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).
This drug may cause fatigue, if affected, do not drive or operate machinery.
Monitoring Parameters
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
Sofosbuvir Source: National Center for Biotechnology Information. PubChem Database. Sovaldi, CID=45375808, https://pubchem.ncbi.nlm.nih.gov/compound/Sovaldi (accessed on Jan. 23, 2020)
Ledipasvir Source: National Center for Biotechnology Information. PubChem Database. Ledipasvir, CID=67505836, https://pubchem.ncbi.nlm.nih.gov/compound/Ledipasvir (accessed on Jan. 23, 2020)
J05AP51 - sofosbuvir and ledipasvir ; Belongs to the class of antivirals for treatment of HCV infections. Used in the treatment of hepatitis C viral infections.
References
Anon. Ledipasvir and Sofosbuvir. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 01/02/2018.Harvoni Tablet, Film-coated (Gilead Sciences, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 01/02/2018.Joint Formulary Committee. Sofosbuvir with Ledipasvir. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 01/02/2018.
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