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Bictegravir, Emtricitabine, and Tenofovir Alafenamide

Medically reviewed on August 12, 2018

Pronunciation

(bik TEG ra vir em trye SYE ta been & ten OF oh vir al a FEN a mide)

Index Terms

  • Bictegravir Sodium, Emtricitabine, and Tenofovir Alafenamide
  • Biktarvy
  • Emtricitabine, Bictegravir, and Tenofovir Alafenamide
  • Tenofovir Alafenamide, Bictegravir, and Emtricitabine

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Biktarvy: Bictegravir 50 mg, emtricitabine 200 mg, and tenofovir alafenamide 25 mg

Brand Names: U.S.

  • Biktarvy

Pharmacologic Category

  • Antiretroviral, Integrase Inhibitor (Anti-HIV)
  • Antiretroviral, Reverse Transcriptase Inhibitor, Nucleoside (Anti-HIV)
  • Antiretroviral, Reverse Transcriptase Inhibitor, Nucleotide (Anti-HIV)

Pharmacology

Bictegravir, an integrase inhibitor, inhibits HIV integrase by binding to the integrase-active site and blocking the strand transfer step of DNA integration. Emtricitabine is a cytosine analogue and tenofovir alafenamide is converted intracellularly to tenofovir (adenosine nucleotide analog) and subsequently phosphorylated by cellular kinases to the active moiety, tenofovir diphosphate. Emtricitabine and tenofovir alafenamide interfere with HIV viral RNA-dependent DNA polymerase activities resulting in inhibition of viral replication.

Metabolism

Bictegravir: By CYP3A enzymes and hepatic glucuronidation mediated by UGT1A1

Emtricitabine: Not significantly metabolized

Tenofovir alafenamide: Converted intracellulary by hydrolysis (non-CYP enzymes) to tenofovir then phosphorylated by cellular kinases to the active moiety, tenofovir diphosphate; minimal extent by CYP3A

Excretion

Bictegravir: Feces (60.3%), urine (35%); Emtricitabine: Feces (13.7%), urine (70%); Tenofovir alafenamide: Feces (31.7%), urine (<1%)

Time to Peak

Bictegravir: 2 to 4 hours; Emtricitabine: 1.5 to 2 hours; Tenofovir alafenamide: 0.5 to 2 hours

Half-Life Elimination

Bictegravir: 17.3 hours; Emtricitabine: 10.4 hours; Tenofovir alafenamide: 0.51 hours (active metabolite, tenofovir diphosphate: 150 to 180 hours [intracellular])

Protein Binding

Bictegravir: >99%; Emtricitabine <4%; Tenofovir alafenamide ~80%

Use: Labeled Indications

HIV-1 infection, treatment: Treatment of HIV-1 infection (as a complete regimen) in adults as initial therapy in those with no antiretroviral treatment history; or to replace a stable antiretroviral regimen in those who are virologically suppressed (HIV-1 RNA <50 copies/mL) for ≥3 months with no history of treatment failure and no known substitutions associated with resistance to the individual components.

Contraindications

Coadministration with dofetilide, rifampin

Dosing: Adult

HIV-1 infection, treatment: Oral: One tablet once daily

Dosing: Geriatric

Refer to adult dosing.

Dosing: Renal Impairment

CrCl ≥30 mL/minute: No dosage adjustment necessary.

CrCl <30 mL/minute: Use is not recommended.

Dosing: Hepatic Impairment

Mild to moderate impairment (Child-Pugh class A or B): No dosage adjustments necessary.

Severe impairment (Child-Pugh class C): Use is not recommended (has not been studied).

Administration

Oral: Administer with or without food.

Storage

Store below 30°C (86°F); dispense in original container.

Drug Interactions

Acyclovir-Valacyclovir: May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Acyclovir-Valacyclovir. Monitor therapy

Adefovir: May diminish the therapeutic effect of Tenofovir Products. Adefovir may increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Adefovir. Avoid combination

Aminoglycosides: May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Aminoglycosides. Monitor therapy

Antacids: May decrease the serum concentration of Bictegravir. Management: Bictegravir, emtricitabine, and tenofovir alafenamide can be administered while fasting at least 2 hours before antacids. Giving with or 2 hours after antacids is not recommended. Consider therapy modification

Cabozantinib: MRP2 Inhibitors may increase the serum concentration of Cabozantinib. Monitor therapy

