- ACRONYMS AND DEFINITIONS
- AASLD - American Association for the Study of Liver Disease
- HBV - Hepatitis B virus
- HCV - Hepatitis C virus
- PI - Package Insert
- ULN - Upper Limit of Normal
- DRUGS IN CLASS
- Mavyret is part of a new generation of antiviral medications that are highly effective against hepatitis C
- Mavyret is a combination pill that contains 2 medications - glecaprevir and pibrentasvir
- See Hepatitis C treatment for a list of other HCV drugs
- MECHANISM OF ACTION
- Glecaprevir
- Glecaprevir is HCV NS3/4A protease inhibitor
- HCV NS3/4A protease cleaves HCV-encoded polyprotein into the individual proteins NS3, NS4A, NS4B, NS5A, and NS5B. These proteins form a complex that is necessary for viral replication.
- Pibrentasvir
- Pibrentasvir is an inhibitor of the HCV NS5A protein which is essential for viral replication and virion assembly
- FDA-APPROVED INDICATIONS
- Adults and pediatric patients ≥ 3 years old:
- No cirrhosis or Child-Pugh A - Treatment of HCV genotypes 1, 2, 3, 4, 5, and 6
- No cirrhosis or Child-Pugh A who previously have been treated with a regimen containing an HCV NS5A inhibitor or an NS3/4A protease inhibitor, but not both - Treatment of HCV genotype 1
- HEPATITIS C TREATMENT
- In trials, Mavyret was > 90% effective in eradicating HCV in all subtypes of disease for which it is indicated
- SIDE EFFECTS
- General
- In trials, the incidence of side effects with Mavyret was similar to placebo
- The most common side effects reported were headache (13%), fatigue (11%), and nausea (8%)
- Side effects were similar in patients receiving Mavyret for 8, 12, and 16 weeks
- The type and severity of side effects in subjects with Child-Pugh A were comparable to those seen in subjects without cirrhosis
- Bilirubin elevations
- In trials, total bilirubin elevations > 2 X ULN were observed in 3.5% of Mavyret-treated patients and in 0% of placebo-treated patients
- The effects of Mavyret on bilirubin levels may be due to its inhibitory action on OATP1B1/B3 and UGT1A1
- CONTRAINDICATIONS
- Moderate or severe liver disease (Child-Pugh B or C) or those with any history of prior hepatic decompensation
- Coadministration with rifampin
- Coadministration with atazanavir
- PRECAUTIONS
- Kidney disease
- No dose adjustment is necessary for patients with mild, moderate or severe renal impairment, including those on dialysis
- Liver disease
- Child-Pugh A: No dose adjustment necessary
- Child-Pugh B or C: DO NOT USE
- History of hepatic decompensation: DO NOT USE
- Rare cases of worsening liver function or liver failure have occurred in patients with moderate to severe liver disease who took Mavyret. Mavyret should also not be used in patients with a history of hepatic decompensation.
- In patients with compensated cirrhosis (Child Pugh A) or evidence of advanced liver disease such as portal hypertension, perform hepatic laboratory testing as clinically indicated; and monitor for signs and symptoms of hepatic decompensation such as the presence of jaundice, ascites, hepatic encephalopathy, and variceal hemorrhage. Discontinue Mavyret in patients who develop evidence of hepatic decompensation.
- Hepatitis B coinfection
- In October 2016, the FDA placed a boxed warning on all new hepatitis C drugs about the possible reactivation of hepatitis B infection in coinfected patients who are taking direct-acting antiviral hepatitis C drugs
- At the time of the warning, the FDA had identified 24 cases of hepatitis B reactivation in patients taking these drugs. Reactivation occurred in patients who were HBsAg positive and in those who were HBsAg negative and anti-HBc positive (see interpreting HBV screening results for more).
- The FDA recommends that providers check all patients for hepatitis B coinfection (HBsAg and anti-HBc) before starting therapy and that they monitor patients for reactivation during and after therapy
- See AASLD guidelines for HBV coinfected patients for more
- MONITORING THERAPY
- DRUG INTERACTIONS
- NOTE: Drug interactions presented here are NOT all-inclusive. Other interactions may exist. The interactions presented here are meant to encompass commonly prescribed medications and/or interactions that are well-documented. Always consult your physician or pharmacist before taking medications concurrently. CLICK HERE for more information on drug interactions.
- Glecaprevir and pibrentasvir
- See the Mavyret PI for a complete list of potential drug interactions
- Carbamazepine - DO NOT COMBINE. Carbamazepine may decrease plasma levels and efficacy.
