Bictegravir, Emtricitabine, and Tenofovir Alafenamide (Monograph)

Drug class: HIV Integrase Inhibitors

Medically reviewed by Drugs.com on Dec 13, 2023. Written by ASHP.

Introduction

Antiretroviral; fixed combination of bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF).¹ Bictegravir (BIC) is an HIV-1 integrase strand transfer inhibitor (INSTI); emtricitabine (FTC) is an HIV-1 nucleoside reverse transcriptase inhibitor (NRTI), and tenofovir alafenamide (TAF) is an HIV-1 nucleotide reverse transcriptase inhibitor.¹

Uses for Bictegravir, Emtricitabine, and Tenofovir Alafenamide

Treatment of HIV Infection

Used as a complete regimen for treatment of HIV-1 infection in adults and pediatric patients weighing ≥14 kg who are antiretroviral-naïve (have not previously received antiretroviral therapy [ART]) or to replace the current antiretroviral regimen in those who are virologically suppressed (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 bictegravir, emtricitabine, or tenofovir.^{1 2 3 8 9 11 12 14 15 16 17 18 19}

Bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) is a co-formulation of 2 nucleotide/nucleoside reverse transcriptase inhibitors (NRTIs; tenofovir alafenamide and emtricitabine) and an integrase strand transfer inhibitor (INSTI; bictegravir); consult guidelines for the most current information on the place in therapy for this regimen.^{200 201 202}

Selection of an initial antiretroviral regimen should be individualized based on factors such as virologic efficacy, toxicity, pill burden, dosing frequency, drug-drug interaction potential, resistance test results, comorbid conditions, access, and cost.^{200 201 202}

Related/similar drugs

Descovy, tenofovir, Atripla, Stribild, Complera, Epzicom

Bictegravir, Emtricitabine, and Tenofovir Alafenamide Dosage and Administration

General

Pretreatment Screening

• Determine S_cr, estimated Cl_cr, urine glucose, and urine protein prior to initiation of BIC/FTC/TAF.¹ In patients with chronic kidney disease, also assess serum phosphorus.¹

• Test for HBV infection prior to initiation of BIC/FTC/TAF.¹

Patient Monitoring

• Monitor S_cr, estimated Cl_cr, urine glucose, and urine protein during treatment with BIC/FTC/TAF in all patients as clinically appropriate.¹ In patients with chronic kidney disease, also assess serum phosphorus.¹

• For several months after discontinuation of BIC/FTC/TAF, closely follow hepatic laboratory and clinical monitoring for signs of acute exacerbation of hepatitis B in patients coinfected with HBV infection.¹

Administration

Oral Administration

Administer fixed combination of BIC/FTC/TAF orally once daily without regard to food.¹

Dosage

BIC/FTC/TAF tablets contain bictegravir sodium, emtricitabine, and tenofovir alafenamide fumarate; dosage of bictegravir sodium expressed in terms of bictegravir and dosage of tenofovir alafenamide fumarate expressed in terms of tenofovir alafenamide.¹

Fixed-combination tablets of BIC/FTC/TAF are available in 2 different strengths: bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg, and bictegravir 30 mg, emtricitabine 120 mg, and tenofovir alafenamide 15 mg.¹

Pediatric Patients

HIV-1 Infection

Oral

Pediatric patients ≥25 kg: 1 tablet of BIC/FTC/TAF (bictegravir 50 mg, emtricitabine 200 mg, tenofovir alafenamide 25 mg) once daily.¹

Pediatric patients ≥14 kg to <25 kg: 1 tablet of BIC/FTC/TAF (bictegravir 30 mg, emtricitabine 120 mg, tenofovir alafenamide 15 mg) once daily.¹

Adults

HIV-1 Infection

Oral

1 tablet of BIC/FTC/TAF (bictegravir 50 mg, emtricitabine 200 mg, tenofovir alafenamide 25 mg) once daily.¹

Special Populations

Hepatic Impairment

Mild or moderate hepatic impairment (Child-Pugh class A or B): Dosage adjustments not needed.¹

Severe hepatic impairment (Child-Pugh class C): Not recommended.¹

Renal Impairment

Estimated Cl_cr ≥30 mL/minute: Dosage adjustments not needed.¹

Estimated Cl_cr 15 to <29 mL/minute: Not recommended.¹ Not studied in pediatric patients with an estimated Cl_cr < 30 mL/minute.¹

