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Bictegravir, Emtricitabine, and Tenofovir Alafenamide

Class: HIV Integrase Inhibitors
Chemical Name: 2,5-Methanopyrido[1′,2′:4,5]pyrazino[2,1-b][1,3]oxazepine-10-carboxamide, 2,3,4,5,7,9,13,13a-octahydro-8-hydroxy-7,9-dioxo-N-[(2,4,6-trifluorophenyl)methyl]-, sodium salt
Molecular Formula: C21H17F3N3NaO5C8H10FN3O3SC23H31O7N6P
CAS Number: 1611493-60-7

Medically reviewed by Drugs.com. Last updated on June 29, 2020.

Warning

    HBV Infection
  • 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;1 218 221 may occur with fixed combination of bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF).1

  • 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.1 If appropriate, initiation of HBV treatment may be warranted.1 (See HIV-infected Individuals Coinfected with HBV under Cautions.)

Introduction

Antiretroviral; fixed combination of bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF).1 Bictegravir (BIC) is an HIV integrase strand transfer inhibitor (INSTI); emtricitabine (FTC) is an HIV nucleoside reverse transcriptase inhibitor (NRTI), and tenofovir alafenamide (TAF) is an HIV nucleotide reverse transcriptase inhibitor.1 200

Uses for Bictegravir, Emtricitabine, and Tenofovir Alafenamide

Treatment of HIV Infection

Treatment of HIV-1 infection in antiretroviral-naive (have not previously received antiretroviral therapy)1 2 3 11 12 200 or antiretroviral-experienced (previously treated) adults and pediatric patients weighing ≥25 kg.1 8 9 13

Fixed combination of BIC/FTC/TAF is used alone as a complete regimen for treatment of HIV-1 infection;1 200 concomitant use with other antiretrovirals not recommended.1

For initial treatment in antiretroviral-naive adults, experts state that BIC/FTC/TAF is a recommended INSTI-based regimen for most patients.200

For initial treatment in antiretroviral-naive pediatric patients, experts state that BIC/FTC/TAF is a preferred INSTI-based regimen for adolescents ≥12 years of age weighing ≥25 kg and an alternative INSTI-based regimen for children ≥6 years of age weighing ≥25 kg.201

For antiretroviral-experienced adults or pediatric patients weighing ≥25 kg, manufacturer states that BIC/FTC/TAF can be used to replace the current antiretroviral regimen in those with plasma HIV-1 RNA levels <50 copies/mL on a stable antiretroviral regimen for ≥3 months who have no history of treatment failure and are infected with HIV-1 with no known substitutions associated with resistance to the antiretroviral components of the fixed combination (i.e., bictegravir, emtricitabine, tenofovir).1

Most appropriate antiretroviral regimen cannot be defined for every clinical scenario; select regimen based on information regarding antiretroviral potency, potential rate of resistance development, known toxicities, potential for pharmacokinetic interactions, and patient's virologic, immunologic, and clinical characteristics.200 201 202 Guidelines for the management of HIV infection, including specific recommendations for initial treatment in antiretroviral-naive patients and recommendations for changing antiretroviral regimens, are available at [Web].200 201 202

Bictegravir, Emtricitabine, and Tenofovir Alafenamide Dosage and Administration

General

  • Determine Scr, estimated Clcr, urine glucose, and urine protein prior to initiation of 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 (See Renal Impairment under Cautions.)

  • Test for HBV infection prior to initiation of BIC/FTC/TAF.1 (See HIV-infected Individuals Coinfected with HBV under Cautions.)

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;1 dosage of bictegravir sodium expressed in terms of bictegravir and dosage of tenofovir alafenamide fumarate expressed in terms of tenofovir alafenamide.1

Each fixed-combination tablet of BIC/FTC/TAF contains bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg.1

Pediatric Patients

Treatment of HIV-1 Infection in Antiretroviral-naive or Antiretroviral-experienced Pediatric Patients
Oral

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

Adults

Treatment of HIV-1 Infection in Antiretroviral-naive or Antiretroviral-experienced Adults
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 (See Hepatic Impairment under Cautions.)

Renal Impairment

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

Estimated Clcr <30 mL/minute: Not recommended.1 (See Renal Impairment under Cautions.)

