Bictegravir + Emtricitabine + Tenofovir Alafenamide

Indications

Bictegravir + Emtricitabine + Tenofovir Alafenamide is used for: Human Immunodeficiency Virus Infection, Indicated as complete regimen for treatment of human immunodeficiency virus type 1 (HIV-1) infection in patients who are antiretroviral therapy (ART)-naïve or to replace current ART regimen in virologically suppressed patients (HIV-1 RNA <50 copies/mL) on a stable antiretroviral regimen with no history of treatment failure and no known substitutions associated with resistance to individual components

Adult Dose

Oral HIV-1 infection Adult: 1 tablet PO qDay Hepatic impairment Mild-to-moderate (Child-Pugh class A or B): No dosage adjustment necessary Severe (Child-Pugh class C): Not studied; use not recommended

Child Dose

HIV Infection Indicated as a complete regimen for treatment of HIV-1 infection in adults and pediatric patients weighing ?25 kg who are ART-naïve or replacing current antiretroviral regimen in those who are virologically-suppressed (HIV-1 RNA <50 copies/mL) on a stable antiretroviral with no history of treatment failure and no known substitutions associated with resistance to the individual components <25 kg: Safety and efficacy not established >25 kg: 1 tablet PO qDay

Renal Dose

Renal impairment CrCl ?30 mL/min: No dosage adjustment necessary CrCl <30 mL/min: Not recommended

Administration

Contra Indications

Coadministration with dofetilide and/or rifampin

Precautions

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, autoimmune hepatitis) 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, reported with use; suspend treatment if patient develops signs or symptoms of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis, even in absence of marked transaminase elevations)

Pregnancy-Lactation

Pregnancy There is insufficient human data on use of bictegravir/emtricitabine/tenofovir AF during pregnancy to inform a drug-associated risk of birth defects and miscarriage Bictegravir and tenofovir AF use in women during pregnancy has not been evaluated Emtricitabine (FTC) use during pregnancy in a limited number of women reported to the APR showed no difference in overall risk of major birth defects for FTC 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

Interactions

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

Adverse Effects

Side effects of Bictegravir + Emtricitabine + Tenofovir Alafenamide : 1-10% Adults 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%) Children Insomnia, grade 2 Anxiety, grade 2 Frequency Not Defined Children Abdominal pain

Mechanism of Action

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) 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