Sofosbuvir-Velpatasvir

Sofosbuvir/Velpatasvir is a combination prescription medication used for the treatment of chronic hepatitis C.

• Sofosbuvir/Velpatasvir is available under the following different brand names: Epclusa

Adult and pediatric dosage

Tablet

• 200mg/50mg
• 400mg/100mg

Oral pellets

• 150mg/37.5mg

Chronic Hepatitis C

Adult dosage

• 1 tablet (400 mg sofosbuvir/100 mg Velpatasvir) orally every day
• Treatment duration for treatment-naïve and treatment-experienced liver transplant recipients
  • Without cirrhosis or with compensated cirrhosis (Child-Pugh A): Sofosbuvir/Velpatasvir for 12 weeks
  • With decompensated cirrhosis (Child-Pugh B or C): Sofosbuvir/Velpatasvir plus ribavirin for 12 weeks
  • Weight-based ribavirin dose
    • Below 75 kg: 1000 mg/day orally divided twice daily
    • Above 75 kg: 1200 mg/day orally divided twice daily
    • Modify ribavirin starting dose and on-treatment dosage based on hemoglobin and creatinine clearance

Pediatric dosage

• Below 3 years: Safety and efficacy not established
• Above 3 years
  • Oral pellets
    • Below 17 kg: 150 mg sofosbuvir/37.5 mg Velpatasvir orally every day
  • Oral tablet(s) or pellets
    • 17 to 29  kg: 200 mg sofosbuvir/50 mg Velpatasvir orally every day
    • Above 30 kg: 400 mg sofosbuvir/100 mg Velpatasvir orally every day
  • Treatment duration for treatment-naïve and treatment-experienced liver transplant recipients
    • Without cirrhosis or with compensated cirrhosis (Child-Pugh A): Sofosbuvir/Velpatasvir for 12 weeks
    • With decompensated cirrhosis (Child-Pugh B or C): Sofosbuvir/Velpatasvir plus ribavirin for 12 weeks
  • Weight-based ribavirin dose
    • Below 47 kg: 15 mg/kg/day orally (divided dose AM and PM)
    • 47-49 kg: 600 mg/day orally(1 x 200 mg AM, 2 x 200 mg PM)
    • 50-65 kg: 800 mg/day orally (2 x 200 mg AM, 2 x 200 mg PM)
    • 66-80 kg: 1000 mg/day orally (2 x 200 mg AM, 3 x 200 mg PM)
    • Above 80 kg: 1200 mg/day orally (3 x 200 mg AM, 3 x 200 mg PM)

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Common side effects of Sofosbuvir/Velpatasvir include:

• tiredness, 
• headache,
• nausea,
•  diarrhea, or 
• difficulty sleeping.

Serious side effects of Sofosbuvir/Velpatasvir include:

• rash, 
• itching/swelling (especially of the face/tongue/throat),
• severe dizziness,
• trouble breathing,
• mental/mood changes (such as depression),
•  unusual tiredness

Rare side effects of Sofosbuvir/Velpatasvir include:

• none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Sofosbuvir/Velpatasvir has severe interactions with the following drug:
  • ritonavir
• Sofosbuvir/Velpatasvir has serious interactions with at least 44 other drugs:
• Sofosbuvir/Velpatasvir has moderate interactions with at least 91 other drugs.
• Sofosbuvir/Velpatasvir has minor interactions with the following drug:
  • ribociclib

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• Sofosbuvir/Velpatasvir plus ribavirin combination regimen is contraindicated in patients for whom ribavirin is contraindicated

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Sofosbuvir/Velpatasvir?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Sofosbuvir/Velpatasvir?”

