nucleoside reverse transcriptase inhibitors
integrase strand transfer inhibitors
Management of HIV infection in patients who have no antiretroviral treatment history or in those on a stable antiretroviral regimen with HIV-1 RNA <50 copies/mL for ≥3 mo 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).
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.
Slowed progression of HIV infection and decreased occurrence of sequelae.
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 and 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)
|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|
- Concurrent use of dofetilide or rifampin;
- Severe renal impairment;
- 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 <25 kg (safety and effectiveness not established).
Adverse Reactions/Side Effects
CNS: abnormal dreams, dizziness, fatigue, headache, insomnia
GI: LACTIC ACIDOSIS/HEPATOMEGALY WITH STEATOSIS, diarrhea, ↑ amylase, ↑ liver enzymes, nausea
GU: renal impairment
MS: ↑ creatine kinase
Misc: ACUTE EXACERBATION OF HEPATITIS B, immune reconstitution syndrome
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- 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.
St. John's wort may ↓ bictegravir and tenofovir levels and their effectiveness; avoid concurrent use.
PO (Adults and Children) ≥25 kg) 1 tablet once daily
Tablets: bictegravir 50 mg/emtricitabine 200 mg/tenofovir alafenamide 25 mg
- 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). Therapy should be suspended 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 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.
- 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.
- 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 does not 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: Advise patient taking oral contraceptives to use a nonhormonal method of birth control during therapy. If pregnancy is suspected notify health care professional promptly. Encourage pregnant women to enroll in the Antiretroviral Pregnancy Registry by calling 1-800-258-4263. Advise female patient to avoid breast feeding during therapy.
- Emphasize the importance of regular follow-up exams and blood counts to determine progress and monitor for side effects.
- Delayed progression of AIDS and decreased opportunistic infections in patients with HIV.
- Decrease in viral load and increase in CD4 cell counts.
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