Pharmacologic class: Non-nucleoside reverse transcriptase inhibitor (NNRTI)
Active ingredient: Rilpivirine 25 mg; tablets.
Indication: HIV-1 infection in antiretroviral treatment-naïve adult patients, in combination with other antiretroviral agents.
Pharmacology: Rilpivirine is a diarylpyrimidine NNRTI of HIV-1 and inhibits HIV-1 replication by noncompetitive inhibition of HIV-1 reverse transcriptase.
Clinical trials: The efficacy of rilpivirine is based on the analyses of 48-week data from two Phase 3 trials TMC278-C209 and TMC278-C215 and from a 96-week (with extension to 192 weeks) Phase 2b trial in antiretroviral treatment-naïve adults.
Antiretroviral treatment-naïve HIV-1 infected subjects enrolled in the Phase 3 trials had a plasma HIV-1 RNA ≥5,000 copies/mL and were screened for susceptibility to nucleos(t)ide reverse transcriptase inhibitors (N[t]RTIs) and for absence of specific NNRTI resistance-associated mutations (RAMs).
In TMC278-C209, the background regimen (BR) was tenofovir disoproxil fumarate + emtricitabine. In TMC278-C215, the BR consisted of one of the following: tenofovir disoproxil fumarate + emtricitabine or zidovudine + lamivudine or abacavir + lamivudine. Based on the pooled data from both trials at 48 weeks, the proportion of subjects with <50 HIV-1 RNA copies/mL receiving rilpivirine 25 mg (N=686) compared with subjects receiving efavirenz (N=682) was 83% and 80%, respectively. The mean CD4+ cell count increase from baseline was 192 cells/mm3 for rilpivirine-treated subjects and 176 cells/mm3 for efavirenz-treated subjects.
Study TMC278-C204 enrolled 368 HIV-1-infected treatment-naïve adult subjects who had a plasma HIV-1 RNA ≥5,000 copies/mL, previously received two or fewer weeks of treatment with an N(t)RTI or protease inhibitor, had no prior use of NNRTIs, and were screened for susceptibility to N(t)RTI and for absence of specific NNRTI RAMs. At 96 weeks, the proportion of subjects with <50 HIV-1 RNA copies/mL receiving rilpivirine 25 mg (N=93) compared with subjects receiving efavirenz (N=89) was 76% and 71%, respectively. The mean increase from baseline in CD4+ counts was 146 x 106 cells/mm3 in subjects receiving rilpivirine 25 mg and 160 x 106 cells/mm3 in subjects receiving efavirenz. At 192 weeks, 63% of subjects who originally received 25 mg once daily achieved HIV RNA <50 copies/mL compared to 61% of subjects in the control group.
Adults: Take with a meal. 25 mg once daily.
Children: Not recommended.
Contraindications: Concomitant carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, rifampin, rifapentine, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole, dexamethasone (more than single dose), St. John’s wort.
Warnings/Precautions: May prolong QTc interval with supratherapeutic doses. Severe renal or hepatic impairment. Pregnancy (Cat. B). Nursing mothers: not recommended.
Interactions: Concomitant NNRTIs: not recommended. Potentiated by CYP3A inhibitors. Antagonized by CYP3A inducers (see Contraindications). May antagonize azole antifungals (monitor for breakthrough fungal infections), methadone (monitor). Separate antacids (by at least two hours before or at least four hours after) and H2-receptor antagonists (by at least 12 hours before or four hours after) rilpivirine; drugs that increase gastric pH may result in decreased plasma concentrations. Caution with drugs with a known risk for torsades de pointes.
Adverse reactions: Depression, insomnia, headache, rash; fat redistribution, immune reconstitution syndrome.
How supplied: Tabs — 30
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