Estimated Cl_cr <15 mL/minute not receiving hemodialysis: Not recommended.¹

Estimated Cl_cr <15 mL/minute, anti-retroviral naïve, and receiving hemodialysis: Not recommended.¹

In antiretroviral experienced adults receiving hemodialysis, administer the dose of BIC/FTC/TAF on hemodialysis days after treatment.¹

Geriatric Use

Dosage adjustments not needed; however, increased sensitivity cannot be ruled out.¹

Cautions for Bictegravir, Emtricitabine, and Tenofovir Alafenamide

Contraindications

• Concomitant use of dofetilide is contraindicated since concomitant use may result in serious and/or life-threatening adverse effects due to possible increased dofetilide plasma concentrations.¹

• Concomitant use of rifampin is contraindicated since substantially decreased plasma bictegravir concentrations may occur and may result in loss of virologic response and development of resistance.¹

Warnings/Precautions

Warnings

HIV-infected Individuals Coinfected with HBV

Test all HIV-infected patients for presence of HBV before initiating antiretroviral therapy.¹

Severe acute exacerbations of HBV infection reported following discontinuance of preparations containing emtricitabine and/or TDF in HIV-infected patients with HBV infection (see Boxed Warning).¹ HBV exacerbations have been associated with hepatic decompensation and hepatic failure.¹ Such reactions could occur with BIC/FTC/TAF.¹

Closely monitor hepatic function (using both clinical and laboratory follow-up) for at least several months after BIC/FTC/TAF is discontinued in patients coinfected with HIV and HBV.¹ If appropriate, initiation of HBV treatment may be warranted.¹

Other Warnings and Precautions

Interactions

Concomitant use with certain drugs may result in drug interactions.¹ May lead to loss of therapeutic effect and possible development of resistance or possible adverse effects from increased exposures of concomitant drugs.¹

Consider potential for drug interactions prior to and during treatment with BIC/FTC/TAF and monitor for adverse effects associated with concomitant drugs.¹

Renal Toxicity

Renal impairment, including acute renal failure, proximal renal tubulopathy, and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), reported in patients receiving tenofovir prodrugs (e.g., TDF).¹

Determine S_cr, estimated Cl_cr, urine glucose, and urine protein prior to initiating BIC/FTC/TAF and monitor during treatment in all patients as clinically appropriate.¹ In patients with chronic kidney disease, also assess serum phosphorus.¹

BIC/FTC/TAF not recommended in patients with estimated Cl_cr15 to <30 mL/minute, and in patients with ESRD (estimated Cl_cr <15 mL/minute) who are not receiving hemodialysis, or who are receiving hemodialysis and are antiretroviral naïve.¹

Patients receiving a tenofovir prodrug who have impaired renal function or are receiving a nephrotoxic agent (e.g., high-dose or multiple NSAIAs) are at increased risk of developing adverse renal effects.¹

Discontinue BIC/FTC/TAF in patients who develop clinically important decreases in renal function or evidence of Fanconi syndrome.¹

Lactic Acidosis and Severe Hepatomegaly with Steatosis

Lactic acidosis and severe hepatomegaly with steatosis (sometimes fatal) reported in patients receiving HIV NRTIs, including emtricitabine and TDF, alone or in conjunction with other antiretrovirals.¹

Interrupt BIC/FTC/TAF treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (signs of hepatotoxicity may include hepatomegaly and steatosis even in the absence of marked increases in serum aminotransferase concentrations).¹

Immune Reconstitution Syndrome

During initial treatment, patients who respond to antiretroviral therapy may develop an inflammatory response to indolent or residual opportunistic infections (e.g., Mycobacterium avium complex [MAC], M. tuberculosis, cytomegalovirus [CMV], Pneumocystis jirovecii [formerly P. carinii]); this may necessitate further evaluation and treatment.¹

Autoimmune disorders (e.g., Graves' disease, polymyositis, Guillain-Barré syndrome, autoimmune hepatitis) also reported in the setting of immune reconstitution; time to onset is more variable and can occur many months after initiation of antiretroviral therapy.¹

Use of Fixed Combinations

Consider cautions, precautions, contraindications, and interactions associated with each component of BIC/FTC/TAF.¹ Consider cautionary information applicable to specific populations (e.g., pregnant or nursing women, individuals with hepatic or renal impairment, geriatric patients) for each drug in the fixed combination.¹

BIC/FTC/TAF is used alone as a complete regimen; use in conjunction with other antiretrovirals not recommended.¹