Calcium Salts: May decrease the serum concentration of Bictegravir. Management: Bictegravir, emtricitabine, and tenofovir alafenamide can be administered with calcium salts under fed conditions, but coadministration with or 2 hours after a caclium salt is not recommended under fasting conditions. Consider therapy modification

CarBAMazepine: May decrease the serum concentration of Tenofovir Alafenamide. Avoid combination

Cidofovir: May increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Cidofovir. Monitor therapy

Cobicistat: May enhance the adverse/toxic effect of Tenofovir Products. More specifically, cobicistat may impair proper tenofovir monitoring and dosing. Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Bictegravir. Management: Rifampin is specifically contraindicated, and the use of carbamazepine, phenytoin, or phenobarbital is not recommended when alternatives are acceptable Monitor therapy

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Bictegravir. Monitor therapy

Diclofenac (Systemic): May enhance the nephrotoxic effect of Tenofovir Products. Management: Seek alternatives to this combination whenever possible. Avoid use of tenofovir with multiple NSAIDs or any NSAID given at a high dose. Consider therapy modification

Dofetilide: Bictegravir may increase the serum concentration of Dofetilide. Avoid combination

Fosphenytoin-Phenytoin: May decrease the serum concentration of Tenofovir Alafenamide. Avoid combination

Ganciclovir-Valganciclovir: Tenofovir Products may increase the serum concentration of Ganciclovir-Valganciclovir. Ganciclovir-Valganciclovir may increase the serum concentration of Tenofovir Products. Monitor therapy

Iron Salts: May decrease the serum concentration of Bictegravir. Management: Bictegravir, emtricitabine, and tenofovir alafenamide can be administered with iron salts under fed conditions, but coadministration with or 2 hours after an iron salt is not recommended under fasting conditions. Exceptions: Ferric Carboxymaltose; Ferric Gluconate; Ferric Hydroxide Polymaltose Complex; Ferric Pyrophosphate Citrate; Ferumoxytol; Iron Dextran Complex; Iron Isomaltoside; Iron Sucrose. Consider therapy modification

LamiVUDine: May enhance the adverse/toxic effect of Emtricitabine. Avoid combination

MetFORMIN: Bictegravir may increase the serum concentration of MetFORMIN. Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: May enhance the nephrotoxic effect of Tenofovir Products. Management: Seek alternatives to these combinations whenever possible. Avoid use of tenofovir with multiple NSAIDs or any NSAID given at a high dose. Consider therapy modification

Orlistat: May decrease the serum concentration of Antiretroviral Agents. Monitor therapy

OXcarbazepine: May decrease the serum concentration of Tenofovir Alafenamide. Avoid combination

PHENobarbital: May decrease the serum concentration of Tenofovir Alafenamide. Avoid combination

Primidone: May decrease the serum concentration of Tenofovir Alafenamide. Avoid combination

Rifabutin: May decrease the serum concentration of Tenofovir Alafenamide. Avoid combination

Rifabutin: May decrease the serum concentration of Bictegravir. Avoid combination

RifAMPin: May decrease the serum concentration of Tenofovir Alafenamide. Avoid combination

RifAMPin: May decrease the serum concentration of Bictegravir. Avoid combination

Rifapentine: May decrease the serum concentration of Tenofovir Alafenamide. Avoid combination

Rifapentine: May decrease the serum concentration of Bictegravir. Avoid combination

St John's Wort: May decrease the serum concentration of Tenofovir Alafenamide. Avoid combination

St John's Wort: May decrease the serum concentration of Bictegravir. Avoid combination

Sucralfate: May decrease the serum concentration of Bictegravir. Management: Administer bictegravir, emtricitabine, and tenofovir alafenamide under fasting conditions at least 2 hours before sucralfate. Consider therapy modification

Tipranavir: May decrease the serum concentration of Tenofovir Alafenamide. Avoid combination

Adverse Reactions

Also see individual agents.

1% to 10%:

Central nervous system: Headache (4% to 5%), abnormal dreams (≤3%), fatigue (2% to 3%), dizziness (2%), insomnia (2%), depression (<2%)

Dermatologic: Skin rash (<2%)

Endocrine & metabolic: Increased LDL cholesterol (2% to 3%)

Gastrointestinal: Diarrhea (3% to 6%), nausea (3% to 5%), increased serum amylase (2%), abdominal pain (<2%), dyspepsia (<2%), flatulence (<2%), vomiting (<2%)

Hematologic & oncologic: Decreased neutrophils (2%)

Hepatic: Increased serum bilirubin (3%), increased serum ALT (1% to 2%), increased serum AST (1% to 2%)

Neuromuscular & skeletal: Increased creatine phosphokinase (4%)

Frequency not defined:

Renal: Increased serum creatinine

<1%, postmarketing, and/or case reports: Suicidal ideation

ALERT: U.S. Boxed Warning

Post treatment acute exacerbation of hepatitis B:

Severe acute exacerbations of hepatitis B have been reported in patients who are coinfected with HIV-1 and HBV and have discontinued products containing emtricitabine (FTC) and/or tenofovir disoproxil fumarate (TDF), and may occur with discontinuation of bictegravir/emtricitabine/tenofovir alafenamide.

