected, treatment-experienced, LPV-naive patients. The primary endpoint was the proportion of patients with HIV-1 RNA less than 400 copies/ml at week 48... CONCLUSION: In treatment-experienced, LPV-naive patients, the overall virologic failure rate in the DRV/r arm was low and was associated with limited resistance development. These findings showed that the use of DRV/r in earlier lines of treatment was less likely to lead to cross-resistance to other protease inhibitors compared with LPV/r. 2009 Wolters Kluwer Health | Lippincott Williams & Wilkins

Effect of ritonavir-boosted tipranavir or darunavir on the steady-state pharmacokinetics of elvitegravir. [2008.10.01]
OBJECTIVE: Elvitegravir (EVG) is in phase 3 development in combination with ritonavir (RTV)-boosted protease inhibitors in treatment-experienced, HIV-infected patients. Two studies evaluated pharmacokinetic (PK) interactions among EVG and RTV-boosted tipranavir (TPV/r) or darunavir (DRV/r)... CONCLUSIONS: The PK of EVG and TPV or DRV were not altered after coadministration of EVG with TPV/r or DRV/r. EVG PK was similar with varied RTV doses of 100 mg once daily, 100 mg twice daily, or 200 mg twice daily. EVG can be added to TPV/r or DRV/r regimens without dose adjustment.

Efficacy of once-daily darunavir/ritonavir 800/100 mg in HIV-infected, treatment-experienced patients with no baseline resistance-associated mutations to darunavir. [2008.10.01]
OBJECTIVE: The objective of this study was to examine the potential of once-daily dosing with darunavir/ritonavir 800/100 mg in a HIV-infected, treatment-experienced patient population with no baseline darunavir resistance-associated mutations (RAMs)... CONCLUSIONS: Treatment-experienced, HIV-infected patients with no baseline darunavir RAMs achieved similar high responses with darunavir/r 800/100 mg once daily and 600/100 mg twice daily. This suggests that once-daily darunavir/r 800/100 mg therapy, which has been shown effective in treatment-naive patients and is currently being studied in treatment-experienced patients, shows potential in patients with no darunavir RAMs.

[Darunavir as first-line therapy. The TITAN study] [2008.10]
Lopinavir/ritonavir (LPV/r) has been the gold standard in first line rescue treatment for many years... With the results of the TITAN study, DRV/r must be considered the new gold standard in first line rescue, at least in those patients with a primary mutation in the protease.

[Darunavir in treatment-naive patients. The ARTEMIS study] [2008.10]
The ARTEMIS study compared the efficacy of darunavir/ritonavir at once-daily doses of 800/100 mg versus once- or twice-daily doses of lopinavir/ritonavir, together with 300 mg of tenofovir and 200 mg of emtricitabine, both in once-daily doses, in treatment-naive patients... Once-daily darunavir/ritonavir may be an option in first-line antiretroviral therapy, with the added advantage of a reduced dose of ritonavir and high efficacy in patients with elevated viral loads.

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Clinical Trials Related to Prezista (Darunavir)

TMC114-C202: A Study of Safety, Efficacy, and Tolerability of TMC114 and Low Dose Ritonavir in HIV-1 Infected Patients [Completed]
The purpose of this study is to determine the effectiveness, safety, and tolerability (how well the body stands the drug) of an investigational protease inhibitor (PI) called TMC114 given with low dose ritonavir.

GRACE: A Study to Compare the Effectiveness, Safety and Tolerability of PREZISTA (Darunavir)/Ritonavir by Gender and Race When Administered With Other Antiretroviral Medications in Human Immunodeficiency Virus (HIV) Positive Women and Men. [Active, not recruiting]
The purpose of this study is to evaluate any differences in the effectiveness, safety, and tolerability of PREZISTA (darunavir) 600 mg, administered with ritonavir 100 mg twice a day on virologic response (defined as a viral load of < 50 copies/mL) over a 48-week treatment period in HIV-positive women and men. Additional antiretroviral agents will also be administered and will be chosen by the Investigator based on resistance testing and prior treatment history (referred to as the Optimized Background Regimen (OBR)).

TMC114-C213: A Phase II Randomized, Controlled, Partially Blinded Trial to Investigate Dose-Response of TMC114/RTV in 3-Class-Experienced HIV-1 Infected Patients, Followed by an Open-Label Period on the Recommended Dose of TMC114/RTV. [Completed]
The purpose of this study is to determine the antiviral activity, safety and tolerability of TMC114, formulated as an oral tablet, and administered with a low dose of ritonavir

A Pediatric Trial to Provide Dose Recommendation of TMC114/Rtv in HIV-1 Infected Children and Adolescents [Active, not recruiting]
The purpose of this study is to evaluate pharmacokinetics, short-term safety, tolerability and antiviral activity to support dose recommendations of TMC114 administered in combination with low-dose ritonavir and other antiretroviral (ARV) agents in treatment-experienced, HIV-1 infected pediatric patients aged from 6-17 years.

TMC114-C227: A Study to Evaluate the Effectiveness and Safety of TMC114 (Darunavir) With a Low Dose of Ritonavir as Monotherapy (no Other Anti-HIV Drugs Will be Given) in Patients Who Have Never Been Treated With Antiretrovirals (Anti-HIV Drugs) Previously [Terminated]
This is an open label study (no placebos are used; all patients will receive the true medication) to evaluate the effectiveness of TMC114/rtv in treatment naïve (never previously received anti-HIV drugs), HIV 1 infected patients.

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