emtricitabine/rilpivirine/tenofovir DF (Rx)

Brand and Other Names:Complera
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Dosing & Uses

AdultPediatric

Dosing Forms & Strengths

emtricitabine/rilpivirine/tenofovir DF (ie, tenofovir disoproxil fumarate)

tablet

  • 200mg/25mg/300mg

HIV Infection

Indicated as a complete regimen for treatment of HIV-1 infection in treatment-naïve adults with HIV-1 RNA ≤100,000 copies/mL at start of therapy and in certain virologically suppressed (HIV-1 RNA <50 copies/mL) patients on a stable antiretroviral therapy (ART)

1 tablet (emtricitabine 200 mg/rilpivirine 25 mg/tenofovir 300 mg) PO qDay with a meal

Dosage Modifications

Coadministration with rifabutin

  • Add 1 tablet of rilpivirine 25 mg with Complera for the duration of rifabutin coadministration

Renal impairment

  • Mild (CrCl ≥50 mL/min): No dosage adjustment necessary
  • Moderate or severe (CrCl <50 mL/min): Not recommended

Hepatic impairment

  • Mild to moderate (Child-Pugh class A or B): No dosage adjustments necessary
  • Severe (Child-Pugh class C): Not studied

Dosing Considerations

Prior to initiation and during treatment

  • Test for hepatitis B virus (HBV) infection
  • Assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients
  • Assess serum phosphorus in chronic kidney disease patients

Limitation of use

  • Rilpivirine-treated patients who had >100,000 copies/mL HIV-1 RNA at the start of therapy experienced more virologic failure (HIV-1 RNA ≥50 copies/mL) compared with rilpivirine-treated patients with ≤100,000 copies/mL

Dosage Forms & Strengths

emtricitabine/rilpivirine/tenofovir DF (ie, tenofovir disoproxil fumarate)

tablet

  • 200mg/25mg/300mg

HIV Infection

Indicated as a complete regimen for treatment of HIV-1 infection in treatment-naïve adults and adolescents (≥12 yr who weigh ≥35 kg) with HIV-1 RNA ≤100,000 copies/mL and in certain virologically suppressed (HIV-1 RNA <50 copies/mL) patients on a stable ART regimen at start of therapy in order to replace their current ART regimen

<12 years: Safety and efficacy not established

≥12 years and weight ≥35 kg: 1 tablet (emtricitabine 200 mg/rilpivirine 25 mg/tenofovir 300 mg) PO qDay with a meal

Dosage Modifications

Coadministration with rifabutin

  • Add 1 tablet of rilpivirine 25 mg with Complera for the duration of rifabutin coadministration

Renal impairment

  • Mild (CrCl ≥50 mL/min): No dosage adjustment necessary
  • Moderate or severe (CrCl <50 mL/min): Not recommended

Hepatic impairment

  • Mild to moderate (Child-Pugh class A or B): No dosage adjustments necessary
  • Severe (Child-Pugh class C): Not studied

Dosing Considerations

Prior to initiation and during treatment

  • Test for HBV infection
  • Assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients
  • Assess serum phosphorus in chronic kidney disease patients

Limitation of use

  • Rilpivirine-treated patients who had >100,000 copies/mL HIV-1 RNA at the start of therapy experienced more virologic failure (HIV-1 RNA ≥50 copies/mL) compared with rilpivirine-treated patients with ≤100,000 copies/mL
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Interactions

Interaction Checker

and emtricitabine/rilpivirine/tenofovir DF

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            Adverse Effects

            >10% (rilpivirine)

            Increased ALT (Grade 1: 16%)

            Increased AST (Grade 1: 13%)

            Increased total cholesterol (Grade 1: 13%)

            Increased LDL cholesterol (Grade 1: 11%)

            >10% (emtricitabine and tenofovir)

            Diarrhea

            Nausea

            Fatigue

            Headache

            Dizziness

            Depression

            Insomnia

            Abnormal dreams

            Rash

            1-10% (rilpivirine)

            Increased creatinine (5%)

            Increased total bilirubin (Grade 1: 5%)

            Headache (2%)

            Insomnia (2%)

            Dizziness (1%)

