INN monograph
Tenofovir/Emtricitabine
Human Immunodeficiency Virus Nucleoside Analog Reverse Transcriptase Inhibitor [EPC] · POM
Source-linked · Updated 03 Aug 2026 · Source: Local active-ingredient clinical extract; FDA drug label via OpenFDA/DailyMed; Component monographs (multi-source pipeline); Professional class pharmacology (Antiviral / antiretroviral)
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Contraindications
- 4 CONTRAINDICATIONS BIKTARVY is contraindicated to be co-administered with: dofetilide due to the potential for increased dofetilide plasma concentrations and associated serious and/or life-threatening events [see Drug Interactions (7.5) ] . 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) ] .
- BIKTARVY is contraindicated to be co-administered with: dofetilide.
- ( 4 ) rifampin.
Precautions
- 5 WARNINGS AND PRECAUTIONS 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 Coinfected with HIV-1 and HBV Patients with HIV-1 should be tested for the presence of chronic hepatitis B virus (HBV) infection 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 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.
- Patients coinfected 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
Point of care
Dosing
Adult
2 DOSAGE AND ADMINISTRATION Testing: Prior to or when initiating BIKTARVY test for hepatitis B virus infection. Prior to or when initiating BIKTARVY, and during treatment, 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. ( 2.1 ) Recommended dosage in adults and pediatric patients weighing at least 25 kg: One tablet containing 50 mg BIC, 200 mg FTC, and 25 mg TAF taken once daily with or without food. ( 2.2 ) Recommended dosage in pediatric 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 with or without food. ( 2.3 ) Renal impairment: BIKTARVY is not recommended in patients with estimated creatinine clearance of 15 to below 30 mL/min, or below 15 mL/min who are not receiving chronic hemodialysis, or below 15 mL/min who have no antiretroviral treatment history. ( 2.4 ) Hepatic impairment: BIKTARVY is not recommended in patients with severe hepatic impairment. ( 2.5 ) 2.1 Testing When Initiating and During Treatment with BIKTARVY Prior to or when initiating BIKTARVY, test patients for hepatitis B virus infection [see Warnings and Precautions (5.1) ] . 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 [see Warnings and Precautions (5.4) ]. 2.2 Recommended Dosage in Adults and Pediatric Patients Weighing at Least 25 kg 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: adults and pediatric patients weighing at least 25 kg with an estimated creatinine clearance greater than or equal to 30 mL/min; or 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) ] . 2.3 Recommended Dosage in Pediatric Patients Weighing at Least 14 kg to Less than 25 kg 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: 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. 2.4 Not Recommended in Patients with Severe Renal Impairment BIKTARVY is not recommended in patients with [see Dosage and Administration (2.2 , 2.3) , and Use in Specific Populations (8.6) ] : severe renal impairment (estimated creatinine clearance of 15 to below 30 mL/min); or end stage renal disease (ESRD; estimated creatinine clearance below 15 mL/min who are not receiving chronic hemodialysis; or no antiretroviral treatment history and ESRD who are receiving chronic hemodialysis. 2.5 Not Recommended in Patients with Severe Hepatic Impairment BIKTARVY is not recommended in patients with severe hepatic impairment (Child-Pugh Class C) [see Use in Specific Populations (8.7) , and Clinical Pharmacology (12.3) ].
Paediatric
8.4 Pediatric Use The safety and effectiveness of BIKTARVY have been established as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in 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 resistance to bictegravir or tenofovir [see Indications and Usage (1) , and Dosage and Administration (2.2 , 2.3) ] . Use of BIKTARVY in pediatric patients weighing at least 14 kg is supported by the following: trials in adults [see Clinical Studies (14.1) ] an open-label trial in three age-based cohorts of virologically-suppressed pediatric subjects [see Clinical Studies (14.4) ] Cohort 1: 12 to less than 18 years of age and weighing at least 35 kg receiving BIKTARVY through Week 48 (N=50), Cohort 2: 6 to less than 12 years of age and weighing at least 25 kg receiving BIKTARVY through Week 24 (N=50), and Cohort 3: at least 2 years of age and weighing at least 14 to less than 25 kg through Week 24 (N=22). No pediatric subjects 2 years of age were enrolled; of the 6 pediatric subjects who were 3 years of age at enrollment, 3 subjects weighed between 14 to less than 15 kg. The safety and efficacy of BIKTARVY in these pediatric subjects were similar to that in adults, and there was no clinically significant change in exposure for the components of BIKTARVY [see Adverse Reactions (6.1) , Clinical Pharmacology (12.3) , and Clinical Studies (14.4) ] . Safety and effectiveness of BIKTARVY in pediatric patients weighing less than 14 kg have not been established.
Renal
Dose-adjust renally cleared NRTIs; TDF nephrotoxicity monitoring.
- CrCl 0–120: Confirm renal dosing in product SmPC / primary label.
Hepatic
Several agents hepatotoxic; monitor with HBV/HCV co-infection.
Safety
Drug interactions
- For precautions, contraindications and side effects see Tenofovir and Emtricitabine respectively.
- Fixed-dose/multi-ingredient product.
- Clinical details partially inherited from component monographs: Tenofovir, Emtricitabine.
- Confirm combination SmPC for exact dosing.
