Yaliira Pak - Drug Monograph

Introduction

Yaliira Pak is a combination antiretroviral therapy used in the management of human immunodeficiency virus (HIV-1) infection. This fixed-dose combination contains bictegravir (an integrase strand transfer inhibitor), emtricitabine (a nucleoside reverse transcriptase inhibitor), and tenofovir alafenamide (a nucleotide reverse transcriptase inhibitor). Yaliira Pak represents a complete once-daily single-tablet regimen for treatment-naïve and certain treatment-experienced patients, offering high efficacy with a favorable safety profile.

Mechanism of Action

Yaliira Pak exerts its antiviral effects through three distinct mechanisms:

• Bictegravir: Inhibits HIV integrase by binding to the integrase active site and blocking the strand transfer step of viral DNA integration into host chromosomes
• Emtricitabine: A cytosine analog that undergoes phosphorylation to form emtricitabine 5'-triphosphate, which competes with deoxycytidine 5'-triphosphate and incorporates into viral DNA, resulting in chain termination
• Tenofovir alafenamide: A prodrug that is converted to tenofovir intracellularly, then phosphorylated to tenofovir diphosphate, which inhibits HIV reverse transcriptase by competing with deoxyadenosine 5'-triphosphate and incorporating into viral DNA, causing chain termination

This triple mechanism provides synergistic antiviral activity against HIV-1.

Indications

Yaliira Pak is indicated for:

• Treatment of HIV-1 infection in adults and pediatric patients weighing at least 25 kg
• Use in antiretroviral-naïve patients
• Replacement of current antiretroviral regimen in virologically suppressed (HIV-1 RNA <50 copies/mL) adults with no history of treatment failure and no known substitutions associated with resistance to the individual components

Dosage and Administration

• Renal impairment: Not recommended in patients with CrCl <30 mL/min
• Hepatic impairment: No dosage adjustment needed in mild to moderate impairment; not studied in severe hepatic impairment
• Pediatric patients: For patients ≥25 kg, use same adult dosage
• Elderly patients: No dosage adjustment required, but consider age-related renal function decline

Pharmacokinetics

• Bictegravir: Tmax ≈2 hours; bioavailability ≈80%
• Emtricitabine: Tmax ≈2 hours; bioavailability ≈93%
• Tenofovir alafenamide: Tmax ≈1 hour; bioavailability ≈65% increased with food

• Bictegravir: Protein binding ~99%; Vd ≈18 L
• Emtricitabine: Protein binding <4%; Vd ≈120 L
• Tenofovir alafenamide: Protein binding ~80%; Vd ≈150 L

• Bictegravir: Primarily metabolized by UGT1A1 and CYP3A4
• Emtricitabine: Minimal metabolism
• Tenofovir alafenamide: Hydrolyzed to tenofovir, then phosphorylated intracellularly

• Bictegravir: Terminal half-life ≈18 hours; fecal excretion (80%)
• Emtricitabine: Terminal half-life ≈10 hours; renal excretion (86%)
• Tenofovir alafenamide: Terminal half-life ≈0.5 hours; renal excretion (32%)

Contraindications

• Hypersensitivity to any component of Yaliira Pak
• Coadministration with drugs that strongly induce CYP3A or UGT1A1 that may significantly decrease bictegravir plasma concentrations:

- Rifampin - Carbamazepine - Phenytoin - St. John's wort

Warnings and Precautions

• Post-treatment acute exacerbation of hepatitis B in patients coinfected with HIV and HBV

• Renal impairment: Monitor renal function in patients with or at risk for renal dysfunction
• Lactic acidosis/severe hepatomegaly: Rare but serious cases reported with nucleoside analogs
• Drug resistance: May emerge if Yaliira Pak is used in patients with undetected drug-resistant HIV-1
• Bone effects: Decreases in bone mineral density observed with tenofovir-containing products
• Immune reconstitution syndrome: May occur during initial treatment

Drug Interactions

• Antacids: Separate administration by至少 2 hours
• Polyvalent cations: Separate administration of iron or calcium supplements by至少 2 hours
• CYP3A inducers: Contraindicated with strong inducers (rifampin, carbamazepine, etc.)
• CYP3A inhibitors: May increase bictegravir concentrations
• Nephrotoxic drugs: Increased risk of renal impairment when coadministered

Adverse Effects

• Diarrhea
• Nausea
• Headache
• Fatigue
• Insomnia

• Severe acute exacerbations of hepatitis B
• Renal impairment
• Lactic acidosis
• Hepatotoxicity
• Immune reconstitution syndrome

Monitoring Parameters

• HIV-1 RNA levels
• CD4+ cell count
• Hepatitis B and C serology
• Renal function (serum creatinine, CrCl)
• Urinalysis
• Bone mineral density (if at risk)

• HIV-1 RNA at 2-4 weeks, then every 3-6 months
• CD4+ cell count every 3-6 months
• Renal function every 3-6 months
• Liver function tests
• Signs/symptoms of opportunistic infections
• Adherence assessment

Patient Education

• Take exactly as prescribed; do not miss doses
• May take with or without food
• Report any new symptoms, especially nausea, abdominal pain, dark urine, or yellowing of skin
• Inform all healthcare providers about Yaliira Pak use
• Use effective contraception; discuss pregnancy planning with provider
• Not a cure for HIV; does not prevent transmission to others
• Store at room temperature in original container
• Keep all medical appointments for monitoring

References

1. Sax PE, Pozniak A, Montes ML, et al. Coformulated bictegravir, emtricitabine, and tenofovir alafenamide versus dolutegravir-containing regimens for initial treatment of HIV-1 infection: week 144 results from two randomised, double-blind, non-inferiority, phase 3 trials. Lancet HIV. 2020;7(6):e389-e400.

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(10107):2063-2072.

3. Yaliira Pak [package insert]. Foster City, CA: Gilead Sciences, Inc.; 2023.

4. Department of Health and Human Services. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. Accessed January 2024.

5. Thompson MA, Horberg MA, Agwu AL, et al. Primary Care Guidance for Persons With Human Immunodeficiency Virus: 2020 Update by the HIV Medicine Association of the Infectious Diseases Society of America. Clin Infect Dis. 2021;73(11):e3572-e3605.