Elbasvir

China [CN]

I. Basic Information

Generic Name: Elbasvir

Development Code: MK-8742

CAS Number: 1370468-36-2

Molecular Formula: C₄₀H₄₅F₄N₅O₅

Molecular Weight: 755.81

Original Developer: Merck Sharp & Dohme

Clinical Form: Fixed-dose combination (EBR 50 mg + GZR 100 mg/tablet)

II. Mechanism of Action

Target: HCV NS5A protein (a core regulatory factor in viral replication, assembly, and release)

Mechanism: Potently inhibits NS5A function, blocking viral RNA replication, viral particle assembly, and release.

Activity: Potent picomolar (pM) inhibition against HCV genotypes 1 and 4 (EC₅₀: 0.2–1.0 pM)

Resistance Profile: Maintains activity against common NS5A resistance mutations (e.g., Y93H, Q30D), with a high resistance barrier.

Combination Synergy: Used in combination with grazoprevir (an NS3/4A inhibitor), providing dual-target blockade for high cure rates, low resistance, and short treatment duration.

III. Core Indications (EBR/GZR combination, Zepatier®)

Adult Chronic Hepatitis C (CHC):

Genotype 1 (GT1): Without/with compensated cirrhosis (Child-Pugh A), 12-week treatment, SVR₁₂ ≈ 94%–99%

Genotype 4 (GT4): Without cirrhosis, 12-week treatment, SVR₁₂ ≈ 97%–100%

Treatment-experienced patients: GT1, previous NS5A inhibitor failure, 16-week treatment

Special populations: HIV/HCV co-infection, mild to moderate renal impairment (no dose adjustment required)

IV. Pharmacokinetics (EBR)

Absorption: Peak concentration reached 3–6 hours after oral administration; absorption is not affected by food.

Protein Binding Rate: >99.9% (primarily binds to albumin, α1-) (Acidic Glycoprotein)

Metabolism: Primarily metabolized by CYP3A4 oxidation

Half-life: Approximately 24 hours (once daily administration)

Excretion: Feces > 90%, urine < 1% (no dose adjustment needed for renal impairment)

V. Adverse Reactions (Combination)

Common (≥5%): Fatigue, headache, nausea, diarrhea, insomnia

Serious: Elevated liver enzymes (ALT/AST), elevated bilirubin; contraindicated in decompensated cirrhosis

Contraindications: Child-Pugh B/C cirrhosis, concomitant use with rifampicin, allergy

VI. Drug Interactions (Key)

EBR/GZR is: a P-gp, BCRP, OATP1B1/3 inhibitor; a CYP3A inhibitor

Concomitant use is prohibited with: Rifampicin (significantly reduces EBR/GZR exposure)

Use with caution/monitor: Statins, calcium channel blockers, immunosuppressants, warfarin (may increase blood drug concentration)