Mavyret

Glecaprevir and Pibrentasvir · Tablet, Film Coated · Oral

Prescription (Rx) Hepatitis C Virus NS3/4A Protease Inhibitor Hepatitis C Virus NS5A Inhibitor

Boxed warning. WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN PATIENTS COINFECTED WITH HCV AND HBV Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with MAVYRET. HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct-acting antivirals and were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure, and death. Monitor HCV/HBV coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated [see Warnings and Precautions ( 5.1 )] . WARNING: RISK OF HEPATITIS B VIRUS REACTIVATION IN PATIENTS COINFECTED WITH HCV AND HBV See full prescribing information for complete boxed warning. Hepatitis B…

Uses

1 INDICATIONS AND USAGE MAVYRET is indicated for the treatment of adult and pediatric patients 3 years and older with acute or chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5 or 6 infection without cirrhosis or with compensated cirrhosis (Child-Pugh A). MAVYRET is indicated for the treatment of adult and pediatric patients 3 years and older with HCV genotype 1 infection, who previously have been treated with a regimen containing an HCV NS5A inhibitor or an NS3/4A protease inhibitor (PI), but not both [see Dosage and Administration ( 2.2 ) and Clinical Studies ( 14 )]. MAVYRET is a fixed-dose combination of glecaprevir, a hepatitis C virus (HCV) NS3/4A protease inhibitor, and pibrentasvir, an HCV NS5A inhibitor, and is indicated for the treatment of adult and pediatric patients 3 years and older with acute or chronic HCV genotype (GT) 1, 2, 3, 4, 5 or 6 infection without cirrhosis or with compensated cirrhosis (Child-Pugh A). MAVYRET is indicated for the treatment of adult and pediatric patients 3 years and older with HCV genotype 1 infection, who previously have been treated with a regimen containing an HCV NS5A inhibitor or an NS3/4A protease inhibitor, but not both. ( 1 )

Dosage and administration

Testing Prior to the Initiation of Therapy: Test all patients for HBV infection by measuring HBsAg and anti-HBc. ( 2.1 ) See recommended treatment duration for patients 3 years and older in tables below. ( 2.2 ) Treatment-Naïve Patients 1 HCV Genotype Treatment Duration No Cirrhosis Compensated Cirrhosis (Child-Pugh A) 1, 2, 3, 4, 5, or 6 8 weeks 8 weeks Treatment-naïve patients are those who have not received treatment for the current infection. Treatment-Experienced Patients 1 Treatment Duration HCV Genotype Patients Previously Treated With a Regimen Containing: No Cirrhosis Compensated Cirrhosis (Child-Pugh A) 1 An NS5A inhibitor 2 without prior treatment with an NS3/4A protease inhibitor (PI) 16 weeks 16 weeks An NS3/4A PI 3 without prior treatment with an NS5A inhibitor 12 weeks 12 weeks 1, 2, 4, 5, or 6 PRS 4 8 weeks 12 weeks 3 PRS 4 16 weeks 16 weeks Treatment-experienced patients are those who previously received treatment for the current infection. Treated with prior regimens containing ledipasvir and sofosbuvir or daclatasvir with (peg) interferon and ribavirin. Treated with prior regimens containing simeprevir and sofosbuvir, or simeprevir, boceprevir, or telaprevir with (peg) interferon and ribavirin. PRS=Prior treatment experience with regimens containing (peg) interferon, ribavirin, and/or sofosbuvir, but no prior treatment experience with an HCV NS3/4A PI or NS5A inhibitor. Recommended dosage in adults: Three tablets taken at the same time orally once daily (total daily dose: glecaprevir 300 mg and pibrentasvir 120 mg) with food. ( 2.3 ) Recommended dosage in pediatric patients 3 years and older: Pediatric Patients 3 Years to Less than 12 Years Old: Dosing is based on weight. Refer to Table 3 of the full prescribing information for specific dosing guidelines based on body weight. ( 2.4 ) Instructions for Use should be followed for preparation and administration of MAVYRET oral pellets. ( 2.5 ) Pediatric Patients 12 Years of Age and Older, or Pediatric Patients Weighing at Least 45 kg: three tablets taken at the same time orally once daily (total daily dose: glecaprevir 300 mg and pibrentasvir 120 mg) with food. ( 2.4 ) HCV/HIV-1 co-infection and patients with any degree of renal impairment: Follow the dosage recommendations in the tables above. ( 2.2 ) Liver or Kidney Transplant Recipients: MAVYRET is recommended for 12 weeks in patients 3 years and older who are liver or kidney transplant recipients. A 16-week treatment duration is recommended in genotype 1-infected patients who are NS5A inhibitor-experienced without prior treatment with an NS3/4A PI or in genotype 3-infected patients who are PRS treatment-experienced. ( 2.6 ) 2.1 Testing Prior to the Initiation of Therapy Test all patients for evidence of current or prior HBV infection by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) before initiating HCV treatment with MAVYRET [see Warnings and Precautions ( 5.1 ) ] . 2.2 Recommended Treatment Duration in Patients 3 Years and Older Tables 1 and 2 provide the recommended MAVYRET treatment duration based on the patient population in HCV mono-infected and HCV/HIV-1 co-infected patients with compensated liver disease (with or without cirrhosis) and with or without renal impairment including patients receiving dialysis [see Contraindications ( 4 ) and Clinical Studies ( 14 )] . Refer to Drug Interactions ( 7 ) for dosage recommendations for concomitant HIV-1 antiviral drugs. Table 1. Recommended Duration for Treatment-Naïve Patients 1 HCV Genotype Treatment Duration No Cirrhosis Compensated Cirrhosis (Child-Pugh A) 1, 2, 3, 4, 5, or 6 8 weeks 8 weeks 1. Treatment-naïve patients are those who have not received treatment for the current infection. Table 2. Recommended Duration for Treatment-Experienced Patients 1 Treatment Duration HCV Genotype Patients Previously Treated with a Regimen Containing: No Cirrhosis Compensated Cirrhosis (Child-Pugh A) 1 An NS5A inhibitor 2 without prior treatment with an NS3/4A protease inhibitor (PI) 16 weeks 16 weeks An NS3/4A PI 3 without prior treatment with an NS5A inhibitor 12 weeks 12 weeks 1, 2, 4, 5, or 6 PRS 4 8 weeks 12 weeks 3 PRS 4 16 weeks 16 weeks Treatment-experienced patients are those who previously received treatment for the current infection. In clinical trials, subjects were treated with prior regimens containing ledipasvir and sofosbuvir or daclatasvir with (peg)interferon and ribavirin. In clinical trials, subjects were treated with prior regimens containing simeprevir and sofosbuvir, or simeprevir, boceprevir, or telaprevir with (peg)interferon and ribavirin. PRS=Prior treatment experience with regimens containing (peg)interferon, ribavirin, and/or sofosbuvir, but no prior treatment experience with an HCV NS3/4A PI or NS5A inhibitor. 2.3 Recommended Dosage in Adults MAVYRET tablets are a fixed combination drug product containing glecaprevir 100 mg and pibrentasvir 40 mg in each tablet. The recommended oral dosage of MAVYRET in adults is 3 tablets taken at the same time once daily with food (total daily dose: glecaprevir 300 mg and pibrentasvir 120 mg) [see Clinical Pharmacology ( 12.3 )] . 2.4 Recommended Dosage in Pediatric Patients 3 Years of Age and Older The recommended dosage of MAVYRET in pediatric patients 3 to less than 12 years of age is based on weight. MAVYRET oral pellets are recommended for pediatric patients 3 to less than 12 years old weighing less than 45 kg. MAVYRET oral pellets in packets are a fixed combination drug product containing glecaprevir 50 mg and pibrentasvir 20 mg in each packet. The recommended dosage of MAVYRET in pediatric patients 12 years of age and older, or in pediatric patients weighing at least 45 kg, is three tablets taken at the same time once daily with food (total daily dose: glecaprevir 300 mg and pibrentasvir 120 mg). The dosages for pediatric patients are shown in Table 3 . Table 3.

