Velpatasvir

Usage

• Velpatasvir is an antiviral medication specifically indicated for the treatment of chronic hepatitis C virus (HCV) infection. It is effective against genotypes 1, 2, 3, 4, 5, and 6, including in patients with or without cirrhosis (compensated or decompensated). It is typically used in combination with sofosbuvir, and sometimes also with ribavirin.
• Pharmacological Classification: Direct-acting antiviral agent (DAA), specifically an NS5A inhibitor.
• Mechanism of Action: Velpatasvir inhibits the NS5A protein, which is essential for HCV replication. By blocking NS5A, velpatasvir disrupts the viral life cycle and prevents the virus from multiplying.

Alternate Names

• No commonly used alternate names. However, it’s predominantly known as part of the fixed-dose combination medication with sofosbuvir, marketed under the brand name Epclusa. Vosevi is another brand name which contains sofosbuvir, velpatasvir and voxilaprevir.

How It Works

• Pharmacodynamics: Velpatasvir targets the NS5A protein of the HCV virus, effectively inhibiting viral replication and leading to a reduction in HCV RNA levels.
• Pharmacokinetics:
  • Absorption: Velpatasvir is readily absorbed orally, with peak plasma concentrations occurring within 3 hours. Food can increase its absorption.
  • Metabolism: Primarily metabolized in the liver by CYP2B6, CYP2C8, and CYP3A4 enzymes.
  • Elimination: Excreted mainly in the feces, with minimal renal excretion. The half-life is approximately 15 hours.
• Mode of Action: Velpatasvir acts as an NS5A inhibitor, binding to the NS5A protein and interfering with several crucial steps in the HCV replication cycle, including viral assembly and RNA replication.
• Receptor Binding/Enzyme Inhibition: Velpatasvir’s mechanism of action involves direct binding to the NS5A protein.
• Elimination Pathways: Primarily eliminated via hepatic metabolism and biliary excretion, with minimal renal excretion.

Dosage

Standard Dosage

Adults:

• 400 mg sofosbuvir/100 mg velpatasvir (one tablet of Epclusa) taken orally once daily with or without food.
• Treatment duration is typically 12 weeks, but may extend to 24 weeks for patients with decompensated cirrhosis.

Children:

• Age ≥3 years: Dosage based on weight:
  • <17 kg: 150 mg sofosbuvir/37.5 mg velpatasvir (oral pellets) once daily with food.
  • 17 kg to <30 kg: 200 mg sofosbuvir/50 mg velpatasvir (oral pellets or tablets) once daily.
  • ≥30 kg: 400 mg sofosbuvir/100 mg velpatasvir (one tablet of Epclusa) once daily.
• Treatment duration is usually 12 weeks. For children with decompensated cirrhosis, ribavirin may be added.
• Safety and efficacy have not been established in children younger than 3 years of age.

Special Cases:

• Elderly Patients: No dose adjustment required.
• Patients with Renal Impairment: No dose adjustment required.
• Patients with Hepatic Dysfunction: No dose adjustment required.
• Patients with Comorbid Conditions: Monitor blood glucose in diabetic patients. Dose adjustment may be required for some medications such as rosuvastatin, atorvastatin, or certain immunosuppressants.

Clinical Use Cases

Velpatasvir, as part of Epclusa, is not typically administered in settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. Its primary use is for the outpatient treatment of chronic HCV infection.

Dosage Adjustments

No specific dosage adjustments are required based solely on renal or hepatic impairment, metabolic disorders, or genetic polymorphisms. However, concomitant medications might necessitate dose alterations or close monitoring.

Side Effects

Common Side Effects:

• Headache
• Fatigue

Rare but Serious Side Effects:

• Severe allergic reactions (rash, itching/swelling, severe dizziness, trouble breathing)
• Mental/mood changes (such as depression)

Long-Term Effects:

While generally well-tolerated, data on potential long-term complications specific to Velpatasvir is limited. However, successful treatment of HCV helps decrease the long term adverse effects from the disease itself including reducing chances of liver damage, cirrhosis and liver cancer.

Adverse Drug Reactions (ADR):

Clinically significant ADRs are rare but include severe skin reactions and mood changes, requiring prompt medical intervention.

Contraindications

• Hypersensitivity to velpatasvir or sofosbuvir.
• Co-administration with certain medications (e.g., amiodarone, rifampin, carbamazepine) is contraindicated due to potentially dangerous or ineffective interactions. Epclusa combined with ribavirin is contraindicated in pregnant women and in men whose female partners are pregnant.

