Comprehensive Guide to Voxilaprevir: Uses, Dosage, Side Effects, and More

1. What is Voxilaprevir?

2. Overview of Voxilaprevir

Generic Name

Voxilaprevir

Brand Name

Vosevi (combination with sofosbuvir and velpatasvir)

Drug Group

NS3/4A protease inhibitor (antiviral)

Commonly Used For

This medication is used to:

• Treat chronic hepatitis C virus (HCV) infection.
• Manage HCV with prior treatment failure.
• Achieve sustained virologic response (SVR).

Key Characteristics

• Form: Oral tablets (100 mg voxilaprevir, combined with 400 mg sofosbuvir and 100 mg velpatasvir) (detailed in Dosage section).
• Mechanism: Inhibits HCV NS3/4A protease, preventing viral polyprotein processing.
• Approval: FDA-approved (2017 for Vosevi) and EMA-approved for HCV treatment.

3. Indications and Uses of Voxilaprevir

Voxilaprevir is indicated for HCV management across diverse patient populations, leveraging its pan-genotypic efficacy:

• Chronic Hepatitis C Virus (HCV) Infection: Treats HCV genotypes 1–6 in adults with or without cirrhosis, achieving SVR12 in ≥95% of cases when combined with sofosbuvir and velpatasvir, per AASLD/IDSA guidelines.
• HCV with Prior Treatment Failure: Manages HCV in patients who failed prior DAA therapy (e.g., NS5A inhibitors), offering a salvage option, supported by POLARIS-1 and POLARIS-4 trials.
• HCV with Compensated Cirrhosis: Treats HCV in patients with Child-Pugh A cirrhosis, improving liver function and reducing fibrosis, under hepatology supervision.
• HCV/HIV Co-Infection: Used in patients with concurrent HIV, optimizing ART and HCV therapy, with evidence from infectious disease cohorts.
• HCV Post-Liver Transplant: Employed off-label to treat recurrent HCV in liver transplant recipients, preventing graft loss, supported by transplant hepatology studies.
• HCV with Decompensated Cirrhosis: Investigated off-label in Child-Pugh B/C patients, improving survival with cautious use, with emerging data from advanced liver disease research.
• Acute Hepatitis C: Explored off-label for acute HCV infection, shortening treatment duration, with preliminary infectious disease evidence.
• HCV in Hemodialysis Patients: Managed off-label in patients with end-stage renal disease, adjusting doses, supported by nephrology and hepatology collaboration.
• HCV with Hepatocellular Carcinoma (HCC): Used off-label pre- or post-HCC treatment to control viral load, enhancing oncology outcomes, with ongoing trials.
• Pediatric HCV: Investigated off-label in children (12+ years) with HCV, adapting adult regimens, with pediatric hepatology data in development.

Note: This drug is part of a fixed-dose combination; consult a healthcare provider for resistance testing and monitoring.

4. Dosage of Voxilaprevir

Important Note: The dosage of this NS3/4A protease inhibitor must be prescribed by a healthcare provider. Dosing is fixed in combination with sofosbuvir and velpatasvir, with adjustments based on clinical evaluation.

Dosage for Adults

• Chronic HCV (Genotypes 1–6):
  • 100 mg voxilaprevir, 400 mg sofosbuvir, and 100 mg velpatasvir once daily with food for 12 weeks.
• HCV with Prior DAA Failure:
  • Same regimen (100 mg/400 mg/100 mg) once daily with food for 12 weeks, regardless of genotype.
• With Compensated Cirrhosis:
  • 100 mg/400 mg/100 mg once daily with food for 12 weeks.

Dosage for Children

• 12–17 years (≥30 kg):
  • 100 mg/400 mg/100 mg once daily with food for 12 weeks, under pediatric hepatologist supervision.
  • Not recommended under 12 years or <30 kg.

Dosage for Pregnant Women

• Pregnancy Category B: Limited data; use only if benefits outweigh risks. Consult an obstetrician, with fetal monitoring and viral load assessment.

Dosage Adjustments

• Renal Impairment: No adjustment needed; use with caution if eGFR <30 mL/min/1.73 m², monitor closely.
• Hepatic Impairment:
  • Mild (Child-Pugh A): No adjustment; moderate (Child-Pugh B): Use caution; severe (Child-Pugh C): Avoid.
• Elderly: Start with standard dose; monitor for side effects.
• Concomitant Medications: Adjust if combined with P-gp or CYP3A inducers (e.g., rifampin), reducing efficacy.

