bictegravir/emtricitabine/tenofovir alafenamide

REMS

Management of HIV infection in patients who have no antiretroviral treatment history or in those on a stable antiretroviral regimen who are virologically suppressed (with HIV-1 RNA <50 copies/mL) and no history of treatment failure or no known substitutions associated with resistance to the individual components of the medication (to replace their current antiretroviral regimen).

Action ⬆ ⬇

Bictegravir: Inhibits HIV-1 integrase, which is required for viral replication; Emtricitabine: Phosphorylated intracellularly where it inhibits HIV reverse transcriptase, resulting in viral DNA chain termination; Tenofovir: Phosphorylated intracellularly where it inhibits HIV reverse transcriptase resulting in disruption of DNA synthesis.

Therapeutic effects:

Slowed progression of HIV infection and decreased occurrence of sequelae.

Pharmacokinetics ⬆ ⬇

Absorption: Bictegravir: Extent of absorption following oral administration unknown; Emtricitabine: Well absorbed (93%) following oral administration; Tenofovir: Tenofovir alafenamide is a prodrug, which is hydrolyzed into tenofovir, the active component; absorption enhanced by high-fat meals.

Distribution: Bictegravir, emtricitabine, and tenofovir: Unknown.

Protein Binding: Bictegravir: >99%.

Metabolism/Excretion: Bictegravir: Primarily metabolized by the CYP3A4 isoenzyme and UGT1A1 in the liver; 60% excreted in feces, 35% excreted in urine; Emtricitabine: Undergoes some metabolism, 70% excreted in urine, 14% excreted in feces; Tenofovir: Tenofovir is phosphorylated to tenofovir diphosphate (active metabolite); 32% excreted in feces, <1% excreted in urine.

Half-Life: Bictegravir: 17.3 hr; Emtricitabine: 10.4 hr; Tenofovir alafenamide: 0.51 hr; Tenofovir diphosphate: 150–180 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
bictegravir PO	unknown	2–4 hr	24 hr
emtricitabine PO	unknown	1.5–2 hr	24 hr
tenofovir PO	unknown	0.5–2 hr	24 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Concurrent use of dofetilide or rifampin;
Severe renal impairment (CCr 15–30 mL/min) or end-stage renal disease (CCr <15 mL/min) not receiving hemodialysis;
Patients with no antiretroviral treatment history and end-stage renal disease (CCr <15 mL/min) who are receiving chronic hemodialysis;
Severe hepatic impairment;
Lactation: Breastfeeding not recommended in patients with HIV.

Use Cautiously in:

Hepatitis B co-infection;
History of suicidal ideation or depression (↑ risk of suicidal thoughts);
Renal impairment or receiving nephrotoxic medications (↑ risk of renal impairment);
OB: Use during pregnancy only if potential benefit justifies potential fetal risk;
Pedi: Children weighing 14 kg (safety and effectiveness not established).

Adv. Reactions/Side Effects ⬆ ⬇

GI: ↑amylase, ↑liver enzymes, diarrhea, LACTIC ACIDOSIS/HEPATOMEGALY WITH STEATOSIS, nausea

GU: ACUTE RENAL FAILURE/FANCONI SYNDROME

Hemat: neutropenia

Metab: hyperlipidemia

MS: ↑creatine kinase

Neuro: abnormal dreams, dizziness, fatigue, headache, insomnia

Misc: ACUTE EXACERBATION OF HEPATITIS B, immune reconstitution syndrome

Interactions ⬆ ⬇

Drug-drug:

Bictegravir may ↑ dofetilide levels and the risk of torsades de pointes; concurrent use contraindicated.
Rifampin may ↓ bictegravir levels and its effectiveness; concurrent use contraindicated.
Medications that compete for active tubular secretion, including acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, or aminoglycosides may ↑ emtricitabine and tenofovir levels and toxicity.
Nephrotoxic agents, including NSAIDs↑ risk of nephrotoxicity with tenofovir; avoid concurrent use.
Carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, and rifapentine may ↓ bictegravir and tenofovir levels and their effectiveness; avoid concurrent use.
Administration with antacids, containing magnesium or aluminum↓ absorption of bictegravir; take ≥2 hr before or ≥6 hr after magnesium- or aluminum-containing antacids.
Administration with supplements or antacids containing calcium or iron↓ absorption of bictegravir; take at the same time as calcium or iron supplements with food (and not on an empty stomach).
May ↑ metformin levels.

