Mavyret (Glecaprevir/Pibrentasvir) Treatment Regimen for Hepatitis C
For most patients with chronic hepatitis C, Mavyret should be administered as 3 tablets (glecaprevir 300 mg/pibrentasvir 120 mg total daily dose) taken once daily with food for 8 weeks in treatment-naïve patients without cirrhosis or with compensated cirrhosis, or 12 weeks in treatment-experienced patients with compensated cirrhosis. 1
Dosing by Treatment History and Cirrhosis Status
Treatment-Naïve Patients (All Genotypes 1-6)
- Without cirrhosis: 8 weeks of treatment 2, 1
- With compensated cirrhosis (Child-Pugh A): 8 weeks of treatment 2, 1
Treatment-Experienced Patients
For patients previously treated with pegylated interferon, ribavirin, and/or sofosbuvir (but NOT NS5A inhibitors or NS3/4A protease inhibitors):
- Genotypes 1,2,4,5,6 without cirrhosis: 8 weeks 1
- Genotypes 1,2,4,5,6 with compensated cirrhosis: 12 weeks 2, 1
- Genotype 3 without cirrhosis: 12 weeks 2
- Genotype 3 with compensated cirrhosis: 16 weeks 2, 1
For patients previously treated with NS5A inhibitor (without prior NS3/4A protease inhibitor):
- Genotype 1, all cirrhosis statuses: 16 weeks 1
For patients previously treated with NS3/4A protease inhibitor (without prior NS5A inhibitor):
- Genotype 1, all cirrhosis statuses: 12 weeks 1
Administration Details
Mavyret must be taken with food because glecaprevir plasma exposure increases 83-163% when taken with food compared to fasted state 2. The standard adult dose is 3 tablets containing 100 mg glecaprevir and 40 mg pibrentasvir each, taken together once daily 1.
Special Populations
Renal Impairment
No dose adjustment is required for any degree of renal impairment, including end-stage renal disease requiring dialysis. 2, 1 This makes Mavyret particularly advantageous for patients with severe renal dysfunction where sofosbuvir-based regimens require caution 3.
Liver Transplant Recipients
Liver or kidney transplant recipients should receive 12 weeks of treatment, with 16 weeks recommended for genotype 1 patients who are NS5A inhibitor-experienced or genotype 3 patients who are treatment-experienced 1.
HIV Coinfection
The same treatment regimens and durations apply to HIV/HCV coinfected patients, but careful evaluation of drug-drug interactions with antiretroviral therapy is mandatory 2, 3. Mavyret is contraindicated with atazanavir-containing regimens and not recommended with other HIV protease inhibitors due to significant increases in glecaprevir concentrations 2.
Critical Contraindications and Warnings
Absolute Contraindications
Mavyret is contraindicated in patients with:
- Moderate or severe hepatic impairment (Child-Pugh B or C) 1
- Any history of prior hepatic decompensation 2, 1
- Current use of atazanavir or rifampin 1
- Concomitant use of ethinylestradiol-containing contraception (due to risk of ALT elevations) 2
The contraindication in decompensated cirrhosis is critical because glecaprevir exposure increases 11-fold in Child-Pugh C cirrhosis, creating unacceptable safety risks 2.
Hepatitis B Reactivation Risk
All patients must be tested for HBsAg and anti-HBc before initiating Mavyret because HBV reactivation has been reported during HCV treatment with direct-acting antivirals, with some cases resulting in fulminant hepatitis, hepatic failure, and death 1.
Drug-Drug Interactions
Proton Pump Inhibitors
Limit proton pump inhibitors to doses equivalent to omeprazole 40 mg or less because higher doses have not been studied and may significantly decrease glecaprevir concentrations 2. While data indicate that omeprazole 40 mg (which decreases glecaprevir Cmax by 64%) does not affect SVR rates, exceeding this dose is not recommended 2.
Immunosuppressants
In transplant recipients, carefully monitor immunosuppressant drug levels (particularly tacrolimus and cyclosporine) during and after Mavyret treatment because glecaprevir is a weak CYP3A inhibitor and may increase immunosuppressant concentrations 2, 1.
Monitoring Requirements
Pre-Treatment Assessment
- Confirm HCV viremia (HCV RNA or core antigen) 2
- Assess for cirrhosis using FIB-4 score >3.25, transient elastography >12.5 kPa, or clinical evidence 2
- Screen for HBV infection (HBsAg and anti-HBc) 1
- Evaluate drug-drug interactions comprehensively 2
On-Treatment Monitoring
No routine laboratory monitoring is required during treatment for most patients 2. However:
- Patients on diabetes medications: Monitor for symptomatic hypoglycemia 2
- Patients on warfarin: Monitor INR for subtherapeutic anticoagulation 2
Post-Treatment Assessment
Measure HCV RNA at 12 weeks or later after treatment completion to confirm sustained virologic response (SVR12), which indicates virologic cure 2, 4. For patients with cirrhosis, continue hepatocellular carcinoma surveillance with ultrasound every 6 months indefinitely, even after achieving SVR 4, 3.
Efficacy Data
SVR12 rates with Mavyret exceed 95% across all genotypes in treatment-naïve patients without cirrhosis 2, 5. Real-world data confirm these high cure rates, with one study showing 99.4% SVR in patients with cirrhosis receiving routine clinical care 6. The 8-week regimen in cirrhotic patients achieved 92-95% SVR rates in clinical practice 6.
Common Pitfalls to Avoid
- Do not use Mavyret in any patient with decompensated cirrhosis (Child-Pugh B or C), as this is an absolute contraindication due to dramatically increased drug exposure 1
- Do not forget to take with food, as this significantly impacts glecaprevir absorption 2, 1
- Do not overlook HBV screening, as reactivation can be fatal 1
- Do not use with ethinylestradiol-containing contraceptives; recommend progestogen-only contraception instead 2
- Do not exceed omeprazole 40 mg equivalent for proton pump inhibitors 2