Safety
Adverse effects
- 6 ADVERSE REACTIONS The following adverse reactions are discussed in other sections of the labeling: Severe Acute Exacerbations of Hepatitis B [see Warnings and Precautions (5.1) ] .
- Immune Reconstitution Syndrome [see Warnings and Precautions (5.3) ] .
- New Onset or Worsening Renal Impairment [see Warnings and Precautions (5.4) ].
- Lactic Acidosis/Severe Hepatomegaly with Steatosis [see Warnings and Precautions (5.5) ].
- Most common adverse reactions (incidence greater than or equal to 5%, all grades) are diarrhea, nausea, and headache.
- ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Gilead Sciences, Inc. at 1-800-GILEAD-5 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
- Clinical Trials in Adults with No Antiretroviral Treatment History The primary safety assessment of BIKTARVY was based on data from two randomized, double-blind, active-controlled trials, Trial 1489 and Trial 1490, that enrolled 1274 HIV-1 infected adult subjects with no antiretroviral treatment history through Week 144.
- After Week 144, subjects received open-label BIKTARVY in an optional extension phase for an additional 96 weeks (end of study).
- A total of 634 and 1025 subjects received one tablet of BIKTARVY once daily during the double-blind (Week 144) and extension phases, respectively [see Clinical Studies (14.2) ] .
- The most common adverse reactions (all Grades) reported in at least 5% of subjects in the BIKTARVY group in either Trial 1489 or Trial 1490 were diarrhea, nausea, and headache.
- The proportion of subjects who discontinued treatment through Week 144 with BIKTARVY, abacavir [ABC]/dolutegravir [DTG]/ lamivudine [3TC]), or DTG + FTC/TAF, due to adverse events, regardless of severity, was 1%, 2%, and 2%, respectively.
- Table 1 displays the frequency of adverse reactions (all Grades) greater than or equal to 2% in the BIKTARVY group.
- Table 1 Adverse Reactions Frequencies of adverse reactions are based on all adverse events attributed to trial drugs by the investigator.
- No adverse reactions of Grade 2 or higher occurred in > 1% of subjects treated with BIKTARVY.
Use
Indications
- 1 INDICATIONS AND USAGE 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: 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.
- BIKTARVY is a three-drug combination of bictegravir (BIC), a human immunodeficiency virus type 1 (HIV-1) integrase strand transfer inhibitor (INSTI), and emtricitabine (FTC) and tenofovir alafenamide (TAF), both HIV-1 nucleoside analog reverse transcriptase inhibitors (NRTIs), and is 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.
Pharmacology
Mode of action
12.
Full mechanism text
12.1 Mechanism of Action BIKTARVY is a fixed dose combination of antiretroviral drugs bictegravir (BIC), emtricitabine (FTC), and tenofovir alafenamide (TAF) [see Microbiology (12.4) ] .
ADME
Pharmacokinetics & PD
| Onset | Varies (hours–days) |
|---|---|
| Duration | Regimen-dependent; ART lifelong |
| Route | ORAL / IV / TOPICAL |
| Absorption | T max (h) Values reflect administration of BIKTARVY with or without food. 2.0–4.0 1.5–2.0 0.5–2.0 Effect of high-fat meal (relative to fasting) Values refer to geometric mean ratio [high-fat meal/ fasting] in PK parameters and (90% confidence interval). High fat meal is approxima... |
| Distribution | % bound to human plasma proteins >99 <4 ~80 Blood-to-plasma ratio 0.64 0.6 1.0 |
| Metabolism | Metabolic pathway(s) CYP3A UGT1A1 Not significantly metabolized Cathepsin A In vivo , 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... |
| Elimination | t 1/2 (h) t 1/2 values refer to median (Q1, Q3) terminal plasma |
| Half-life | of 150–180 hours within PBMCs. 17.3 (14.8, 20.7) 10.4 (9.0, 12.0) 0.51 (0.45, 0.62) |
Full PK/PD text
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action BIKTARVY is a fixed dose combination of antiretroviral drugs bictegravir (BIC), emtricitabine (FTC), and tenofovir alafenamide (TAF) [see Microbiology (12.4) ] . 12.2 Pharmacodynamics Cardiac Electrophysiology In a thorough QT/QTc trial in 48 healthy subjects, BIC at doses 1.5 and 6 times the recommended dose did not affect the QT/QTc interval and did not prolong the PR interval. In a thorough QT/QTc trial in 48 healthy subjects, TAF at the recommended dose or at a dose 5 times the recommended dose, did not affect the QT/QTc interval and did not prolong the PR interval. The effect of FTC on the QT interval is not known. Effects on Serum Creatinine Mean change from baseline in serum creatinine in healthy subjects who received BIC 75 mg (1.5 times the approved recommended dosage) once daily with food for 14 days was 0.1 mg per dL on Days 7 and 14 compared to placebo. BIC did not have a significant effect on the estimated creatinine clearance or on the actual glomerular filtration rate (determined by the clearance of probe drug, iohexol). 