Cautions for Bictegravir, Emtricitabine, and Tenofovir Alafenamide

Contraindications

  • Concomitant use with dofetilide or rifampin.1 (See Specific Drugs under Interactions.)

Warnings/Precautions

Warnings

HIV-infected Individuals Coinfected with HBV

Test all HIV-infected patients for presence of HBV before initiating antiretroviral therapy.1 200

Severe acute exacerbations of HBV infection reported following discontinuance of preparations containing emtricitabine and/or TDF in HIV-infected patients with HBV infection.1 218 221 HBV exacerbations have been associated with hepatic decompensation and hepatic failure.1 218 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 (See Specific Drugs under Interactions.)

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 cases of acute renal failure and Fanconi syndrome (renal tubular injury with severe hypophosphatemia), reported in patients receiving tenofovir prodrugs (e.g., TDF).1 221

Determine Scr, estimated Clcr, 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 (See Renal Impairment under Cautions.)

BIC/FTC/TAF not recommended in patients with estimated Clcr <30 mL/minute.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 (See Interactions.)

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.1 218 221

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]);1 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;1 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.1 218 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.1 218

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

Specific Populations

Pregnancy

Antiretroviral Pregnancy Registry at 800-258-4263 or [Web].1 202

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

Some experts state that data are insufficient to make recommendations regarding use BIC/FTC/TAF in antiretroviral-naive or antiretroviral-experienced pregnant women or women of childbearing potential trying to conceive.202

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;1 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.1 202

Pediatric Use

Safety and efficacy not established in pediatric patients weighing <25 kg.1

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

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.1

Hepatic Impairment

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

Renal Impairment

Determine Scr, estimated Clcr, 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 Clcr <30 mL/minute.1 (See Renal Toxicity under Cautions.)

Common Adverse Effects

Diarrhea,1 2 3 8 nausea,1 2 3 headache,1 2 3 8 upper respiratory tract infection,2 3 8 nasopharyngitis,2 3 8 fatigue,2 3 arthralgia,8 lymphadenopathy.3

Interactions for Bictegravir, Emtricitabine, and Tenofovir Alafenamide

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;1 does not inhibit P-gp.1

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

Bictegravir inhibits renal organic cation transporter (OCT) 2;1 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;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;1 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;1 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

Drug

Interaction

Comments

α1-Adrenergic blocking agents (e.g., alfuzosin, doxazosin, silodosin, tamsulosin, terazosin

Bictegravir not expected to affect concentrations of these α1-adrenergic blocking agents200

Dosage adjustments not needed if used with BIC/FTC/TAF200

β-Adrenergic blocking agents (e.g., metoprolol, timolol)

Metoprolol, timolol: Bictegravir not expected to affect concentrations of these drugs200

Metoprolol, timolol: Dosage adjustments not needed if used with BIC/FTC/TAF200

Aminoglycosides (e.g., gentamicin)

Competition for active tubular secretion may increase concentrations of emtricitabine, tenofovir, and/or the aminoglycoside;1 may increase risk of adverse effects1

Avoid concomitant use1

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 bictegravir1

Administration of bictegravir in fasting state 2 hours after antacid containing aluminum, magnesium, and simethicone: Decreased concentrations and AUC of bictegravir1

Administration of bictegravir in fasting state 2 hours before antacid containing aluminum, magnesium, and simethicone: No clinically important interactions1

Other cation-containing antacids: Possible decreased bictegravir concentrations1

Antacids containing aluminum or magnesium: Give BIC/FTC/TAF under fasting conditions ≥2 hours before or 6 hours after antacid;1 200 do not give simultaneously with or 2 hours after antacid1

Antacids containing calcium carbonate: May give simultaneously with BIC/FTC/TAF with food;1 200 do not give under fasting conditions simultaneously with or 2 hours after antacid1 200

Antiarrhythmic agents

Amiodarone: Pharmacokinetic interactions not expected200

Digoxin, dronedarone, flecainide, systemic lidocaine, mexiletine, propafenone, quinidine: Bictegravir not expected to affect concentrations of these antiarrhythmic agents200

Disopyramide: Possible increased disopyramide concentrations200

Dofetilide: Possible increased dofetilide concentrations and increased risk of serious and/or life-threatening adverse effects1