Drug-Natural Products:

St. John's wort may ↓ bictegravir and tenofovir levels and their effectiveness; avoid concurrent use.

Route/Dosage ⬆ ⬇

PO (Adults and Children ≥25 kg): 1 tablet (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg) once daily
PO (Children 14–24 kg): 1 tablet (bictegravir 30 mg/emtricitabine 120 mg/tenofovir alafenamide 15 mg) once daily.

Renal Impairment

PO (Adults ): Virologically suppressed with CCr <15 mL/min and receiving chronic hemodialysis: 1 tablet (bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg) once daily (on days of hemodialysis, give dose after hemodialysis session).

Availability ⬆ ⬇

Tablets: bictegravir 30 mg/emtricitabine 120 mg/tenofovir alafenamide 15 mg; bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg

Assessment ⬆ ⬇

Assess patient for change in severity of HIV symptoms and for symptoms of opportunistic infections during therapy.
May cause lactic acidosis and severe hepatomegaly with steatosis. Monitor patient for signs (increased serum lactate levels, elevated liver enzymes, liver enlargement on palpation). Suspended therapy if clinical or laboratory signs occur.

Lab Test Considerations:

Monitor viral load and CD4 cell count regularly during therapy.
- Test patients for chronic hepatitis B virus (HBV) before initiating therapy. Medication is not indicated for treatment of HBV. Exacerbations of HBV have occurred upon discontinuation of therapy.
- Assess serum creatinine, estimated CCr, urine glucose and urine protein prior to and periodically during therapy. Also monitor serum phosphorous in patients with chronic kidney disease. Discontinue therapy in patients who develop clinically significant ↓ renal function or evidence of Fanconi syndrome.
- Monitor liver function tests in patients co-infected with HIV and HBV who discontinue Biktarvy. May cause an exacerbation of hepatitis B. May cause ↑ AST, ALT, bilirubin, creatine kinase, serum amylase, serum lipase, and triglycerides.
- May cause ↓ neutrophil count.
- May cause ↑ LDL cholesterol.

Implementation ⬆ ⬇

PO: Administer once daily without regard for food.
Administer medication at least 2 hr before or 6 hr after antacids containing aluminum or magnesium. Medication may be taken with food at same time as supplements or antacids containing iron or calcium.
- For virologically-suppressed adults with estimated creatinine clearance <15 mL per min who are receiving chronic hemodialysis: On days of hemodialysis, administer daily dose after completion of hemodialysis treatment.

Patient/Family Teaching ⬆ ⬇

Emphasize the importance of taking medication as directed. Do not take more than prescribed amount and do not stop taking without consulting health care professional. Take missed doses as soon as remembered, but not if almost time for next dose; do not double doses. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
Instruct patient that medication should not be shared with others.
Inform patient that medication does not cure AIDS or prevent associated or opportunistic infections. Therapy may reduce the risk of transmission of HIV to others through sexual contact or blood contamination. Caution patient to use a condom and to avoid sharing needles or donating blood to prevent spreading the AIDS virus to others.
Instruct patient to notify health care professional immediately if symptoms of lactic acidosis (tiredness or weakness, unusual muscle pain, trouble breathing, stomach pain with nausea and vomiting, cold especially in arms or legs, dizziness, fast or irregular heartbeat) or if signs of hepatotoxicity (yellow skin or whites of eyes, dark urine, light colored stools, lack of appetite for several days or longer, nausea, abdominal pain) occur.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially St. John's wort.
Advise patient to notify health care professional if signs and symptoms of immune reconstitution syndrome (signs and symptoms of an infection) occur.
Rep: May cause fetal harm. Advise patient taking oral contraceptives to use a nonhormonal method of birth control during therapy. If pregnancy is suspected notify health care professional promptly. Inform pregnant women about the Antiretroviral Pregnancy Registry. Enroll patient by calling 1-800-258-4263. Advise female patient to avoid breastfeeding.
Emphasize the importance of regular follow-up exams and blood counts to determine progress and monitor for side effects.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