Dosage forms and strengths

3 DOSAGE FORMS AND STRENGTHS MAVYRET is available as tablets or pellets for oral use. Tablets: pink, oblong-shaped, film-coated, and debossed with “NXT” on one side. Each tablet contains 100 mg glecaprevir and 40 mg of pibrentasvir. Oral pellets: pink and yellow coated pellets in unit-dose packets. Each packet contains 50 mg glecaprevir and 20 mg pibrentasvir. Tablets: 100 mg glecaprevir and 40 mg pibrentasvir. ( 3 ) Oral Pellets: 50 mg glecaprevir and 20 mg pibrentasvir. ( 3 )

Contraindications

4 CONTRAINDICATIONS MAVYRET is contraindicated in patients with moderate or severe hepatic impairment (Child-Pugh B or C) or those with any history of prior hepatic decompensation [see Warnings and Precautions ( 5.2 ), Use in Specific Populations ( 8.7 ) and Clinical Pharmacology ( 12.3 )] . MAVYRET is contraindicated with atazanavir or rifampin [see Drug Interaction ( 7.3 ) and Clinical Pharmacology ( 12.3 )] . Patients with moderate or severe hepatic impairment (Child-Pugh B or C) or those with any history of prior hepatic decompensation. ( 4 , 5.2 ) Coadministration with atazanavir or rifampin. ( 4 )