12.3 Pharmacokinetics The pharmacokinetic (PK) properties of BIKTARVY components are provided in Table 4. The multiple dose PK parameters of BIKTARVY components (based on population pharmacokinetic analysis) are provided in Table 5. Table 4 Pharmacokinetic Properties of the Components of BIKTARVY Bictegravir (BIC) Emtricitabine (FTC) Tenofovir Alafenamide (TAF) PBMCs=peripheral blood mononuclear cells; CES1=carboxylesterase 1 Absorption T max (h) Values reflect administration of BIKTARVY with or without food. 2.0–4.0 1.5–2.0 0.5–2.0 Effect of high-fat meal (relative to fasting) Values refer to geometric mean ratio [high-fat meal/ fasting] in PK parameters and (90% confidence interval). High fat meal is approximately 800 kcal, 50% fat. AUC ratio 1.24 (1.16, 1.33) 0.96 (0.93, 0.99) 1.63 (1.43, 1.85) C max ratio 1.13 (1.06, 1.20) 0.86 (0.78, 0.93) 0.92 (0.73, 1.14) Distribution % bound to human plasma proteins >99 <4 ~80 Blood-to-plasma ratio 0.64 0.6 1.0 Elimination t 1/2 (h) t 1/2 values refer to median (Q1, Q3) terminal plasma half-life. Note that the active metabolite of TAF, tenofovir diphosphate, has a half-life of 150–180 hours within PBMCs. 17.3 (14.8, 20.7) 10.4 (9.0, 12.0) 0.51 (0.45, 0.62) Metabolism Metabolic pathway(s) CYP3A UGT1A1 Not significantly metabolized Cathepsin A In vivo , 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. (PBMCs) CES1 (hepatocytes) Excretion Major route of elimination Metabolism Glomerular filtration and active tubular secretion Metabolism % of dose excreted in urine Dosing in mass balance studies: single dose administration of [ 14 C] BIC; single dose administration of [ 14 C] FTC after multiple dosing of FTC for ten days; single dose administration of [ 14 C] TAF. 35 70 <1 % of dose excreted in feces 60.3 13.7 31.7 Table 5 Multiple Dose PK Parameters of BIC, FTC, and TAF Following Oral Administration of BIKTARVY in HIV-Infected Adults Parameter Mean (CV%) Bictegravir Emtricitabine Tenofovir Alafenamide CV=Coefficient of Variation; NA=Not Applicable C max (microgram per mL) 6.15 (22.9) 2.13 (34.7) 0.121 (15.4) AUC tau (microgram∙h per mL) 102 (26.9) 12.3 (29.2) 0.142 (17.3) C trough (microgram per mL) 2.61 (35.2) 0.096 (37.4) NA Specific Populations Patients with Renal Impairment No clinically relevant differences in the pharmacokinetics of BIC, TAF, or its metabolite tenofovir were observed between subjects with severe renal impairment (estimated creatinine clearance of 15 to less than 30 mL/min, by Cockcroft-Gault method) and healthy subjects in Phase 1 studies. In a separate Phase 1 study of FTC alone, FTC exposures were increased in subjects with severe renal impairment. The pharmacokinetics of BIC, FTC and TAF were evaluated in a subset of HIV-1 infected virologically-suppressed subjects with ESRD (estimated creatinine clearance less than 15 mL/min, by Cockcroft-Gault method) receiving chronic hemodialysis in Trial 1825. The pharmacokinetics of TAF were similar between healthy subjects and subjects with ESRD receiving chronic hemodialysis; increases in FTC and tenofovir exposures in subjects with ESRD were not considered clinically relevant. Median (minimum, maximum) BIC C trough values in subjects (n=7) with ESRD who received BIKTARVY were 846 ng/mL (288, 1810) compared to 2540 ng/mL (757, 6499) in subjects (N=584) with normal renal function. Despite significantly lower BIC C trough values in the virologically-suppressed ESRD population, virologic suppression was maintained [see Use in Specific Populations (8.6) , and Clinical Studies (14.3) ] . Patients with Hepatic Impairment Bictegravir: Clinically relevant changes in the pharmacokinetics of BIC were not observed in subjects with moderate (Child-Pugh Class B) hepatic impairment. Emtricitabine: The pharmacokinetics of FTC has not been studied in subjects with hepatic impairment; however, FTC is not significantly metabolized by liver enzymes, so the impact of hepatic impairment should be limited. Tenofovir Alafenamide: Clinically relevant changes in the pharmacokinetics of TAF or its metabolite tenofovir were not observed in subjects with mild or moderate (Child-Pugh Class A and B) hepatic impairment [see Use in Specific Populations (8.7) ] . Hepatitis B and/or Hepatitis C Virus Coinfection The pharmacokinetics of BIC, FTC, and TAF have not been evaluated in subjects coinfected with hepatitis B and/or C virus. Geriatric Patients The pharmacokinetics of BIC, FTC, and TAF have not been fully evaluated in the elderly (65 years of age and older). Population pharmacokinetics analysis of HIV-infected subjects in Phase 3 trials of BIKTARVY showed that age did not have a clinically relevant effect on exposures of BIC and TAF up to 74 years of age [see Use in Specific Populations (8.5) ] . Pediatric Patients Mean BIC C trough was lower in 50 pediatric patients aged 12 to less than 18 years and weighing at least 35 kg who received BIKTARVY in Trial 1474 relative to adults following administration of BIKTARVY, but was not considered clinically significant based on exposure-response relationships; exposures of FTC and TAF in these pediatric patients were similar to those in adults (Table 6). Table 6 Multiple Dose PK Parameters of BIC, FTC, and TAF Following Oral Administration of BIKTARVY in HIV-Infected Pediatric Subjects Aged 12 to less than 18 years Parameter Mean (CV%) Bictegravir From Population PK analysis of cohort 1 of Trial 1474 (n=50 for BIC; n=49 for TAF). Emtricitabine From Intensive PK analysis of cohort 1 of Trial 1474 (n=24). Tenofovir Alafenamide CV=Coefficient of Variation; NA=Not Applicable C max (microgram per mL) 6.24 (27.1) 2.69 (34.0) 0.133 (70.2) AUC tau (microgram∙h per mL) 89.1 (31.0) 13.6 (21.7) 0.196 (50.3) C trough (microgram per mL) 1.78 (44.4) 0.064 (25.0) NA Mean BIC C max , and exposures of FTC and TAF (AUC tau and C max ) achieved in 50 pediatric