Specific Populations

Pregnancy

Antiretroviral Pregnancy Registry at 800-258-4263 or [Web].¹

Manufacturer states that data are insufficient regarding use of BIC/FTC/TAF in pregnant women to inform a drug-associated risk of birth defects or miscarriage.¹

In animals, no evidence of adverse developmental outcomes when individual components of BIC/FTC/TAF were administered in rabbits at exposures that were not maternally toxic or in rats and mice at exposures greater than those in humans at recommended human dosage.¹

Lactation

Not known whether bictegravir or tenofovir alafenamide distributed into human milk.¹ Emtricitabine is distributed into human milk.¹

Bictegravir detected in plasma of nursing rat pups, likely due to presence of bictegravir in milk.¹ Tenofovir distributed into milk in rats and rhesus monkey after administration of TDF; not known whether tenofovir alafenamide distributed into animal milk.¹

Not known whether BIC/FTC/TAF affects human milk production or affects breast-fed infant.¹

Instruct HIV-infected women not to breast-feed because of risk of HIV transmission and risk of adverse effects in the infant.¹

Pediatric Use

Safety and efficacy not established in pediatric patients weighing <14 kg.¹

Adverse effects in pediatric patients are similar to those reported in adults.¹

Geriatric Use

In studies of virologically-suppressed patients ≥65 years of age, no overall differences in safety or efficacy observed between older adults and younger adults; however, greater sensitivity of some older individuals cannot be ruled out.¹

Hepatic Impairment

BIC/FTC/TAF not recommended in patients with severe hepatic impairment (Child-Pugh class C); data not available regarding pharmacokinetics or safety in such patients.¹

Renal Impairment

Determine S_cr, estimated Cl_cr, urine glucose, and urine protein prior to initiating BIC/FTC/TAF and monitor during treatment in all patients as clinically appropriate.¹ In patients with chronic kidney disease, also assess serum phosphorus.¹

No clinically important differences in pharmacokinetics of bictegravir, tenofovir alafenamide, or tenofovir in patients with severe renal impairment compared to healthy controls.¹

Common Adverse Effects

Most common adverse reactions (≥5%): diarrhea, nausea, headache.¹

Drug Interactions

Bictegravir is a substrate of CYP3A;¹ emtricitabine is not a substrate of CYP isoenzymes.²¹⁸ Bictegravir and tenofovir alafenamide do not inhibit CYP isoenzymes (including CYP3A) at clinically relevant concentrations;¹ emtricitabine does not inhibit CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6, or 3A4.²¹⁸

Bictegravir is a substrate of UGT1A1.¹ Bictegravir and tenofovir alafenamide do not inhibit UGT1A1.¹

Tenofovir alafenamide is a substrate of P-glycoprotein (P-gp) transport; does not inhibit P-gp.¹

Tenofovir alafenamide is a substrate of breast cancer resistance protein (BCRP); does not inhibit BCRP.¹

Bictegravir inhibits renal organic cation transporter (OCT) 2; tenofovir alafenamide does not inhibit OCT2.¹ Bictegravir and tenofovir alafenamide do not inhibit OCT1.¹

Bictegravir inhibits multidrug and toxin extrusion transporter (MATE) 1; tenofovir alafenamide does not inhibit MATE1.¹

Bictegravir and tenofovir alafenamide do not inhibit renal organic anion transporter (OAT) 1 and OAT3 and do not inhibit hepatic organic anion transporter polypeptide (OATP) 1B1 or OATP1B3.¹

Bictegravir and tenofovir alafenamide do not inhibit bile salt export pump (BSEP).¹

Drugs Affecting Hepatic Microsomal Enzymes and Uridine Diphosphate-glucuronosyltransferase

Potent inducers of CYP3A that also are inducers of UGT1A1 enzyme: May decrease bictegravir plasma concentrations; possible decreased antiretroviral efficacy and development of resistance.¹

Potent inhibitors of CYP3A that also are inhibitors of UGT1A1: May increase bictegravir plasma concentrations.¹

Drugs Affecting P-glycoprotein Transport

Inducers of P-gp: May decrease absorption and plasma concentrations of tenofovir alafenamide; possible decreased antiretroviral efficacy and development of resistance.¹

Inhibitors of P-gp and BCRP: May increase absorption and plasma concentrations of tenofovir alafenamide.¹

