Sofosbuvir + Velpatasvir


Concise Prescribing Info
Indications/Uses
Chronic hepatitis C.
Dosage/Direction for Use
Adult : PO Each tab contains sofosbuvir 400 mg and velpatasvir 100 mg: 1 tab once daily.
Dosage Details
Oral
Chronic hepatitis C
Adult: Available preparation:
Sofosbuvir 400 mg and velpatasvir 100 mg

1 tab once daily. For patients with decompensated cirrhosis or HCV genotype 3 with compensated cirrhosis, ribavirin may be added. If vomiting occurs within 3 hours of dosing, an additional tablet is needed. Treatment duration: 12 weeks; up to 24 weeks, if necessary (with ribavirin).
Administration
May be taken with or without food.
Contraindications
Hypersensitivity. Concomitant use of potent P-glycoprotein (P-gp) and CYP inducers. Lactation.
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. Pregnancy.
Adverse Reactions
Gastrointestinal disorders: Nausea, diarrhoea.
General disorders and administration site conditions: Fatigue, weakness, irritability.
Immune system disorders: Angioedema.
Investigations: Increased serum lipase, creatine phosphokinase.
Musculoskeletal and connective tissue disorders: Arthralgia, back pain.
Nervous system disorders: Headache.
Psychiatric disorders: Insomnia, depression.
Respiratory, thoracic and mediastinal disorders: Cough, 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).
MonitoringParameters
Monitor CBC, INR, LFT, and calculated GFR within 12 weeks prior to initiation of therapy, repeat after 4 weeks of therapy and as clinically indicated. Perform HCV genotype and subtype and quantitative HCV viral load testing at baseline, after 4 weeks of therapy, then after 12 weeks after completion of therapy. Measure hepatitis B surface antigen (HBsAg) and hepatitis core antibody (anti-HBc) prior to initiation. Monitor for signs of hepatitis flare or HBV reactivation.
Drug Interactions
Reduced plasma concentration with moderate P-gp or CYP inducers (e.g. efavirenz, modafinil, oxcarbazepine). May cause fluctuations in INR when given with warfarin. May increase the serum concentration of digoxin and rosuvastatin.
Velpatasvir: Decreased concentration with antacids (Al and Mg hydroxide), H2-receptor antagonists (e.g. famotidine), and proton pump inhibitors (e.g. omeprazole).
Potentially Fatal: Significantly reduced plasma concentration with potent P-gp or CYP inducers (e.g. rifampicin, phenobarbital, phenytoin, carbamazepine) resulting in loss of efficacy. Risk of severe bradycardia and heart block with amiodarone.
Food Interaction
Significantly reduced plasma concentration with St John’s wort, avoid use.
Action
Description: Sofosbuvir and velpatasvir reduce viral load by inhibiting hepatitis C virus (HCV) 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.
Velpatasvir inhibits the HCV nonstructural 5A (NS5A) protein necessary for RNA viral replication and assembly.
Pharmacokinetics:
Absorption: Sofosbuvir: Time to peak plasma concentration: 0.5-1 hour.
Velpatasvir: Time to peak plasma concentration: 3 hours.
Distribution: Sofosbuvir: Plasma protein binding: 61-65%.
Velpatasvir: Plasma protein binding: >99.5%.
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.
Velpatasvir: Metabolised in the liver.
Excretion: Sofosbuvir: Mainly via urine (80%); faeces (14%). Elimination half-life: 0.5 hour.
Velpatasvir: Mainly via faeces (94%); urine (0.4%). Elimination half-life: 15 hours.
Chemical Structure

Chemical Structure Image
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)


Chemical Structure Image
Velpatasvir

Source: National Center for Biotechnology Information. PubChem Database. Velpatasvir, CID=67683363, https://pubchem.ncbi.nlm.nih.gov/compound/Velpatasvir (accessed on Jan. 23, 2020)

Storage
Store below 30°C.
MIMS Class
ATC Classification
J05AP55 - sofosbuvir and velpatasvir ; Belongs to the class of antivirals for treatment of HCV infections. Used in the treatment of hepatitis C viral infections.
References
Anon. Sofosbuvir and Velpatasvir. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 02/02/2018.

Epclusa Tablet, Film Coated (Gilead Sciences, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 02/02/2018.

Joint Formulary Committee. Sofosbuvir with Velpatasvir. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 02/02/2018.

Disclaimer: This information is independently developed by MIMS based on Sofosbuvir + Velpatasvir 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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