Amiodarone, digoxin, dronedarone, flecainide, systemic lidocaine, mexiletine, propafenone, quinidine: Dosage adjustments not needed if used with BIC/FTC/TAF200

Disopyramide: Monitor for disopyramide-associated adverse effects if used with BIC/FTC/TAF200

Dofetilide: Concomitant use with BIC/FTC/TAF contraindicated1

Anticoagulants

Apixaban, betrixaban, dabigatran, edoxaban, rivaroxaban: Bictegravir not expected to affect concentrations of these anticoagulants200

Warfarin: Bictegravir not expected to affect warfarin concentrations200

Apixaban, betrixaban, dabigatran, edoxaban, rivaroxaban: Dosage adjustments not needed if used with BIC/FTC/TAF200

Warfarin: Dosage adjustments not needed if used with BIC/FTC/TAF200

Anticonvulsants

Carbamazepine: Possible decreased bictegravir concentrations;1 200 decreased tenofovir concentrations and AUC1

Oxcarbazepine: Possible decreased bictegravir and tenofovir concentrations1 200

Eslicarbazepine: Possible decreased bictegravir concentrations200

Ethosuximide, lamotrigine: Pharmacokinetic interactions with bictegravir not expected200

Phenobarbital, phenytoin: Decreased bictegravir and tenofovir concentrations expected1

Valproic acid: Data not available regarding use with bictegravir200

Carbamazepine, oxcarbazepine: Concomitant use with BIC/FTC/TAF not recommended;200 consider alternative anticonvulsant1 200 or alternative to BIC/FTC/TAF200

Eslicarbazepine: Consider alternative anticonvulsant or alternative to BIC/FTC/TAF200

Ethosuximide, lamotrigine: Dosage adjustments not needed if used with BIC/FTC/TAF200

Phenobarbital, phenytoin: Concomitant use with BIC/FTC/TAF not recommended;1 consider alternative anticonvulsant200

Valproic acid: If used with BIC/FTC/TAF, monitor valproic acid concentrations and virologic response200

Antidiabetic agents (metformin, saxagliptin with or without dapagliflozin)

Metformin: Increased metformin concentrations and AUC if used with bictegravir and tenofovir alafenamide1

Saxagliptin or fixed combination of dapagliflozin and saxagliptin (dapagliflozin/saxagliptin): Bictegravir not expected to affect concentrations of these antidiabetic agents200

Metformin: If used with BIC/FTC/TAF, consider risks and benefits1 and monitor for metformin adverse effects200

Saxagliptin, dapagliflozin/saxagliptin: Dosage adjustments not needed if used with BIC/FTC/TAF200

Antifungals, azoles (isavuconazonium, itraconazole, posaconazole, voriconazole)

Isavuconazonium, itraconazole, posaconazole: Increased bictegravir concentrations expected or possible200

Voriconazole: Increased bictegravir AUC when used with voriconazole under fasting conditions;1 bictegravir peak concentrations not affected1

Isavuconazonium, itraconazole, posaconazole: Dosage adjustments not needed if used with BIC/FTC/TAF200

Voriconazole: Dosage adjustments not needed if used with BIC/FTC/TAF200

Antimycobacterials (rifabutin, rifampin, rifapentine)

Rifabutin: Decreased bictegravir concentrations and AUC when used with bictegravir in fasting state;1 possible decreased tenofovir concentrations1

Rifampin: Decreased bictegravir concentrations and AUC when used with bictegravir in fed state;1 possible decreased tenofovir concentrations1

Rifapentine: Decreased bictegravir and tenofovir concentrations expected1

Rifabutin, rifapentine: Concomitant use with BIC/FTC/TAF not recommended1 200

Rifampin: Concomitant use with BIC/FTC/TAF contraindicated1

Antiplatelet agents

Clopidogrel, prasugrel, ticagrelor, vorapaxar: Bictegravir not expected to affect concentrations of these antiplatelet agents200

Clopidogrel, prasugrel, ticagrelor, vorapaxar: Dosage adjustments not needed if used with BIC/FTC/TAF200

Antipsychotic agents

Aripiprazole, brexpiprazole, cariprazine, iloperidone, lurasidone, pimavanserin, pimozide, quetiapine: Bictegravir not expected to affect concentrations of these antipsychotic agents200