patients between the ages of 6 to less than 12 years and weighing at least 25 kg, and in 22 pediatric patients at least 2 years of age and weighing at least 14 to less than 25 kg who received BIKTARVY in Trial 1474 were higher than exposures in adults; however, the increases were not considered clinically significant as the safety profiles were similar in adult and pediatric patients (Tables 7 and 8) [see Use in Specific Populations (8.4) ] . Table 7 Multiple Dose PK Parameters of BIC, FTC, and TAF Following Oral Administration of BIKTARVY in HIV-Infected Pediatric Subjects Aged 6 to less than 12 years Parameter Mean (CV%) Bictegravir From Population PK analysis of cohort 2 of Trial 1474 (n=50 for BIC; n=47 for TAF). Emtricitabine From Intensive PK analysis of cohort 2 of Trial 1474 (n=25 except n=24 for C trough ). Tenofovir Alafenamide CV=Coefficient of Variation; NA=Not Applicable C max (microgram per mL) 9.46 (24.3) 3.89 (31.0) 0.205 (44.6) AUC tau (microgram∙h per mL) 128 (27.8) 17.6 (36.9) 0.278 (40.3) C trough (microgram per mL) 2.36 (39.0) 0.227 (323) NA Table 8 Multiple Dose PK Parameters of BIC, FTC, and TAF Following Oral Administration of BIKTARVY in HIV-Infected Pediatric Subjects at Least 2 Years of Age Cohort 3 of Trial 1474 enrolled pediatric subjects from 3 to 9 years of age. and Weighing at Least 14 to Less than 25 kg Parameter Mean (CV%) Bictegravir From Population PK analysis of cohort 3 of Trial 1474 (n=22). Emtricitabine From Intensive PK analysis of cohort 3 of Trial 1474 (n=12 except n=11 for C trough for FTC). Tenofovir Alafenamide CV=Coefficient of Variation; NA=Not Applicable C max (microgram per mL) 9.15 (44.8) 3.85 (34.7) 0.414 (31.0) AUC tau (microgram∙h per mL) 126 (42.4) 15.0 (21.9) 0.305 (42.6) C trough (microgram per mL) 2.43 (40.1) 0.210 (243) NA Race and Gender No clinically relevant changes in the pharmacokinetics of BIC, FTC, and TAF were observed based on gender or race. Drug Interaction Studies As BIKTARVY is a complete regimen for the treatment of HIV-1 infection, comprehensive information regarding potential drug-drug interactions with other antiretroviral agents is not provided. BIC is a substrate of CYP3A and UGT1A1. BIC is an inhibitor of OCT2 and MATE1. At clinically relevant concentrations, BIC is not an inhibitor of hepatic transporters OATP1B1, OATP1B3, OCT1, BSEP, renal transporters OAT1 and OAT3, or CYP (including CYP3A) or UGT1A1 enzymes. TAF is a substrate of P-gp and BCRP. At clinically relevant concentrations, TAF is not an inhibitor of drug transporters P-gp, BCRP, hepatic transporters OATP1B1, OATP1B3, OCT1, BSEP, renal transporters OAT1, OAT3, OCT2, MATE1, or CYP (including CYP3A) or UGT1A1 enzymes. Drug interaction studies were conducted with BIKTARVY or its components. Tables 9 and 10 summarize the pharmacokinetic effects of other drugs on BIC and TAF, respectively. Table 11 summarizes the pharmacokinetic effects of BIKTARVY or its components on other drugs. Effect of Other Drugs on BIKTARVY Components Table 9 Effect of Other Drugs on BIC All interaction studies conducted in healthy volunteers. Coadministered Drug Dose of Coadministered Drug (mg) BIC (mg) Mean Ratio of BIC Pharmacokinetic Parameters (90% CI); No effect = 1.00 C max AUC C min NA= Not Applicable Ledipasvir/Sofosbuvir (fed) 90/400 once daily 75 once daily 0.98 (0.94, 1.03) 1.00 (0.97, 1.03) 1.04 (0.99, 1.09) Rifabutin (fasted) 300 once daily 75 once daily 0.80 (0.67, 0.97) 0.62 (0.53, 0.72) 0.44 (0.37, 0.52) Rifampin (fed) 600 once daily 75 single dose 0.72 (0.67, 0.78) 0.25 (0.22, 0.27) NA Sofosbuvir/ velpatasvir/ voxilaprevir (fed) 400/100/100+100 voxilaprevir Study conducted with additional voxilaprevir 100 mg to achieve voxilaprevir exposures expected in HCV-infected patients. once daily 50 once daily 0.98 (0.94, 1.01) 1.07 (1.03, 1.10) 1.10 (1.05, 1.17) Voriconazole (fasted) 300 twice daily 75 single dose 1.09 (0.96, 1.23) 1.61 (1.41, 1.84) NA Maximum strength antacid (simultaneous administration, fasted) 20 mL Maximum strength antacid contained 80 mg aluminum hydroxide, 80 mg magnesium hydroxide, and 8 mg simethicone, per mL. single dose (oral) 50 single dose 0.20 (0.16, 0.24) 0.21 (0.18, 0.26) NA Maximum strength antacid (2 h after BIKTARVY fasted) 20 mL single dose (oral) 50 single dose 0.93 (0.88, 1.00) 0.87 (0.81, 0.93) NA Maximum strength antacid (2 h before BIKTARVY fasted) 20 mL single dose (oral) 50 single dose 0.42 (0.33, 0.52) 0.48 (0.38, 0.59) NA Maximum strength antacid (simultaneous administration, fed Reference treatment administered under fasted conditions. ) 20 mL single dose (oral) 50 single dose 0.51 (0.43, 0.62) 0.53 (0.44, 0.64) NA Calcium carbonate (simultaneous administration, fasted) 1200 single dose 50 single dose 0.58 (0.51, 0.67) 0.67 (0.57, 0.78) NA Calciu
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Special populations
Pregnancy & lactation
Pregnancy