Warnings and precautions

Risk of Hepatitis B Virus Reactivation: Test all patients for evidence of current or prior HBV infection before initiation of HCV treatment. Monitor HCV/HBV coinfected patients for HBV reactivation and hepatitis flare during HCV treatment and post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated. ( 5.1 ) Risk of Hepatic Decompensation/Failure in Patients with Evidence of Advanced Liver Disease: Hepatic decompensation/failure, including fatal outcomes, have been reported mostly in patients with cirrhosis and baseline moderate or severe liver impairment (Child-Pugh B or C). Monitor for clinical and laboratory evidence of hepatic decompensation. Discontinue MAVYRET in patients who develop evidence of hepatic decompensation/failure. ( 5.2 ) 5.1 Risk of Hepatitis B Virus Reactivation in Patients Coinfected with HCV and HBV Hepatitis B virus (HBV) reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV direct-acting antivirals, and who were not receiving HBV antiviral therapy. Some cases have resulted in fulminant hepatitis, hepatic failure and death. Cases have been reported in patients who are HBsAg positive and also in patients with serologic evidence of resolved HBV infection (i.e., HBsAg negative and anti-HBc positive). HBV reactivation has also been reported in patients receiving certain immunosuppressant or chemotherapeutic agents; the risk of HBV reactivation associated with treatment with HCV direct-acting antivirals may be increased in these patients. HBV reactivation is characterized as an abrupt increase in HBV replication manifesting as a rapid increase in serum HBV DNA level. In patients with resolved HBV infection reappearance of HBsAg can occur. Reactivation of HBV replication may be accompanied by hepatitis, i.e., increase in aminotransferase levels and, in severe cases, increases in bilirubin levels, liver failure, and death can occur. Test all patients for evidence of current or prior HBV infection by measuring HBsAg and anti- HBc before initiating HCV treatment with MAVYRET. In patients with serologic evidence of HBV infection, monitor for clinical and laboratory signs of hepatitis flare or HBV reactivation during HCV treatment with MAVYRET and during post-treatment follow-up. Initiate appropriate patient management for HBV infection as clinically indicated. 5.2 Risk of Hepatic Decompensation/Failure in Patients with Evidence of Advanced Liver Disease Postmarketing cases of hepatic decompensation/failure, including those with fatal outcomes, have been reported in patients treated with HCV NS3/4A protease inhibitor-containing regimens, including MAVYRET. Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The majority of patients with severe outcomes had evidence of advanced liver disease with moderate or severe hepatic impairment (Child-Pugh B or C) prior to initiating therapy with MAVYRET, including some patients reported as having compensated cirrhosis with mild liver impairment (Child-Pugh A) at baseline but with a prior decompensation event (i.e., prior history of ascites, variceal bleeding, encephalopathy). Rare cases of hepatic decompensation/failure were reported in patients without cirrhosis or with compensated cirrhosis (Child-Pugh A); many of these patients had evidence of portal hypertension. Events also occurred in patients taking a concomitant medication not recommended for coadministration, or in patients with confounding factors such as serious liver-related medical or surgical comorbidities. Cases typically occurred within the first 4 weeks of treatment (median of 27 days). 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/failure. MAVYRET is contraindicated in patients with moderate to severe hepatic impairment (Child-Pugh B or C) or those with any history of prior hepatic decompensation [see Contraindications ( 4 ), Adverse Reactions ( 6.1 ), Use in Specific Populations ( 8.7 ), and Clinical Pharmacology ( 12.3 )] . 5.3 Risk of Reduced Therapeutic Effect Due to Concomitant Use of MAVYRET with Carbamazepine, Efavirenz Containing Regimens, or St. John’s Wort Carbamazepine, efavirenz, and St. John’s wort may significantly decrease plasma concentrations of glecaprevir and pibrentasvir, leading to reduced therapeutic effect of MAVYRET. The use of these agents with MAVYRET is not recommended.

