The following points should be considered when initiating therapy with COMPLERA in patients with no antiretroviral treatment history (1, 12.4, 14):

• More rilpivirine-treated subjects with HIV-1 RNA greater than 100,000 copies/mL at the start of therapy experienced virologic failure (HIV-1 RNA ≥50 copies/mL) compared to rilpivirine-treated subjects with HIV-1 RNA less than or equal to 100,000 copies/mL.
• Regardless of HIV-1 RNA level at the start of therapy, more rilpivirine-treated subjects with CD4+ cell count less than 200 cells/mm3 at the start of therapy experienced virologic failure compared to subjects with CD4+ cell count greater than or equal to 200 cells/mm3.
• The observed virologic failure rate in rilpivirine-treated subjects conferred a higher rate of overall treatment resistance and cross-resistance to the NNRTI class compared to efavirenz.
• More subjects treated with rilpivirine developed tenofovir- and lamivudine/emtricitabine-associated resistance compared to efavirenz.

The efficacy of COMPLERA was established in patients who were virologically-suppressed (HIV-1 RNA <50 copies/mL) on stable ritonavir-boosted protease inhibitor-containing regimen. The following points should be met when considering replacing the current regimen with COMPLERA in virologically-suppressed (HIV-1 RNA <50 copies/mL) patients (1,14):

• Patients should have no history of virologic failure.
• Patients should have been suppressed (HIV-1 RNA <50 copies/mL) for at least 6 months prior to switching therapy.
• Patients should currently be on their first or second antiretroviral regimen prior to switching therapy.
• Patients should have no current or past history of resistance to any of the three components of COMPLERA.

Additional monitoring of HIV-1 RNA and regimen tolerability is recommended after replacing therapy to assess for potential virologic failure or rebound. (1)
DOSAGE AND ADMINISTRATION

• Dose in patients 12 years of age and older: One tablet (containing 200 mg of emtricitabine, 25 mg of rilpivirine, and 300 mg of tenofovir disoproxil fumarate) taken once daily with food. (2)
• Dose in renal impairment: Should not be administered in patients with estimated creatinine clearance below 50 mL per minute. (2)
• With rifabutin coadministration, an additional 25 mg tablet of rilpivirine (Edurant) once per day is recommended to be taken concomitantly with COMPLERA and with a meal for the duration of the rifabutin coadministration. (2,7.5,12.3)

Coadministration of COMPLERA is contraindicated with drugs where significant decreases in rilpivirine plasma concentrations may occur, which may result in loss of virologic response and possible resistance and cross-resistance. (4)
WARNINGS AND PRECAUTIONS

• Skin and Hypersensitivity Reactions: Severe skin and hypersensitivity reactions have been reported during postmarketing experience, including cases of Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS). Immediately discontinue treatment if hypersensitivity or rash with systemic symptoms or elevations in hepatic serum biochemistries develops and closely monitor clinical status, including hepatic serum biochemistries. (5.3)
• New onset or worsening renal impairment: Can include acute renal failure and Fanconi syndrome. Assess estimated creatinine clearance before initiating treatment with COMPLERA. In patients at risk for renal dysfunction, assess estimated creatinine clearance, serum phosphorus, urine glucose, and urine protein before initiating treatment with COMPLERA and periodically during treatment. Avoid administering COMPLERA with concurrent or recent use of nephrotoxic drugs. (5.4)
• Caution should be given to prescribing COMPLERA with drugs that may reduce the exposure of rilpivirine. (5.5)
• Caution should be given to prescribing COMPLERA with drugs with a known risk of Torsade de Pointes. (5.5)
• Depressive disorders: Severe depressive disorders have been reported. Immediate medical eva luation is recommended for severe depressive disorders. (5.6)
• Hepatotoxicity: Hepatic adverse events have been reported in patients receiving a rilpivirine-containing regimen. Monitor liver-associated tests before and during treatment with COMPLERA in patients with underlying hepatic disease or marked elevations in liver-associated tests. Also consider monitoring liver-associated tests in patients without risk factors. (5.7)
• Decreases in bone mineral density (BMD): Consider monitoring BMD in patients with a history of pathologic fracture or other risk factors of osteoporosis or bone loss. (5.8)
• Coadministration with other products: Do not use with drugs containing emtricitabine or tenofovir disoproxil fumarate, including ATRIPLA, EMTRIVA, STRIBILD, TRUVADA, and VIREAD, or with drugs containing lamivudine. Do not administer in combination with HEPSERA. Do not coadminister in combination with rilpivirine (Edurant) unless required for dose adjustment when coadministered with rifabutin. (5.9)
• Redistribution/accumulation of body fat: Observed in patients receiving antiretroviral therapy. (5.10)
• Immune reconstitution syndrome: May necessitate further eva luation and treatment. (5.11)

Most common adverse reactions to rilpivirine (incidence greater than or equal to 2%, Grades 2–4) are depressive disorders, insomnia, and headache. (6.1)

Most common adverse reactions to emtricitabine and tenofovir disoproxil fumarate (incidence greater than or equal to 10%) are diarrhea, nausea, fatigue, headache, dizziness, depression, insomnia, abnormal dreams, and rash. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Gilead Sciences, Inc. at 1-800-GILEAD-5 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

• COMPLERA is a complete regimen for the treatment of HIV-1 infection; therefore, COMPLERA should not be administered with other antiretroviral medications for treatment of HIV-1 infection.
• CYP3A4 inducers or inhibitors: Drugs that induce or inhibit CYP3A4 may affect the plasma concentrations of rilpivirine. (7.1)
• Drugs that increase gastric pH: Drugs that increase gastric pH may decrease plasma concentrations of rilpivirine. (7.2)

• Pregnancy: Use during pregnancy only if the potential benefit justifies the potential risk. (8.1)
• Nursing mothers: Women infected with HIV should be instructed not to breastfeed due to the potential for HIV transmission. (8.3)
• Pediatrics: Safety and effectiveness have not been established in patients less than 12 years of age. (8.4)