8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to BIKTARVY during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263. Risk Summary There are insufficient human data on the use of BIKTARVY during pregnancy to inform a drug-associated risk of birth defects and miscarriage. Dolutegravir, another integrase inhibitor, has been associated with neural tube defects (NTDs) (see Data ) . Discuss the benefit-risk of using BIKTARVY with individuals of childbearing potential, particularly if pregnancy is being planned. BIKTARVY use during pregnancy has been evaluated in a limited number of women reported to the APR; consequently, there are insufficient BIC data from the APR to adequately assess the risk of major birth defects. Reports of pregnant individuals treated with other drug products containing TAF or FTC contribute to APR's overall risk assessment for these components. Available data from the APR show no statistically significant difference in the overall risk of major birth defects for FTC or TAF compared with the background rate for major birth defects of 2.7% in a U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP) (see Data ) . The rate of miscarriage is not reported in the APR. The estimated background rate of miscarriage in the clinically recognized pregnancies in the U.S. general population is 15–20%. In animal reproduction studies, no evidence of adverse developmental outcomes was observed with the components of BIKTARVY at exposures that were either not maternally toxic (rabbits) or greater than (rats and mice) those in humans at the recommended human dose (RHD) ( see Data ). During organogenesis, systemic exposures (AUC) to BIC were approximately 36 (rats) and 0.6 times (rabbits), to FTC were approximately 60 (mice) and 108 times (rabbits), and to TAF were approximately 2 (rats) and 78 times (rabbits) the exposure at the RHD of BIKTARVY. In rat pre/postnatal development studies, maternal systemic exposures (AUC) were 30 times (BIC), 60 times (FTC), and 19 times (TDF) the exposures of each component in humans at the RHD. Data Human Data Prospective reports from the APR of overall major birth defects in pregnancies exposed to the components of BIKTARVY are compared with a U.S. background major birth defect rate. Methodological limitations of the APR include the use of MACDP as the external comparator group. The MACDP population is not disease-specific, evaluates women and infants from a limited geographic area, and does not include outcomes for births that occurred at less than 20 weeks gestation. Bictegravir (BIC): Data from an observational study in Botswana showed that dolutegravir, another integrase inhibitor, was associated with increased risk of neural tube defects when administered at the time of conception and in early pregnancy. Data available to date from other sources including the APR, clinical trials, and postmarketing data are insufficient to address this risk with BIC. There are an insufficient number of reports to the APR to adequately assess the risk of major birth defects associated with BIC exposure. The APR has received prospective reports of 3 birth defects among 100 (3.0%) first trimester exposures to BIC-containing regimens during pregnancy resulting in live births. No birth defects were reported among 40 exposures during the second/third trimester. Emtricitabine (FTC): Based on prospective reports to the APR of over 5,400 exposures to FTC-containing regimens during pregnancy resulting in live births (including over 3,900 exposed in the first trimester and over 1,500 exposed in the second/third trimester), the prevalence of birth defects in live births was 2.6% (95% CI: 2.2% to 3.2%) and 2.7% (95% CI: 1.9% to 3.7%) following first and second/third trimester exposure, respectively, to FTC-containing regimens. Tenofovir Alafenamide (TAF): Based on prospective reports to the APR of over 660 exposures to TAF-containing regimens during pregnancy resulting in live births (including over 520 exposed in the first trimester and over 130 exposed in the second/third trimester), the prevalence of birth defects in live births was 4.2% (95% CI: 2.6% to 6.3%) and 3.0% (95% CI: 0.8% to 7.5%) following first and second/third trimester exposure, respectively, to TAF-containing regimens. Animal Data Bictegravir: BIC was administered orally to pregnant rats (5, 30, or 300 mg/kg/day) and rabbits (100, 300, or 1000 mg/kg/day) on gestation days 7 through 17, and 7 through 19, respectively. No adverse embryo-fetal effects were observed in rats and rabbits at BIC exposures (AUC) of up to approximately 36 (rats) and 0.6 (rabbits) times the exposure in humans at the RHD of BIKTARVY. Spontaneous abortion, increased clinical signs [fecal changes, thin body, and cold-to-touch], and decreased body weight were observed at a maternally toxic dose in rabbits (1000 mg/kg/day; approximately 1.4 times higher than human exposure at the RHD). In a pre/postnatal development study, BIC was administered orally to pregnant rats (up to 300 mg/kg/day) from gestation days 6 to lactation/post-partum day 24. No significant adverse effects were observed in the offspring exposed daily from before birth ( in utero ) through lactation at maternal and pup exposures (AUC) of approximately 30 and 11 times higher, respectively, than human exposures at the RHD. Emtricitabine: FTC was administered orally to pregnant mice (250, 500, or 1000 mg/kg/day) and rabbits (100, 300, or 1000 mg/kg/day) through organogenesis (on gestation days 6 through 15, and 7 through 19, respectively). No significant toxicological effects were observed in embryo-fetal toxicity studies performed with emtricitabine in mice at exposures approximately 60 times higher and in rabbits at approximately 108 times higher than human exposures at the RHD. In a pre/postnatal development study