Side effects

In subjects receiving MAVYRET, the most commonly reported adverse reactions (greater than 10%) are headache and fatigue. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AbbVie Inc. at 1-800-633-9110 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in clinical trials of MAVYRET cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Overall Adverse Reactions in Subjects with Chronic HCV Infection without Cirrhosis or with Compensated Cirrhosis (Child-Pugh A) The adverse reactions data for MAVYRET in subjects without cirrhosis or with compensated cirrhosis (Child-Pugh A) were derived from nine registrational Phase 2 and 3 trials which evaluated approximately 2,300 adults infected with genotype 1, 2, 3, 4, 5, or 6 HCV who received MAVYRET for 8, 12 or 16 weeks [see Clinical Studies ( 14 ) ] . The overall proportion of subjects who permanently discontinued treatment due to adverse reactions was 0.1% for subjects who received MAVYRET for 8, 12 or 16 weeks. The most common adverse reactions, all grades, observed in greater than or equal to 5% of subjects receiving 8, 12, or 16 weeks of treatment with MAVYRET were headache (13%), fatigue (11%), and nausea (8%). In subjects receiving MAVYRET who experienced adverse reactions, 80% had an adverse reaction of mild severity (Grade 1). One subject experienced a serious adverse reaction. Adverse reactions (type and severity) were similar for subjects receiving MAVYRET for 8, 12 or 16 weeks. The type and severity of adverse reactions in subjects with compensated cirrhosis (Child-Pugh A) were similar to those seen in subjects without cirrhosis. Adverse Reactions in Subjects with Chronic HCV Infection without Cirrhosis ENDURANCE-2 Among 302 treatment-naïve or PRS treatment-experienced, HCV genotype 2-infected adults without cirrhosis enrolled in ENDURANCE-2, adverse reactions (all intensity) occurring in at least 5% of subjects treated with MAVYRET for 12 weeks are presented in Table 4 . In subjects treated with MAVYRET for 12 weeks, 32% reported an adverse reaction, of which 98% had adverse reactions of mild or moderate severity. No subjects treated with MAVYRET or placebo in ENDURANCE-2 permanently discontinued treatment due to an adverse drug reaction. Table 4. Adverse Reactions Reported in ≥5% of Treatment-Naïve and PRS-Experienced Adults without Cirrhosis Receiving MAVYRET for 12 Weeks in ENDURANCE-2 Adverse Reaction MAVYRET 12 Weeks (N = 202) % Placebo 12 Weeks (N = 100) % Headache 9 6 Nausea 6 2 Diarrhea 5 2 ENDURANCE-3 Among 505 treatment-naïve, HCV genotype 3-infected adults without cirrhosis enrolled in ENDURANCE-3, adverse reactions (all intensity) occurring in at least 5% of subjects treated with MAVYRET for 8 or 12 weeks are presented in Table 5 . In subjects treated with MAVYRET, 45% reported an adverse reaction, of which 99% had adverse reactions of mild or moderate severity. The proportion of subjects who permanently discontinued treatment due to adverse reactions was 0%, < 1% and 1% for the MAVYRET 8-week arm, MAVYRET 12 week arm and DCV + SOF arm, respectively. Table 5. Adverse Reactions Reported in ≥5% of Treatment-Naïve Adults without Cirrhosis Receiving MAVYRET for 8 Weeks or 12 Weeks in ENDURANCE-3 Adverse Reaction MAVYRET* 8 Weeks (N = 157) % MAVYRET 12 Weeks (N = 233) % DCV 1 + SOF 2 12 Weeks (N = 115) % Headache 16 17 15 Fatigue 11 14 12 Nausea 9 12 12 Diarrhea 7 3 3 1 DCV=daclatasvir 2 SOF=sofosbuvir * The 8-week arm was a non-randomized treatment arm. Adverse Reactions in Subjects with Chronic HCV Infection with Compensated Cirrhosis (Child-Pugh A) The safety of MAVYRET in HCV GT 1, 2, 3, 4, 5, or 6 subjects with compensated cirrhosis is based on data from 288 adults from the Phase 2/3 registrational trials treated with MAVYRET for 12 or more weeks and 343 adults from EXPEDITION-8 treated with MAVYRET for 8 weeks. The adverse reactions observed were generally consistent with those observed in clinical studies of MAVYRET in non-cirrhotic subjects [see Clinical Studies ( 14 )] . In the Phase 2/3 registrational trials, the adverse reactions reported in greater than or equal to 5% of compensated cirrhotic subjects (n=288) treated across all durations of MAVYRET were fatigue (15%), headache (14%), nausea (8%), diarrhea (6%), and pruritus (6%). In EXPEDITION-8, the adverse reactions reported in greater than or equal to 5% of compensated cirrhotic subjects (n=343) were fatigue (8%), pruritus (7%), and headache (6%). No subjects with compensated cirrhosis in the Phase 2/3 registrational trials (without severe renal impairment) or in EXPEDITION-8 discontinued treatment with MAVYRET due to an adverse reaction. Adverse Reactions in Subjects with Chronic HCV Infection with Severe Renal Impairment Including Those on Dialysis The safety of MAVYRET in subjects with chronic kidney disease (Stage 4 or Stage 5 including subjects on dialysis) with genotypes 1, 2, 3, 4, 5 or 6 chronic HCV infection without cirrhosis or with compensated cirrhosis (Child-Pugh A) was assessed in 104 adults (EXPEDITION-4) who received MAVYRET for 12 weeks. The most common adverse reactions observed in greater than or equal to 5% of subjects receiving 12 weeks of treatment with MAVYRET were pruritus (17%), fatigue (12%), nausea (9%), asthenia (7%), and headache (6%). In subjects treated with MAVYRET who reported an adverse reaction, 90% had adverse reactions of mild or moderate severity (Grade 1 or 2). The proportion of subjects who permanently discontinued treatment due to adverse reactions was 2%.

