Bictegravir + Emtricitabine + Tenofovir Alafenamide

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

Oral HIV-1 infection Indicated as a complete regimen for the treatment of HIV-1 infection in adults: • who have no antiretroviral treatment history or • to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no known or suspected substitutions associated with resistance to bictegravir or tenofovir Adult: 1 tablet (50 mg BIC, 200 mg FTC, and 25 mg TAF) once daily

Oral HIV-1 infection Indicated as a complete regimen for the treatment of HIV-1 infection in adults and pediatric patients weighing at least 14 kg: • who have no antiretroviral treatment history or • to replace the current antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no known or suspected substitutions associated with resistance to bictegravir or tenofovir Child patients weighing at least 25 kg: 1 tablet (50 mg BIC, 200 mg FTC, and 25 mg TAF) once daily Child patients weighing at least 14 kg to less than 25 kg: One tablet containing 30 mg BIC, 120 mg FTC, and 15 mg TAF taken once daily

Renal impairment CrCl >30 mL/min: No dosage adjustment necessary Virologically suppressed adults with ESRD (CrCl <15 mL/min) on chronic hemodialysis: On hemodialysis days, administer daily dose after completing hemodialysis Severe Not recommended for CrCl 15 to <30 mL/min ESRD not on hemodialysis No ART history and ESRD in patients who are receiving chronic hemodialysis

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

May taken with or without food

Coadministration with dofetilide and/or rifampin

Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF), and may occur with discontinuation of BIKTARVY. Closely monitor hepatic function in these patients. If appropriate, anti-hepatitis B therapy may be warranted 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) Monitoring Parameters Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients coinfected with HIV-1 and HBV who discontinue therapy

Not Classi 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

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 Contraindicated (4) dofetilide elvitegravir/cobicistat/emtricitabine/tenofovir DF lamivudine rifampin Serious (11) atidarsagene autotemcel betibeglogene autotemcel carbamazepine elivaldogene autotemcel elivaldogene autotemcel enasidenib leniolisib letermovir lovotibeglogene autotemcel oxcarbazepine sotorasib

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

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