Bictegravir Sodium, Emtricitabine, and Tenofovir Alafenamide Fumarate (Monograph)

Drug class: HIV Integrase Inhibitors

Medically reviewed by Drugs.com on Oct 10, 2024. Written by ASHP.

Warning

Severe, acute exacerbations of HBV reported following discontinuance of preparations containing emtricitabine and/or the tenofovir prodrug tenofovir disoproxil fumarate (TDF; tenofovir DF) in patients coinfected with HIV and HBV; may occur with fixed combination of bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF).
Monitor hepatic function closely with both clinical and laboratory follow-up for at least several months after BIC/FTC/TAF discontinued in patients coinfected with HIV and HBV. If appropriate, initiation of HBV treatment may be warranted.

Introduction

Antiretroviral; fixed combination of bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF). 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.

Uses for Bictegravir Sodium, Emtricitabine, and Tenofovir Alafenamide Fumarate

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) 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 known or suspected substitutions associated with resistance to bictegravir or tenofovir.

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. Consult guidelines for the most current information on the place in therapy for this regimen.

Bictegravir Sodium, Emtricitabine, and Tenofovir Alafenamide Fumarate Dosage and Administration

General

Pretreatment Screening

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

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. In patients with chronic kidney disease, also assess serum phosphorus.
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.

Dispensing and Administration Precautions

The Institute for Safe Medication Practices (ISMP) list of error-prone abbreviations, symbols, and dose designations states that the use of abbreviations for antiretroviral medications (e.g., DOR, TAF, TDF) during the medication use process should be avoided as their use has been associated with serious medication errors.

Administration

Oral Administration

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

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.

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.

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.

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.

Adults

HIV-1 Infection

Oral

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

Special Populations

Hepatic Impairment

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

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

Renal Impairment

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

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

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

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

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

Geriatric Use

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

Pregnancy

Recommended dosage is 1 tablet containing 50 mg of bictegravir, 200 mg of emtricitabine, and 25 mg of tenofovir alafenamide once daily. Reduced drug exposures have been observed with use of BIC/FTC/TAF in pregnancy. Monitor viral load closely.

Cautions for Bictegravir Sodium, Emtricitabine, and Tenofovir Alafenamide Fumarate

Contraindications

Concomitant use of dofetilide since use may result in serious and/or life-threatening adverse effects due to possible increased dofetilide plasma concentrations.
Concomitant use of rifampin since substantially decreased plasma bictegravir concentrations may occur and result in loss of virologic response and development of resistance.

Warnings/Precautions

Warnings

Severe Acute Exacerbation of Hepatitis B in Patients Coinfected with HIV and HBV

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

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). HBV exacerbations have been associated with hepatic decompensation and hepatic failure. Such reactions could occur with BIC/FTC/TAF.

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. If appropriate, initiation of HBV treatment may be warranted.

Other Warnings and Precautions

Risk of Adverse Reactions or Loss of Virologic Response Due to Drug Interactions

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

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

New Onset or Worsening Renal Impairment

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).

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. In patients with chronic kidney disease, also assess serum phosphorus.

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.

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.

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

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.

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).

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.

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.

Use of Fixed Combinations

Consider cautions, precautions, contraindications, and interactions associated with each component of BIC/FTC/TAF. 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.

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

Specific Populations

Pregnancy

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

Manufacturer states that data regarding use of BIC, FTC, and TAF in pregnant women have not established a drug-associated risk of birth defects, miscarriage, or other adverse maternal or fetal outcomes.

Lactation

BIC, FTC, and TAF are present in human milk. No reported adverse effects of FTC or TAF on the breastfed child; no data exist on the effects of BIC on breastfed children.

Not known whether BIC/FTC/TAF affects human milk production.

Per HHS perinatal HIV transmission guideline, inform patients that feeding with appropriate formula or pasteurized donor human milk from a milk bank eliminates postnatal HIV transmission risk to the infant. Additionally, achieving and maintaining viral suppression with antiretroviral therapy during pregnancy and postpartum reduces risk of breastfeeding HIV transmission to <1%, but not does not completely eliminate risk. Replacement feeding with formula or banked pasteurized donor milk is recommended when patients with HIV are not on antiretroviral therapy and/or do not have a suppressed viral load during pregnancy (at a minimum throughout the third trimester), as well as at delivery.

Pediatric Use

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

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

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.

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.

Renal Impairment

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

Common Adverse Effects

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

Drug Interactions

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

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

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

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

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

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

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.

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

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.

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

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.

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

Drugs Affecting Breast Cancer Resistance Protein

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

Drugs Affected by Renal Organic Cation Transporters

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

Drugs Affected by Multidrug and Toxin Extrusion Transporter

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

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.