Drug interactions

Carbamazepine, efavirenz, and St. John’s wort may decrease concentrations of glecaprevir and pibrentasvir. Coadministration of carbamazepine, efavirenz containing regimens, and St. John’s wort with MAVYRET is not recommended. ( 5.3 ) Clearance of HCV infection with direct-acting antivirals may lead to changes in hepatic function, which may impact safe and effective use of concomitant medications. Frequent monitoring of relevant laboratory parameters (INR or blood glucose) and dose adjustments of certain concomitant medications may be necessary. ( 7.3 ) Medication- Assisted Treatment (MAT) for Opioid Use Disorder. ( 7.4 ) Consult the full prescribing information prior to and during treatment for potential drug interactions. ( 4 , 7 , 12.3 ) 7.1 Mechanisms for the Potential Effect of MAVYRET on Other Drugs Glecaprevir and pibrentasvir are inhibitors of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and organic anion transporting polypeptide (OATP) 1B1/3. Coadministration with MAVYRET may increase plasma concentration of drugs that are substrates of P-gp, BCRP, OATP1B1 or OATP1B3. Glecaprevir and pibrentasvir are weak inhibitors of cytochrome P450 (CYP) 3A, CYP1A2, and uridine glucuronosyltransferase (UGT) 1A1. 7.2 Mechanisms for the Potential Effect of Other Drugs on MAVYRET Glecaprevir and pibrentasvir are substrates of P-gp and/or BCRP. Glecaprevir is a substrate of OATP1B1/3. Coadministration of MAVYRET with drugs that inhibit hepatic P-gp, BCRP, or OATP1B1/3 may increase the plasma concentrations of glecaprevir and/or pibrentasvir. Coadministration of MAVYRET with drugs that induce P-gp/CYP3A may decrease glecaprevir and pibrentasvir plasma concentrations. Carbamazepine, phenytoin, efavirenz, and St. John’s wort may significantly decrease plasma concentrations of glecaprevir and pibrentasvir, leading to reduced therapeutic effect of MAVYRET. The use of these agents with MAVYRET is not recommended [see Warnings and Precautions ( 5.3 ) and Clinical Pharmacology ( 12.3 )] . 7.3 Established and Other Potential Drug Interactions Clearance of HCV infection with direct-acting antivirals may lead to changes in hepatic function, which may impact the safe and effective use of concomitant medications. For example, altered blood glucose control resulting in serious symptomatic hypoglycemia has been reported in diabetic patients in postmarketing case reports and published epidemiological studies. Management of hypoglycemia in these cases required either discontinuation or dose modification of concomitant medications used for diabetes treatment. Frequent monitoring of relevant laboratory parameters (e.g. International Normalized Ratio [INR] in patients taking warfarin, blood glucose levels in diabetic patients) or drug concentrations of concomitant medications such as CYP P450 substrates with a narrow therapeutic index (e.g. certain immunosuppressants) is recommended to ensure safe and effective use. Dose adjustments of concomitant medications may be necessary. Table 6 provides the effect of MAVYRET on concentrations of coadministered drugs and the effect of coadministered drugs on glecaprevir and pibrentasvir [see Contraindications ( 4 ) , Warnings and Precautions ( 5.3 ) , and Clinical Pharmacology ( 12.3 ) ] . All interaction studies were performed in adults. Table 6. Potentially Significant Drug Interactions Identified in Drug Interaction Studies Concomitant Drug Class: Drug Name Effect on Concentration Clinical Comments Antiarrhythmics: Digoxin ↑ digoxin Measure serum digoxin concentrations before initiating MAVYRET. Reduce digoxin concentrations by decreasing the dose by approximately 50% or by modifying the dosing frequency and continue monitoring. Anticoagulants: Dabigatran etexilate ↑ dabigatran If MAVYRET and dabigatran etexilate are coadministered, refer to the dabigatran etexilate prescribing information for dabigatran etexilate dose modifications in combination with P-gp inhibitors in the setting of renal impairment. Anticonvulsants: Carbamazepine ↓ glecaprevir ↓ pibrentasvir Coadministration may lead to reduced therapeutic effect of MAVYRET and is not recommended. Antimycobacterials: Rifampin ↓ glecaprevir ↓ pibrentasvir Coadministration is contraindicated because of potential loss of therapeutic effect [see Contraindications ( 4 ) ] . Ethinyl Estradiol-Containing Products: Ethinyl estradiol-containing medications such as combined oral contraceptives ↔ glecaprevir ↔ pibrentasvir MAVYRET may be used with products containing 20 mcg or less of ethinyl estradiol. Coadministration of MAVYRET with products containing more than 20 mcg of ethinyl estradiol may increase the risk of ALT elevations and is not recommended. Herbal Products: St. John’s wort ( hypericum perforatum ) ↓ glecaprevir ↓ pibrentasvir Coadministration may lead to reduced therapeutic effect of MAVYRET and is not recommended. HIV-Antiviral Agents: Atazanavir ↑ glecaprevir ↑ pibrentasvir Coadministration is contraindicated due to increased risk of ALT elevations [see Contraindications ( 4 ) ] . Darunavir Lopinavir Ritonavir ↑ glecaprevir ↑ pibrentasvir Coadministration is not recommended. Efavirenz ↓ glecaprevir ↓ pibrentasvir Coadministration may lead to reduced therapeutic effect of MAVYRET and is not recommended. HMG-CoA Reductase Inhibitors: Atorvastatin Lovastatin Simvastatin ↑ atorvastatin ↑ lovastatin ↑ simvastatin Coadministration may increase the concentration of atorvastatin, lovastatin, and simvastatin. Increased statin concentrations may increase the risk of myopathy, including rhabdomyolysis. Coadministration with these statins is not recommended. Pravastatin ↑ pravastatin Coadministration may increase the concentration of pravastatin. Increased statin concentrations may increase the risk of myopathy, including rhabdomyolysis. Reduce pravastatin dose by 50% when coadministered with MAVYRET. Rosuvastatin ↑ rosuvastatin Coadministration may significantly increase the concentration of rosuvastatin.

