Schedule H

Oral

• Tablet: 400 mg

• Fixed-Dose Combinations (FDCs):

• Sofosbuvir 400 mg + Ledipasvir 90 mg

• Sofosbuvir 400 mg + Velpatasvir 100 mg

• Sofosbuvir 400 mg + Daclatasvir 60 mg

INDICATIONS + DOSING — FOR CLINICIAN USE ONLY

Primary Indications (Approved / Standard in India)

Chronic Hepatitis C Virus (HCV) Infection – Adults

Important: Sofosbuvir must NOT be used as monotherapy. Always use in combination with other direct-acting antivirals based on HCV genotype, cirrhosis status, and prior treatment history.

Regimen Selection Based on Clinical Scenario:

Clinical Scenario Recommended Combination Duration

All genotypes, treatment-naïve, no cirrhosis Sofosbuvir + Daclatasvir 12 weeks

All genotypes, treatment-naïve, compensated cirrhosis Sofosbuvir + Daclatasvir 24 weeks OR 12 weeks with Ribavirin

All genotypes, treatment-experienced Sofosbuvir + Daclatasvir ± Ribavirin 24 weeks

Genotype 1, 4, 5, 6, no cirrhosis Sofosbuvir + Ledipasvir 12 weeks

Genotype 1, 4, 5, 6, compensated cirrhosis Sofosbuvir + Ledipasvir 24 weeks OR 12 weeks with Ribavirin

All genotypes (pan-genotypic option) Sofosbuvir + Velpatasvir 12 weeks

Decompensated cirrhosis (Child-Pugh B/C) Sofosbuvir + Velpatasvir + Ribavirin 12 weeks (specialist only)

Dosing for Sofosbuvir Component:

Component Details

Starting dose 400 mg once daily

Titration Not applicable

Usual maintenance dose 400 mg once daily

Maximum dose 400 mg/day

Clinical Notes:

• Administer with or without food

• Take at approximately the same time each day

• If using with Ribavirin: Ribavirin dose is weight-based (1000 mg/day if <75 kg; 1200 mg/day if ≥75 kg in divided doses)

• Pan-genotypic regimens (Sofosbuvir + Daclatasvir or Sofosbuvir + Velpatasvir) preferred when genotype testing unavailable

• Treatment decisions per NVHCP and AIIMS protocols

Secondary Indications – Adults (Off-label)

Not applicable. Sofosbuvir is approved exclusively for chronic HCV infection in India. No established off-label indications.

PAEDIATRIC DOSING (Specialist Only)

Primary Indication: Chronic Hepatitis C Virus Infection

Minimum age: 3 years

Eligibility: Children with confirmed chronic HCV infection and detectable HCV RNA

Weight-based dosing:

Body Weight Sofosbuvir Dose Formulation

≥35 kg 400 mg once daily Tablet

17–<35 kg 200 mg once daily Half tablet or paediatric formulation if available

<17 kg Not recommended Refer to specialist centre

Component Details

Starting dose Weight-based as per table above

Titration Not applicable

Usual maintenance dose As per weight band

Maximum dose 400 mg/day

Combination Partner:

• Combine with age-appropriate DAA (ledipasvir, velpatasvir, or daclatasvir) as per genotype

• Ribavirin may be added in cirrhosis (weight-based dosing: 15 mg/kg/day in two divided doses)

Duration: 12–24 weeks depending on cirrhosis status and prior treatment

Safety Monitoring:

• Liver function tests at baseline, week 4, week 12, and end of treatment

• Complete blood count if using Ribavirin

• HCV RNA at baseline, end of treatment, and 12 weeks post-treatment (SVR12)

• Growth parameters

Secondary Indications – Paediatrics (Off-label)

Not applicable.

Age restriction: Not recommended below 3 years of age. Use in children requires specialist paediatric hepatology/gastroenterology supervision. Available under NVHCP at designated centres.