Aripiprazole, brexpiprazole, cariprazine, iloperidone, lurasidone, pimavanserin, pimozide, quetiapine: Dosage adjustments not needed if used with BIC/FTC/TAF200

Benzodiazepines

Clonazepam, clorazepate, diazepam, estazolam, flurazepam, triazolam: Bictegravir not expected to affect concentrations of these benzodiazepines200

Midazolam: No clinically important effect on midazolam concentrations if used with bictegravir and tenofovir alafenamide;1 clinically important pharmacokinetic interactions with BIC/FTC/TAF not expected1

Clonazepam, clorazepate, diazepam, estazolam, flurazepam, midazolam, triazolam: Dosage adjustments not needed if used with BIC/FTC/TAF200

Bosentan

Possible decreased bictegravir concentrations200

Dosage adjustments not needed if used with BIC/FTC/TAF200

Buffered preparations

Buffered preparations containing polyvalent cations: Possible decreased bictegravir concentrations1

Buprenorphine

Buprenorphine (buccal, sublingual, subdermal implant): Bictegravir not expected to affect buprenorphine or norbuprenorphine concentrations200

Dosage adjustments not needed if used with BIC/FTC/TAF200

Bupropion

Bictegravir not expected to affect bupropion concentrations200

Dosage adjustments not needed if used with BIC/FTC/TAF200

Buspirone

Bictegravir not expected to affect buspirone concentrations200

Dosage adjustments not needed if used with BIC/FTC/TAF200

Calcifediol

Bictegravir not expected to affect calcifediol concentrations200

Dosage adjustments not needed if used with BIC/FTC/TAF200

Calcium-channel blocking agents

Diltiazem: Possible increased bictegravir concentrations200

Other calcium-channel blocking agents: Pharmacokinetic interactions with bictegravir not expected200

Diltiazem and other calcium-channel blocking agents: Dosage adjustments not needed if used with BIC/FTC/TAF200

Calcium supplements

Calcium carbonate: Decreased bictegravir concentrations and AUC when administered simultaneously in fasting state;1 no clinically important interactions when administered simultaneously in fed state1

Give BIC/FTC/TAF and supplements containing calcium simultaneously with food;1 do not give simultaneously in fasting state or 2 hours after supplements containing calcium1 200

Cisapride

Bictegravir not expected to affect cisapride concentrations200

Dosage adjustments not needed if used with BIC/FTC/TAF200

Colchicine

Bictegravir not expected to affect colchicine concentrations200

Dosage adjustments not needed if used with BIC/FTC/TAF200

Corticosteroids

Betamethasone, budesonide, prednisone, prednisolone (systemic): Pharmacokinetic interactions with bictegravir not expected200

Dexamethasone (systemic): Possible decreased bictegravir concentrations200

Beclomethasone, budesonide, ciclesonide, fluticasone, mometasone (orally inhaled or intranasal): Pharmacokinetic interactions with bictegravir not expected200

Betamethasone, methylprednisolone, prednisolone, triamcinolone (intra-articular, epidural, intraorbital): Pharmacokinetic interactions with bictegravir not expected200

Betamethasone, budesonide, prednisone, prednisolone (systemic): Dosage adjustments not needed if used with BIC/FTC/TAF200

Dexamethasone (systemic): Experts state consider alternative corticosteroid or alternative antiretroviral;200 if concomitant use with BIC/FTC/TAF considered necessary, monitor virologic response200

Beclomethasone, budesonide, ciclesonide, fluticasone, mometasone (orally inhaled or intranasal): Dosage adjustments not needed if used with BIC/FTC/TAF200

Betamethasone, methylprednisolone, prednisolone, triamcinolone (intra-articular, epidural, intraorbital): Dosage adjustments not needed if used with BIC/FTC/TAF200

Dronabinol

Bictegravir not expected to affect dronabinol concentrations200

Dosage adjustments not needed if used with BIC/FTC/TAF200

Elbasvir and grazoprevir

Fixed combination of elbasvir and grazoprevir (elbasvir/grazoprevir): No effect on bictegravir concentrations expected200