Drugs Affecting Breast Cancer Resistance Protein

Inhibitors of P-gp and BCRP: May increase absorption and plasma concentrations of tenofovir alafenamide.¹

Drugs Affected by Renal Organic Cation Transporters

Drugs eliminated by OCT2: Possible increased concentrations of these drugs.¹

Drugs Affected by Multidrug and Toxin Extrusion Transporter

Drugs eliminated by MATE1: Possible increased concentrations of these drugs.¹

Drugs Affecting Renal Function

Drugs that reduce renal function or compete for active tubular secretion: Potential increased concentrations of emtricitabine, tenofovir, and/or concomitant drug.¹

Specific Drugs

Bictegravir, Emtricitabine, and Tenofovir Alafenamide Pharmacokinetics

Absorption

Bioavailability

Following oral administration of individual components of BIC/FTC/TAF with or without food, peak plasma concentrations of bictegravir, emtricitabine, and tenofovir occur at 2–4, 1.5–2, and 0.5–2 hours, respectively.¹

Food

Relative to fasting, administration of BIC/FTC/TAF components with high-fat meal (approximately 800 kcal, 50% fat) increases mean systemic exposures of bictegravir and tenofovir by 24 and 63%, respectively; no change in mean systemic exposures of emtricitabine.¹

Distribution

Extent

Bictegravir: Not known whether distributed into human milk.¹ Detected in plasma of nursing rat pups, likely due to presence of bictegravir in milk.¹

Emtricitabine: Distributed into human milk.¹

Tenofovir alafenamide: Not known whether distributed into human milk.¹ Following administration of tenofovir DF in rats and rhesus monkeys, tenofovir distributed into milk.¹

Plasma Protein Binding

Bictegravir: >99%.¹

Emtricitabine: <4%.¹

Tenofovir alafenamide: Approximately 80%.¹

Elimination

Metabolism

Bictegravir: Metabolized by CYP3A and UGT1A1.¹

Emtricitabine: Converted intracellularly to active 5′-triphosphate metabolite; not substantially metabolized further.¹

Tenofovir alafenamide: Prodrug of tenofovir; hydrolyzed intracellularly in peripheral blood mononuclear cells (PBMCs) and macrophages by cathepsin A to form tenofovir; subsequently metabolized to active metabolite (tenofovir diphosphate).¹ In vitro studies indicate tenofovir alafenamide also converted to tenofovir by carboxylesterase 1 (CES1) in hepatocytes.¹

Elimination Route

Bictegravir: 60% in feces, 35% in urine.¹

Emtricitabine: 70% in urine, 14% in feces.¹ Removed by hemodialysis (approximately 30% of a dose over 3 hours); not known whether removed by peritoneal dialysis.¹

Tenofovir alafenamide: 32% in feces, <1% in urine.¹ Removed by hemodialysis.¹

Half-life

Bictegravir: 17.3 hours.¹

Emtricitabine: 10.4 hours.¹

Tenofovir alafenamide: 0.5 hours; active metabolite (tenofovir diphosphate) half-life within PBMCs is 150–180 hours.¹

Special Populations

Mild hepatic impairment (Child-Pugh class A): No clinically important effect on pharmacokinetics of tenofovir alafenamide.¹

Moderate hepatic impairment (Child-Pugh class B): No clinically important effect on pharmacokinetics of bictegravir or tenofovir alafenamide.¹ Hepatic impairment not expected to affect pharmacokinetics of emtricitabine.¹

Severe hepatic impairment (Child-Pugh class C): Effect on bictegravir, emtricitabine, and tenofovir alafenamide not evaluated.¹

Severe renal impairment: No clinically important differences in pharmacokinetics of bictegravir, emtricitabine, or tenofovir alafenamide in severe renal impairment (estimated Cl_cr 15–30 mL/minute) and in virologically-suppressed patients with ESRD (estimated Cl_cr <15 mL/minute) undergoing chronic hemodialysis.¹

Pediatric patients ≥2 years of age weighing ≥14 to <25 kg: No clinically important differences in pharmacokinetics of bictegravir, emtricitabine, or tenofovir alafenamide compared with adults.¹

Age: Population pharmacokinetics analysis of HIV-infected patients receiving BIC/FTC/TAF shows that age does not have a clinically important effect on bictegravir or tenofovir alafenamide exposures in adults up to 74 years of age.¹

Race and gender: No clinically important differences in pharmacokinetics of bictegravir, emtricitabine, or tenofovir alafenamide.¹