with FTC, mice were administered doses up to 1000 mg/kg/day; no significant adverse effects directly related to drug were observed in the offspring exposed daily from before birth ( in utero ) through sexual maturity at daily exposures (AUC) of approximately 60 times higher than human exposures at the RHD. Tenofovir alafenamide: TAF was administered orally to pregnant rats (25, 100, or 250 mg/kg/day) and rabbits (10, 30, or 100 mg/kg/day) through organogenesis (on gestation days 6 through 17, and 7 through 20, respectively). No adverse embryo-fetal effects were observed in rats and rabbits at TAF exposures of approximately 2 (rats) and 78 (rabbits) times higher than the exposure in humans at the recommended daily dose of BIKTARVY. TAF is rapidly converted to tenofovir; the observed tenofovir exposure in rats and rabbits were 55 (rats) and 86 (rabbits) times higher than human tenofovir exposures at the RHD. Since TAF is rapidly converted to tenofovir and lower tenofovir exposures in rats and mice were observed after TAF administration compared to TDF administration, a pre/postnatal development study in rats was conducted only with TDF. Doses up to 600 mg/kg/day were administered through lactation; no adverse effects were observed in the offspring on gestation day 7 [and lactation day 20] at tenofovir exposures of approximately 12 [19] times higher than the exposures in humans at the RHD of BIKTARVY.
Lactation
Pediatrics: Not recommended for patients weighing less than 14 kg. ( 8.4 ) 8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to BIKTARVY during pregnancy. Healthcare providers are encouraged to register patients by calling the Antiretroviral Pregnancy Registry (APR) at 1-800-258-4263. Risk Summary There are insufficient human data on the use of BIKTARVY during pregnancy to inform a drug-associated risk of birth defects and miscarriage. Dolutegravir, another integrase inhibitor, has been associated with neural tube defects (NTDs) (see Data ) . Discuss the benefit-risk of using BIKTARVY with individuals of childbearing potential, particularly if pregnancy is being planned. BIKTARVY use during pregnancy has been evaluated in a limited number of women reported to the APR; consequently, there are insufficient BIC data from the APR to adequately assess the risk of major birth defects. Reports of pregnant individuals treated with other drug products containing TAF or FTC contribute to APR's overall risk assessment for these components. Available data from the APR show no statistically significant difference in the overall risk of major birth defects for FTC or TAF compared with the background rate for major birth defects of 2.7% in a U.S. reference population of the Metropolitan Atlanta Congenital Defects Program (MACDP) (see Data ) . The rate of miscarriage is not reported in the APR. The estimated background rate of miscarriage in the clinically recognized pregnancies in the U.S. general population is 15–20%. In animal reproduction studies, no evidence of adverse developmental outcomes was observed with the components of BIKTARVY at exposures that were either not maternally toxic (rabbits) or greater than (rats and mice) those in humans at the recommended human dose (RHD) ( see Data ). During organogenesis, systemic exposures (AUC) to BIC were approximately 36 (rats) and 0.6 times (rabbits), to FTC were approximately 60 (mice) and 108 times (rabbits), and to TAF were approximately 2 (rats) and 78 times (rabbits) the exposure at the RHD of BIKTARVY. In rat pre/postnatal development studies, maternal systemic exposures (AUC) were 30 times (BIC), 60 times (FTC), and 19 times (TDF) the exposures of each component in humans at the RHD. Data Human Data Prospective reports from the APR of overall major birth defects in pregnancies exposed to the components of BIKTARVY are compared with a U.S. background major birth defect rate. Methodological limitations of the APR include the use of MACDP as the external comparator group. The MACDP population is not disease-specific, evaluates women and infants from a limited geographic area, and does not include outcomes for births that occurred at less than 20 weeks gestation. Bictegravir (BIC): Data from an observational study in Botswana showed that dolutegravir, another integrase inhibitor, was associated with increased risk of neural tube defects when administered at the time of conception and in early pregnancy. Data available to date from other sources including the APR, clinical trials, and postmarketing data are insufficient to address this risk with BIC. There are an insufficient number of reports to the APR to adequately assess the risk of major birth defects associated with BIC exposure. The APR has received prospective reports of 3 birth defects among 100 (3.0%) first trimester exposures to BIC-containing regimens during pregnancy resulting in live births. No birth defects were reported among 40 exposures during the second/third trimester. Emtricitabine (FTC): Based on prospective reports to the APR of over 5,400 exposures to FTC-containing regimens during pregnancy resulting in live births (including over 3,900 exposed in the first trimester and over 1,500 exposed in the second/third trimester), the prevalence of birth defects in live births was 2.6% (95% CI: 2.2% to 3.2%) and 2.7% (95% CI: 1.9% to 3.7%) following first and second/third