Biktarvy Tablet

BIKTARVY is indicated as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in adults and pediatric patients weighing at least 14 kg:

1. with no antiretroviral treatment history, or
2. with an antiretroviral treatment history and not virologically suppressed, with no known or suspected substitutions associated with resistance to the integrase strand inhibitor class, emtricitabine, or tenofovir, or
3. 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 [see Dosage and Administration (2.4), and Use in Specific Populations (8.1)].

BIKTARVY is contraindicated to be co-administered with:

1. dofetilide due to the potential for increased dofetilide plasma concentrations and associated serious and/or life-threatening events [see Drug Interactions (7.5)].
2. rifampin due to decreased BIC plasma concentrations, which may result in the loss of therapeutic effect and development of resistance to BIKTARVY [see Drug Interactions (7.5)].

The concomitant use of BIKTARVY with certain other drugs may result in known or potentially significant drug interactions, some of which may lead to [see Contraindications (4), and Drug Interactions (7.5)]:

1. Loss of therapeutic effect of BIKTARVY and possible development of resistance.
2. Possible clinically significant adverse reactions from greater exposures of concomitant drugs.

See Table 3 for steps to prevent or manage these possible and known significant drug interactions, including dosing recommendations. Consider the potential for drug interactions prior to and during BIKTARVY therapy; review concomitant medications during BIKTARVY therapy; and monitor for the adverse reactions associated with the concomitant drugs.

The following adverse reactions are discussed in other sections of the labeling:

1. Severe Acute Exacerbations of Hepatitis B [see Warnings and Precautions (5.1)].
2. Immune Reconstitution Syndrome [see Warnings and Precautions (5.3)].
3. New Onset or Worsening Renal Impairment [see Warnings and Precautions (5.4)].
4. Lactic Acidosis/Severe Hepatomegaly with Steatosis [see Warnings and Precautions (5.5)].

• Immune reconstitution syndrome: May necessitate further evaluation and treatment. (5.3)

• New onset or worsening renal impairment: Assess serum creatinine, estimated creatinine clearance, urine glucose and urine protein when initiating BIKTARVY and during therapy as clinically appropriate in all patients. Also assess serum phosphorus in patients with chronic kidney disease. (5.4)

• Lactic acidosis/severe hepatomegaly with steatosis: Discontinue treatment in patients who develop symptoms or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity. (5.5) 5.1 Severe Acute Exacerbation of Hepatitis B in Patients with HIV-1 and HBV

Patients with HIV-1 should be tested for the presence of chronic hepatitis B virus (HBV) before or when initiating antiretroviral therapy [see Dosage and Administration (2.1)].

Severe acute exacerbations of hepatitis B (e.g., liver decompensation and liver failure) have been reported in patients with HIV-1 and HBV who have discontinued products containing FTC and/or tenofovir disoproxil fumarate (TDF), and may occur with discontinuation of BIKTARVY. Patients with HIV-1 and HBV who discontinue BIKTARVY should be closely monitored with both clinical and laboratory follow-up for at least several months after stopping treatment. If appropriate, anti-hepatitis B therapy may be warranted, especially in patients with advanced liver disease or cirrhosis, since post-treatment exacerbation of hepatitis may lead to hepatic decompensation and liver failure. 5.2 Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions

The concomitant use of BIKTARVY with certain other drugs may result in known or potentially significant drug interactions, some of which may lead to

[see Contraindications (4), and Drug Interactions (7.5)]: • Loss of therapeutic effect of BIKTARVY and possible development of resistance.

• Possible clinically significant adverse reactions from greater exposures of concomitant drugs.

See Table 3 for steps to prevent or manage these possible and known significant drug interactions, including dosing recommendations. Consider the potential for drug interactions prior to and during BIKTARVY therapy; review concomitant medications during BIKTARVY therapy; and monitor for the adverse reactions associated with the concomitant drugs. 5.3 Immune Reconstitution Syndrome

Immune reconstitution syndrome has been reported in patients treated with combination antiretroviral therapy. During the initial phase of combination antiretroviral treatment, patients whose immune system responds may develop an inflammatory response to indolent or residual opportunistic infections [such as

Mycobacterium avium

infection, cytomegalovirus,

Pneumocystis jirovecii

pneumonia (PCP), or tuberculosis], which may necessitate further evaluation and treatment.

Autoimmune disorders (such as Graves’ disease, polymyositis, Guillain-Barré syndrome, and autoimmune hepatitis) have also been reported to occur in the setting of immune reconstitution; however, the time to onset is more variable, and can occur many months after initiation of treatment. 5.4 New Onset or Worsening Renal Impairment

Postmarketing cases of renal impairment, including acute renal failure, proximal renal tubulopathy (PRT), and Fanconi syndrome, have been reported with TAF-containing products; while most of these cases were characterized by potential confounders that may have contributed to the reported renal events, it is also possible these factors may have predisposed patients to tenofovir-related adverse events

[see Adverse Reactions (6.1, 6.2)].

BIKTARVY is not recommended in patients with severe renal impairment (estimated creatinine clearance of 15 to below 30 mL/min), or patients with ESRD (estimated creatinine clearance below 15 mL/min) who are not receiving chronic hemodialysis, or patients with no antiretroviral treatment history and ESRD who are receiving chronic hemodialysis [see Dosage and Administration (2.4), and Use in Specific Populations (8.6)].