Dosage adjustments not needed if used with BIC/FTC/TAF200

Eluxadoline

Bictegravir not expected to affect eluxadoline concentrations200

Dosage adjustments not needed if used with BIC/FTC/TAF200

Emtricitabine

In vitro evidence of synergistic antiretroviral effects with bictegravir6

Eplerenone

Bictegravir not expected to affect eplerenone concentrations200

Dosage adjustments not needed if used with BIC/FTC/TAF200

Ergot alkaloids (dihydroergotamine, ergotamine, methylergonovine)

Bictegravir not expected to affect ergot alkaloid concentrations200

Dosage adjustments not needed if used with BIC/FTC/TAF200

Estrogens and progestins

Estradiol, estrogen, conjugated estrogens: Bictegravir not expected to affect estrogen concentrations200

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 alafenamide1 200

Ethinyl estradiol or norgestimate: Clinically important interactions with BIC/FTC/TAF not expected1

Other hormonal contraceptives (e.g., transdermal systems, vaginal ring, injections): Data not available regarding use with bictegravir200

Drospirenone, medroxyprogesterone, micronized progesterone: Bictegravir not expected to affect concentrations of these hormones200

Estradiol, estrogen, conjugated estrogens: Dosage adjustments not needed if used with BIC/FTC/TAF200

Drospirenone, medroxyprogesterone, progesterone: Dosage adjustments not needed if used with BIC/FTC/TAF200

Fentanyl

Bictegravir not expected to affect fentanyl concentrations200

Dosage adjustments not needed if used with BIC/FTC/TAF200

Flibanserin

Bictegravir not expected to affect flibanserin concentrations200

Dosage adjustments not needed if used with BIC/FTC/TAF200

Glecaprevir and pibrentasvir

Fixed combination of glecaprevir and pibrentasvir (glecaprevir/pibrentasvir): No effect on bictegravir concentrations expected200

Dosage adjustments not needed if used with BIC/FTC/TAF200

Goserelin

Bictegravir not expected to affect goserelin concentrations200

Dosage adjustments not needed if used with BIC/FTC/TAF200

Histamine H2-receptor antagonists

No effect on bictegravir concentrations expected200

Dosage adjustments not needed if used with BIC/FTC/TAF200

HMG-CoA reductase inhibitors

Atorvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin: Bictegravir not expected to affect concentrations of these statins200

Atorvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, simvastatin: Dosage adjustments not needed if used with BIC/FTC/TAF200

Immunosuppressive agents

Cyclosporine, everolimus, sirolimus, tacrolimus: Bictegravir not expected to affect concentrations of these immunosuppressive agents200

Cyclosporine, everolimus, sirolimus, tacrolimus: Dosage adjustments not needed if used with BIC/FTC/TAF200

Iron preparations

Ferrous fumarate: Decreased concentrations and AUC of bictegravir when administered simultaneously in fasting state;1 no clinically important interactions when administered simultaneously in fed state1

Give BIC/FTC/TAF and iron preparations simultaneously with food;1 do not give simultaneously in fasting state or 2 hours after iron preparations1

Ivabradine

Bictegravir not expected to affect ivabradine concentrations200

Dosage adjustments not needed if used with BIC/FTC/TAF200

Laxatives

Laxatives containing polyvalent cations: Possible decreased bictegravir concentrations1

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;1 clinically important interactions with BIC/FTC/TAF not expected1

Dosage adjustments not needed if used with BIC/FTC/TAF200

Leuprolide

Bictegravir not expected to affect leuprolide concentrations200

Dosage adjustments not needed if used with BIC/FTC/TAF200

Lomitapide

Bictegravir not expected to affect lomitapide concentrations200

Dosage adjustments not needed if used with BIC/FTC/TAF200

Macrolides (azithromycin, clarithromycin, erythromycin)

Azithromycin: Bictegravir not expected to affect azithromycin concentrations200

Clarithromycin, erythromycin: Possible increased bictegravir concentrations200

Azithromycin, clarithromycin, erythromycin: Dosage adjustments not needed if used with BIC/FTC/TAF200

Methadone

Bictegravir not expected to affect methadone concentrations200

Dosage adjustments not needed if used with BIC/FTC/TAF200

Nefazodone

Bictegravir not expected to affect nefazodone concentrations200

Dosage adjustments not needed if used with BIC/FTC/TAF200

NSAIAs

High-dose or multiple NSAIAs: Competition for active tubular secretion may increase concentrations of emtricitabine, tenofovir, and/or the NSAIA;1 may increase risk of adverse effects1