trimester exposure, respectively, to FTC-containing regimens. Tenofovir Alafenamide (TAF): Based on prospective reports to the APR of over 660 exposures to TAF-containing regimens during pregnancy resulting in live births (including over 520 exposed in the first trimester and over 130 exposed in the second/third trimester), the prevalence of birth defects in live births was 4.2% (95% CI: 2.6% to 6.3%) and 3.0% (95% CI: 0.8% to 7.5%) following first and second/third trimester exposure, respectively, to TAF-containing regimens. Animal Data Bictegravir: BIC was administered orally to pregnant rats (5, 30, or 300 mg/kg/day) and rabbits (100, 300, or 1000 mg/kg/day) on gestation days 7 through 17, and 7 through 19, respectively. No adverse embryo-fetal effects were observed in rats and rabbits at BIC exposures (AUC) of up to approximately 36 (rats) and 0.6 (rabbits) times the exposure in humans at the RHD of BIKTARVY. Spontaneous abortion, increased clinical signs [fecal changes, thin body, and cold-to-touch], and decreased body weight were observed at a maternally toxic dose in rabbits (1000 mg/kg/day; approximately 1.4 times higher than human exposure at the RHD). In a pre/postnatal development study, BIC was administered orally to pregnant rats (up to 300 mg/kg/day) from gestation days 6 to lactation/post-partum day 24. No significant adverse effects were observed in the offspring exposed daily from before birth ( in utero ) through lactation at maternal and pup exposures (AUC) of approximately 30 and 11 times higher, respectively, than human exposures at the RHD. Emtricitabine: FTC was administered orally to pregnant mice (250, 500, or 1000 mg/kg/day) and rabbits (100, 300, or 1000 mg/kg/day) through organogenesis (on gestation days 6 through 15, and 7 through 19, respectively). No significant toxicological effects were observed in embryo-fetal toxicity studies performed with emtricitabine in mice at exposures approximately 60 times higher and in rabbits at approximately 108 times higher than human exposures at the RHD. In a pre/postnatal development study with FTC, mice were administered doses up to 1000 mg/kg/day; no significant adverse effects directly related to drug were observed in the offspring exposed daily from before birth ( in utero ) through sexual maturity at daily exposures (AUC) of approximately 60 times higher than human exposures at the RHD. Tenofovir alafenamide: TAF was administered orally to pregnant rats (25, 100, or 250 mg/kg/day) and rabbits (10, 30, or 100 mg/kg/day) through organogenesis (on gestation days 6 through 17, and 7 through 20, respectively). No adverse embryo-fetal effects were observed in rats and rabbits at TAF exposures of approximately 2 (rats) and 78 (rabbits) times higher than the exposure in humans at the recommended daily dose of BIKTARVY. TAF is rapidly converted to tenofovir; the observed tenofovir exposure in rats and rabbits were 55 (rats) and 86 (rabbits) times higher than human tenofovir exposures at the RHD. Since TAF is rapidly converted to tenofovir and lower tenofovir exposures in rats and mice were observed after TAF administration compared to TDF administration, a pre/postnatal development study in rats was conducted only with TDF. Doses up to 600 mg/kg/day were administered through lactation; no adverse effects were observed in the offspring on gestation day 7 [and lactation day 20] at tenofovir exposures of approximately 12 [19] times higher than the exposures in humans at the RHD of BIKTARVY. 8.2 Lactation Risk Summary It is not known whether BIKTARVY or all of the components of BIKTARVY are present in human breast milk, affects human milk production, or has effects on the breastfed infant. Based on published data, FTC has been shown to be present in human breast milk. BIC was detected in the plasma of nursing rat pups likely due to the presence of BIC in milk, and tenofovir has been shown to be present in the milk of lactating rats and rhesus monkeys after administration of TDF (see Data ) . It is unknown if TAF is present in animal milk. Potential risks of breastfeeding include: (1) HIV-1 transmission to HIV-1 negative infants; (2) developing viral resistance in HIV-1 positive infants; and (3) adverse reactions in a breastfed infant similar to those seen in adults. Data Animal Data Bictegravir: BIC was detected in the plasma of nursing rat pups in the pre/postnatal development study (post-natal day 10), likely due to the presence of BIC in milk. Tenofovir alafenamide: Studies in rats and monkeys have demonstrated that tenofovir is secreted in milk. Tenofovir was excreted into the milk of lactating rats following oral administration of TDF (up to 600 mg/kg/day) at up to approximately 24% of the median plasma concentration in the highest dosed animals at lactation day 11 . Tenofovir was excreted into the milk of lactating monkeys following a single subcutaneous (30 mg/kg) dose of tenofovir at concentrations up to approximately 4% of plasma concentration, resulting in exposure (AUC) of approximately 20% of plasma exposure. 