SOFOSBUVIR

Clinical safety rating: safe

Animal studies have demonstrated safety

How it works

NS5B RNA-dependent RNA polymerase inhibitor; inhibits viral replication by acting as a chain terminator following incorporation into the growing RNA strand.

What the body does with it

Metabolism	Metabolized by cathepsin A (CatA) and carboxylesterase 1 (CES1) to the active metabolite GS-461203; further dephosphorylation by nucleotide phosphatase. Not significantly metabolized by CYP450 enzymes.
Excretion	Primarily biliary/fecal (77-80% of dose eliminated in feces as unchanged drug; 14% in urine as sofosbuvir metabolite GS-331007). Renal elimination of GS-331007 accounts for 14% of total clearance.
Half-life	Terminal t1/2 of sofosbuvir is 0.4-0.5 h; major circulating metabolite GS-331007 has terminal t1/2 of 15-25 h. The long t1/2 of GS-331007 supports once-daily dosing.
Protein binding	Sofosbuvir: 61-65% bound to human plasma proteins (primarily albumin); GS-331007: <1% bound.
Volume of Distribution	Sofosbuvir: Vd/F approximately 0.1-0.2 L/kg (component metabolites have limited distribution); GS-331007: 0.3-0.4 L/kg. Indicates low to moderate distribution into tissues.
Bioavailability	Sofosbuvir: approximately 37-44% (oral administration). Peak plasma concentrations reached within 0.5-2 h.
Onset of Action	Rapid antiviral effect: significant HCV RNA decline within 6-12 hours after oral administration.
Duration of Action	Once-daily dosing; sustained suppression of HCV RNA achieved with continuous therapy. Clinical effect duration extends throughout 24-hour dosing interval.

Classification & Brands

Dosing & administration

400 mg orally once daily, typically in combination with other direct-acting antivirals.

Dosage form	TABLET
Renal impairment	No dose adjustment required for GFR ≥30 mL/min. For GFR <30 mL/min or ESRD, safety and efficacy not established; use with caution and consider alternative therapy.
Liver impairment	No dose adjustment required for mild, moderate, or severe hepatic impairment (Child-Pugh A, B, or C).
Pediatric use	For children ≥3 years and ≥17 kg: weight-based dosing (200 mg for 17 to <35 kg; 400 mg for ≥35 kg) once daily in combination with other antivirals. For children <3 years: safety and efficacy not established.
Geriatric use	No specific dose adjustment required; limited data in patients >65 years, but no significant differences in safety or efficacy observed.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Strong P-gp inducers may decrease levels Generally well-tolerated with fatigue and headache being common.

Breastfeeding	Sofosbuvir is excreted in human milk; M/P ratio not reported. Limited data suggest low risk; however, caution advised. Discontinue breastfeeding or drug based on importance to mother.
Teratogenic Risk	Sofosbuvir is not teratogenic in animal studies; human data limited. No known fetal risk in any trimester based on available evidence. However, use only if clearly needed.
Fetal Monitoring

Warnings & precautions

■ FDA Black Box Warning

Not applicable; no boxed warning for sofosbuvir alone. However, combination regimens with amiodarone may cause serious symptomatic bradycardia.

Side Effect Profile

Common Effects	Fatigue
Serious Effects

Absolute Contraindications

Concomitant use with amiodarone in patients with significant cardiac abnormalities or predisposing conditions; hypersensitivity to sofosbuvir or any component of the formulation; coadministration with potent P-glycoprotein inducers (e.g., rifampin, St. John's wort).

Clinical Precautions

Precautions

Risk of hepatitis B virus (HBV) reactivation in patients coinfected with HCV and HBV; bradycardia when used with amiodarone, especially in patients also taking beta-blockers or with cardiac comorbidities; use with caution in renal impairment (eGFR <30 mL/min/1.73 m2) as safety not established.

Clinical Tips & Counseling

Drug interactions

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