These highlights do not include all the information needed to use COMPLERA safely and effectively. See full prescribing information for COMPLERA.
COMPLERA ® (emtricitabine, rilpivirine, tenofovir disoproxil fumarate) tablets, for oral use
Initial U.S. Approval: 2011 WARNING: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B See full prescribing information for complete boxed warning.
Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including tenofovir disoproxil fumarate, a component of COMPLERA. (5.1)
COMPLERA is not approved for the treatment of chronic hepatitis B virus (HBV) infection. Severe acute exacerbations of hepatitis B have been reported in patients coinfected with HIV-1 and HBV who have discontinued EMTRIVA or VIREAD, two of the components of COMPLERA. Hepatic function should be monitored closely in these patients. If appropriate, initiation of anti-hepatitis B therapy may be warranted. (5.2)
COMPLERA, a combination of two nucleoside analog HIV-1 reverse transcriptase inhibitors (emtricitabine and tenofovir disoproxil fumarate) and one non-nucleoside reverse transcriptase inhibitor (rilpivirine), is indicated for use as a complete regimen for the treatment of HIV-1 infection in (1) adult patients with no antiretroviral treatment history and with HIV-1 RNA less than or equal to 100,000 copies/mL at the start of therapy, and (2) in certain virologically-suppressed (HIV-1 RNA <50 copies/mL) adult patients on a stable antiretroviral regimen at start of therapy in order to replace their current antiretroviral treatment regimen (see below). (1, 14)
The following points should be considered when initiating therapy with COMPLERA in adult 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) adults (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)
COMPLERA is not recommended for patients less than 18 years of age. (1, 8.4) DOSAGE AND ADMINISTRATION
Recommended dose: 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)
DOSAGE FORMS AND STRENGTHS
Tablets: 200 mg of emtricitabine, 25 mg of rilpivirine, and 300 mg of tenofovir disoproxil fumarate. (3) CONTRAINDICATIONS
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, rilpivirine or tenofovir disoproxil fumarate including ATRIPLA, EMTRIVA, STRIBILD, TRUVADA, 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)
ADVERSE REACTIONS
Most common adverse drug reactions to rilpivirine (incidence greater than or equal to 2%, Grades 2–4) are depressive disorders, insomnia, and headache. (6.1)
Most common adverse drug reactions to emtricitabine and tenofovir disoproxil fumarate (incidence ≥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
DRUG INTERACTIONS
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)
USE IN SPECIFIC POPULATIONS
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: Not recommended for patients less than 18 years of age. (8.4)
See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.
Sections or subsections omitted from the full prescribing information are not listed.
1 INDICATIONS AND USAGE
COMPLERA, a combination of two nucleoside analog HIV 1 reverse transcriptase inhibitors (emtricitabine and tenofovir disoproxil fumarate) and one non-nucleoside reverse transcriptase inhibitor (rilpivirine), is indicated for use as a complete regimen for the treatment of HIV-1 infection in adult patients with no antiretroviral treatment history and with HIV-1 RNA less than or equal to 100,000 copies/mL at the start of therapy, and in certain virologically-suppressed (HIV-1 RNA <50 copies/mL) adult patients on a stable antiretroviral regimen at start of therapy in order to replace their current antiretroviral treatment regimen (see below).
The following points should be considered when initiating therapy with COMPLERA in adult patients with no antiretroviral treatment history:
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 [See Clinical Studies (14)].
Regardless of HIV-1 RNA level at the start of therapy, more rilpivirine-treated subjects with CD4+ cell count less than 200 cells/mm3 experienced virologic failure compared to rilpivirine-treated subjects with CD4+ cell count greater than or equal to 200 cells/mm3 [See Clinical Studies (14)].
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 [See Microbiology (12.4)].
More subjects treated with rilpivirine developed tenofovir and lamivudine/emtricitabine associated resistance compared to efavirenz [See Microbiology (12.4)].
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 adults [See Clinical Studies (14)]:
Patients should have no history of virologic failure.
Patients should have been stably 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.
Adults: The recommended dose of COMPLERA is one tablet taken orally once daily with food [See Clinical Pharmacology (12.3)].
Renal Impairment: Because COMPLERA is a fixed-dose combination, it should not be prescribed for patients requiring dose reduction such as those with moderate or severe renal impairment (estimated creatinine clearance below 50 mL per minute).
Rifabutin Coadministration: If COMPLERA is coadministered with rifabutin, 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 [See Drug Interactions (7.5) and Clinical Pharmacology (12.3)].
3 DOSAGE FORMS AND STRENGTHS
COMPLERA is available as tablets. Each tablet contains 200 mg of emtricitabine (FTC), 27.5 mg of rilpivirine hydrochloride (equivalent to 25 mg of rilpivirine) and 300 mg of tenofovir disoproxil fumarate (tenofovir DF or TDF, equivalent to 245 mg of tenofovir disoproxil).
The tablets are purplish-pink, capsule-shaped, film-coated, debossed with "GSI" on one side and plain-faced on the other side.
4 CONTRAINDICATIONS
COMPLERA should not be coadministered with the following drugs, as significant decreases in rilpivirine plasma concentrations may occur due to CYP3A enzyme induction or gastric pH increase, which may result in loss of virologic response and possible resistance to COMPLERA or to the class of NNRTIs [See Drug Interactions (7) and Clinical Pharmacology (12.3)]:
the anticonvulsants carbamazepine, oxcarbazepine, phenobarbital, phenytoin
the antimycobacterials rifampin, rifapentine
proton pump inhibitors, such as dexlansoprazole, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole
the glucocorticoid systemic dexamethasone (more than a single dose)