Drug Interactions

• Potent P-gp inducers (e.g., rifampin, St. John’s wort) can reduce velpatasvir levels.
• Moderate to potent inducers of CYP2B6, CYP2C8, or CYP3A4 (e.g., carbamazepine, phenytoin, phenobarbital) can also reduce velpatasvir levels.
• Velpatasvir can increase levels of certain drugs (e.g., rosuvastatin, digoxin).
• Consult detailed drug interaction references for a comprehensive list.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: B1 (Australian classification for velpatasvir monotherapy), not assigned by the US FDA. Epclusa is contraindicated with ribavirin in pregnancy.
• Fetal Risks: Limited data in humans. Animal studies have not shown significant fetal harm with velpatasvir alone. However, ribavirin is known to be teratogenic.
• Breastfeeding: Velpatasvir’s excretion in human breast milk is unknown. Amounts in breast milk are likely very low due to high protein binding. Some experts recommend against breastfeeding when velpatasvir is used with ribavirin.
• Safer alternatives should be considered during pregnancy and breastfeeding.

Drug Profile Summary

• Mechanism of Action: NS5A inhibitor, disrupts HCV replication.
• Side Effects: Generally well-tolerated, common side effects are headache and fatigue. Rare but serious side effects include severe allergic reactions and mood changes.
• Contraindications: Hypersensitivity, co-administration with certain drugs (amiodarone, rifampin, etc.). Epclusa with ribavirin is contraindicated during pregnancy.
• Drug Interactions: Multiple interactions, including P-gp and CYP enzyme interactions; consult references.
• Pregnancy & Breastfeeding: Limited data; use with caution. Avoid Epclusa with ribavirin during pregnancy and consider safer alternatives during breastfeeding.
• Dosage: Adults: Epclusa 400/100 mg once daily. Children: Weight-based dosing. Refer to the dosage section for specifics.
• Monitoring Parameters: HCV RNA levels, liver function tests, monitor concomitant drug levels as indicated.

Popular Combinations

• Sofosbuvir: This combination (Epclusa) is a standard treatment for many HCV genotypes.
• Ribavirin: Sometimes added for patients with decompensated cirrhosis or specific genotypes.

Precautions

• General Precautions: Screen for HBV infection before starting treatment. Monitor for drug interactions and adverse reactions.
• Specific Populations:
  • Pregnant Women: Epclusa with ribavirin is contraindicated. Velpatasvir monotherapy should be used with caution.
  • Breastfeeding Mothers: Use with caution.
  • Children & Elderly: No major age-specific precautions, though pediatric dosage is weight-based.
• Lifestyle Considerations: Alcohol consumption should be minimized or avoided due to its potential to worsen liver disease.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Velpatasvir?

A: Velpatasvir is usually prescribed as part of Epclusa (with sofosbuvir), with a standard adult dose of one 400 mg sofosbuvir/100 mg velpatasvir tablet taken orally once daily. Pediatric dosing is weight-based. See the “Dosage” section above for details.

Q2: How does Velpatasvir work against HCV?

A: Velpatasvir targets the NS5A protein of the HCV virus, inhibiting its function and blocking viral replication.

Q3: What are the common side effects of Velpatasvir?

A: Headache and fatigue are the most common side effects.

Q4: Are there any contraindications for using Velpatasvir?

A: Yes, contraindications include hypersensitivity to the drug and concomitant use of certain medications like amiodarone, rifampin, and carbamazepine. Epclusa with ribavirin is contraindicated during pregnancy.

Q5: Can Velpatasvir be used during pregnancy or breastfeeding?

A: Epclusa in combination with ribavirin is contraindicated during pregnancy. Velpatasvir monotherapy should be used with caution in pregnancy only if the potential benefits outweigh the risks. Caution should be also applied when breastfeeding and consultation with a specialist and discussion of risks/benefits is warranted.

Q6: How long is a typical course of treatment with Velpatasvir?

A: Most patients will take Velpatasvir (as part of Epclusa) for 12 weeks, but the duration can be 24 weeks in certain cases, such as patients with decompensated cirrhosis.

Q7: Does Velpatasvir interact with other medications?

A: Yes, Velpatasvir is known to interact with numerous medications, including some commonly used drugs. Refer to a comprehensive drug interaction resource or consult a pharmacist to assess potential interactions.

Q8: What should I monitor in patients taking Velpatasvir?

A: Monitor HCV RNA levels to assess treatment response. Periodic liver function tests are also recommended. Monitor relevant lab values for drugs taken concomitantly, especially those with narrow therapeutic indices.

Q9: Is Velpatasvir used alone or in combination with other drugs?

A: Velpatasvir is primarily used in fixed-dose combination with sofosbuvir. In some cases, ribavirin is also added to the treatment regimen.

Q10: How should I counsel patients starting on Velpatasvir therapy?

A: Inform patients about potential side effects, emphasize the importance of adherence, discuss potential drug interactions, and advise against alcohol consumption. Address any concerns or questions they might have about the treatment.