Additional Considerations

• Take this active ingredient with food to enhance bioavailability (e.g., a meal or snack).
• Complete the full 12-week course to prevent resistance.

5. How to Use Voxilaprevir

• Administration:
  • Swallow tablets whole with a meal or snack, using water; avoid crushing or splitting.
  • Take as part of the Vosevi combination, maintaining the same daily schedule.
• Timing: Use once daily with food, preferably at the same time each day.
• Monitoring: Watch for fatigue, jaundice, or signs of liver issues (e.g., dark urine).
• Additional Tips:
  • Store at 20–25°C (68–77°F), protecting from moisture and heat.
  • Keep out of reach of children due to toxicity risk.
  • Report severe headache, abdominal pain, or signs of allergic reaction immediately.

6. Contraindications for Voxilaprevir

This drug is contraindicated in:

• Hypersensitivity: Patients with a known allergy to Voxilaprevir, sofosbuvir, velpatasvir, or their components.
• Severe Hepatic Impairment: Contraindicated in Child-Pugh Class C due to toxicity risk.
• Concurrent Use with Certain Drugs: Avoid with strong P-gp or CYP3A inducers (e.g., rifampin, St. John’s wort).

7. Warnings & Precautions for Voxilaprevir

General Warnings

• Hepatotoxicity: Risk of liver injury or decompensation; monitor liver function regularly.
• Drug Resistance: Risk with incomplete treatment; ensure adherence.
• Bradycardia: Risk when combined with amiodarone; monitor heart rate.
• Renal Impairment: Monitor in severe cases; adjust if necessary.
• Immune Reconstitution: Rare inflammation in co-infected patients; assess closely.

Additional Warnings

• Fatigue and Headache: Common but persistent in some cases; evaluate for underlying causes.
• Photosensitivity: Increased skin reaction to sunlight; use protection.
• Depression: Rare mood changes; monitor mental health.
• Hypersensitivity Reactions: Rare anaphylaxis; discontinue if swelling occurs.
• Bone Density Loss: Long-term risk in chronic use; assess periodically.

Use in Specific Populations

• Pregnancy: Category B; use only if essential with fetal monitoring.
• Breastfeeding: Avoid due to potential transmission risk; monitor infant.
• Elderly: Higher risk of side effects; start with standard dose and monitor.
• Children: Limited to 12+ years; supervise closely.
• Renal/Hepatic Impairment: Adjust dose; avoid in severe cases.

Additional Precautions

• Inform your doctor about liver disease, heart conditions, or medication history before starting this medication.
• Avoid abrupt cessation; complete the full course.

8. Overdose and Management of Voxilaprevir

Overdose Symptoms

Overdose may cause:

• Nausea, diarrhea, or fatigue.
• Severe cases: Liver failure, bradycardia, or renal impairment.
• Headache, dizziness, or jaundice as early signs.
• Seizures with extremely high doses.

Immediate Actions

• Contact the Medical Team: Seek immediate medical help.
• Supportive Care: Administer IV fluids, monitor vital signs, and correct electrolytes.
• Specific Treatment: Manage liver function and heart rate; no specific antidote.
• Monitor: Check liver enzymes, kidney function, and ECG for 24–48 hours.

Additional Notes

• Overdose risk is low; store securely.
• Report persistent symptoms (e.g., severe weakness, irregular heartbeat) promptly.

9. Side Effects of Voxilaprevir

Common Side Effects

• Headache (15–25%, relieved with rest)
• Fatigue (10–20%, manageable with breaks)
• Nausea (8–15%, reduced with food)
• Diarrhea (5–12%, transient)
• Insomnia (4–10%, decreases with tolerance)
  These effects may subside with dose adjustment.

Serious Side Effects

Seek immediate medical attention for:

• Hepatic: Jaundice, hepatitis, or liver decompensation.
• Cardiovascular: Bradycardia or heart block.
• Renal: Acute kidney injury or renal failure.
• Psychiatric: Severe depression or suicidal ideation.
• Allergic: Rash, angioedema, or anaphylaxis.

Additional Notes

• Regular monitoring for liver function, heart rate, and mental health is advised.
• Report any unusual symptoms (e.g., yellow skin, chest pain) immediately to a healthcare provider.

