bictegravir/emtricitabine/tenofovir AF (Rx)

Brand and Other Names:Biktarvy
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

bictegravir/emtricitabine/tenofovir AF

tablet

  • 50mg/200mg/25mg

HIV Infection

Three-drug combination of bictegravir (BIC), a human immunodeficiency virus type 1 (HIV-1) integrase strand transfer inhibitor (INSTI); emtricitabine (FTC); and tenofovir alafenamide (TAF), both HIV-1 nucleoside analog reverse transcriptase inhibitors (NRTIs)

Indicated as a complete regimen for HIV-1 infection in adults who are antiretroviral therapy (ART)-naïve or to replace current ART regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) on a stable regimen for at least 3 months with no history of treatment failure and no known substitutions associated with resistance to the individual components

1 tablet PO qDay with or without food

See also Administration

Dosage Modifications

Hepatic impairment

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

Renal impairment

  • CrCl ≥30 mL/min: No dosage adjustment necessary
  • CrCl <30 mL/min: Not recommended

Dosing Considerations

Testing when initiating and during treatment

  • Prior to or when initiating bictegravir/emtricitabine/tenofovir AF, test patients for hepatitis B virus infection
  • Prior to or when initiating and during treatment with bictegravir/emtricitabine/tenofovir AF, assess serum creatinine, estimated CrCl, urine glucose, and urine protein in all patients as clinically appropriate; in patients with chronic kidney disease, also assess serum phosphorus

<18 years: Safety and efficacy not established

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Interactions

Interaction Checker

and bictegravir/emtricitabine/tenofovir AF

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            Adverse Effects

            1-10%

            Diarrhea (3-6%)

            Nausea (3-5%)

            Headache (4-5%)

            Creatine kinase ≥10x ULN (4%)

            Abnormal dreams (<3%)

            Fasting LDL-C >190 mg/dL (2-3%)

            Fatigue (2-3%)

            Dizziness (2%)

            Insomnia (2%)

            Neutrophil <750 mm³ (2%)

            Amylase >2x ULN (2%)

            ALT >5x ULN (1-2%)

            AST >5x ULN (1-2%)

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            Warnings

            Black Box Warnings

            Severe acute exacerbations of hepatitis B reported in patients who are coinfected with HIV-1 and HBV and have discontinued emtricitabine or tenofovir, and they may occur with discontinuation of bictegravir/emtricitabine/tenofovir AF

            Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue bictegravir/emtricitabine/tenofovir AF

            If appropriate, antihepatitis B therapy may be warranted

            Contraindications

            Coadministration with dofetilide may increase the dofetilide plasma concentrations and potentiate associated serious and/or life-threatening events

            Coadministration with rifampin may decrease bictegravir plasma concentrations, which may result in the loss of therapeutic effect and development of resistance to bictegravir/emtricitabine/tenofovir AF

            Cautions

            Patients with HIV-1 infection should be tested for the presence of chronic hepatitis B virus (HBV) before initiating antiretroviral therapy (ART); not approved for the treatment of chronic HBV infection (see Black Box Warnings)

            Immune reconstitution syndrome reported in patients treated with combination ART therapy; autoimmune disorders (eg, Graves disease, polymyositis, Guillain-Barré syndrome) may occur in the setting of immune reconstitution; time to onset varies and can occur many months after initiation of treatment

            Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including emtricitabine, and tenofovir DF, alone or in combination with other antiretrovirals; suspend treatment if patient develops signs or symptoms of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis, even in the absence of marked transaminase elevations)

            New-onset or worsening renal impairment

            • Cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia) reported with the use of tenofovir prodrugs; monitor estimated CrCl, urine glucose, and urine protein in all patients prior to initiating and during therapy; additionally, monitor serum phosphorus in patients with chronic kidney disease
            • Assess serum creatinine, serum phosphorous, estimated CrCl, urine glucose, and urine protein before initiating drug and during therapy in all patients as clinically appropriate
            • Discontinue drug if clinically significant decreases in renal function or evidence of Fanconi syndrome develop
            • Avoid concurrent or recent use of nephrotoxic drug, including nonsteroidal anti-inflammatory drugs, owing to increased risk of developing renal-related adverse reactions

