emtricitabine/rilpivirine/tenofovir AF (Rx)

Brand and Other Names:Odefsey
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

emtricitabine/rilpivirine/tenofovir AF

tablet

  • 200mg/25mg/25mg

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, and in certain virologically suppressed (HIV-1 RNA <50 copies/mL) patients on a stable antiretroviral therapy (ART) regimen at start of therapy in order to replace their current ART regimen

1 tablet (emtricitabine 200 mg/rilpivirine 25 mg/tenofovir 25 mg) PO qDay with food

Dosage Modifications

Coadministration with rifabutin

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

Renal impairment

  • Mild-to-moderate (eCrCl ≥30 mL/min): No dosage adjustment necessary
  • Severe or ESRD (eCrCl <30 mL/min): Not recommended

Hepatic impairment

  • Mild-to-moderate (Child-Pugh A or B): No dosage adjustment required
  • Severe (Child-Pugh C): Not recommended; data are insufficient in this population

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 AF

tablet

  • 200mg/25mg/25mg

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 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 25 mg) PO qDay with food

Dosage Modifications

Coadministration with rifabutin

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

Renal impairment

  • Mild-to-moderate (eCrCl ≥30 mL/min): No dosage adjustment necessary
  • Severe or ESRD (eCrCl <30 mL/min): Not recommended

Hepatic impairment

  • Mild-to-moderate (Child-Pugh A or B): No dosage adjustment required
  • Severe (Child-Pugh C): Not recommended; data are insufficient in this population

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
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Interactions

Interaction Checker

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            Adverse Effects

            >10%

            Headache (rilpivirine) (19%)

            Depression (rilpivirine) (19%)

            Somnolence (rilpivirine) (14%)

            Nausea (rilpivirine) (11%)

            1-10%

            Nausea (10%)

            Mild/moderate depression (rilpivirine) (9%)

            Dizziness (rilpivirine) (8%)

            Abdominal pain (rilpivirine) (8%)

            Vomiting (rilpivirine) (6%)

            Rash (rilpivirine) (6%)

            Headache (2%)

            Sleep disturbances (2%)

            Severe depression (rilpivirine) (1%)

            Flatulence (1%)

            Abnormal dreams (1%)

            Diarrhea (1%)

            Frequency Not Defined

            Lactic acidosis

            Exacerbation of hepatitis B in coinfected patients

            Postmarketing Reports

            Rilpivirine

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

            Black Box Warnings

            Post treatment 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

            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

            Severe acute exacerbation of hepatitis B in patients 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

            Severe depressive disorders reported; immediate medical evaluation recommended

            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

            Fat redistribution and accumulation observed with ART therapy

            Immune reconstitution syndrome reported, including the occurrence of autoimmune disorders (eg, Grave disease, polymyositis, Guillain-Barre syndrome) with variable time to onset

            Decreases in bone mineral density (BMD) and cases of osteomalacia associated with proximal renal tubulopathy reported with tenofovir; consider monitoring BMD with a history of pathologic fracture or if risk factors for bone loss exist

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

            Lactic acidosis/severe hepatomegaly with steatosis may occur

            Drug interactions overview

            • Coadministration with P-gp/BCRP inhibitors may increase absorption and plasma concentration of tenofovir AF; P-gp inducwea may decrease ]absorption of TAF, resulting in decreased plasma concentration of TAF, which may lead to loss of therapeutic effect of Odefsey and development of resistance
            • Coadministration with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of FTC, tenofovir, and other renally eliminated drugs
            • 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
              • Supratherapeutic rilpivirine doses (ie, 75 mg and 300 mg qDay) shown to prolong the QTc interval; caution when coadministered with a drug known to increase risk of torsade de pointes
              • Rilpivirine use with proton pump inhibitors is contraindicated and use of RPV with H2-receptor antagonists requires staggered administration (see Contraindications)
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            Pregnancy

            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

            Insufficient human data on use during pregnancy to inform a drug-associated risk of birth defects and miscarriage

            TAF use in women during pregnancy has not been evaluated; emtricitabine (FTC) and rilpivirine (RPV) use during pregnancy has been evaluated in a limited number of women reported to the APR

            Available data show no difference in the risk of overall major birth defects for FTC (2.4%) compared with the background rate for major birth defects of 2.7%

            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 per mL)

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

            Lactation

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

            Based on published data, FTC has shown to be present in human breast milk;

            Unknown if RPV and TAF are present in human breast milk; RPV is present in rat milk and tenofovir has been shown to be present in the milk of lactating rats and rhesus monkeys after administration

            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 AF: An NRTI and prodrug of tenofovir; inhibits HIV-1 RT by competing with the natural substrate deoxyadenosine 5′-triphosphate and, after incorporation into DNA, by DNA chain termination

            Absorption

            Peak plasma concentration: 2.1 mcg/mL (emtricitabine); 0.16 mcg/mL (TAF)

            Peak plasma time: 4hr (rilpivirine); 3hr (emtricitabine); 1hr (TAF)

            AUC: 11.7 mcg·hr per mL (emtricitabine); 2.2 mcg·hr per mL (rilpivirine); 0.21 mcg·hr per mL (TAF)

            Distribution

            Protein bound: ~99% (rilpivirine); <4% (emtricitabine); ~80% (TAF)

            Metabolism

            Rilpivirine is metabolized by CYP3A4 pathway

            Emtricitabine is not significantly metabolized

            Tenofovir AF is converted from tenofovir AF to tenofovir through hydrolysis primarily by carboxyesterase 1 (CES1) in primary hepatocytes; also metabolized by Cathepsin A in peripheral blood mononuclear cells (PBMCs) and minimally metabolized by CYP3A4

            Elimination

            Half-life: 50 hr (rilpivirine); 10 hr (emtricitabine); 0.51 hr (TAF)

            Excretion in urine: 6% (rilpivirine); 70% (emtricitabine); <1% (TAF)

            Excretion in feces: 85% (rilpivirine); 13.7% (emtricitabine); 31.7 % (TAF)

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            Administration

            Oral Administration

            Take with food

            Storage

            Store <30°C (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.
            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.
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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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