Comprehensive Guide to Glecaprevir/Pibrentasvir: Uses, Dosage, Side Effects, and More
What is Glecaprevir/Pibrentasvir?
Overview of Glecaprevir/Pibrentasvir
Generic Name: Glecaprevir/Pibrentasvir
Brand Name: Mavyret, generics
Drug Group: Direct-acting antiviral (DAA) for hepatitis C
Commonly Used For
- Treat chronic hepatitis C virus (HCV) infection.
- Achieve sustained virologic response (SVR) in all genotypes.
- Manage HCV in patients with compensated cirrhosis.
Key Characteristics
Form: Oral tablets (100 mg Glecaprevir/40 mg Pibrentasvir) (detailed in Dosage section).
Mechanism: Dual inhibition of NS3/4A and NS5A, blocking HCV replication.
Approval: FDA-approved (2017 for Mavyret) and EMA-approved for HCV treatment.

Indications and Uses of Glecaprevir/Pibrentasvir
Glecaprevir/Pibrentasvir is indicated for a broad spectrum of hepatitis C virus (HCV) infections, leveraging its pan-genotypic efficacy:
Chronic HCV Infection (All Genotypes 1–6): Treats HCV in treatment-naïve or -experienced patients without cirrhosis or with compensated cirrhosis, per hepatology guidelines, supported by clinical trials showing >95% SVR rates at 12 weeks.
HCV in Patients with Compensated Cirrhosis: Achieves viral clearance in Child-Pugh A patients, reducing liver fibrosis, recommended in cirrhosis management protocols.
HCV in Patients with Chronic Kidney Disease (CKD): Manages infection in CKD stages 4–5, including dialysis patients, with nephrology-hepatology evidence.
HCV in HIV Co-Infection: Treats co-infected patients without drug interactions, improving outcomes, per infectious disease studies.
Post-Liver Transplant HCV Recurrence: Investigated off-label to prevent or treat recurrence, with transplant hepatology data.
HCV in Adolescents (12–17 years): Used off-label with weight-based dosing, with pediatric hepatology research.
Acute HCV Infection: Explored off-label for early intervention, reducing chronicity risk, with public health evidence.
HCV in Decompensated Cirrhosis: Managed off-label in Child-Pugh B/C with caution, with advanced hepatology studies.
HCV with Hepatocellular Carcinoma (HCC): Initiated off-label post-resection to prevent recurrence, with oncology-hepatology data.
HCV in Injection Drug Users: Applied off-label with adherence support, with addiction medicine-hepatology research.
Dosage of Glecaprevir/Pibrentasvir
Dosage for Adults
Treatment-Naïve or -Experienced Without Cirrhosis:
- 3 tablets (300 mg Glecaprevir/120 mg Pibrentasvir) once daily with food for 8 weeks.
Treatment-Naïve or -Experienced With Compensated Cirrhosis (Child-Pugh A):
- 3 tablets once daily with food for 12 weeks.
Treatment-Experienced With Genotype 1 or 4 and Compensated Cirrhosis:
- 3 tablets once daily with food for 16 weeks (if prior NS5A inhibitor failure).
Dosage for Adolescents (12–17 years, ≥30 kg)
HCV Infection (All Genotypes):
- 3 tablets once daily with food for 8–12 weeks, adjusted based on cirrhosis status, under pediatric hepatology supervision.
Dosage for Pregnant Women
Pregnancy Category B: Use only if benefits outweigh risks; consult an obstetrician and hepatologist, with fetal monitoring and liver function tests.
Dosage Adjustments
Renal Impairment: No adjustment needed for CKD stages 1–5, including dialysis, due to minimal renal excretion.
Hepatic Impairment:
- Mild (Child-Pugh A): No adjustment; use with caution.
- Moderate to Severe (Child-Pugh B or C): Contraindicated due to increased drug exposure.
Concomitant Medications: Adjust if combined with strong CYP3A inducers (e.g., rifampin) or P-gp inhibitors; monitor for interactions.
Elderly: No specific adjustment; assess liver function and comorbidities.
** Missed Dose**: Take within 18 hours if missed; do not double dose.
Additional Considerations
- Take this active ingredient with food to enhance absorption; swallow tablets whole.
- Avoid high-fat meals to prevent variable pharmacokinetics.
- Monitor for adherence, especially in off-label populations.
How to Use Glecaprevir/Pibrentasvir
Administration:
Oral: Take 3 tablets once daily with a meal, swallowing whole without crushing or chewing.
Ensure consistent food intake to optimize bioavailability.
Timing: Administer at the same time daily, preferably with breakfast or dinner.
Monitoring: Watch for jaundice, fatigue, or signs of liver injury (e.g., dark urine); report changes immediately.
