Usage
- Sofosbuvir + Velpatasvir is prescribed for the treatment of chronic hepatitis C virus (HCV) infection in adults and children aged 3 years and older with HCV genotypes 1, 2, 3, 4, 5, and 6, including those without cirrhosis, with compensated cirrhosis (Child-Pugh A), and with decompensated cirrhosis (Child-Pugh B or C) used in combination with ribavirin. It is also used in liver transplant recipients.
- Pharmacological classification: Direct-acting antiviral agent.
- Mechanism of action: Sofosbuvir is a nucleotide analog inhibitor of HCV NS5B polymerase, which is essential for viral RNA replication. Velpatasvir is an HCV NS5A inhibitor, which is essential for viral replication and assembly. Together, they provide a dual mechanism of action against HCV.
Alternate Names
- The combination is often referred to as SOF/VEL.
- Brand Name: Epclusa
How It Works
- Pharmacodynamics: SOF/VEL targets specific viral proteins essential for HCV replication, leading to a decrease in viral load and ultimately viral eradication.
- Pharmacokinetics:
- Absorption: Velpatasvir’s absorption is reduced with increasing gastric pH. Sofosbuvir is a prodrug that’s metabolized to its active form, GS-461203.
- Metabolism: Sofosbuvir is extensively metabolized in the liver. Velpatasvir is also metabolized in the liver, primarily by CYP2B6, CYP2C8, and CYP3A4.
- Elimination: Sofosbuvir is primarily eliminated in urine, while Velpatasvir is mainly excreted in feces.
- Mode of Action: Sofosbuvir acts as a defective substrate for the HCV NS5B RNA polymerase, causing chain termination during RNA replication. Velpatasvir binds to NS5A, disrupting viral replication and assembly.
- Receptor binding, enzyme inhibition, or neurotransmitter modulation: Sofosbuvir inhibits NS5B polymerase. Velpatasvir inhibits NS5A.
- Elimination pathways: Sofosbuvir is primarily renally excreted, while Velpatasvir undergoes hepatic excretion.
Dosage
Standard Dosage
Adults:
- One tablet (400 mg sofosbuvir/100 mg velpatasvir) orally once daily with or without food for 12 weeks.
- Patients with decompensated cirrhosis (Child-Pugh B or C) should receive ribavirin concomitantly.
Children (3 years and older):
- Dosage is weight-based:
- <17 kg: 150 mg sofosbuvir/37.5 mg velpatasvir orally once daily.
- 17 to <30 kg: 200 mg sofosbuvir/50 mg velpatasvir orally once daily.
- ≥30 kg: 400 mg sofosbuvir/100 mg velpatasvir orally once daily.
- Treatment duration: 12 weeks.
- For children younger than 6 years, administer oral pellets with food.
- Liver transplant recipients: 12 weeks, with ribavirin added for those with decompensated cirrhosis.
Special Cases:
- Elderly Patients: No dose adjustment required.
- Patients with Renal Impairment: No dose adjustment needed.
- Patients with Hepatic Dysfunction: No dose adjustment necessary.
- Patients with Comorbid Conditions: Monitor closely, especially those with diabetes (risk of hypoglycemia) or cardiac conditions (especially if taking amiodarone).
Clinical Use Cases
SOF/VEL is not typically used in situations like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. It is specifically indicated for chronic HCV treatment.
Dosage Adjustments
Dose adjustments are not required for renal or hepatic impairment. However, adjustments may be needed for drug interactions or for patients with other medical conditions.
Side Effects
Common Side Effects:
- Fatigue
- Headache
- Nausea
- Diarrhea
- Difficulty sleeping
Rare but Serious Side Effects:
- Hepatitis B reactivation (in patients with current or prior HBV infection)
- Severe allergic reactions (angioedema, rash, trouble breathing)
- Symptomatic bradycardia (especially with amiodarone)
Long-Term Effects:
Long-term side effects are not well established, but monitoring for hepatitis B reactivation is essential.