            Nausea (1%)

            Depressive disorder (1%)

            Abnormal dreams (1%)

            Rash (1%)

            1-10% (emtricitabine or tenofovir)

            Abdominal pain

            Dyspepsia

            Vomiting

            Fever

            Pain

            Nasopharyngitis

            Pneumonia

            Sinusitis

            Upper respiratory tract infection

            Arthralgia

            Back pain

            Myalgia

            Paresthesia

            Peripheral neuropathy (including peripheral neuritis and neuropathy)

            Anxiety

            Increased cough

            Rhinitis

            Skin discoloration (hyperpigmentation of palms/soles)

            Postmarketing Reports

            Rilpivirine

            • Renal and urinary disorders: Nephrotic syndrome
            • Skin and subcutaneous tissue disorders: Severe skin and hypersensitivity reactions including DRESS (Drug Reaction with Eosinophilia and Systemic Symptoms)

            Tenofovir

            • Immune system disorders: Allergic reaction, including angioedema
            • Metabolism and nutrition disorders: Lactic acidosis, hypokalemia, hypophosphatemia
            • Respiratory, thoracic, and mediastinal disorders: Dyspnea
            • Gastrointestinal disorders: Pancreatitis, increased amylase, abdominal pain
            • Hepatobiliary disorders: Hepatic steatosis, hepatitis, increased liver enzymes (most commonly AST, ALT gamma GT)
            • Skin and subcutaneous tissue disorders: Rash
            • Musculoskeletal and connective tissue disorders: Rhabdomyolysis, osteomalacia
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            Warnings

            Black Box Warnings

            Posttreatment acute exacerbation of hepatitis B

            • Severe acute exacerbations of hepatitis B reported with coinfection of HBV and HIV-1 and have discontinued emtricitabine (FTC) or tenofovir, which are components of Complera
            • Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months after discontinuing treatment in patients who are coinfected with HIV-1 and HBV; if appropriate, initiation of antihepatitis B therapy may be warranted

            Contraindications

            Hypersensitivity

            Coadministration of the following drugs

            • Anticonvulsants (eg, carbamazepine, oxcarbazepine, phenobarbital, phenytoin)
            • Antimycobacterials (eg, rifabutin, rifampin, rifapentine)
            • Glucocorticoid systemic dexamethasone (more than a single dose)
            • St. John’s wort
            • Proton pump inhibitors (eg, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole)

            Cautions

            Lactic acidosis/severe hepatomegaly with steatosis

            Coinfection with HIV-1 and HBV (see Black Box Warnings)

            Severe skin and hypersensitivity reactions reported, including cases of drug reaction with eosinophilia and systemic symptoms (DRESS) with rilpivirine (RPV)-containing regimens; discontinue therapy immediately if signs or symptoms of severe skin or hypersensitivity reactions develop, including but not limited to, severe rash or rash accompanied by fever, blisters, mucosal involvement, conjunctivitis, facial edema, angioedema, hepatitis, or eosinophilia; monitor and initiate appropriate therapy

            Hepatic adverse events reported in patients receiving an RPV-containing regimen; a few cases of hepatic toxicity reported in adults who had no preexisting hepatic disease or other identifiable risk factors

            Renal impairment, including cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), with tenofovir DF (TDF)

            Redistribution/accumulation of body fat observed in patients receiving antiretroviral therapy

            May increase risk for immune reconstitution syndrome

            Severe depressive disorders reported; immediate medical evaluation recommended

            Bone effects of tenofovir DF

            • Bone mineral density may decrease
            • Osteomalacia associated with proximal renal tubulopathy, manifested as bone pain or pain in extremities and which may contribute to fractures, reported