Use in specific populations

8.1 Pregnancy Risk Summary No adequate human data are available to establish whether or not MAVYRET poses a risk to pregnancy outcomes. In animal reproduction studies, no adverse developmental effects were observed when the components of MAVYRET were administered separately during organogenesis at exposures up to 53 times (rats; glecaprevir) or 51 and 1.5 times (mice and rabbits, respectively; pibrentasvir) the human exposures at the recommended dose of MAVYRET (see Data ) . No definitive conclusions regarding potential developmental effects of glecaprevir could be made in rabbits, since the highest achieved glecaprevir exposure in this species was only 7% (0.07 times) of the human exposure at the recommended dose. There were no effects with either compound in rodent pre/post-natal developmental studies in which maternal systemic exposures (AUC) to glecaprevir and pibrentasvir were approximately 47 and 74 times, respectively, the exposure in humans at the recommended dose (see Data ) . The background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Glecaprevir Glecaprevir was administered orally to pregnant rats (up to 120 mg/kg/day) and rabbits (up to 60 mg/kg/day) during the period of organogenesis (gestation days (GD) 6 to 18, and GD 7 to 19, respectively). No adverse embryo-fetal effects were observed in rats at dose levels up to 120 mg/kg/day (53 times the exposures in humans at the recommended human dose (RHD)). In rabbits, the highest glecaprevir exposure achieved was 7% (0.07 times) of the exposure in humans at RHD. As such, data in rabbits during organogenesis are not available for glecaprevir systemic exposures at or above the exposures in humans at the RHD. In the pre/post-natal developmental study in rats, glecaprevir was administered orally (up to 120 mg/kg/day) from GD 6 to lactation day 20. No effects were observed at maternal exposures 47 times the exposures in humans at the RHD. Pibrentasvir Pibrentasvir was administered orally to pregnant mice and rabbits (up to 100 mg/kg/day) during the period of organogenesis (GD 6 to 15, and GD 7 to 19, respectively). No adverse embryo-fetal effects were observed at any studied dose level in either species. The systemic exposures at the highest doses were 51 times (mice) and 1.5 times (rabbits) the exposures in humans at the RHD. In the pre/post-natal developmental study in mice, pibrentasvir was administered orally (up to 100 mg/kg/day) from GD 6 to lactation day 20. No effects were observed at maternal exposures approximately 74 times the exposures in humans at the RHD. 8.2 Lactation Risk Summary It is not known whether the components of MAVYRET are excreted in human breast milk, affect human milk production, or have effects on the breastfed infant. When administered to lactating rodents, the components of MAVYRET were present in milk, without effect on growth and development observed in the nursing pups (see Data ) . The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for MAVYRET and any potential adverse effects on the breastfed child from MAVYRET or from the underlying maternal condition. Data No significant effects of glecaprevir or pibrentasvir on growth and post-natal development were observed in nursing pups at the highest doses tested (120 mg/kg/day for glecaprevir and 100 mg/kg/day for pibrentasvir). Maternal systemic exposure (AUC) to glecaprevir and pibrentasvir was approximately 47 or 74 times the exposure in humans at the RHD. Systemic exposure in nursing pups on post-natal day 14 was approximately 0.6 to 2.2 % of the maternal exposure for glecaprevir and approximately one quarter to one third of the maternal exposure for pibrentasvir. Glecaprevir or pibrentasvir was administered (single dose; 5 mg/kg oral) to lactating rats, 8 to 12 days post parturition. Glecaprevir in milk was 13 times lower than in plasma and pibrentasvir in milk was 1.5 times higher than in plasma. Parent drug (glecaprevir or pibrentasvir) represented the majority (>96%) of the total drug-related material in milk. 8.4 Pediatric Use No dosage adjustment of MAVYRET is required in pediatric patients 12 years and older or weighing at least 45 kg. The recommended dosage of MAVYRET in pediatric patients 3 to less than 12 years of age is based on weight [see Dosage and Administration ( 2.2 , 2.4 ) , Clinical Pharmacology ( 12.3 ) and Clinical Studies ( 14.10 ) ] . The safety, efficacy, and pharmacokinetics of MAVYRET in HCV GT1, 2, 3, or 4 infected pediatric patients 3 years and older is based on data from an open-label trial in 127 subjects with chronic HCV infection, without cirrhosis, and aged 3 years to less than 18 years who were either treatment-naïve (n=114) or treatment-experienced (n=13) and received MAVYRET for 8, 12 or 16 weeks (DORA-Part 1 and Part 2). The adverse reactions observed in subjects 3 years to less than 18 years of age were consistent with those observed in clinical trials of MAVYRET in adults with chronic HCV infection with the exception of vomiting, rash and abdominal pain upper which were observed more frequently in pediatric subjects less than 12 years of age compared to adults [see Adverse Reactions ( 6.1 ) ] . The efficacy results observed in this trial were consistent with those observed in clinical trials of MAVYRET in adults [see Clinical Studies ( 14.10 ) ] . Use of MAVYRET in pediatric patients with acute HCV infection is supported by extrapolation of safety and efficacy data from adult patients with acute HCV infection and adult and pediatric patients with chronic HCV infection. It is expected that adult and pediatric patients with acute HCV infection have similar disease response to treatment.

