Approved June 2006
Prezista (darunavir) is a HIV-1 protease inhibitor (PI). It is designed to disrupt formation of HIV viral particles in infected patients.
Prezista is specifically indicated for the treatment of HIV-1 infections in combination with ritonavir and other antiviral agents in treatment-experienced patients, including patients who have failed prior courses of treatment with other PIs.
Prezista is supplied as an orange, oval-shaped, film-coated tablet for oral administration. The recommended initial dosing regimen is 600 mg twice daily, in combination with 100 mg ritonavir twice daily, with food.
Trials TMC114-C213 and -C202
The accelerated approval of Prezista for the treatment of HIV-1 infections was based on 24-week data from a pair of ongoing, randomized phase IIb trials, dubbed TMC114-C213 and TMC114-C202, which were ongoing at the time of approval. Both trials investigated the efficacy of the drug in antiretroviral treatment-experienced HIV-1 infected adult subjects. In both studies, all subjects demonstrated at least 1 primary PI resistance mutation (D30N, M46I/L, G48V, I50L/V, V82A/F/S/T, I84V, L90M) at patient screening. Subjects in both studies received 600 mg Prezista plus 100 mg ritonavir twice daily plus an optimized background regimen (OBR), including at least 2 nucleoside reverse transcriptase inhibitors (NRTI) with or without enfurvirtide, or a control regimen consisting of an investigator-selected PI regimen plus OBR. The 24 week data set included 318 subjects in TMC114-C213 and 319 subjects in TMC114-C202 who had completed 24 weeks of treatment or discontinued earlier. Pooled data from the two studies indicated that 69.5% of subjects receiving the Prezista regimen achieved virologic response, as measured by a reduction of HIV-1 RNA of at least 1log10 from baseline at week 24, compared to a 21.0% reduction for the control regimen. Mean change from baseline was -1.89 log10 copies/mL for Prezista vs. -0.48 log10 copies/mL for control. In addition, 63% of subjects achieved HIV-1 RNA levels <400 copies/mL, and 45.0% achieved levels < 50 copies/mL at week 24, vs. 19% and 12.1% for control, respectively. 26.0% of subjects were failed to sufficiently respond to treatment on the Prezista regimen, vs. 71% for control. Increase from basline in mean CD4+ cell counts were greater for Prezista (92 cells/mm3) than control 17 cells/mm3).
Trials TMC114-C215 and -C208
Additional data supporting the approval of Prezista were ontained from a pair of non-randomized clinical trials, dubbed TMC114-C215 and TMC114-C208. These data included 24-week results from 246 subjects receiving the 600 mg Prezista/100 mg ritonavir twice daily regimen. These data indicated that 65% of subjects achieved a reduction in HIV-1 RNA of at least 1log10, 57% achieved levels <400 copies/mL, and 40% achieved levels <50 copies/mL, compared to baseline; mean reduction was 1.65log10 copies/mL. Mean CD4+ counts increased by 80 cells/mm3 from baseline at week 20.
Ongoing Study Commitments
Adverse events associated with the use of Prezista may include, but are not limited to, the following:
Administration of Prezista has been associated with incidence of rare, severe, potentially life threatening skin reactions, including erythema multiforme and Stevens-Johnson Syndrome. Patients are advised to monitor their skin for signs of rash while taking Prezista, and treatment should be discontinued if severe rash develops.
In addition, certain laboratory abnormalities were associated with the use of Prezista (laboratory abmormalities are a common concern with PI administration). These included, but were not limited to, eleavations of levels of triglycerides, pancreatic amylase, aspartate aminotransferase, total cholesterol, gamma glutamyl transferase, pancreatic lipase, partial thromboplastin, and alanine aminotransferase, and decreases in white blood cell counts. The magnitude of these abnormalities were generally lower for Prezista than for comparator PI regimens, though not for all measures. Careful monitoring of laboratory values is recommended while on Prezista therapy.
Pharmacokinetic changes have been noted when Prezista is co-administered with other medications, including changes in absoption, total exposure, and elimination of one or both drugs. Some of these interactions may neccessitate adjustment of dose schedule and careful monitoring of tolerability. Affected medications include but are not limited to: the NNRTI HIV medication efavirenz; the PI HIV medications lopinavir and saquinavir; the anticoagulant warfarin; certain antidepressants, including SSRIs; certain antifungal agents; certain statin cholesterol medications; and the narcotic analgesic methadone. It is recommended patients consult their physicians to discuss any potential drug interations or dosing adjustments.
Risks of adverse reactions, some of which are potentially serious or life threatening, have been identified when co-administering Prezista with a number of medications. These include, but are not limited to: the antihistamines astemizole and terfenadine; ergot derivatives including dihydroergotamine, ergonovine, ergotamine, methylergonovine; the gastrointestinal motility agent cisapride; the neuroleptic pimozide; and the hypnotic sedatives midazolam and triazolam. The risks associated with these interactions should be thoroughly discussed with a medical professional, and use of alternative therapies should be considered, as appropriate.
Prezista is an inhibitor of HIV-1 protease, designed to selectively inhibits the cleavage of HIV encoded Gag-Pol polyproteins in infected cells, thereby preventing the formation of mature virus particles.
For additional information regarding Prezista or HIV-1 infections, please visit the Prezista web page.
The Prezista (darunavir) drug information shown above is licensed from Thomson CenterWatch. The information provided here is for general educational purposes only and does not constitute medical or pharmaceutical advice which should be sought from qualified medical and pharmaceutical advisers.