- Cyclosporine - Cyclosporine may raise Mavyret exposure. Do not combine in patients who require > 100 mg of cyclosporine a day.
- Dabigatran (Pradaxa®) - Mavyret may raise dabigatran levels. See dabigatran for information on dosing dabigatran with p-glycoprotein inhibitors.
- Digoxin - Mavyret may raise digoxin levels. Decrease digoxin dose by 50% when given with Mavyret.
- Efavirenz - DO NOT COMBINE. Efavirenz may decrease plasma levels and efficacy.
- Ethinyl estradiol (OCPs, HRT) - DO NOT COMBINE. Concomitant therapy may increase the risk of ALT elevations.
- HIV medications (darunavir, lopinavir, ritonavir, atazanavir) - DO NOT COMBINE. May increase Mavyret exposure and lead to toxicity.
- Phenytoin - DO NOT COMBINE. Phenytoin may decrease plasma levels and efficacy.
- Rifampin - DO NOT COMBINE. Rifampin may decrease plasma levels and efficacy.
- Statins
- Atorvastatin (Lipitor®) - DO NOT COMBINE. Atorvastatin exposure is increased raising the risk of myopathy.
- Lovastatin (Mevacor®) - DO NOT COMBINE. Lovastatin exposure is increased raising the risk of myopathy.
- Simvastatin (Zocor®) - DO NOT COMBINE. Simvastatin exposure is increased raising the risk of myopathy.
- Pravastatin (Pravachol®) - Pravastatin exposure is increased raising the risk of myopathy. Reduce pravastatin dose by 50%.
- Rosuvastatin (Crestor®) - Rosuvastatin exposure is increased raising the risk of myopathy. Rosuvastatin dose should not exceed 10 mg.
- Fluvastatin (Lescol®) - Fluvastatin exposure is increased raising the risk of myopathy. Use lowest approved dose of fluvastatin.
- Pitavastatin (Livalo®) - Pitavastatin exposure is increased raising the risk of myopathy. Use lowest approved dose of pitavastatin.
- St. John's Wort - DO NOT COMBINE. St. John's Wort may decrease plasma levels and efficacy.
- Warfarin - Mavyret may cause fluctuations in INR values in patients receiving warfarin. Monitor INR closely during concomitant therapy.
- Metabolism and clearance
- Glecaprevir
- P-glycoprotein - substrate and inhibitor
- BCRP - substrate and inhibitor
- OATP1B1/B3 - substrate and inhibitor
- CYP3A4 - weak inhibitor
- CYP1A2 - weak inhibitor
- UGT1A1 - weak inhibitor
- Pibrentasvir
- P-glycoprotein - substrate and inhibitor
- BCRP - substrate and inhibitor
- OATP1B1/B3 - inhibitor
- CYP3A4 - weak inhibitor
- CYP1A2 - weak inhibitor
- UGT1A1 - weak inhibitor
- DOSING
- Dosage forms
- Tablet
- One tablet contains glecaprevir 100 mg and pibrentasvir 40 mg
- Oral pellets
- One packet contains glecaprevir 50 mg and pibrentasvir 20 mg
- Comes in carton of 28 packets
- Dosing
- Adults: Three Mavyret tablets once daily with food. Food increases absorption.
- See Mavyret PI [sec 2] for pediatric dosing recommendations
| Treatment-naïve patients | ||
|---|---|---|
| HCV GN | No cirrhosis | Child-Pugh A |
| 1,2,3,4,5, and 6 | 8 weeks | 8 weeks |
| Treatment-experienced patients | |||
|---|---|---|---|
| HCV GN | Previous treatment | No cirrhosis | Child-Pugh A |
| 1 | An NS5A inhibitor without prior treatment with an NS3/4A protease inhibitor | 16 weeks | 16 weeks |
| 1 | An NS3/4A protease inhibitor without prior treatment with an NS5A inhibitor | 12 weeks | 12 weeks |
| 1, 2, 4, 5, 6 | ✝PRS | 8 weeks | 12 weeks |
| 3 | ✝PRS | 16 weeks | 16 weeks |
| Liver or kidney transplant recipients | ||
|---|---|---|
| HCV GN | Previous treatment | Duration |
| 1, 2, 3, 4, 5, 6 | None | 12 weeks |
| 1 | NS5A inhibitor-experienced without prior treatment with an NS3/4A protease inhibitor | 16 weeks |
| 3 | ✝PRS | 16 weeks |
- LONG TERM SAFETY
- Mavyret was FDA-approved in 2017
- There is no long-term safety data available
- BIBLIOGRAPHY
- 1 - Manufacturer's package insert