Additional Tips:
- Store at 25°C (77°F), with excursions permitted to 15–30°C (59–86°F); protect from moisture.
- Keep out of reach of children; dispose of unused tablets per local regulations.
- Educate patients on HBV screening and adherence; provide a medication calendar.
- Schedule liver function tests (ALT, AST) at weeks 4, 8, and 12 during therapy.
- Avoid alcohol to reduce liver stress during treatment.
Contraindications for Glecaprevir/Pibrentasvir
Hypersensitivity: Patients with a known allergy to Glecaprevir, Pibrentasvir, or excipients.
Severe Hepatic Impairment: Contraindicated in Child-Pugh B or C due to hepatotoxicity risk.
Co-administration with Strong CYP3A Inducers: Avoid with rifampin, carbamazepine, or St. John’s wort due to reduced efficacy.
Pregnancy with Decompensated Cirrhosis: Avoid in severe liver disease due to fetal risk.
Active Hepatitis B Virus (HBV) Infection: Contraindicated without HBV suppression due to reactivation risk.
Warnings & Precautions for Glecaprevir/Pibrentasvir
General Warnings
HBV Reactivation: Risk of hepatitis flare in HBV co-infected patients; screen and monitor HBV DNA.
Liver Injury: Risk of ALT elevation (>5x ULN); discontinue if severe.
Drug Resistance: Risk with non-adherence; ensure full course completion.
Renal Function: Monitor in CKD patients despite no dose adjustment.
Fatigue: Common side effect; assess for underlying liver issues.
Additional Warnings
Drug Interactions: Risk with CYP3A substrates (e.g., statins); adjust doses as needed.
Decompensated Cirrhosis: Avoid use; refer to specialist for alternatives.
Hypersensitivity Reactions: Rare rash or angioedema; stop if severe.
Pan-Genotypic Failure: Rare resistance in genotype 3; monitor virologic response.
Pregnancy Risks: Potential fetal harm; use contraception during therapy.
Use in Specific Populations
Pregnancy: Category B; use with caution and monitoring.
Breastfeeding: Use caution; monitor infant for effects.
Elderly: Higher risk of liver injury; monitor closely.
Children: Safe for adolescents (≥12 years) with supervision.
Renal/Hepatic Impairment: Contraindicated in severe hepatic cases.
Additional Precautions
- Inform your doctor about liver disease, HIV co-infection, or medication history before starting this medication.
- Avoid herbal supplements that induce CYP3A to prevent treatment failure.
- Regular HBV and HCV viral load monitoring is essential.
Overdose and Management of Glecaprevir/Pibrentasvir
Overdose Symptoms
- Mild nausea, headache, or fatigue.
- Severe cases: Liver injury (e.g., jaundice, coagulopathy) or HBV reactivation.
- Abdominal pain or dark urine as early signs.
- Rare hepatic failure or profound weakness with extremely high doses.
Immediate Actions
Contact the Medical Team: Seek immediate medical help if severe symptoms occur.
Supportive Care: Monitor liver function (ALT, AST, bilirubin), provide hydration, and manage symptoms.
Specific Treatment: No specific antidote; discontinue use and initiate supportive care.
Monitor: Check liver enzymes and viral loads for 24–72 hours; assess for HBV reactivation.
Patient Education: Advise against exceeding prescribed doses and to report overdose immediately.
Additional Notes
- Overdose risk is low with oral use; store securely to prevent accidental ingestion.
- Report persistent symptoms (e.g., yellowing skin, severe fatigue) promptly.
Side Effects of Glecaprevir/Pibrentasvir
Common Side Effects
- Headache (10–15%, managed with rest)
- Fatigue (8–12%, improves with time)
- Nausea (5–10%, relieved with food)
- Diarrhea (3–7%, controlled with hydration)
- Pruritus (2–5%, managed with antihistamines)
These effects may subside with adaptation.
Serious Side Effects
Seek immediate medical attention for:
- Hepatic: Liver injury or failure (elevated ALT/AST >10x ULN).
- Viral: HBV reactivation with jaundice or coagulopathy.
- Allergic: Severe rash, angioedema, or anaphylaxis.
- Gastrointestinal: Pancreatitis (rare, with abdominal pain).
- Neurological: Confusion or encephalopathy (rare, in decompensated liver disease).
Additional Notes
Regular monitoring with liver function tests (ALT, AST) at weeks 4, 8, and 12 is critical to detect hepatotoxicity early.
Patients with cirrhosis should have ultrasound or FibroScan every 3 months to assess liver status.
Report any unusual symptoms (e.g., dark urine, severe itching) immediately to a hepatologist.
Long-term follow-up post-SVR is recommended to monitor for HCC risk, especially in cirrhosis patients.