Avoid BIC/FTC/TAF in patients who are receiving or have recently received a nephrotoxic drug (e.g., high-dose or multiple NSAIAs)1

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;1 may increase risk of adverse effects1

Phosphodiesterase type 5 inhibitors (avanafil, sildenafil, tadalafil, vardenafil)

Bictegravir not expected to affect concentrations of PDE5 inhibitors200

Dosage adjustments not needed if used with BIC/FTC/TAF200

Proton-pump inhibitors

No effect on bictegravir concentrations200

Dosage adjustments not needed if used with BIC/FTC/TAF200

Ranolazine

Bictegravir not expected to affect ranolazine concentrations200

Dosage adjustments not needed if used with BIC/FTC/TAF200

Selective β2-adrenergic agonists

Arformoterol, formoterol, indacaterol, olodaterol, salmeterol (orally inhaled): Bictegravir not expected to affect concentrations of the β2-adrenergic agonist200

Arformoterol, formoterol, indacaterol, olodaterol, salmeterol (orally inhaled): Dosage adjustments not needed200

Sofosbuvir

Clinically important interactions with BIC/FTC/TAF not expected1 200

Dosage adjustments not needed if used with BIC/FTC/TAF200

Sofosbuvir and velpatasvir

Fixed combination of sofosbuvir and velpatasvir (sofosbuvir/velpatasvir): Clinically important interactions with BIC/FTC/TAF not expected1

Dosage adjustments not needed if used with BIC/FTC/TAF200

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;1 clinically important interactions with BIC/FTC/TAF not expected1 200

Dosage adjustments not needed if used with BIC/FTC/TAF200

Spironolactone

Bictegravir not expected to affect spironolactone concentrations200

Dosage adjustments not needed if used with BIC/FTC/TAF200

SSRIs

Citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline: Pharmacokinetic interactions with bictegravir not expected200

Citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline: Dosage adjustments not needed if used with BIC/FTC/TAF200

St. John’s wort (Hypericum perforatum)

Possible decreased concentrations of bictegravir and tenofovir alafenamide1

Concomitant use with BIC/FTC/TAF not recommended1

Sucralfate

Possible decreased bictegravir concentrations1

Suvorexant

Bictegravir not expected to affect suvorexant concentrations200

Dosage adjustments not needed if used with BIC/FTC/TAF200

Tenofovir alafenamide (TAF)

In vitro evidence of synergistic antiretroviral effects with bictegravir6

Testosterone

Bictegravir not expected to affect testosterone concentrations200

Dosage adjustments not needed if used with BIC/FTC/TAF200

Tramadol

Bictegravir not expected to affect tramadol concentrations200

Dosage adjustments not needed if used with BIC/FTC/TAF200

Trazodone

Bictegravir not expected to affect trazodone concentrations200

Dosage adjustments not needed if used with BIC/FTC/TAF200

Tricyclic antidepressants (amitriptyline, desipramine, doxepin, imipramine, nortriptyline)

Bictegravir not expected to affect concentrations of tricyclic antidepressants200

Dosage adjustments not needed if used with BIC/FTC/TAF200

Zolpidem

Bictegravir not expected to affect zolpidem concentrations200

Dosage adjustments not needed if used with BIC/FTC/TAF200

Bictegravir, Emtricitabine, and Tenofovir Alafenamide Pharmacokinetics

Absorption

Bioavailability

Following oral administration of individual components of BIC/FTC/TAF, peak plasma concentrations of bictegravir, emtricitabine, and tenofovir occur at 2–4, 1.5–2, and 0.5–2 hours, respectively.1 5

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;1 no change in mean systemic exposures of emtricitabine.1

Distribution

Extent

Bictegravir: Not known whether crosses placenta.202

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 5

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;1 not substantially metabolized further.1

Tenofovir alafenamide: Prodrug of tenofovir;1 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);1 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;1 active metabolite (tenofovir diphosphate) half-life within PBMCs is 150–180 hours.1 7

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, tenofovir alafenamide, or tenofovir compared with healthy individuals.1