Specific Drugs

Drug	Interaction	Comments
Aminoglycosides (e.g., gentamicin)	Competition for active tubular secretion may increase concentrations of emtricitabine, tenofovir, and/or the aminoglycoside; may increase risk of adverse effects	Avoid concomitant use
Antacids, aluminum-, calcium-, or magnesium-containing	Simultaneous administration of antacid containing aluminum, magnesium, and simethicone in fed or fasting state: Decreased concentrations and AUC of bictegravir Administration of bictegravir in fasting state 2 hours after antacid containing aluminum, magnesium, and simethicone: Decreased concentrations and AUC of bictegravir Administration of bictegravir in fasting state 2 hours before antacid containing aluminum, magnesium, and simethicone: No clinically important interactions Other cation-containing antacids: Possible decreased bictegravir concentrations	Antacids containing aluminum or magnesium: Give BIC/FTC/TAF under fasting conditions ≥2 hours before or 6 hours after antacid; do not give simultaneously with or 2 hours after antacid Antacids containing calcium carbonate: May give simultaneously with BIC/FTC/TAF with food; do not give under fasting conditions simultaneously with or 2 hours after antacid
Anticonvulsants	Carbamazepine: Possible decreased bictegravir concentrations; decreased tenofovir concentrations and AUC Oxcarbazepine: Possible decreased bictegravir and tenofovir concentrations Phenobarbital, phenytoin: Decreased bictegravir and tenofovir concentrations expected	Carbamazepine, oxcarbazepine: Consider alternative anticonvulsant Phenobarbital, phenytoin: Concomitant use with BIC/FTC/TAF not recommended;
Antimycobacterials (rifabutin, rifampin, rifapentine)	Rifabutin: Decreased bictegravir concentrations and AUC when used with bictegravir in fasting state; possible decreased tenofovir concentrations Rifampin: Decreased bictegravir concentrations and AUC when used with bictegravir in fed state; possible decreased tenofovir concentrations Rifapentine: Decreased bictegravir and tenofovir concentrations expected	Rifabutin, rifapentine: Concomitant use with BIC/FTC/TAF not recommended Rifampin: Concomitant use with BIC/FTC/TAF contraindicated
Buffered preparations	Buffered preparations containing polyvalent cations: Possible decreased bictegravir concentrations
Calcium supplements	Calcium carbonate: Decreased bictegravir concentrations and AUC when administered simultaneously in fasting state; no clinically important interactions when administered simultaneously in fed state	Give BIC/FTC/TAF and supplements containing calcium simultaneously with food; do not give simultaneously in fasting state or 2 hours after supplements containing calcium
Dofetilide	Possible increased dofetilide concentrations and increased risk of serious and or life-threatening events	Concomitant use with BIC/FTC/TAF contraindicated
Estrogens and progestins	Oral contraceptives containing norgestimate and ethinyl estradiol: No clinically important effect on ethinyl estradiol, norelgestromin, or norgestrel concentrations when used concomitantly with bictegravir or tenofovir alafenamide Ethinyl estradiol or norgestimate: Clinically important interactions with BIC/FTC/TAF not expected
Iron preparations	Ferrous fumarate: Decreased concentrations and AUC of bictegravir when administered simultaneously in fasting state; no clinically important interactions when administered simultaneously in fed state	Give BIC/FTC/TAF and iron preparations simultaneously with food; do not give simultaneously in fasting state or 2 hours after iron preparations
Laxatives	Laxatives containing polyvalent cations: Possible decreased bictegravir concentrations
Ledipasvir and sofosbuvir	Fixed combination of ledipasvir and sofosbuvir (ledipasvir/sofosbuvir): No clinically important effect on bictegravir, tenofovir alafenamide, ledipasvir, or sofosbuvir concentrations if used with bictegravir or tenofovir alafenamide; clinically important interactions with BIC/FTC/TAF not expected
Metformin	Increased metformin concentrations and AUC if used with bictegravir and tenofovir alafenamide	If used with BIC/FTC/TAF, consider risks and benefits
Midazolam	No clinically significant drug interactions observed
NSAIAs	High-dose or multiple NSAIAs: Competition for active tubular secretion may increase concentrations of emtricitabine, tenofovir, and/or the NSAIA; may increase risk of adverse effects	Avoid BIC/FTC/TAF in patients who are receiving or have recently received a nephrotoxic drug (e.g., high-dose or multiple NSAIAs)
Nucleoside and nucleotide antivirals (acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir)	Acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir: Competition for active tubular secretion may increase concentrations of emtricitabine, tenofovir, and/or the concomitant antiviral; may increase risk of adverse effects
Sertraline	No clinically significant interactions observed
Sofosbuvir	Clinically important interactions with BIC/FTC/TAF not expected
Sofosbuvir and velpatasvir	Fixed combination of sofosbuvir and velpatasvir (sofosbuvir/velpatasvir): Clinically important interactions with BIC/FTC/TAF not expected
Sofosbuvir, velpatasvir, and voxilaprevir	Fixed combination of sofosbuvir, velpatasvir, and voxilaprevir (sofosbuvir/velpatasvir/voxilaprevir): No clinically important effects on bictegravir, tenofovir alafenamide, sofosbuvir, velpatasvir, or voxilaprevir concentrations if used with bictegravir or tenofovir alafenamide; clinically important interactions with BIC/FTC/TAF not expected
St. John’s wort (Hypericum perforatum)	Possible decreased concentrations of bictegravir and tenofovir alafenamide	Concomitant use with BIC/FTC/TAF not recommended
Sucralfate	Possible decreased bictegravir concentrations
Voriconazole	Increased bictegravir AUC when used with voriconazole under fasting conditions; bictegravir peak concentrations not affected