8.4 Pediatric Use The safety and effectiveness of BIKTARVY have been established as a complete regimen for the treatment of human immunodeficiency virus type 1 (HIV-1) infection in 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 resistance to bictegravir or tenofovir [see Indications and Usage (1) , and Dosage and Administration (2.2 , 2.3) ] . Use of BIKTARVY in pediatric patients weighing at least 14 kg is supported by the following: trials in adults [see Clinical Studies (14.1) ] an open-label trial in three age-based cohorts of virologically-suppressed pediatric subjects [see Clinical Studies (14.4) ] Cohort 1: 12 to less than 18 years of age and weighing at least 35 kg receiving BIKTARVY through Week 48 (N=50), Cohort 2: 6 to less than 12 years of age and weighing at least 25 kg receiving BIKTARVY through Week 24 (N=50), and Cohort 3: at least 2 years of age and weighing at least 14 to less than 25 kg through Week 24 (N=22). No pediatric subjects 2 years of age were enrolled; of the 6 pediatric subjects who were 3 years of age at enrollment, 3 subjects weighed between 14 to less than 15 kg. The safety and efficacy of BIKTARVY in these pediatric subjects were similar to that in adults, and there was no clinically significant change in exposure for the components of BIKTARVY [see Adverse Reactions (6.1) , Clinical Pharmacology (12.3) , and Clinical Studies (14.4) ] . Safety and effectiveness of BIKTARVY in pediatric patients weighing less than 14 kg have not been established. 8.5 Geriatric Use Clinical trials in virologically-suppressed subjects (Trials 4449, 1844, and 1878) included 111 subjects aged 65 years and over who received BIKTARVY, including 86 patients from an open-label, single-arm trial of subjects aged 65 years and over who were switched from their previous antiretroviral regimen to BIKTARVY [see Clinical Studies (14.3) ]. Of the total number of BIKTARVY-treated patients in these trials, 100 (90%) were 65 to 74 years of age, and 11 (10%) were 75 to 84 years of age. No overall differences in safety or effectiveness were observed between elderly subjects and adults between 18 and less than 65 years of age, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. 8.6 Renal Impairment The pharmacokinetics, safety, virologic and immunologic responses of FTC and TAF (components of BIKTARVY) were evaluated in a single arm, open-label trial (Trial 1825) in virologically-suppressed adults with ESRD (estimated creatinine clearance of less than 15 mL/min)…
Diet
Food & alcohol
- Drug & food interactions (label) 7 DRUG INTERACTIONS Because BIKTARVY is a complete regimen, coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended. ( 7.1 ) Consult the Full Prescribing Information prior to and during treatment for important drug interactions. ( 4 , 5.2 , 7 , 12.3 ) 7.1 Other Antiretroviral Medications Because BIKTARVY is a complete regimen, coadministration with other antiretroviral medications for the treatment of HIV-1 infection is not recommended [see Indications and Usage (1) ] . Comprehensive information regarding potential drug-drug interactions with other antiretroviral medications is not provided because the safety and efficacy of concomitant HIV-1 antiretroviral therapy is unknown. 7.2 Potential for BIKTARVY to Affect Other Drugs BIC inhibits organic cation transporter 2 (OCT2) and multidrug and toxin extrusion transporter 1 (MATE1) in vitro . Coadministration of BIKTARVY with drugs that are substrates of OCT2 and MATE1 (e.g., dofetilide) may increase their plasma concentrations (see Table 3 ). 7.3 Potential Effect of Other Drugs on One or More Components of BIKTARVY BIC is a substrate of CYP3A and UGT1A1. A drug that is a strong inducer of CYP3A and also an inducer of UGT1A1 can substantially decrease the plasma concentrations of BIC which may lead to loss of therapeutic effect of BIKTARVY and development of resistance [see Clinical Pharmacology (12.3) ] . The use of BIKTARVY with a drug that is a strong inhibitor of CYP3A and also an inhibitor of UGT1A1 may significantly increase the plasma concentrations of BIC. TAF is a substrate of P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP). Co-administration of drugs that inhibit P-gp and BCRP may increase the absorption and plasma concentrations of TAF [see Clinical Pharmacology (12.3) ] . Co-administration of drugs that induce P-gp activity are expected to decrease the absorption of TAF, resulting in decreased plasma concentration of TAF, which may lead to loss of therapeutic effect of BIKTARVY and development of resistance (see Table 3 ). 7.4 Drugs Affecting Renal Function Because FTC and tenofovir are primarily excreted by the kidneys by a combination of glomerular filtration and active tubular secretion, coadministration of BIKTARVY with drugs that reduce renal function or compete for active tubular secretion may increase concentrations of FTC, tenofovir, and other renally eliminated drugs and this may increase the risk of adverse reactions. 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 [see Warnings and Precautions (5.4) ] . 7.5 Established and Potentially Significant Drug Interactions Table 3 provides a listing of established or potentially clinically significant drug interactions with recommended prevention or management strategies. The dr
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Sources & disclaimer
Source: Local active-ingredient clinical extract; FDA drug label via OpenFDA/DailyMed; Component monographs (multi-source pipeline); Professional class pharmacology (Antiviral / antiretroviral)
Clinical review date not recorded.
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