• Mild impairment (Child-Pugh A): No dose adjustment required

• Moderate impairment (Child-Pugh B): No dose adjustment required; use with caution; avoid Ribavirin if possible due to anaemia risk

• Severe impairment (Child-Pugh C — decompensated cirrhosis): Can be used but specialist supervision essential; preferably use Sofosbuvir + Velpatasvir ± Ribavirin; monitor closely for hepatic decompensation

• Known hypersensitivity to sofosbuvir or any excipient

• Monotherapy for HCV — ineffective and promotes resistance

• Concurrent use with potent P-glycoprotein (P-gp) inducers:

• Rifampicin

• Carbamazepine

• Phenytoin

• Phenobarbital

• St. John's Wort

• Ribavirin-containing regimens in pregnancy or in women/men not using effective contraception

• Severe renal impairment (eGFR <30 mL/min) unless no alternative and under specialist care

• Hepatitis B co-infection: Risk of HBV reactivation during or after HCV treatment; screen all patients for HBsAg before starting; monitor and consider HBV prophylaxis if indicated

• Concurrent amiodarone use: Risk of severe symptomatic bradycardia, including fatal cases; avoid if possible; if unavoidable, cardiac monitoring for at least 48 hours after initiation

• Concurrent beta-blocker use: May potentiate bradycardia risk with amiodarone

• Decompensated cirrhosis: Monitor for worsening hepatic function; Ribavirin may exacerbate anaemia

• HIV-HCV co-infection: Review antiretroviral regimen for drug interactions before starting

• Diabetes mellitus: Successful HCV treatment may improve glycaemic control; monitor blood glucose and adjust antidiabetic therapy as needed

Aspect Details

Overall safety Limited human data for sofosbuvir; animal studies show no teratogenicity

Ribavirin combinations Contraindicated — Ribavirin is highly teratogenic (Category X); strict contraception required in both sexes during and for 6 months after Ribavirin

Preferred approach Defer HCV treatment until after delivery if possible

When it may be used May consider Ribavirin-free regimen (Sofosbuvir + Daclatasvir or Sofosbuvir + Velpatasvir) if treatment cannot be deferred; specialist decision only

Monitoring LFTs, viral load, fetal growth and anomaly scans

Aspect Details

Compatibility Sofosbuvir alone: Limited data; likely low excretion in breast milk; probably compatible

Ribavirin combinations Contraindicated — Ribavirin must be avoided during breastfeeding

Preferred approach Defer treatment or use Ribavirin-free regimen

Drug levels in milk Unknown for sofosbuvir; Ribavirin potentially significant

Infant monitoring If sofosbuvir used without Ribavirin: routine monitoring; no specific concerns documented

• Recommended starting dose: 400 mg once daily (same as younger adults)

• Titration: Not applicable

• Extra risks:

• Age-related decline in renal function — assess eGFR before initiation

• Polypharmacy — review for drug interactions

• Monitor haemoglobin closely if Ribavirin is added

• Consider overall hepatic reserve and comorbidities

Interacting Drug Effect/Mechanism Recommendation

Rifampicin Potent P-gp inducer — markedly reduces sofosbuvir levels Contraindicated

Carbamazepine, Phenytoin, Phenobarbital P-gp and CYP inducers — reduce sofosbuvir efficacy Contraindicated

St. John's Wort P-gp inducer Contraindicated

Amiodarone Severe symptomatic bradycardia, potentially fatal Avoid; if essential, cardiac monitoring for ≥48 hours

Tipranavir/ritonavir Reduces sofosbuvir levels via P-gp induction Avoid combination

Rosuvastatin (with Ledipasvir/Sofosbuvir) Increased rosuvastatin exposure — myopathy risk Limit rosuvastatin to 10 mg/day or use alternative statin

Interacting Drug Effect/Mechanism Recommendation

Tenofovir disoproxil fumarate (TDF) Increased TDF exposure when used with Ledipasvir/Sofosbuvir Monitor renal function; avoid TDF-containing regimens if eGFR borderline

Efavirenz, Nevirapine May modestly reduce DAA levels Monitor HCV response; generally can be used