Pregnancy

Pediatric use

8.4 Pediatric Use No dosage adjustment of MAVYRET is required in pediatric patients 12 years and older or weighing at least 45 kg. The recommended dosage of MAVYRET in pediatric patients 3 to less than 12 years of age is based on weight [see Dosage and Administration ( 2.2 , 2.4 ) , Clinical Pharmacology ( 12.3 ) and Clinical Studies ( 14.10 ) ] . The safety, efficacy, and pharmacokinetics of MAVYRET in HCV GT1, 2, 3, or 4 infected pediatric patients 3 years and older is based on data from an open-label trial in 127 subjects with chronic HCV infection, without cirrhosis, and aged 3 years to less than 18 years who were either treatment-naïve (n=114) or treatment-experienced (n=13) and received MAVYRET for 8, 12 or 16 weeks (DORA-Part 1 and Part 2). The adverse reactions observed in subjects 3 years to less than 18 years of age were consistent with those observed in clinical trials of MAVYRET in adults with chronic HCV infection with the exception of vomiting, rash and abdominal pain upper which were observed more frequently in pediatric subjects less than 12 years of age compared to adults [see Adverse Reactions ( 6.1 ) ] . The efficacy results observed in this trial were consistent with those observed in clinical trials of MAVYRET in adults [see Clinical Studies ( 14.10 ) ] . Use of MAVYRET in pediatric patients with acute HCV infection is supported by extrapolation of safety and efficacy data from adult patients with acute HCV infection and adult and pediatric patients with chronic HCV infection. It is expected that adult and pediatric patients with acute HCV infection have similar disease response to treatment. No clinically meaningful differences in MAVYRET exposures are expected among pediatric patients with acute HCV infection and pediatric patients with chronic HCV infection [see Clinical Pharmacology ( 12.3 )]. In pediatric patients with cirrhosis, history of a kidney and/or liver transplant, or HCV GT5 or 6 infection, the safety and efficacy of MAVYRET are supported by the comparable glecaprevir and pibrentasvir exposures observed between pediatric subjects and adults [see Clinical Pharmacology ( 12.3 ) ] . The safety and effectiveness of MAVYRET in children less than 3 years of age have not been studied.

Geriatric use

8.5 Geriatric Use In clinical trials of MAVYRET in subjects with chronic HCV infection, 328 subjects were age 65 years and over (14% of the total number of subjects in the Phase 2 and 3 clinical trials), and 47 (2%) subjects were age 75 and over. In a clinical trial of MAVYRET in subjects with acute HCV infection, 16 subjects were age 65 years and over (6%), and 1 (0.3%) subject was age 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger subjects. No dosage adjustment of MAVYRET is warranted in geriatric patients [see Clinical Pharmacology ( 12.3 ) ] .

Overdosage

In case of overdose, the patient should be monitored for any signs and symptoms of toxicities. Appropriate symptomatic treatment should be instituted immediately. Glecaprevir and pibrentasvir are not significantly removed by hemodialysis.

Description

11 DESCRIPTION MAVYRET contains glecaprevir, a HCV NS3/4A PI, and pibrentasvir a HCV NS5A inhibitor. MAVYRET is available as a fixed dose combination tablet or coated pellets in unit-dose packets for oral administration. Glecaprevir/Pibrentasvir Film-Coated Immediate Release Tablets Each tablet contains 100 mg of glecaprevir and 40 mg of pibrentasvir. Glecaprevir and pibrentasvir are presented as a co-formulated, fixed-dose combination, immediate release bilayer tablet. The tablet contains the following inactive ingredients: colloidal silicon dioxide, copovidone (type K 28), croscarmellose sodium, hypromellose 2910, iron oxide red, lactose monohydrate, polyethylene glycol 3350, propylene glycol monocaprylate (type II), sodium stearyl fumarate, titanium dioxide, and vitamin E (tocopherol) polyethylene glycol succinate. The tablets do not contain gluten. Glecaprevir/Pibrentasvir Coated Oral Pellets MAVYRET oral pellets are small, pink and yellow and supplied in unit-dose packets for oral administration. Each unit-dose of MAVYRET oral pellets in packets contains 50 mg glecaprevir and 20 mg pibrentasvir and the following inactive ingredients: colloidal silicon dioxide, copovidone (type K 28), croscarmellose sodium, hypromellose 2910, iron oxide red, iron oxide yellow, lactose monohydrate, polyethylene glycol/macrogol 3350, propylene glycol monocaprylate (type II), sodium stearyl fumarate, titanium dioxide, vitamin E (tocopherol) polyethylene glycol succinate. The oral pellets do not contain gluten. Glecaprevir drug substance: The chemical name of glecaprevir is (3a R ,7 S ,10 S ,12 R ,21 E ,24a R )-7- tert -butyl- N -{(1 R ,2 R )-2-(difluoromethyl)-1-[(1-methylcyclopropane-1-sulfonyl)carbamoyl]cyclopropyl}-20,20-difluoro-5,8-dioxo-2,3,3a,5,6,7,8,11,12,20,23,24a-dodecahydro-1 H ,10 H -9,12-methanocyclopenta[18,19][1,10,17,3,6]trioxadiazacyclononadecino[11,12- b ]quinoxaline-10-carboxamide hydrate. The molecular formula is C 38 H 46 F 4 N 6 O 9 S (anhydrate) and the molecular weight for the drug substance is 838.87 g/mol (anhydrate). The strength of glecaprevir is based on anhydrous glecaprevir. Glecaprevir is a white to off-white crystalline powder with a solubility of less than 0.1 to 0.3 mg/mL across a pH range of 2–7 at 37°C and is practically insoluble in water, but is sparingly soluble in ethanol. Glecaprevir has the following molecular structure: Pibrentasvir drug substance: The chemical name of pibrentasvir is Methyl {(2 S ,3 R )-1-[(2 S )-2-{5-[(2 R ,5 R )-1-{3,5-difluoro-4-[4-(4-fluorophenyl)piperidin-1-yl]phenyl}-5-(6-fluoro-2-{(2 S )-1-[ N -(methoxycarbonyl)- O -methyl-L-threonyl]pyrrolidin-2-yl}-1 H -benzimidazol-5-yl)pyrrolidin-2-yl]-6-fluoro-1 H -benzimidazol-2-yl}pyrrolidin-1-yl]-3-methoxy-1-oxobutan-2-yl}carbamate. The molecular formula is C 57 H 65 F 5 N 10 O 8 and the molecular weight for the drug substance is 1113.18 g/mol. Pibrentasvir is a white to off-white to light yellow crystalline powder with a solubility of less than 0.1 mg/mL across a pH range of 1–7 at 37°C and is practically insoluble in water, but is freely soluble in ethanol. Pibrentasvir has the following molecular structure: Glecaprevir Pibrentasvir

