API Sofosbuvir

Sofosbuvir More Info

Sofosbuvir (INN), also known as GS-7977, is a direct-acting antiviral (DAA) medication used for the treatment of chronic hepatitis C virus (HCV) infection. It is a nucleotide analog inhibitor of the HCV NS5B RNA-dependent RNA polymerase, essential for viral replication. Sofosbuvir is a prodrug that undergoes intracellular metabolism to form its pharmacologically active form, 2'-deoxy-2'-α-fluoro-β-C-methyluridine-5'-triphosphate (GS-461203). This active metabolite acts as a chain terminator during RNA synthesis, effectively inhibiting viral replication.

Key Product Details:

Chemical Identity:

Molecular Formula: C₂₂H₂₈FN₃O₅P

Molecular Weight: 529.45 g/mol

Physical Form: White to off-white crystalline solid or film-coated tablet.

Pharmacological Classification: Antiviral for systemic use; ATC code: J05AP08 (Gilead Sciences) or J05AP55 (combination).

Mechanism of Action:

Sofosbuvir is a pan-genotypic inhibitor of the HCV NS5B RNA-dependent RNA polymerase, which is essential for viral replication.

It is a nucleotide prodrug that undergoes intracellular metabolism to form the pharmacologically active uridine analog triphosphate (GS-461203), which can be incorporated into HCV RNA by the NS5B polymerase and acts as a chain terminator.

GS-461203 is neither an inhibitor of human DNA and RNA polymerases nor an inhibitor of mitochondrial RNA polymerase.

Dosage Forms and Strengths:

Available as oral tablets (film-coated) and oral pellets (granules) for oral use.

Each dosage form is available in two dose strengths:

400 mg

200 mg (also available as 150 mg pellets).

Combination products (e.g., Sofosbuvir + Velpatasvir) are available in fixed-dose tablets (e.g., 400 mg Sofosbuvir + 100 mg Velpatasvir).

Pharmacokinetics:

Absorption: Sofosbuvir is rapidly absorbed, with a peak plasma concentration observed at -0.5–2 hours post-dose. Food does not significantly affect its absorption.

Distribution: Approximately 61–65% bound to human plasma proteins, independent of drug concentration.

Metabolism: Extensively metabolized in the liver to form the active metabolite (GS-461203) and the inactive metabolite GS-331007, the latter accounting for over 90% of systemic exposure.

Elimination: The majority of the dose is recovered in urine, with renal clearance being the major elimination pathway for GS-331007.

Special Populations:

No dose adjustment is recommended for patients with mild, moderate, and severe hepatic impairment.

For patients with severe renal impairment (eGFR <30 mL/min/1.73 m²), a dose reduction (e.g., 200 mg) is often considered, although the product label may not contain a formal recommendation.

Pharmacokinetics in pediatric patients (≥3 years) are similar to adults.

Clinical Use:

Indicated for the treatment of chronic HCV infection in combination with other antiviral agents (e.g., Ribavirin, Velpatasvir, Ledipasvir).

Regimens vary based on HCV genotype (e.g., Genotype 1 or 4: Sofosbuvir, peginterferon alfa, and ribavirin for 12 weeks; Genotype 2: Sofosbuvir and ribavirin for 12 weeks).

Used in special populations, including patients awaiting liver transplantation and co-infected with HIV, under specific clinical guidance.

References:

Mechanism and Pharmacology: BenchChem Technical Guide, Gilead Sciences Prescribing Information, Sobvi Tablet SPC, SofoBuvir Monograph, WHO Documentation.

Dosage and Forms: DailyMed (Sovaldi), Drugs.com, EMA Guidelines, Mayo Clinic.

Pharmacokinetics: Gilead Prescribing Information, VA Pharmacy Monograph, ANMAT (Argentina) Documentation.