Adverse Drug Reactions (ADR):
- Reactivation of hepatitis B
- Symptomatic bradycardia
- Severe allergic reactions
Contraindications
- Hypersensitivity to sofosbuvir or velpatasvir.
- Coadministration with strong P-gp inducers (e.g., rifampin, St. John’s wort) or moderate to potent CYP inducers (e.g., carbamazepine, phenytoin).
- Coadministration with amiodarone (unless absolutely necessary and with close cardiac monitoring).
- Pregnancy when used with ribavirin.
Drug Interactions
- Drugs that increase gastric pH (e.g., antacids, PPIs) can reduce Velpatasvir absorption. Separate dosing by at least 4 hours.
- P-gp inducers and moderate to potent CYP inducers can reduce SOF/VEL concentrations. Avoid coadministration.
- SOF/VEL can increase concentrations of drugs that are substrates of P-gp, BCRP, OATP1B1, OATP1B3, and OATP2B1. Monitor drug levels and adjust doses as needed.
Pregnancy and Breastfeeding
- Pregnancy: SOF/VEL is not recommended during pregnancy, especially when combined with ribavirin, which is contraindicated.
- Breastfeeding: Not recommended. It is unknown if SOF/VEL or its metabolites are present in breast milk.
Drug Profile Summary
- Mechanism of Action: NS5B polymerase inhibitor and NS5A inhibitor.
- Side Effects: Fatigue, headache, nausea, diarrhea, insomnia. Rarely: hepatitis B reactivation, bradycardia (with amiodarone), allergic reactions.
- Contraindications: Hypersensitivity, strong P-gp/CYP inducers, amiodarone (generally).
- Drug Interactions: Drugs affecting gastric pH, P-gp/CYP inducers, substrates of P-gp, BCRP, OATPs.
- Pregnancy & Breastfeeding: Not recommended.
- Dosage: Adults: 400mg/100mg once daily; Pediatric: Weight-based dosing.
- Monitoring Parameters: LFTs, HCV RNA, HBV serologies (if applicable), renal function (with ribavirin), cardiac function (with amiodarone).
Popular Combinations
- Ribavirin: Used in patients with decompensated cirrhosis or genotype 3 with compensated cirrhosis.
Precautions
- Test for HBV infection before starting therapy.
- Monitor for HBV reactivation during and after treatment.
- Caution in patients with cardiac conditions, especially when taking amiodarone.
- Monitor diabetic patients for hypoglycemia.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Sofosbuvir + Velpatasvir?
A: Adults: 400 mg sofosbuvir/100 mg velpatasvir once daily. Children: Weight-based dosing.
Q2: What are the most common side effects?
A: Fatigue, headache, nausea, diarrhea, and difficulty sleeping.
Q3: Can Sofosbuvir + Velpatasvir be used in patients with cirrhosis?
A: Yes, it can be used in patients with compensated or decompensated cirrhosis, although ribavirin is added for those with decompensated cirrhosis.
Q4: What are the contraindications to using this medication?
A: Hypersensitivity, coadministration with strong P-gp/CYP inducers, and generally, amiodarone. Ribavirin-containing regimens are contraindicated in pregnancy.
Q5: What monitoring is required during treatment?
A: LFTs, HCV RNA viral load, renal function (with ribavirin), and HBV serologies (if applicable). Monitor diabetic patients for hypoglycemia and patients on amiodarone for bradycardia.
Q6: How is Sofosbuvir + Velpatasvir administered?
A: Orally as a single tablet, once daily, with or without food. For children under 6 years of age, administer the oral pellets with food.
Q7: What is the duration of treatment?
A: Typically 12 weeks.
Q8: Can this drug be used in patients with renal impairment?
A: Yes, no dose adjustment is needed.
Q9: Is there a risk of drug interactions?
A: Yes. Consult a drug interaction resource for a complete list. Be mindful of drugs affecting gastric pH and P-gp/CYP modulators.
Q10: What is the significance of HBV reactivation?
A: HBV reactivation can occur during or after HCV treatment and can lead to serious liver problems, including liver failure. HBV testing is crucial before starting treatment.