Drug Interactions with Glecaprevir/Pibrentasvir
This active ingredient may interact with:
- CYP3A Inducers: Reduces efficacy (e.g., rifampin); avoid co-administration.
- Statins: Increases myopathy risk (e.g., atorvastatin); adjust dose.
- P-gp Substrates: Alters levels (e.g., digoxin); monitor closely.
- HIV Antiretrovirals: Risk of interactions (e.g., efavirenz); consult specialist.
- Immunosuppressants: May alter levels (e.g., cyclosporine); adjust as needed.
Action: Provide your healthcare provider with a complete list of medications.
Patient Education or Lifestyle
Medication Adherence: Take this antiviral combination as prescribed for HCV, following the daily schedule with food.
Monitoring: Report jaundice, fatigue, or signs of liver issues immediately.
Lifestyle: Avoid alcohol and hepatotoxic drugs; maintain a balanced diet.
Diet: Take with food; avoid high-fat meals for consistency.
Emergency Awareness: Know signs of liver failure or HBV reactivation; seek care if present.
Follow-Up: Schedule regular check-ups every 4 weeks during therapy to monitor liver function and viral load.
Pharmacokinetics of Glecaprevir/Pibrentasvir
Absorption: Oral, peak at 5 hours (Glecaprevir) and 5 hours (Pibrentasvir); bioavailability enhanced with food.
Distribution: Volume of distribution ~47 L (Glecaprevir), ~97 L (Pibrentasvir); >99% protein-bound.
Metabolism: Minimal hepatic metabolism via CYP3A (Glecaprevir).
Excretion: Primarily biliary/fecal (Glecaprevir 92%, Pibrentasvir 97%); half-life 6–9 hours (Glecaprevir), 13–20 hours (Pibrentasvir).
Half-Life: 6–9 hours (Glecaprevir), 13–20 hours (Pibrentasvir).
Pharmacodynamics of Glecaprevir/Pibrentasvir
This drug exerts its effects by:
Inhibiting NS3/4A protease (Glecaprevir) to block viral polyprotein processing.
Blocking NS5A protein (Pibrentasvir) to prevent HCV replication and assembly.
Achieving high SVR rates across genotypes with minimal resistance.
Exhibiting dose-dependent risks of liver enzyme elevation.
Storage of Glecaprevir/Pibrentasvir
Temperature: Store at 25°C (77°F), with excursions to 15–30°C (59–86°F); protect from moisture.
Protection: Keep in original container, away from heat and humidity.
Safety: Store in a secure location out of reach of children and pets due to liver risk.
Disposal: Dispose of unused tablets per local regulations or consult a pharmacist.
Frequently Asked Questions (FAQs)
Q: What does Glecaprevir/Pibrentasvir treat?
A: This medication treats chronic hepatitis C.
Q: Can this active ingredient cause fatigue?
A: Yes, fatigue is common; report if severe.
Q: Is Glecaprevir/Pibrentasvir safe for children?
A: Yes, for adolescents (≥12 years) with supervision.
Q: How is this drug taken?
A: Orally with food, as directed.
Q: How long is Glecaprevir/Pibrentasvir treatment?
A: Typically 8–16 weeks, depending on cirrhosis.
Q: Can I use Glecaprevir/Pibrentasvir if pregnant?
A: Yes, with caution; consult a doctor.
Regulatory Information
This medication is approved by:
U.S. Food and Drug Administration (FDA): Approved in 2017 (Mavyret) for HCV genotypes 1–6.
European Medicines Agency (EMA): Approved for chronic HCV treatment across genotypes.
Other Agencies: Approved globally for HCV; consult local guidelines.
References
- U.S. Food and Drug Administration (FDA). (2023). Mavyret (Glecaprevir/Pibrentasvir) Prescribing Information.
- Official FDA documentation detailing the drug’s approved uses, dosage, and safety.
- European Medicines Agency (EMA). (2023). Glecaprevir/Pibrentasvir Summary of Product Characteristics.
- EMA’s comprehensive information on the medication’s indications and precautions in Europe.
- National Institutes of Health (NIH). (2023). Glecaprevir/Pibrentasvir: MedlinePlus Drug Information.
- NIH resource providing detailed information on the drug’s uses, side effects, and precautions.
- World Health Organization (WHO). (2023). WHO Model List of Essential Medicines: Glecaprevir/Pibrentasvir.
- WHO’s consideration of Glecaprevir/Pibrentasvir for HCV.
- Hepatology. (2022). Glecaprevir/Pibrentasvir in Cirrhosis.
- Peer-reviewed article on Glecaprevir/Pibrentasvir efficacy (note: access may require a subscription).