In an adult with chronic hepatitis C who is treatment‑naïve, has no decompensated cirrhosis (Child‑Pugh A or no cirrhosis), and no contraindicated medications, what is the recommended Mavyret (glecaprevir + pibrentasvir) dosing regimen, treatment duration, and monitoring?

Mavyret (Glecaprevir/Pibrentasvir) Treatment for Chronic Hepatitis C

Recommended Dosing Regimen

For treatment-naïve adults without cirrhosis or with compensated cirrhosis (Child-Pugh A), administer glecaprevir 300 mg/pibrentasvir 120 mg (three tablets) orally once daily with food for 8 weeks. 1, 2, 3

• The medication must be taken with food, as glecaprevir plasma exposure increases 83-163% when administered with food compared to fasted state 1
• This 8-week duration applies to all HCV genotypes (1-6) in treatment-naïve patients without cirrhosis or with Child-Pugh A cirrhosis 1, 3

Treatment Duration by Clinical Scenario

Treatment-Naïve Patients

• Without cirrhosis or with compensated cirrhosis (Child-Pugh A): 8 weeks for all genotypes 1, 3

Treatment-Experienced Patients

The duration varies based on prior treatment history 3:

• Prior NS5A inhibitor (without prior NS3/4A protease inhibitor): 16 weeks for genotype 1; standard duration for other genotypes 3
• Prior NS3/4A protease inhibitor (without prior NS5A inhibitor): 12 weeks for genotype 1 3
• Prior peginterferon/ribavirin/sofosbuvir only (no NS5A or NS3/4A inhibitor): 8 weeks for genotypes 1,2,4,5,6 without cirrhosis; 12 weeks with compensated cirrhosis 3
• Genotype 3 with prior peginterferon/ribavirin/sofosbuvir: 16 weeks regardless of cirrhosis status 3

Pre-Treatment Assessment Requirements

Before initiating Mavyret, obtain the following 2, 3:

• HCV RNA quantitative testing to confirm active viremia 2
• HCV genotype determination (though simplified pangenotypic approach allows treatment without genotyping if unavailable) 1
• Hepatitis B testing: HBsAg and anti-HBc to assess for HBV coinfection, as HBV reactivation can occur during HCV treatment 4, 3
• Fibrosis staging using non-invasive methods (FIB-4 or APRI scores) to determine presence of cirrhosis, which affects treatment duration 1, 2
• Comprehensive drug-drug interaction screening 1, 2

Critical Contraindications and Drug Interactions

Absolute Contraindications

Do not use Mavyret in the following situations 1, 3:

• Moderate or severe hepatic impairment (Child-Pugh B or C): Glecaprevir exposure increases 5-fold in Child-Pugh B and 12-fold in Child-Pugh C cirrhosis 1
• Atazanavir-containing HIV regimens 1
• Ethinylestradiol-containing contraceptives: Risk of ALT elevations; use progestogen-only contraception instead 1
• Strong CYP3A/P-gp inducers: Rifampin, carbamazepine, phenytoin, St. John's wort, efavirenz 1, 5

Important Drug Interactions Requiring Caution

• Proton pump inhibitors: Limit to omeprazole 40 mg daily or equivalent; higher doses may reduce glecaprevir concentrations by 64% 1
• Tacrolimus and other narrow therapeutic index CYP3A substrates: Monitor closely as glecaprevir is a weak CYP3A inhibitor 1
• Darunavir, lopinavir, cyclosporin: May increase glecaprevir concentrations 1

Monitoring During Treatment

Routine Monitoring

• No routine laboratory monitoring is required during the 8-week treatment course in uncomplicated cases 2
• Patients with diabetes: Monitor glucose levels during and after treatment for hypoglycemia, as HCV clearance can alter insulin sensitivity 4
• Patients on warfarin: Monitor INR during and after treatment due to potential alterations in anticoagulation response 4

Post-Treatment Assessment

• SVR12 testing (HCV RNA at 12 weeks post-treatment): Can be omitted in adherent patients without high-risk behaviors, given the >95% cure rates 1, 2
• High-risk populations (people who inject drugs, men who have sex with men): Require SVR12 testing and yearly HCV RNA testing thereafter to detect reinfection 1

Special Populations

Renal Impairment

No dose adjustment required for any degree of renal impairment, including end-stage renal disease on dialysis 1, 5, 6

• Glecaprevir AUC increases <56% across all stages of renal disease, which is not clinically significant 1
• This makes Mavyret particularly advantageous for patients with chronic kidney disease stages 4-5 6

HIV Coinfection

Use the same dosing as HCV monoinfection 1, 3

• Compatible with most antiretroviral regimens except atazanavir and efavirenz-based regimens 1
• Compatible with integrase inhibitors including elvitegravir/cobicistat 1

Liver or Kidney Transplant Recipients

Treat for 12 weeks (extended from standard 8 weeks) 3

• 16 weeks for genotype 1 patients who are NS5A inhibitor-experienced or genotype 3 patients who are peginterferon/ribavirin/sofosbuvir-experienced 3

Expected Outcomes

Mavyret achieves sustained virologic response rates of 95-99% across all genotypes and patient populations with compensated liver disease 2, 7, 6:

• 99% SVR12 in patients with compensated cirrhosis 7
• 97.5% SVR12 in patients without cirrhosis 6
• 100% SVR12 in adolescents aged 12-17 years 1, 8

Safety Profile

The most common adverse events are 1, 5, 7:

• Headache (14-20% of patients) 1, 7
• Fatigue (19% of patients) 7
• Nausea 1

Serious adverse events are rare (<1%), and treatment discontinuation due to adverse events occurs in <1% of patients 6. No cases of drug-induced liver injury or clinically relevant hepatic decompensation have been reported 6.

Common Pitfalls to Avoid

1. Do not prescribe Mavyret to patients with Child-Pugh B or C cirrhosis—the dramatic increase in glecaprevir exposure makes this unsafe 1
2. Do not co-prescribe with ethinylestradiol-containing contraceptives—switch to progestogen-only methods before starting treatment 1
3. Do not exceed omeprazole 40 mg daily equivalent when co-prescribing proton pump inhibitors—higher doses significantly reduce glecaprevir absorption 1
4. Do not forget to take with food—fasting reduces glecaprevir exposure by up to 83% 1
5. Screen for hepatitis B before treatment—HBV reactivation can occur during HCV therapy 3