Drug reference

Sofosbuvir

Antiviral · Hepatitis C

AntiviralHepatitis C

CDSCO approvedSchedule H

EXCRETION

—

not curated

INTERACTIONS

12 major

SEVERE in our sources

PREGNANCY

Possible risk of neonatal goitre; use only if no

FDA category + note

Top interactionssee all 12 →

AcebutololSevereTextbookHarrison 22e · unknown
AtenololSevereTextbookHarrison 22e · unknown
BetaxololSevereTextbookHarrison 22e · unknown
BisoprololSevereTextbookHarrison 22e · unknown

Mechanism

Sofosbuvir is a nucleotide prodrug that is metabolized intracellularly by cellular kinases to its active uridine triphosphate analogue (GS-461203), which is incorporated by the HCV NS5B RNA-dependent RNA polymerase into the elongating viral RNA chain, causing obligate chain termination due to the 2'-fluoro-2'-C-methyluridine modification. It has pangenotypic activity against all HCV genotypes (1-6) and a high genetic barrier to resistance. Combined with NS5A inhibitors (ledipasvir, velpatasvir), it achieves sustained virological response rates exceeding 95%.

Indications

HCV infection (active against all genotypes) in combination with other direct-acting antivirals (DAAs) (e.g., ledipasvir, daclatasvir, velpatasvir, voxilaprevir)

Dosing

Adult: ▶ INITIALLY BY INTRAVENOUS INJECTION ▶ Adult: Initially 300 mg, dose to be considered after administration of adrenaline, dose should be given from a pre-ﬁlled syringe or diluted in 20 mL Glucose 5%, then (by intravenous injection) 150 mg if required, followed by (by intravenous infusion) 900 mg/24 hours IMPORTANT SAFETY INFORMATION MHRA/CHM ADVICE: SOFOSBUVIR WITH DACLATASVIR; SOFOSBUVIR AND LEDI…
Pediatric: Weight-based dosing (as part of combination products) for children 3 years or older (LDV/SOF) or 6 years or older (SOF/VEL)
Renal adjustment: No renal restrictions on the use of sofosbuvir-based therapies to treat HCV based on safety and efficacy data
Hepatic adjustment: No dose adjustment needed for moderate and severe hepatic impairment

Pharmacokinetics

Half-life

0.4 h (sofosbuvir); 27 h (GS-331007)

Bioavailability

At least 80%

Protein binding

63% (sofosbuvir); minimal (GS-331007)

Metabolism

Hydrolysis to GS-331007 (inactive metabolite); not a CYP substrate, inhibitor, or inducer

Excretion

Primarily in the urine via tubular secretion and glomerular filtration as GS-331007

Contraindications

Concomitant use with amiodarone (especially with daclatasvir, ledipasvir, or simeprevir) unless other antiarrhythmics are ineffective or contraindicated, due to risk of severe bradycardia and heart block.

Side effects

Common

HeadacheFatigueNauseaAstheniaInsomniaDiarrhea

Serious

Severe bradycardia (when taken with amiodarone)
Heart block (when taken with amiodarone)
Bradycardia (when coadministered with amiodarone in DAA regimens)
Pacemaker insertion (when coadministered with amiodarone in DAA regimens)
Fatal cardiac arrest (when coadministered with amiodarone in DAA regimens)

Pregnancy & lactation

Pregnancy

Possible risk of neonatal goitre; use only if no

Drug interactions

Acebutolol

Severe

Textbook

Severe bradycardia.

Extreme caution advised if amiodarone is co-administered with sofosbuvir and a beta blocker.