Bictegravir Sodium, Emtricitabine, and Tenofovir Alafenamide Fumarate 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.

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.

Distribution

Extent

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

Emtricitabine: Distributed into human milk.

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

Plasma Protein Binding

Bictegravir: >99%.

Emtricitabine: <4%.

Tenofovir alafenamide: Approximately 80%.

Elimination

Metabolism

Bictegravir: Metabolized by CYP3A and UGT1A1.

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

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). In vitro studies indicate tenofovir alafenamide also converted to tenofovir by carboxylesterase 1 (CES1) in hepatocytes.

Elimination Route

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

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

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

Half-life

Bictegravir: 17.3 hours.

Emtricitabine: 10.4 hours.

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

Special Populations

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

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

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

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.

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.

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.

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

Stability

Storage

Oral

Tablets

Store bottles at <30°C.

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

Actions and Spectrum

BIC/FTC/TAF is a fixed-combination antiretroviral containing bictegravir, emtricitabine, and tenofovir alafenamide.
Bictegravir (BIC) is an HIV INSTI. Inhibits activity of HIV-1 integrase, an enzyme that integrates HIV DNA into the host cell genome. Active against HIV-1; also has some in vitro activity against HIV type 2 (HIV-2).
Emtricitabine (FTC) is an HIV NRTI. Inactive until converted intracellularly to an active 5′-triphosphate metabolite. Active against HIV-1 and also has some in vitro activity against HIV-2.
Tenofovir alafenamide (TAF) is a nucleotide reverse transcriptase inhibitor antiretroviral classified as an HIV NRTI. 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). Active against HIV-1 and has some in vitro activity against HIV-2.
HIV-1 resistant to bictegravir, emtricitabine, or tenofovir produced in vitro. In clinical trials evaluating BIC/FTC/TAF, no specific bictegravir or NRTI resistance-associated substitutions emerged in patients considered to be virologic treatment failures.
Cross-resistance between bictegravir and other HIV INSTIs (e.g., dolutegravir, elvitegravir, raltegravir) reported. Cross-resistance also occurs among HIV NRTIs.

Advice to Patients

Advise patients of the critical need for compliance with HIV therapy and importance of remaining under the care of a clinician. Stress 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.
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.
Inform patients that testing for HBV infection is recommended before antiretroviral therapy is initiated. 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.
Advise patients that renal impairment, including cases of acute renal failure or Fanconi syndrome, has occurred in patients receiving tenofovir prodrugs. 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]).
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. 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.
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. 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. Advise patients to immediately inform a healthcare provider if any symptoms of infection occur.
Inform caregivers that the BIC/FTC/TAF tablet may be split for children with difficulty swallowing the whole tablet. If the tablet is split, the portions must all be taken within approximately 10 minutes.
Advise 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.
Advise women to inform their clinicians if they are or plan to become pregnant or plan to breast-feed. Inform patients that there is a registry that monitors fetal outcomes of women exposed to BIC/FTC/TAF during pregnancy.
Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

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.

Bictegravir Sodium, Emtricitabine, and Tenofovir Alafenamide Fumarate
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Tablets, film-coated	Bictegravir Sodium 30 mg (of bictegravir), Emtricitabine 120 mg, and Tenofovir Alafenamide Fumarate 15 mg (of tenofovir alafenamide)	Biktarvy	Gilead
		Bictegravir Sodium 50 mg (of bictegravir), Emtricitabine 200 mg, and Tenofovir Alafenamide Fumarate 25 mg (of tenofovir alafenamide)	Biktarvy	Gilead