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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].
MAVYRET is a fixed-dose combination tablet containing glecaprevir and pibrentasvir for oral administration. Glecaprevir is a HCV NS3/4A PI, and pibrentasvir is a HCV NS5A inhibitor.
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.
The chemical name of glecaprevir is (3aR,7S,10S,12R,21E,24aR)-7-tert-butyl-N-{(1R,2R)-2(difluoromethyl)-1-[(1-methylcyclopropane-1-sulfonyl)carbamoyl]cyclopropyl}-20,20-difluoro5,8-dioxo-2,3,3a,5,6,7,8,11,12,20,23,24a-dodecahydro-1H,10H-9,12methanocyclopenta[18,19][1,10,17,3,6]trioxadiazacyclononadecino[11,12-b]quinoxaline-10carboxamide hydrate.
The molecular formula is C38H46F4N6O9S (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:
 |
The chemical name of pibrentasvir is Methyl {(2S,3R)-1-[(2S)-2-{5-[(2R,5R)-1-{3,5-difluoro-4[4-(4-fluorophenyl)piperidin-1-yl]phenyl}-5-(6-fluoro-2-{(2S)-1-[N-(methoxycarbonyl)-Omethyl-L-threonyl]pyrrolidin-2-yl}-1H-benzimidazol-5-yl)pyrrolidin-2-yl]-6-fluoro-1Hbenzimidazol-2-yl}pyrrolidin-1-yl]-3-methoxy-1-oxobutan-2-yl}carbamate.
The molecular formula is C57H65F5N10O8 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:
 |
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)].
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)].
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 Patients1
| HCV Genotype | Treatment Duration | ||||
| No Cirrhosis | Compensated Cirrhosis (Child-Pugh A) |
||||
| 1, 2, 3, 4, 5, or 6 | 8 weeks | 8 weeks | |||
|
|||||
Table 2. Recommended Duration for Treatment-Experienced Patients1
| Treatment Duration | |||
| HCV Genotype | Patients Previously Treated with a Regimen Containing: |
No Cirrhosis | Compensated Cirrhosis (Child-Pugh A) |
| 1 | An NS5A inhibitor2 without prior treatment with an NS3/4A protease inhibitor (PI) | 16 weeks | 16 weeks |
| An NS3/4A PI3 without prior treatment with an NS5A inhibitor | 12 weeks | 12 weeks | |
| 1, 2, 4, 5, or 6 | PRS4 | 8 weeks | 12 weeks |
| 3 | PRS4 | 16 weeks | 16 weeks |
|
|||
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)].
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. Recommended Dosage in Pediatric Patients 3 Years of Age and Older
| Body Weight (kg) or Age (yrs) | Daily Dose of glecaprevir/pibrentasvir | Dosing of MAVYRET | |||
| Less than 20 kg | 150 mg/60 mg per day | Three 50 mg/20 mg packets of oral pellets once daily | |||
| 20 kg to less than 30 kg | 200 mg/80 mg per day | Four 50 mg/20 mg packets of oral pellets once daily | |||
| 30 kg to less than 45 kg | 250 mg/100 mg per day | Five 50 mg/20 mg packets of oral pellets once daily | |||
| 45 kg and greater OR 12 years of age and older | 300 mg/120 mg per day | Three 100 mg/40 mg tablets once daily1 (see Recommended Dosage in Adults) | |||
| 1 Pediatric patients weighing 45 kg and greater who are unable to swallow tablets may take six 50 mg/20 mg packets of oral pellets once daily. Dosing with oral pellets has not been studied for pediatric patients weighing greater than 45 kg [see Clinical Pharmacology (12.3)]. | |||||
See the MAVYRET oral pellets full Instructions for Use for details on the preparation and administration.
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 protease inhibitor or in genotype 3-infected patients who are PRS treatment-experienced [see Clinical Studies (14.8)].
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 Contraindications (4), Warnings and Precautions (5.2), Use in Specific Populations (8.7) and Clinical Pharmacology (12.3)].
MAVYRET is available as tablets or pellets for oral use.
| 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 €œNXT€Â on one side.
Store at or below 30°C (86°F).
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).
Manufactured by AbbVie Inc., North Chicago, IL 60064 MAVYRET is a trademark of AbbVie Inc. © 2025 AbbVie Inc. All rights reserved.
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.
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.
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) % |
DCV1 + SOF2 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. |
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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.
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%.
The safety of MAVYRET in subjects with HIV-1 co-infection with genotypes 1, 2, 3, 4 or 6 chronic HCV infection without cirrhosis or with compensated cirrhosis (Child-Pugh A) was assessed in 153 adults (EXPEDITION-2) who received MAVYRET for 8 or 12 weeks. Thirty- three subjects with HIV-1 coinfection also received 8 or 12 weeks of therapy in ENDURANCE-1.