Pediatric patients ≥6 years of age weighing ≥25 kg: No clinically important differences in pharmacokinetics of bictegravir, emtricitabine, or tenofovir alafenamide compared with adults.1

Pregnant women: Data not available to date regarding pharmacokinetics during pregnancy.202

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

Stability

Storage

Oral

Tablets

<30°C.1

Store in original container; keep tightly closed.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;1 6 7 also has some in vitro activity against HIV type 2 (HIV-2).1 6

  • Emtricitabine (FTC) is an HIV NRTI.1 218 Inactive until converted intracellularly to an active 5′-triphosphate metabolite.1 218 After conversion, active against HIV-1 and also has some in vitro activity against HIV-2.1 218

  • 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;1 221 also active against HBV.221

  • HIV-1 resistant to bictegravir,1 6 10 emtricitabine,1 or tenofovir1 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.1 There is some evidence that bictegravir may possess a higher barrier to resistance development than some other HIV INSTIs (e.g., elvitegravir, raltegravir).6 10

  • Cross-resistance between bictegravir and other HIV INSTIs (e.g., dolutegravir, elvitegravir, raltegravir) reported.1 6 10 Cross-resistance also occurs among HIV NRTIs.1

Advice to Patients

  • Critical nature of compliance with HIV therapy and importance of remaining under the care of a clinician.1 200 Importance of taking as prescribed; do not alter or discontinue antiretroviral regimen without consulting clinician.1 200

  • Advise patients that the fixed combination of bictegravir, emtricitabine, and tenofovir alafenamide (BIC/FTC/TAF) is a complete regimen for treatment of HIV-1 infection and should not be used in conjunction with other antiretrovirals.1

  • Antiretroviral therapy is not a cure for HIV infection; opportunistic infections and other complications associated with HIV disease may still occur.200

  • Advise patients that early initiation of antiretroviral therapy and sustained decreases in plasma HIV RNA have been associated with reduced risk of progression to acquired immunodeficiency syndrome (AIDS) and death.200

  • Advise patients that effective antiretroviral regimens can decrease HIV concentrations in blood and genital secretions and strict adherence to such regimens in conjunction with risk-reduction measures may decrease, but cannot absolutely eliminate, the risk of secondary transmission of HIV to others.200 Importance of continuing to practice safer sex (e.g., using latex or polyurethane condoms to minimize sexual contact with body fluids) and reducing high-risk behaviors (e.g., reusing or sharing needles).200

  • Importance of reading patient information provided by the manufacturer.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 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.1 Importance of not using BIC/FTC/TAF concomitantly with or shortly after nephrotoxic agents (e.g., high-dose or multiple NSAIAs).1

  • Advise patients that lactic acidosis and severe hepatomegaly with steatosis, including fatalities, have occurred in patients receiving HIV NRTIs, including emtricitabine and/or tenofovir DF, in conjunction with other antiretrovirals.1 Importance of contacting 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 Importance of immediately informing a healthcare provider if any symptoms of infection occur.1

  • Importance of informing 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

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

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

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 50 mg (of bictegravir), Emtricitabine 200 mg, and Tenofovir Alafenamide Fumarate 25 mg (of tenofovir alafenamide)

Biktarvy

Gilead

AHFS DI Essentials™. © Copyright 2021, Selected Revisions June 29, 2020. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

References

1. Gilead Sciences. Biktarvy (bictegravir, emtricitabine, tenofovir alafenamide) tablets prescribing information. Foster City, CA; 2019 Aug.

2. Gallant J, Lazzarin A, Mills A et al. Bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection (GS-US-380-1489): a double-blind, multicentre, phase 3, randomised controlled non-inferiority trial. Lancet. 2017; 390:2063-72. http://www.ncbi.nlm.nih.gov/pubmed/28867497?dopt=AbstractPlus

3. Sax P, Pozniak A, Montes M. Coformulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide, for initial treatment of HIV-1 infection (GS-US-380-1490): a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Lancet. 2017; 390:2073-82. http://www.ncbi.nlm.nih.gov/pubmed/28867499?dopt=AbstractPlus

5. Gallant J, Thompson M, DeJesus E. Antiviral activity, safety, and pharmacokinetics of bictegravir as 10-day monotherapy in HIV-1-infected adults. J Acquir Immune Defic Syndr. 2017; 75:61–66.