Antacids, H2-blockers, PPIs (with Ledipasvir combination) Reduced ledipasvir absorption in acidic environment Separate antacids by 4 hours; use lowest PPI dose (equivalent to omeprazole 20 mg); administer simultaneously with or before Ledipasvir

Digoxin Increased digoxin absorption via P-gp inhibition Monitor digoxin levels

Methadone, Buprenorphine Slightly increased opioid exposure Monitor for sedation; usually no dose adjustment needed

Warfarin INR may fluctuate during and after HCV treatment Monitor INR frequently during treatment

Atorvastatin (with Ledipasvir/Sofosbuvir) Increased statin exposure Use lowest effective statin dose; monitor for myopathy

• Fatigue

• Headache

• Nausea

• Insomnia

• Irritability

• Pruritus

• Asthenia

• Anaemia (when combined with Ribavirin)

• Severe symptomatic bradycardia — reported with concurrent amiodarone; potentially fatal; requires immediate discontinuation and cardiac monitoring

• Hepatitis B reactivation — may cause fulminant hepatitis, hepatic failure, or death; screen and monitor all patients

• Severe anaemia — with Ribavirin combination; may require Ribavirin dose reduction or blood transfusion

• Hepatic decompensation — in patients with advanced cirrhosis

• Hypersensitivity reactions — rare; discontinue if severe

→ Serious adverse effects require immediate discontinuation and specialist consultation

Phase Parameters

Baseline HCV RNA (quantitative), HCV genotype (if available), LFTs (ALT, AST, bilirubin), serum creatinine/eGFR, CBC with differential, HBsAg and anti-HBc serology (mandatory), HIV serology, INR (if on warfarin), pregnancy test (women of childbearing potential)

During treatment LFTs at week 4 and week 12; CBC weekly for first month if on Ribavirin, then monthly; HCV RNA at week 4 (optional) and end of treatment

After treatment HCV RNA at 12 weeks post-treatment (SVR12) and 24 weeks (SVR24); LFTs if abnormal during treatment

If HBV co-infected Monitor HBV DNA and LFTs during and for ≥6 months after HCV treatment

Single-agent:

• Hepcinat® (Natco)

• MyHep® (Mylan)

• Sofovir® (Hetero)

• SoviHep® (Zydus Cadila)

• Sofab® (Abbott)

• Resof® (Dr. Reddy's)

Fixed-Dose Combinations:

• NLEM status: Yes (Sofosbuvir included in NLEM 2022)

• NPPA controlled: Price ceiling applicable

• Government supply: Available free under National Viral Hepatitis Control Programme (NVHCP) at designated treatment centres for eligible patients

• Never use sofosbuvir as monotherapy — always combine with appropriate DAA partner based on genotype and clinical scenario

• Mandatory HBV screening before treatment — HBV reactivation can be fatal; screen all patients for HBsAg and anti-HBc before initiating therapy

• Avoid amiodarone — risk of fatal bradycardia; if unavoidable, inpatient cardiac monitoring essential for at least 48 hours

• Pan-genotypic regimens preferred when genotype testing unavailable — Sofosbuvir + Daclatasvir or Sofosbuvir + Velpatasvir cover all genotypes

• Ribavirin is teratogenic — ensure strict contraception in both male and female patients during and for 6 months after treatment

• Check for free government supply — NVHCP provides free HCV treatment at designated centres; always assess patient eligibility

Sofosbuvir; hepatitis C; HCV; antiviral; DAA; NS5B inhibitor; pan-genotypic; NLEM India; NVHCP; pregnancy-caution; renal-caution; amiodarone-interaction

RxIndia v1.1 — 18 Jan 2025

• CDSCO approved prescribing information

• Indian Pharmacopoeia

• National List of Essential Medicines (NLEM) 2022, India

• National Viral Hepatitis Control Programme (NVHCP) Operational Guidelines

• AIIMS Standard Treatment Guidelines for Hepatitis C

• API Textbook of Medicine (11th Edition) — Viral Hepatitis chapter

• ICMR Guidance on Hepatitis C Management

• Goodman & Gilman's The Pharmacological Basis of Therapeutics (13th Edition)