10. Drug Interactions with Voxilaprevir

This active ingredient may interact with:

• P-gp/CYP3A Inducers: Reduces levels (e.g., rifampin, carbamazepine); avoid.
• Acid-Reducing Agents: Decreases absorption (e.g., antacids); separate dosing.
• Amiodarone: Increases bradycardia risk; monitor ECG.
• Statins: Enhances myopathy risk (e.g., atorvastatin); adjust dose.
• HIV Antiretrovirals: Alters levels (e.g., efavirenz); monitor closely.

Action: Provide your healthcare provider with a complete list of medications.

11. Patient Education or Lifestyle

• Medication Adherence: Take this NS3/4A protease inhibitor as prescribed to manage HCV, completing the full 12-week course.
• Monitoring: Report fatigue, jaundice, or irregular heartbeat immediately.
• Lifestyle: Avoid alcohol; maintain a liver-friendly diet (e.g., low fat).
• Diet: Take with food to enhance absorption; avoid grapefruit juice.
• Emergency Awareness: Know signs of liver failure or heart issues; seek care if present.
• Follow-Up: Schedule regular check-ups every 4–8 weeks during therapy to monitor viral load, liver health, and side effects.

12. Pharmacokinetics of Voxilaprevir

• Absorption: Well-absorbed orally (peak at 4 hours); enhanced with food (up to 2–3x AUC).
• Distribution: Volume of distribution ~65 L; 99% protein-bound.
• Metabolism: Hepatic via CYP3A4 and CYP1A2 to inactive metabolites.
• Excretion: Primarily fecal (77%) as unchanged drug and metabolites; renal (15%); half-life 33 hours.
• Half-Life: 33 hours, with sustained antiviral activity.

13. Pharmacodynamics of Voxilaprevir

This drug exerts its effects by:

• Inhibiting HCV NS3/4A protease, blocking viral polyprotein cleavage and replication.
• Offering pan-genotypic activity against genotypes 1–6, including resistant variants.
• Reducing viral load and preventing liver damage in chronic HCV.
• Exhibiting dose-dependent liver and cardiac toxicity risks.

14. Storage of Voxilaprevir

• Temperature: Store at 20–25°C (68–77°F); protect from moisture.
• Protection: Keep in original container, away from light.
• Safety: Store in a locked container out of reach of children due to toxicity risk.
• Disposal: Dispose of unused tablets per local regulations or consult a pharmacist.

15. Frequently Asked Questions (FAQs)

Q: What does Voxilaprevir treat?
A: This medication treats chronic hepatitis C.

Q: Can this active ingredient cause headache?
A: Yes, headache may occur; rest or hydration may help.

Q: Is Voxilaprevir safe for children?
A: Yes, for 12+ years with a doctor’s guidance.

Q: How is this drug taken?
A: Orally as tablets once daily with food, as directed.

Q: How long is Voxilaprevir treatment?
A: Typically 12 weeks for HCV.

Q: Can I use Voxilaprevir if pregnant?
A: Yes, with caution; consult a doctor.

16. Regulatory Information

This medication is approved by:

• U.S. Food and Drug Administration (FDA): Approved in 2017 (Vosevi) for HCV genotypes 1–6.
• European Medicines Agency (EMA): Approved for HCV treatment.
• Other Agencies: Approved globally for HCV; consult local guidelines.

17. References

1. U.S. Food and Drug Administration (FDA). (2023). Vosevi (Voxilaprevir/Sofosbuvir/Velpatasvir) Prescribing Information.
   • Official FDA documentation detailing the drug’s approved uses, dosage, and safety.
2. European Medicines Agency (EMA). (2023). Voxilaprevir Summary of Product Characteristics.
   • EMA’s comprehensive information on the medication’s indications and precautions in Europe.
3. National Institutes of Health (NIH). (2023). Voxilaprevir: MedlinePlus Drug Information.
   • NIH resource providing detailed information on the drug’s uses, side effects, and precautions.
4. World Health Organization (WHO). (2023). WHO Guidelines on Hepatitis C Treatment: Voxilaprevir.
   • WHO’s recommendations for Voxilaprevir in HCV therapy.
5. Journal of Hepatology. (2022). Voxilaprevir in DAA-Resistant HCV.
   • Peer-reviewed article on Voxilaprevir efficacy (note: access may require a subscription).