Patients taking tenofovir prodrugs who have impaired renal function and those taking nephrotoxic agents including non-steroidal anti-inflammatory drugs are at increased risk of developing renal-related adverse reactions.

Prior to or when initiating BIKTARVY, and during treatment with BIKTARVY, assess serum creatinine, estimated creatinine clearance, urine glucose and urine protein in all patients as clinically appropriate. In patients with chronic kidney disease, also assess serum phosphorus. Discontinue BIKTARVY in patients who develop clinically significant decreases in renal function or evidence of Fanconi syndrome. 5.5 Lactic Acidosis/Severe Hepatomegaly with Steatosis

Lactic acidosis and severe hepatomegaly with steatosis, including fatal cases, have been reported with the use of nucleoside analogs, including emtricitabine, a component of BIKTARVY, and tenofovir DF, another prodrug of tenofovir, alone or in combination with other antiretrovirals. Treatment with BIKTARVY should be suspended in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (which may include hepatomegaly and steatosis even in the absence of marked transaminase elevations).

BIKTARVY is a three-drug fixed dose combination product containing bictegravir (BIC), emtricitabine (FTC), and tenofovir alafenamide (TAF). The recommended dosage of BIKTARVY is one tablet containing 50 mg of BIC, 200 mg of FTC, and 25 mg of TAF taken orally once daily with or without food in [see Dosage and Administration (2.4)]:

1. adults and pediatric patients weighing at least 25 kg with an estimated creatinine clearance greater than or equal to 30 mL/min; or
2. virologically-suppressed adults with an estimated creatinine clearance below 15 mL/min who are receiving chronic hemodialysis. On days of hemodialysis, administer the daily dose of BIKTARVY after completion of hemodialysis treatment [see Use in Specific Populations (8.4, 8.6), and Clinical Pharmacology (12.3)].

The recommended dosage of BIKTARVY is one tablet containing 30 mg of BIC, 120 mg of FTC, and 15 mg of TAF taken orally once daily with or without food in:

1. pediatric patients weighing at least 14 kg to less than 25 kg with an estimated creatinine clearance greater than or equal to 30 mL/min [see Use in Specific Populations (8.4, 8.6), and Clinical Pharmacology (12.3)].

For children unable to swallow a whole tablet, the tablet can be split and each part taken separately as long as all parts are ingested within approximately 10 minutes.

The recommended dosage of BIKTARVY in pregnant individuals is one tablet containing 50 mg of BIC, 200 mg of FTC, and 25 mg of TAF taken orally once daily with or without food in pregnant individuals who are virologically-suppressed (HIV-1 RNA less than 50 copies per mL) on a stable antiretroviral regimen with no known substitutions associated with resistance to any of the individual components of BIKTARVY. Lower exposures of BIKTARVY were observed during pregnancy; therefore, viral load should be monitored closely [see Drug Interactions (7.5), Use in Specific Populations (8.1), and Clinical Pharmacology (12.3)].

BIKTARVY tablets are available in two dose strengths:

1. 50 mg/200 mg/25 mg tablets: 50 mg of bictegravir (BIC) (equivalent to 52.5 mg of bictegravir sodium), 200 mg of emtricitabine (FTC), and 25 mg of tenofovir alafenamide (TAF) (equivalent to 28 mg of tenofovir alafenamide fumarate). These tablets are purplish brown, capsule-shaped, film-coated, and debossed with “GSI” on one side and “9883” on the other side.
2. 30 mg/120 mg/15 mg tablets: 30 mg of BIC (equivalent to 31.5 mg of bictegravir sodium), 120 mg of FTC, and 15 mg of TAF (equivalent to 16.8 mg of tenofovir alafenamide fumarate). These tablets are pink, capsule-shaped, film-coated, and either debossed with “GSI” on one side and “B” on the other side; or with a non-functional bisecting score line on one side and “BVY” on the other side.

The concomitant use of BIKTARVY with certain other drugs may result in known or potentially significant drug interactions, some of which may lead to [see Contraindications (4), and Drug Interactions (7.5)]:

1. Loss of therapeutic effect of BIKTARVY and possible development of resistance.
2. Possible clinically significant adverse reactions from greater exposures of concomitant drugs.

See Table 3 for steps to prevent or manage these possible and known significant drug interactions, including dosing recommendations. Consider the potential for drug interactions prior to and during BIKTARVY therapy; review concomitant medications during BIKTARVY therapy; and monitor for the adverse reactions associated with the concomitant drugs.

Table 3 provides a listing of established or potentially clinically significant drug interactions with recommended prevention or management strategies. The drug interactions described are based on studies conducted with either BIKTARVY, the components of BIKTARVY (BIC, FTC, and TAF) as individual agents, or are drug interactions that may occur with BIKTARVY [see Contraindications (4), Warnings and Precautions (5.2), and Clinical Pharmacology (12.3)].

Based on drug interaction studies conducted with BIKTARVY or the components of BIKTARVY, no clinically significant drug interactions have been observed when BIKTARVY is combined with the following drugs: ethinyl estradiol, ledipasvir/sofosbuvir, midazolam, norgestimate, sertraline, sofosbuvir, sofosbuvir/velpatasvir, and sofosbuvir/velpatasvir/voxilaprevir.