FDA Approves BIKTARVY (bictegravir, embitcitabine, tenofovir alafenamide) for HIV-1 Infection in Adults Who Have No Antiretroviral Treatment History or to Replace Current Antiretroviral Regimen in Those Who Are Virologically Suppressed

FDA Approves BIKTARVY (bictegravir, embitcitabine, tenofovir alafenamide) for HIV-1 Infection in Adults Who Have No Antiretroviral Treatment History or to Replace Current Antiretroviral Regimen in Those Who Are Virologically Suppressed

On February 7, 2018, the U.S. Food and Drug Administration (FDA) approved BIKTARVY (bictegravir (BIC), emtricitabine (FTC), and tenofovir alafenamide (TAF)) 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 < 50 copies/mL) on a stable antiretroviral regimen for ≥ 3 months with no history of treatment failure and no known substitutions associated with resistance to the individual components of BIKTARVY. 

Test patients for hepatitis B virus infection prior to or when initiating BIKTARVY. Assess serum creatinine, estimated creatinine clearance, urine glucose, and urine protein in all patients as clinically appropriate, prior to or when initiating BIKTARVY, and during treatment. In patients with chronic kidney disease, also assess serum phosphorus. 

The approved recommended dosage of BIKTARVY is one tablet (BIC 50 mg, FTC 200 mg, and TAF 25 mg) once daily with or without food. 

Severe acute exacerbations of hepatitis B (HBV) have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing FTC and/or tenofovir disoproxil fumarate (TDF), and may occur with discontinuation of BIKTARVY. 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 BIKTARVY. If appropriate, anti-HBV therapy may be warranted.

Mechanism of Action (MOA), General Pharmacokinetics (PK), and Pharmacodynamics (PD) 

• MOA: BIKTARVY is a three-drug fixed-dose antiretroviral combination of BIC, FTC, and TAF. BIC is an HIV-1 integrase strand transfer inhibitor, and FTC and TAF are both HIV-1 nucleoside analog reverse transcriptase inhibitors.  
• Absorption: Tmax for BIC is 2-4 hrs, FTC is 1.5-2 hrs, and TAF is 0.5-2 hrs.  
• Distribution: Protein binding for BIC is > 99%, FTC is < 4%, and TAF is approximately 80%.  
• Elimination: Terminal half-life for BIC is 17.3 hrs, FTC is 10.4 hrs, and TAF is 0.51 hrs.   
• Metabolism: BIC is primarily metabolized by CYP3A and UGT1A1; FTC is not significantly metabolized; TAF is metabolized to tenofovir by cathepsin A in PBMCs and macrophages, and by CES1 in hepatocytes.  
• Excretion: Following administration of a single radiolabeled dose, 35% of the BIC dose was recovered in urine and 60.3% in feces. FTC undergoes glomerular filtration and active tubular secretion with 70% of the dose excreted in urine and 13.7% in feces. Less than 1% of the TAF dose was excreted in urine, and 31.7% in feces.   

Drug Interactions

Contraindicated with BIKTARVY: 

• Dofetilide
• Rifampin 

Not recommended with BIKTARVY:

• Certain antimycobacterials (rifabutin, rifapentine)
• Certain anticonvulsants (carbamazepine, oxcarbazepine, phenobarbital, phenytoin) 
• St. John’s wort

Other prevention or management recommendations with BIKTARVY coadministration:

• Metformin: Refer to metformin prescribing information to assess the benefit and risk of concomitant use with BIKTARVY.
• Antacids containing aluminum, magnesium, or calcium: BIKTARVY can be taken under fasting conditions 2 hours before these antacids. Routine administration of BIKTARVY simultaneously with, or 2 hours after, is not recommended. 
• Supplements containing calcium or iron: BIKTARVY can be taken with food with these supplements. Routine administration of BIKTARVY under fasting conditions simultaneously with, or 2 hours after, is not recommended.
• Drugs that reduce renal function or compete for active tubular secretion: Monitor adverse reactions for FTC, tenofovir, and other renally eliminated drugs. Some examples of drugs that are eliminated by active tubular secretion include, but are not limited to, acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, aminoglycosides (e.g., gentamicin), and high-dose or multiple NSAIDs. 

Additional information regarding drug interactions can be found in the full prescribing information linked below.  

Use in Specific Populations

• Renal impairment: BIKTARVY is not recommended in patients with severe renal impairment (CLcr < 30 mL/min). No dosage adjustment of BIKTARVY is recommended in patients with CLcr > 30 mL/min. 
• Hepatic impairment: BIKTARVY is not recommended in patients with severe hepatic impairment (Child-Pugh C). No dosage adjustment of BIKTARVY is recommended in patients with mild or moderate hepatic impairment (Child-Pugh A or B).

Efficacy and Safety

Efficacy and safety of BIKTARVY were demonstrated in 4 randomized, active controlled trials (3 double-blind and 1 open-label) in HIV-1 adults with no antiretroviral treatment history or who were virologically suppressed. Additional information regarding efficacy trial(s) can be found in the full prescribing information linked below.  

The most common adverse reactions (incidence ≥ 5%, all grades) are diarrhea, nausea, and headache.