Cautions

• Hepatitis B virus reactivation
  • Hepatitis B virus (HBV) reactivation was reported in HCV/HBV coinfected patients undergoing or who completed treatment with HCV DDAs, and were not receiving HBV antiviral therapy
  • HBV reactivation is characterized as an abrupt increase in HBV replication manifesting as a rapid increase in serum HBV DNA level (see Black Box Warnings and Dosing Considerations)
  • HBV reactivation was also reported in patients receiving certain immunosuppressants or chemotherapeutic agents
  • The risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may increase in these patients
  • Reactivation of HBV replication may be accompanied by hepatitis, eg, increases in aminotransferase levels and, in severe cases, increases in bilirubin levels, liver failure, and death may occur
  • In patients with serologic evidence of HBV infection, monitor for clinical and laboratory signs of hepatitis flare or HBV reactivation during HCV treatment and during post-treatment follow-up; initiate appropriate patient management for HBV infection as clinically indicated
  • If administered with ribavirin, warnings and precautions for ribavirin apply to this combination; see ribavirin prescribing information
• Bradycardia
  • Coadministration with amiodarone is not recommended
  • Postmarketing cases of symptomatic bradycardia and cases requiring pacemaker intervention were reported when amiodarone was coadministered with the regimen
  • Serious symptomatic bradycardia may occur if sofosbuvir is coadministered with amiodarone in combination with another direct-acting antiviral (eg, daclatasvir, simeprevir)
  • Bradycardia has generally occurred within hours to days, but reports have been observed up to 2 weeks after initiating HCV treatment
  • Patients also taking beta-blockers, or those with underlying cardiac comorbidities, and/or advanced liver disease may be at increased risk for symptomatic bradycardia with coadministration of amiodarone
  • For patients taking amiodarone who have no other alternative viable treatment options and who will require coadministration, counsel patients about the risk of symptomatic bradycardia and monitor cardiac activity in an in-patient setting for the first 48 hours of coadministration, after which outpatient or self-monitoring of the heart rate should occur daily through at least first 2 weeks of treatment
  • Patients receiving therapy who need to start amiodarone therapy due to no other alternative viable treatment options should undergo similar cardiac monitoring as outlined above
  • Because of amiodarone’s long half-life, patients discontinuing amiodarone just before starting therapy should also undergo similar cardiac monitoring
• Drug interaction overview
  • Drugs affecting sofosbuvir/Velpatasvir
    • Sofosbuvir and Velpatasvir are substrates of drug transporters P-gp and BCRP while GS-331007 (the predominant circulating metabolite of sofosbuvir) is not
    • In vitro, slow metabolic turnover of Velpatasvir by CYP2B6, CYP2C8, and CYP3A4 was observed
    • Drugs that are potent P-gp inducers and/or moderate-to-potent inducers of CYP2B6, CYP2C8, or CYP3A4 (eg, rifampin, carbamazepine, St. John’s wort) may significantly decrease sofosbuvir and/or Velpatasvir plasma concentrations, leading to potentially reduced therapeutic effect; avoid coadministration
  • Drugs that increase gastric pH
    • Coadministration with drugs that increase gastric pH is expected to decrease Velpatasvir serum concentration
    • See the Administration section for how long is needed between sofosbuvir/Velpatasvir doses and drugs that increase gastric pH
  • Sofosbuvir/Velpatasvir effect on other drugs
    • Velpatasvir inhibits drug transporters P-gp, BCRP, OATP1B1, OATP1B3, and OATP2B1
    • Coadministration with drugs that are substrates of these transporters may increase the exposure of such drugs
    • Frequent monitoring of relevant laboratory parameters (eg, International Normalized Ratio [INR] in patients taking warfarin, blood glucose levels in diabetic patients) or drug concentrations of concomitant medications such as cytochrome P450 substrates with a narrow therapeutic index (eg, certain immunosuppressants) recommended to ensure safe and effective use; dose adjustments of concomitant medications may be necessary

Pregnancy and Lactation

• Contraindicated if administered with ribavirin in pregnant women and in men whose female partners are pregnant
• There are no adequate data available to establish pregnancy risk for sofosbuvir or Velpatasvir
• Lactation
  • Unknown if sofosbuvir, Velpatasvir, or their metabolites are distributed in human breast milk
  • Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or the underlying maternal condition
  • If the regimen includes ribavirin, refer to the ribavirin prescribing information