emtricitabine/rilpivirine/tenofovir DF (Rx)

Brand and Other Names:Complera
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

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

tablet

  • 200mg/25mg/300mg
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HIV Infection

Indicated as complete regimen for treatment of HIV-1 infection in treatment-naïve adults 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

Combination consists of 2 NRTIs (ie, emtricitabine and tenofovir) and 1 NNRTI (ie, rilpivirine)

Indicated as complete regimen for treatment of HIV-1 infection in treatment-naïve adults

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

Initiation considerations

  • More patients treated with rilpivirine who had >100,000 copies/mL HIV-1 RNA at the start of therapy experienced virologic failure compared with those with <100,000 copies/mL
  • Observed virologic failure rate in rilpivirine-treated patients conferred a higher rate of overall treatment resistance and cross-resistance to the NNRTI class compared to efavirenz
  • More patients treated with rilpivirine developed lamivudine/emtricitabine associated resistance compared to efavirenz

Dosage Modifications

Renal impairment

  • CrCl ≥50 mL/min: Dose adjustment not necessary
  • CrCl <50 mL/min: Do not use

Dosing Considerations

Initiating in ART-naive patients

  • More patients treated with rilpivirine who had >100,000 copies/mL HIV-1 RNA at the start of therapy experienced virologic failure compared with those with <100,000 copies/mL
  • Observed virologic failure rate in rilpivirine-treated patients conferred a higher rate of overall treatment resistance and cross-resistance to the NNRTI class compared to efavirenz
  • More patients treated with rilpivirine developed lamivudine/emtricitabine associated resistance compared to efavirenz

Replacing current ART regimen in virologically-suppressed adults

  • Patients should:
  • Have no history of virologic failure
  • Have been stably suppressed (HIV-1 RNA <50 copies/mL) for at least 6 months before switching therapy
  • Currently be on their 1st or 2nd ART regimen before switching therapy
  • Have no current or past history of resistance to emtricitabine/rilpivirine/tenofovir

Dosage Forms & Strengths

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

tablet

  • 200mg/25mg/300mg

HIV Infection

Indicated as complete regimen for treatment of HIV-1 infection in treatment-naïve adults and adolescents aged ≥12 yr who weigh at least 35 kg

Combination consists of 2 NRTIs (ie, emtricitabine and tenofovir) and 1 NNRTI (ie, rilpivirine)

<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

Initiation considerations

  • More patients treated with rilpivirine who had >100,000 copies/mL HIV-1 RNA at the start of therapy experienced virologic failure compared with those with <100,000 copies/mL
  • Observed virologic failure rate in rilpivirine-treated patients conferred a higher rate of overall treatment resistance and cross-resistance to the NNRTI class compared to efavirenz
  • More patients treated with rilpivirine developed lamivudine/emtricitabine associated resistance compared to efavirenz

Dosage Modifications

Renal impairment

  • CrCl ≥50 mL/min: Dose adjustment not necessary
  • CrCl <50 mL/min: Do not use

Dosing Considerations

Initiating in ART-naive patients

  • More patients treated with rilpivirine who had >100,000 copies/mL HIV-1 RNA at the start of therapy experienced virologic failure compared with those with <100,000 copies/mL
  • Observed virologic failure rate in rilpivirine-treated patients conferred a higher rate of overall treatment resistance and cross-resistance to the NNRTI class compared to efavirenz
  • More patients treated with rilpivirine developed lamivudine/emtricitabine associated resistance compared to efavirenz

Replacing current ART regimen in virologically-suppressed adults

  • Patients should:
  • Have no history of virologic failure
  • Have been stably suppressed (HIV-1 RNA <50 copies/mL) for at least 6 months before switching therapy
  • Currently be on their 1st or 2nd ART regimen before switching therapy
  • Have no current or past history of resistance to emtricitabine/rilpivirine/tenofovir
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Interactions

Interaction Checker

and emtricitabine/rilpivirine/tenofovir DF

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    Interactions Found

    Contraindicated

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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

            Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including tenofovir, in combination with other antiretrovirals

            Not approved for chronic hepatitis B virus (HBV) infection

            Safety and efficacy is not established with coinfection of HBV and HIV-1

            Severe acute exacerbations of hepatitis B have been reported with coinfection of HBV and HIV-1 and have discontinued emtricitabine or tenofovir, which are components of Complera

            Hepatic function should be monitored closely with both clinical and laboratory follow-up for at least several months after discontinuing Complera in patients who are coinfected with HIV-1 and HBV; if appropriate, initiation of antihepatitis B therapy may be warranted

            Contraindications

            Hypersensitivity

            Coadministration with proton pump inhibitors (eg, esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole) may decrease rilpivirine absorption by increasing gastric pH, resulting in decreased plasma concentration; may result in loss of virologic response and possibly cause resistance to NNRTIs

            CYP3A enzyme inducers

            • May result in loss of virologic response and possible resistance to NNRTIs
            • Anticonvulsants (eg, carbamazepine, oxcarbazepine, phenobarbital, phenytoin)
            • Antimycobacterials (eg, rifabutin, rifampin, rifapentine)
            • Glucocorticoid systemic dexamethasone (more than a single dose)
            • St. John’s wort

            Cautions

            Lactic acidosis/severe hepatomegaly with steatosis (see Black Box Warnings)

            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-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; clinical status including laboratory parameters should be monitored and appropriate therapy should be initiated

            Assess CrCl before initiating treatment; monitor CrCl and serum phosphorus in patients at risk

            Avoid concurrent or recent use of nephrotoxic drugs

            Avoid drugs that may reduce the exposure of rilpivirine (see Contraindications)

            Coadministration with drugs known to increase QT interval and increase risk of Torsade de Pointes

            Severe depressive disorders reported; immediate medical evaluation recommended

            Do not use with drugs containing emtricitabine, rilpivirine or tenofovir disoproxil fumarate including Atripla, Edurant, Emtriva, Truvada, Viread, or with drugs containing lamivudine

            Do not administer in combination with adefovir (Hepsera)

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

            May increase risk for immune reconstitution syndrome

            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, have been reported
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            Pregnancy & Lactation

            Pregnancy Category: B; Antiretroviral Pregnancy Registry 1-800-258-4263

            Lactation: Unknown whether distributed in breast milk; the CDC recommends that mothers should not breastfeed their infants because of risk of postnatal HIV transmission

            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

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            Images

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            Formulary

            FormularyPatient Discounts

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            • View the formulary and any restrictions for each plan.
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            • Compare formulary status to other drugs in the same class.
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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.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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