Mechanism of action

12.1 Mechanism of Action Mechanism of Action MAVYRET is a fixed-dose combination of glecaprevir and pibrentasvir, which are direct-acting antiviral agents against the hepatitis C virus [see Microbiology ( 12.4 ) ] .

How supplied

Tablets Configuration Content Package Size NDC Monthly carton (blister pack) 4 weekly cartons 7 daily blisters/carton 3 tablets/blister 84 tablets 0074-2625-04 Monthly carton (wallet) 4 weekly cartons 7 daily wallets/carton 3 tablets/wallet 84 tablets 0074-2625-28 8-Week Carton 2 monthly cartons 4 weekly cartons/monthly carton 7 daily wallets/carton 3 tablets/wallet 168 tablets 0074-2625-56 Bottle 84 tablets 0074-2625-84 MAVYRET tablets are pink-colored, film-coated, oblong biconvex shaped, debossed with “NXT” on one side. Store at or below 30°C (86°F). MAVYRET Oral Pellets MAVYRET oral pellets are dispensed in child-resistant unit-dose packets in cartons. Each carton contains 28 packets. Each packet contains 50 mg glecaprevir/20 mg pibrentasvir pink and yellow oral pellets. The NDC number is 0074-2600-28. Store at or below 30°C (86°F).

Patient information

Advise the patient to read the FDA-approved patient labeling ( Patient Information ). Risk of Hepatitis B Virus Reactivation in Patients Coinfected with HCV and HBV Inform patients that HBV reactivation can occur in patients coinfected with HBV during or after treatment of HCV infection. Advise patients to tell their healthcare provider if they have a history of hepatitis B virus infection [see Warnings and Precautions ( 5.1 ) ] . Risk of Hepatic Decompensation/Failure in Patients with Evidence of Advanced Liver Disease Advise patients to seek medical evaluation immediately for symptoms of worsening liver problems such as nausea, tiredness, yellowing of the skin or white part of the eyes, bleeding or bruising more easily than normal, confusion, loss of appetite, diarrhea, dark or brown urine, dark or bloody stool, swelling of the stomach area (abdomen) or pain in the upper right side of the stomach area, sleepiness, or vomiting of blood [see Warnings and Precautions ( 5.2 )] . Drug Interactions Inform patients that MAVYRET may interact with some drugs; therefore, patients should be advised to report to their healthcare provider the use of any prescription, non-prescription medication or herbal products [see Contraindications ( 4 ) , Warnings and Precautions ( 5.3 ) and Drug Interactions ( 7 ) ] . Administration For MAVYRET oral pellets, advise patients or caregivers to read and follow the Instructions for Use for preparing the correct dose [see Dosage and Administration ( 2.4 , 2.5 )] . Inform patients it is important to take all three tablets at the same time once daily with food as directed. Inform patients that it is important not to miss or skip doses and to take MAVYRET for the duration that is recommended by the physician [see Dosage and Administration ( 2.2 ) ] . If a dose is missed and it is: Less than 18 hours from the usual time that MAVYRET should have been taken – advise the patient to take the dose as soon as possible and then to take the next dose at the usual time. More than 18 hours from the usual time that MAVYRET should have been taken – advise the patient not to take the missed dose and to take the next dose at the usual time. Manufactured by AbbVie Inc., North Chicago, IL 60064 MAVYRET and its design are trademarks of AbbVie Inc. © 2025 AbbVie Inc. All rights reserved. 20092779

Label text from the FDA structured product label by AbbVie Inc. (revised Jun 25, 2025). Long sections are shortened; the complete label is on DailyMed.

Active ingredients

Pibrentasvir in 2 products
Glecaprevir in 2 products

Mavyret NDC products (2)

NDC	Strength & form	Labeler	Type
0074-2600	Pibrentasvir 20 mg/1; Glecaprevir 50 mg/1 Pellet	AbbVie Inc.	NDA
0074-2625	Pibrentasvir 40 mg/1; Glecaprevir 100 mg/1 Tablet, Film Coated	AbbVie Inc.	NDA