bictegravir/emtricitabine/tenofovir alafenamide

REMS

HIV–1 infection in patients who have no antiretroviral treatment history
HIV-1 infection in patients on a stable antiretroviral regimen who are virologically suppressed (with HIV-1 RNA <50 copies/mL) and have no known or suspected substitutions associated with resistance to bictegravir or tenofovir (to replace their current antiretroviral regimen).
HIV-1 infection in patients with an antiretroviral treatment history who are not virologically suppressed and have no known or suspected substitutions associated with resistance to the integrase strand inhibitor class, emtricitabine, or tenofovir.

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 ⬆ ⬇

Bictegravir

Absorption: Extent of absorption following oral administration unknown.

Distribution: Unknown.

Protein Binding: >99%.

Metabolism/Excretion: Primarily metabolized by the CYP3A4 isoenzyme and UGT1A1 in the liver; 60% excreted in feces; 35% excreted in urine.

Half-Life: 17.3 hr.

Emtricitabine

Absorption: Well absorbed (93%) following oral administration.

Distribution: Unknown.

Metabolism/Excretion: Undergoes some metabolism; 70% excreted in urine; 14% excreted in feces.

Half-Life: 10.4 hr.

Tenofovir Alafenamide

Absorption: Tenofovir alafenamide is a prodrug, which is hydrolyzed into tenofovir, the active component; absorption enhanced by high-fat meals.

Distribution: Unknown.

Metabolism/Excretion: Tenofovir is phosphorylated to tenofovir diphosphate (active metabolite); 32% excreted in feces; <1% excreted in urine.

Half-Life: 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 or end-stage renal disease not receiving hemodialysis;
Patients with no antiretroviral treatment history and end-stage renal disease who are receiving chronic hemodialysis;
Severe hepatic impairment.

Use Cautiously in:

Hepatitis B virus (HBV) coinfection;
History of suicidal ideation or depression (↑ risk of suicidal thoughts);
Renal impairment or receiving nephrotoxic medications (↑ risk of renal impairment);
OB: Recommended in pregnant individuals who are virologically suppressed on a stable antiretroviral regimen with no known substitutions associated with resistance to bictegravir, emtricitabine, or tenofovir alafenamide;
Lactation: Safety of bictegravir not established in breastfeeding; breastfeeding should be supported in people with HIV who are taking antiretroviral therapy as prescribed and are maintaining an undetectable amount of virus in the body;
Pedi: Children weighing <14 kg (safety and effectiveness not established).

Adv. Reactions/Side Effects ⬆ ⬇

GI: ↑amylase, ↑liver enzymes, ACUTE EXACERBATION OF HBV, diarrhea, LACTIC ACIDOSIS/HEPATOMEGALY WITH STEATOSIS, nausea

GU: ACUTE RENAL FAILURE/FANCONI SYNDROME

Hemat: neutropenia

Metab: hyperlipidemia

MS: ↑CK

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

Misc: immune reconstitution syndrome

Interactions ⬆ ⬇

Drug-drug:

Bictegravir may ↑ dofetilide levels and the risk of torsades de pointes; concurrent use contraindicated.
Rifampin may ↓ levels and effectiveness of bictegravir; concurrent use contraindicated.
Medications that compete for active tubular secretion, including acyclovir, cidofovir, ganciclovir, valacyclovir, valganciclovir, or aminoglycosides, may ↑ levels and risk of toxicity of emtricitabine and tenofovir.
Nephrotoxic agents, including NSAIDs, ↑ risk of nephrotoxicity of tenofovir; avoid concurrent use.
Carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin, and rifapentine may ↓ levels and effectiveness of bictegravir and tenofovir; 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 ↑ levels and risk of toxicity of metformin.

Drug-Natural Products:

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

Route/Dosage ⬆ ⬇

PO (Adults and Children ≥25 kg): Bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg once daily
PO (Children 14–<25 kg): 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: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 signs/symptoms of opportunistic infections during therapy.
May cause lactic acidosis and severe hepatomegaly with steatosis. Monitor patient for signs (↑ serum lactate, ↑ liver enzymes, liver enlargement on palpation). If lactic acidosis or severe hepatomegaly occurs, discontinue bictegravir/emtricitabine/tenofovir alafenamide.
Monitor for signs/symptoms of hepatotoxicity (fatigue, nausea, upper abdominal pain, jaundice, scleral icterus, dark urine, clay-colored stools) for several months following therapy discontinuation for patients co-infected with HIV-1 and HBV.

Lab Test Considerations:

Monitor viral load at baseline, with modification of antiretroviral treatment, at 2–8 wk, then every 4–8 wk until values are < 200 copies/mL, then every 3–4 mo; monitoring may be extended to every 6 mo for patients who are immunologically stable, adherent, and with suppressed viral loads for ≥2 yr.
- Monitor CD4 cell count at baseline, with modification of antiretroviral treatment, then every 3–6 mo during at least the 1st 2 yr of treatment and if the CD4 counts are <300 cell/mm³or viremia develops; after 2 yr, monitoring may be extended to every 12 mo for patients who are clinically stable with suppressed viral loads.
- Test patients for chronic HBV before initiating therapy; repeat screening every 12 mo in high-risk patients if results are negative at baseline. Medication is not indicated for treatment of HBV. Exacerbations of HBV have occurred upon discontinuation of therapy.
- Perform hepatitis C antibody testing prior to initiation; repeat screening every 12 mo in high-risk patients if results are negative at baseline.
- Monitor fasting blood glucose or A1c every 3–6 mo in patients with abnormal values at baseline or every 12 mo in patients with normal values at baseline.
- 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 coinfected with HIV and HBV who discontinue Biktarvy. May cause an exacerbation of HBV. May ↑ AST, ALT, bilirubin, CK, serum amylase, serum lipase.
- Monitor CBC with differential at baseline, with modification of antiretroviral treatment; then 6 mo thereafter or every 3–6 months if CD4 testing is done. May ↓ neutrophil count.
- Monitor fasting lipid profile at baseline, with modification of antiretroviral treatment, then every 6 mo in patients with abnormal values at baseline or annually in patients with normal values at baseline. May ↑ LDL—C and triglyceride levels.

Implementation ⬆ ⬇

PO: Administer without regard to food.
Administer medication ≥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.

Patient/Family Teaching ⬆ ⬇

Explain the purpose and side effects of bictegravir/emtricitabine/tenofovir alafenamide. Emphasize the importance of taking as directed. Do not stop taking drug without consulting health care provider. Take missed doses as soon as remembered unless almost time for next dose. Do not double doses or take more than prescribed. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
Emphasize the importance of regular follow-up exams and blood counts to determine progress and monitor for side effects.
Inform patient that medication does not cure HIV or prevent associated or opportunistic infections. Therapy may ↓ 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 HIV to others.
Instruct patient to notify health care provider immediately if signs/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 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 provider of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care provider before taking any new medications, especially St. John’s wort.
Advise patient to notify health care provider if signs/symptoms of immune reconstitution syndrome (signs and symptoms of an infection) occur.
Rep: Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding is planned. In general, women who are receiving combination antiretroviral therapy for HIV—1 infection when pregnancy is discovered should continue their regimen. Interruption of antiretroviral therapy during pregnancy ↑ the rate of mother-to-child transmission of HIV-1. Encourage patients who become pregnant during therapy to join the Antiretroviral Pregnancy Registry that monitors pregnancy outcomes in women exposed to efavirenz during pregnancy. Enroll patient by calling 1-800-258-4263 or visit www.apregistry.com for more information.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