            Drug interactions overview

            • Bictegravir inhibits OCT2 and MATE1; coadministration with drugs that are OCT2 and MATE1 substrates may increase their plasma concentrations (also see Contraindications)
            • Strong CYP3A inducers that also induce UGT1A1 can substantially decrease bictegravir plasma concentrations ,which may lead to loss of therapeutic effect of bictegravir/emtricitabine/tenofovir AF and development of resistance (also see Contraindications)
            • Strong CYP3A4 inhibitors that also inhibit UGT1A1 may significantly increase bictegravir plasma concentrations
            • Coadministration of drugs that inhibit of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) may increase the absorption and plasma concentrations of tenofovir AF
            • Coadministration of drugs that induce P-gp activity are expected to decrease the absorption of tenofovir AF, resulting in decreased plasma concentration of tenofovir AF, which may lead to loss of therapeutic effect of treatment and development of resistance
            • Coadministration with drugs that reduce renal function or compete for active tubular secretion may increasing concentrations of emtricitabine and tenofovir, thereby increase risk of adverse effects
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            Pregnancy

            Pregnancy

            Pregnancy exposure registry monitors pregnancy outcomes in women exposed to bictegravir/emtricitabine/tenofovir AF during pregnancy

            Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263

            Insufficient human data on the use of bictegravir/emtricitabine/tenofovir AF during pregnancy to inform a drug-associated risk of birth defects and miscarriage

            Bictegravir and tenofovir alafenamide use in women during pregnancy has not been evaluated; emtricitabine use during pregnancy in a limited number of women reported to the APR showed no difference in overall risk of major birth defects for emtricitabine compared with the background rate for major birth defects

            Lactation

            The Centers for Disease Control and Prevention do not recommend HIV-infected mothers breastfeed their infants owing to potential risk for postnatal transmission of HIV

            Unknown whether bictegravir/emtricitabine/tenofovir AF or all of the components of the drug are present in human breast milk, affects human milk production, or has effects on the breastfed infant; emtricitabine has been shown to be present in human breast milk

            Owing to 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 while taking this medication

            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

            Bictegravir: HIV-1 integrase strand transfer inhibitor (INSTI); inhibits HIV-1 replication by blocking the strand transfer step of viral DNA integration into the host genome; novel INSTI since it can be dosed once daily without boosting

            Emtricitabine: Nucleoside reverse transcriptase inhibitor (NRTI); cytosine analog phosphorylated to emtricitabine 5'-triphosphate causing inhibition of HIV and RNA dependent DNA polymerase

            Tenofovir alafenamide (AF): NRTI prodrug of tenofovir; compared with tenofovir disoproxil fumarate (tenofovir DF, Viread), tenofovir alafenamide (AF) is a more targeted form of tenofovir that has demonstrated high antiviral efficacy at a dose that is 10 times lower than tenofovir DF, as well as an improved renal and bone safety profile; 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 time: 2-4 hr (BIC); 1.5-2 hr (FTC); 0.5-2 hr (TAF)

            Peak plasma concentration: 6.15 mcg/mL (BIC); 2.13 mcg/mL (FTC); 0.121 mcg/mL(TAF)

            AUC: 102 mcg·h/mL (BIC); 12.3 mcg·h/mL (FTC); 0.142 mcg·h/mL (TAF)

            Effect of high-fat meal

            • AUC ratio: 1.24 (BIC); 0.96 (FTC); 1.63 (TAF)
            • Peak plasma concentration ratio: 1.13 (BIC); 0.86 (FTC); 0.92 (TAF)

            Distribution

            Protein binding: >99% (BIC); <4% (FTC); ~80% (TAF)

            Blood-to-plasma ratio: 0.64 (BIC); 0.6 (FTC); 1 (TAF)

            Metabolism

            Bictegravir

            • Metabolized by CYP3A4 and UGT1A1

            Emtricitabine

            • Not significantly metabolized
            • Metabolized by oxidation

            Tenofovir

            • Tenofovir AF (TAF) is hydrolyzed within cells to form tenofovir (major metabolite), which is phosphorylated to the active metabolite, tenofovir diphosphate
            • In vitro studies have shown that TAF is metabolized to tenofovir by cathepsin A in PBMCs and macrophages, and by CES1 in hepatocytes
            • Upon coadministration with the moderate CYP3A inducer probe efavirenz, TAF exposure was unaffected

            Excretion

            Half-life: 17.3 hr (BIC); 10.4 hr (FTC); 0.51 hr (TAF)

            Excretion, urine: 35% (BIC); 70% (FTC); <1% (TAF)

            Excretion, feces: 60.3% (BIC); 13.7% (FTC); 31.7% (TAF)

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            Administration

            Oral Administration

            For oral use only

            Take once daily with or without food

            Storage

            Tablets

            • Store below 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
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            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.
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            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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