            Drug interactions overview

            • Use of drugs that impair renal function or compete for active tubular secretion may increase serum concentrations of FTC, tenofovir, and/or other renally eliminated drugs
            • Limited information available on potential pharmacodynamic interactions between RPV and drugs that prolong QTc interval; consider alternatives to Complera when coadministered with a drug with a known risk of torsade de pointes
            • Complera is a complete regimen; coadministration with other antiretroviral medications for treatment of HIV-1 infection is not recommended
            • Rilpivirine
              • Rilpivirine is a CYP3A4 substrate
              • Coadministration with CYP3A inducers may decrease plasma levels of RPV and loss of virologic response and possible resistance to RPV or to the class of NNRTIs
              • Coadministration with CYP3A inhibitor may increase plasma levels of RPV
              • Coadministration with drugs that increase gastric pH may decrease plasma levels of RPV and cause loss of virologic response and possible resistance to RPV or to the class of NNRTIs
              • Also see Contraindications
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            Pregnancy & Lactation

            Pregnancy

            Pregnancy exposure registry monitors pregnancy outcomes in individuals exposed to treatment during pregnancy

            Register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263

            Available data from the APR show no increase in overall risk of major birth defects with first-trimester exposure for FTC, RPV, or TDF In a clinical trial, total RPV exposures were generally lower during pregnancy compared with the postpartum period

            Based on HIV-1-infected pregnant individuals who completed a clinical trial through postpartum period with an RPV-based regimen, no dose adjustments are required for pregnant patients who are already on a stable RPV-containing regimen prior to pregnancy and who are virologically suppressed (HIV-1 RNA <50 copies/mL)

            Closely monitor viral load; lower exposures of RPV were observed during pregnancy

            Lactation

            The Centers for Disease Control and Prevention recommends HIV infected mothers not breastfeed their infants to avoid risking postnatal transmission of HIV

            Based on published data, FTC and tenofovir reported to be present in human milk

            No data available on the presence of RPV in human milk; however has been shown to be present in rat milk

            Because of the potential for: HIV transmission (in HIV-negative infants); developing viral resistance (in HIV-positive infants); and adverse reactions in a breastfed infant similar to those seen in adults, instruct mothers not to breastfeed

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Emtricitabine: Nucleoside reverse transcriptase inhibitor (NRTI); following phosphorylation, interferes with HIV viral DNA polymerase and inhibits viral replication; cytosine analogue

            Rilpivirine: Antiviral agent; diarylpyrimidine non-nucleoside reverse transcriptase inhibitor (NNRTI) of HIV-1; inhibits HIV-1 replication by noncompetitive inhibition of HIV-1 reverse transcriptase

            Tenofovir: Nucleoside reverse transcriptase inhibitor (NRTI); following hydrolysis and phosphorylation, inhibits HIV-1 reverse transcriptase by competing with AMP as substrate

            Absorption

            Bioavailability

            • Emtricitabine: 93%
            • Rilpivirine: Exposure 25% higher with combined tablet compared with administration of separate agents; absolute bioavailability unknown
            • Tenofovir: <25% (fasting)

            Peak Plasma Time

            • Emtricitabine: 1-2 hr
            • Rilpivirine: 4-5 hr
            • Tenofovir: 1 hr

            Peak Plasma Concentration

            • Emtricitabine: 1.8 mcg/mL
            • Rilpivirine: 80 ng/mL
            • Tenofovir: 0.3 mcg/mL

            AUC

            • Emtricitabine: 10 mcg•hr/mL
            • Rilpivirine: 2.397 mcg•hr/mL
            • Tenofovir: 2.29 mcg•hr/mL

            Distribution

            Protein Bound

            • Emtricitabine: <4%
            • Rilpivirine: 99.7%
            • Tenofovir: <0.7%

            Metabolism

            Metabolized by

            • Rilpivirine: CYP3A

            Metabolites

            • Emtricitabine: 3′-sulfoxide diastereomers (approximately 9% of the dose) and the glucuronic acid conjugate (approximately 4% of the dose)

            Elimination

            Half-life

            • Emtricitabine: 10 hr
            • Rilpivirine: 50 hr
            • Tenofovir: 17 hr

            Renal clearance

            • Emtricitabine: 213 mL/min
            • Tenofovir: 243.5 mL/min

            Excretion

            • Emtricitabine: Urine 86%; feces 14%
            • Rilpivirine: Urine 6.1%; feces 85%
            • Tenofovir: Urine 70-80%
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            Administration

            Oral Administration

            Take with food

            Storage

            Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F)

            Keep container tightly closed

            Dispense only in original container

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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
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            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
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