Stability

Storage

Oral

Tablets

Store bottles at <30°C.¹

Store blister packs at 25ºC (excursions permitted between 15-30ºC).¹

Actions and Spectrum

• BIC/FTC/TAF is a fixed-combination antiretroviral containing bictegravir, emtricitabine, and tenofovir alafenamide.¹

• Bictegravir (BIC) is an HIV INSTI.¹ Inhibits activity of HIV-1 integrase, an enzyme that integrates HIV DNA into the host cell genome.¹ Active against HIV-1; also has some in vitro activity against HIV type 2 (HIV-2).¹

• Emtricitabine (FTC) is an HIV NRTI.¹ Inactive until converted intracellularly to an active 5′-triphosphate metabolite.¹ Active against HIV-1 and also has some in vitro activity against HIV-2.¹

• Tenofovir alafenamide (TAF) is a nucleotide reverse transcriptase inhibitor antiretroviral classified as an HIV NRTI.¹ Tenofovir alafenamide is a tenofovir prodrug that is inactive until hydrolyzed intracellularly by cathepsin A to form tenofovir and subsequently metabolized by cellular kinases to the active metabolite (tenofovir diphosphate).¹ Active against HIV-1 and has some in vitro activity against HIV-2.¹

• HIV-1 resistant to bictegravir, emtricitabine, or tenofovir produced in vitro.¹ In clinical trials evaluating BIC/FTC/TAF, no specific bictegravir or NRTI resistance-associated substitutions emerged in patients considered to be virologic treatment failures.¹

• Cross-resistance between bictegravir and other HIV INSTIs (e.g., dolutegravir, elvitegravir, raltegravir) reported.¹ Cross-resistance also occurs among HIV NRTIs.¹

Advice to Patients

• Advise patients of the critical need for compliance with HIV therapy and importance of remaining under the care of a clinician.¹ Importance of taking the fixed combination of bictegravir sodium, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) as prescribed; do not alter or discontinue antiretroviral regimen without consulting clinician.¹

• Advise patients that BIC/FTC/TAF is a complete regimen for treatment of HIV-1 infection and should not be used in conjunction with other antiretrovirals.¹

• Inform patients that testing for HBV infection is recommended before antiretroviral therapy is initiated.¹ Also advise patients that severe acute exacerbations of HBV infection have been reported following discontinuance of emtricitabine and/or tenofovir disoproxil fumarate (TDF; tenofovir DF) in HIV-infected patients coinfected with HBV and may occur with BIC/FTC/TAF.¹

• Advise patients that renal impairment, including cases of acute renal failure or Fanconi syndrome, has occurred in patients receiving tenofovir prodrugs.¹ Advise patients to not use BIC/FTC/TAF concomitantly with or shortly after nephrotoxic agents (e.g., high-dose or multiple nonsteroidal anti-inflammatory agents [NSAIAs]).¹

• Advise patients that lactic acidosis and severe hepatomegaly with steatosis, including fatalities, have occurred in patients receiving HIV nucleoside reverse transcriptase inhibitors (NRTIs), including emtricitabine and/or TDF, in conjunction with other antiretrovirals.¹ Advise patients to contact a clinician if symptoms suggestive of lactic acidosis or pronounced hepatotoxicity (e.g., unusual muscle pain, shortness of breath or fast breathing, cold or blue hands and feet, dizziness or lightheadedness, fast or abnormal heartbeat, nausea, vomiting, unusual/unexpected stomach discomfort, weakness or unusual tiredness) occur.¹

• Advise patients that signs and symptoms of inflammation from previous infections may occur soon after initiation of antiretroviral therapy in some individuals with advanced HIV infection (AIDS).¹ These symptoms may be due to an improvement in immune response, enabling the body to fight infections that may have been present with no obvious symptoms.¹ Advise patients to immediately inform a healthcare provider if any symptoms of infection occur.¹

• Inform caregivers that the BIC/FTC/TAF tablet may be split for children with difficulty swallowing the whole tablet.¹ If the tablet is split, the portions must all be taken within approximately 10 minutes.¹

• Adivse patients to inform their clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal supplements (e.g., St. John's wort), as well as any concomitant illnesses.¹

• Advise women to inform their clinicians if they are or plan to become pregnant or plan to breast-feed.¹ Advise HIV-infected women not to breast-feed.¹

• Inform patients of other important precautionary information.¹

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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