6. Tsiang M, Jones G, Goldsmith J. Antiviral activity of bictegravir (GS-9883), a novel potent HIV-1 integrase strand transfer inhibitor with an improved resistance profile. Antimicrob Agents Chemother. 2016; 60:7086–97.

7. Neogi U, Singh K, Aralaguppe S. Ex-vivo antiretroviral potency of newer integrase strand transfer inhibitors cabotegravir and bictegravir in HIV type 1 non-B subtypes. AIDS. 2018; 32:469–76.

8. Molina JM, Ward D, Brar I et al. Switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide from dolutegravir plus abacavir and lamivudine in virologically suppressed adults with HIV-1: 48 week results of a randomised, double-blind, multicentre, active-controlled, phase 3, non-inferiority trial. Lancet HIV. 2018; 5:e357-e365. http://www.ncbi.nlm.nih.gov/pubmed/29925489?dopt=AbstractPlus

9. Daar ES, DeJesus E, Ruane P et al. Efficacy and safety of switching to fixed-dose bictegravir, emtricitabine, and tenofovir alafenamide from boosted protease inhibitor-based regimens in virologically suppressed adults with HIV-1: 48 week results of a randomised, open-label, multicentre, phase 3, non-inferiority trial. Lancet HIV. 2018; 5:e347-e356. http://www.ncbi.nlm.nih.gov/pubmed/29925490?dopt=AbstractPlus

10. Oliveira M, Ibanescu RI, Anstett K et al. Selective resistance profiles emerging in patient-derived clinical isolates with cabotegravir, bictegravir, dolutegravir, and elvitegravir. Retrovirology. 2018; 15:56. http://www.ncbi.nlm.nih.gov/pubmed/30119633?dopt=AbstractPlus

11. Wohl DA, Yazdanpanah Y, Baumgarten A et al. Bictegravir combined with emtricitabine and tenofovir alafenamide versus dolutegravir, abacavir, and lamivudine for initial treatment of HIV-1 infection: week 96 results from a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Lancet HIV. 2019; 6:e355-e363. http://www.ncbi.nlm.nih.gov/pubmed/31068270?dopt=AbstractPlus

12. Stellbrink HJ, Arribas JR, Stephens JL et al. Co-formulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir with emtricitabine and tenofovir alafenamide for initial treatment of HIV-1 infection: week 96 results from a randomised, double-blind, multicentre, phase 3, non-inferiority trial. Lancet HIV. 2019; 6:e364-e372. http://www.ncbi.nlm.nih.gov/pubmed/31068272?dopt=AbstractPlus

13. B/F/TAF FDC in HIV-1 infected virologically suppressed adolescents and children. From ClinicalTrials.gov registry. Accessed 2020 Mar 4. https://www.clinicaltrials.gov/ct2/show/NCT02881320?cond=B%2FF%2Ftaf+FDC

200. Panel on Antiretroviral Guidelines for Adults and Adolescents, US Department of Health and Human Services (HHS). Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. Accessed 2020 Apr 20. Updates may be available at HHS AIDS Information (AIDSinfo) website. http://www.aidsinfo.nih.gov

201. Panel on Antiretroviral Therapy and Medical Management of Children Living with HIV, US Department of Health and Human Services (HHS). Guidelines for the use of antiretroviral agents in pediatric HIV infection. Accessed 2020 Apr 20. Updates may be available at HHS AIDS Information (AIDSinfo) website. http://www.aidsinfo.nih.gov

202. Panel on Treatment of Pregnant Women with HIV Infection and Prevention of Perinatal Transmission, US Department of Health and Human Services (HHS). Recommendations for use of antiretroviral drugs in pregnant women with HIV infection and interventions to reduce perinatal HIV transmission in the United States. Accessed 2020 Apr 20. Updates may be available at HHS AIDS Information (AIDSinfo) website. http://www.aidsinfo.nih.gov

218. Gilead Sciences. Emtriva (emtricitabine) capsules and oral solution prescribing information. Foster City, CA; 2018 Dec.

221. Gilead Sciences. Viread (tenofovir disoproxil fumarate) tablets and powder for oral use prescribing information. Foster City, CA; 2019 Apr.

Frequently Asked Questions