Closely monitor hepatic function with both clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue bictegravir/emtricitabine/tenofovir alafenamide. If appropriate, anti-hepatitis B therapy may be warranted.

Warnings/Precautions

Concerns related to adverse effects:

• Immune reconstitution syndrome: Patients may develop immune reconstitution syndrome, resulting in the occurrence of an inflammatory response to an indolent or residual opportunistic infection during initial HIV treatment or activation of autoimmune disorders (eg, Graves disease, polymyositis, Guillain-Barré syndrome) later in therapy; further evaluation and treatment may be required.

• Lactic acidosis/hepatomegaly: Lactic acidosis and severe hepatomegaly with steatosis, sometimes fatal, have been reported with the use of nucleoside analogs, alone or in combination with other antiretrovirals. Suspend treatment in any patient who develops clinical or laboratory findings suggestive of lactic acidosis or pronounced hepatotoxicity (marked transaminase elevation may/may not accompany hepatomegaly and steatosis).

• Renal toxicity: Cases of acute renal failure and/or Fanconi syndrome have been reported with use of tenofovir prodrugs; patients with preexisting renal impairment and those taking nephrotoxic agents (including NSAIDs) are at increased risk. Assess serum creatinine, estimated CrCl, urine protein, and urine glucose prior to initiation of therapy and during therapy; in patients with chronic kidney disease, also assess serum phosphorus. Discontinue therapy in patients that develop clinically significant decreases in renal function or evidence of Fanconi syndrome.

Disease-related concerns:

• Chronic hepatitis B: [US Boxed Warning]: Severe acute exacerbations of HBV have been reported in patients coinfected with HIV-1 and HBV following discontinuation of antiretroviral therapy. Closely monitor hepatic function with clinical and laboratory follow-up for at least several months in patients who are coinfected with HIV-1 and HBV and discontinue bictegravir/emtricitabine/tenofovir alafenamide therapy. If appropriate, anti-hepatitis B therapy may be warranted, especially in patients with advanced hepatic disease or cirrhosis (post-treatment exacerbation of hepatitis may lead to hepatic decompensation or liver failure). All patients with HIV should be tested for HBV prior to initiation of treatment.

• Hepatic impairment: Use is not recommended in patients with severe hepatic impairment (Child-Pugh class C).

• Renal impairment: Use is not recommended in patients with CrCl <30 mL/minute.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions for more detailed information.

Monitoring Parameters

CD4 count, HIV RNA plasma levels; serum creatinine, urine glucose, urine protein (prior to initiation and as clinically indicated during therapy); serum phosphorus in patients with chronic kidney disease; hepatic function tests, bone density (patients with a history of bone fracture or have risk factors for bone loss); testing for HBV is recommended prior to the initiation of antiretroviral therapy. If used as therapy replacement in virologically suppressed patients meeting criteria, additional HIV-1 RNA and regimen tolerability monitoring is recommended to assess potential virologic failure or rebound. Patients with HIV and HBV coinfection should be monitored for several months following therapy discontinuation.

Pregnancy Considerations

The Health and Human Services (HHS) Perinatal HIV Guidelines note data are insufficient to make recommendations for use of tenofovir alafenamide in pregnant females. Information related to the use of bictegravir in pregnancy is not available.

In general, females who become pregnant on a stable antiretroviral therapy regimen may continue that regimen if viral suppression is effective, appropriate drug exposure can be achieved, contraindications for use in pregnancy are not present, and the regimen is well tolerated (HHS [perinatal] 2017).

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience diarrhea, nausea, or headache. Have patient report immediately to prescriber signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or jaundice), signs of lactic acidosis (fast breathing, tachycardia, abnormal heartbeat, vomiting, fatigue, shortness of breath, severe loss of strength and energy, severe dizziness, feeling cold, or muscle pain or cramps), or signs of infection (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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