Sofosbuvir + Ledipasvir


Concise Prescribing Info
Indications/Uses
Chronic hepatitis C of genotype 1, 4, 5, 6.
Dosage/Direction for Use
Adult : PO Each tab contains sofosbuvir 400 mg and ledipasvir 90 mg: 1 tab once daily.
Dosage Details
Oral
Chronic hepatitis C
Adult: Available preparation:
Sofosbuvir 400 mg and Ledipasvir 90 mg

In patients with HCV genotype 1, 4, 5, or 6 infections: 1 tab once daily, with or without ribavirin. If vomiting occurs within 5 hours of dosing, an additional tab is needed. Treatment duration: 8 or 12 weeks, or 24 weeks if necessary (varies according to HCV genotype and treatment regimen used).
Child: ≥12 years or weighing ≥35 kg: 1 tab once daily. Treatment duration varies according to HCV genotype and treatment regimen used.
Administration
May be taken with or without food.
Contraindications
Hypersensitivity. Lactation. Concomitant use of potent P-glycoprotein (P-gp) inducers and rosuvastatin.
Special Precautions
Patient with hepatitis B virus (HBV) co-infection; decompensated cirrhosis and/or who are awaiting liver transplant or post-liver transplant, and those at high risk of bradyarrhythmia. Children. Pregnancy.
Adverse Reactions
Gastrointestinal disorders: Nausea, diarrhoea.
General disorders and administration site conditions: Fatigue, weakness, irritability.
Immune system disorders: Rarely, angioedema.
Investigations: Increased serum lipase, bilirubin, creatine phosphokinase.
Nervous system disorders: Headache, dizziness.
Psychiatric disorders: Insomnia, depression.
Respiratory, thoracic and mediastinal disorders: Cough, dyspnoea, nasopharyngitis.
Skin and subcutaneous tissue disorders: Rash.
Potentially Fatal: Hepatitis B virus reactivation, resulting in fulminant hepatitis or hepatic failure (in patients with HBV co-infection).
Patient Counseling Information
This drug may cause fatigue, if affected, do not drive or operate machinery.
MonitoringParameters
Screen for current or previous hepatitis B infection by measuring hepatitis B surface antigen (HBsAg) and hepatitis core antibody (anti-HBc) prior to initiation. Monitor bilirubin, liver enzymes, and serum creatinine at baseline and periodically; serum HCV-RNA at baseline, during and after treatment, and when clinically indicated.
Drug Interactions
Reduced plasma concentration with moderate P-gp inducers (e.g. oxcarbazepine). May increase tenofovir exposure. Reduced efficacy with antacids (Al and Mg hydroxide). May increase the serum concentration of digoxin. Reduced anticoagulant effect of vitamin K antagonists.
Potentially Fatal: Significantly reduced plasma concentration with potent P-gp inducers (e.g. rifampicin, phenobarbital, phenytoin, carbamazepine), resulting in loss of efficacy. May cause significant increase in the plasma concentration of rosuvastatin, resulting in myopathy and rhabdomyolysis. Risk of severe bradycardia and cardiac arrest with amiodarone.
Food Interaction
Significantly reduced plasma concentration with St John’s wort, avoid use.
Action
Description: Sofosbuvir and ledipasvir reduce viral load by inhibiting hepatitis C virus RNA replication.
Sofosbuvir, a nucleotide analogue, inhibits hepatitis C virus (HCV) nonstructural 5B (NS5B) RNA-dependent polymerase which is necessary for viral replication. It is a direct-acting antiviral prodrug that has broad genotypic coverage and acts as chain terminator.
Ledipasvir inhibits the HCV nonstructural 5A (NS5A) protein, which is essential for both RNA replication and the assembly of HCV virions.
Pharmacokinetics:
Absorption: Well absorbed.
Sofosbuvir: Time to peak plasma concentration: Approx 0.8-1 hour.
Ledipasvir: Time to peak plasma concentration: 4-4.5 hours.
Distribution: Sofosbuvir: Plasma protein binding: Approx 61-65%.
Ledipasvir: Plasma protein binding: >99.8%.
Metabolism: Sofosbuvir: Extensively metabolised in the liver via hydrolysis to form pharmacologically active nucleoside (uridine) analogue triphosphate GS-461203, followed by dephosphorylation to form nucleoside inactive metabolite GS-331007.
Ledipasvir: Undergoes slow oxidative metabolism.
Excretion: Sofosbuvir: Mainly via urine (80%); faeces (14%). Elimination half-life: Approx 0.5 hour.
Ledipasvir: Mainly via faces (approx 86%); urine (1%). Elimination half-life: 47 hours.
Chemical Structure

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Storage
Store below 30°C.
MIMS Class
ATC Classification
J05AP51 - sofosbuvir and ledipasvir ; Belongs to the class of antivirals for treatment of HCV infections. Used in the treatment of hepatitis C viral infections.
Disclaimer: This information is independently developed by MIMS based on Sofosbuvir + Ledipasvir from various references and is provided for your reference only. Therapeutic uses, prescribing information and product availability may vary between countries. Please refer to MIMS Product Monographs for specific and locally approved prescribing information. Although great effort has been made to ensure content accuracy, MIMS shall not be held responsible or liable for any claims or damages arising from the use or misuse of the information contained herein, its contents or omissions, or otherwise. Copyright © 2020 MIMS. All rights reserved. Powered by MIMS.com
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