The overall safety profile in HCV/HIV-1 co-infected subjects (ENDURANCE-1 and EXPEDITION-2) was similar to that observed in HCV mono-infected subjects. Adverse reactions observed in greater than or equal to 5% of subjects receiving MAVYRET in EXPEDITION-2 for 8 or 12 weeks were fatigue (10%), nausea (8%), and headache (5%).
The safety of MAVYRET was assessed in 100 adult post-liver or -kidney transplant recipients with genotypes 1, 2, 3, 4, or 6 chronic HCV infection without cirrhosis (MAGELLAN-2). The overall safety profile in transplant recipients was similar to that observed in subjects in the Phase 2 and 3 studies, without a history of transplantation. Adverse reactions observed in greater than or equal to 5% of subjects receiving MAVYRET for 12 weeks were headache (17%), fatigue (16%), nausea (8%) and pruritus (7%). In subjects treated with MAVYRET who reported an adverse reaction, 81% had adverse reactions of mild severity. Two percent of subjects experienced a serious adverse reaction, and no subjects permanently discontinued treatment due to adverse reactions.
PWID
The safety of MAVYRET in PWID with chronic HCV GT 1, 2, 3, 4, 5, or 6 infection is based on data from adults and adolescents in Phase 2 and 3 trials in which 62 subjects identified as current/recent PWID (defined as self-reported injection drug use within the last 12 months prior to starting MAVYRET) and 3,282 subjects reported no injection drug use (non-PWID).
Among current/recent PWID, adverse reactions observed in greater than or equal to 5% of subjects were fatigue (16%), headache (13%), diarrhea (6%), and nausea (6%). Among non- PWID subjects, adverse reactions observed in greater than or equal to 5% were headache (7%) and fatigue (6%). Serious adverse reactions and/or adverse reactions leading to treatment discontinuation occurred in one current/recent PWID subject (2%) compared to less than 1% in non-PWID subjects [see Use in Specific Populations (8.8) and Clinical Studies (14.9)].
MAT
The safety of MAVYRET in subjects with chronic HCV GT 1, 2, 3, 4, 5, or 6 infection reporting concomitant use of MAT for opioid use disorder is based on data from adults and adolescents in Phase 2 and 3 trials in which 225 subjects reported concomitant use of MAT and 4,098 subjects reported no concomitant use of MAT.
Among subjects on MAT, adverse reactions observed in greater than or equal to 5% were headache (15%), fatigue (12%), nausea (11%), and diarrhea (6%). Among subjects who were not on MAT, adverse reactions observed in greater than or equal to 5% were headache (9%), fatigue (8%), and nausea (5%). Serious adverse reactions and/or adverse reactions leading to treatment discontinuation were not observed among subjects on MAT and were experienced by less than 1% of subjects not on MAT [see Use in Specific Populations (8.8) and Clinical Studies (14.9)].
The safety of MAVYRET in subjects with acute HCV GT 1, 2, 3, or 4 infection was assessed in 286 adults who received MAVYRET for 8 weeks. Among these subjects, 142 had HIV-1 co- infection, 41 identified as current/recent PWID, and 21 reported concomitant use of MAT. At baseline, 49% of subjects had ALT elevations greater than 3 x upper limit of normal (ULN), 13% had ALT elevations greater than 10 x ULN, and 12% had total bilirubin elevations greater than ULN. The overall safety profile in these subjects was similar to that observed in subjects with chronic HCV infection. Serious adverse reactions and/or adverse reactions leading to treatment discontinuation were not observed among subjects with acute HCV infection.
The most commonly reported adverse reactions were fatigue (3%), asthenia (2%), headache (2%) and diarrhea (2%) [see Use in Specific Populations (8.4), Use in Specific Populations (8.5) Clinical Studies (14.11)].
The safety of MAVYRET in HCV GT 1, 2, 3, or 4 infected adolescents is based on data from a Phase 2/3 open-label trial in 47 subjects aged 12 years to less than 18 years without cirrhosis treated with MAVYRET for 8 or 16 weeks (DORA-Part 1). The adverse reactions observed in subjects 12 years to less than 18 years of age were consistent with those observed in clinical trials of MAVYRET in adults. The only adverse reaction observed in greater than or equal to 5% of subjects receiving MAVYRET in DORA Part 1 was fatigue (6%). No subjects discontinued or interrupted treatment with MAVYRET due to an adverse reaction.
The safety of MAVYRET in HCV GT 1, 2, 3, or 4 infected pediatric subjects aged 3 years to less than 12 years is based on data from a Phase 2/3 open-label trial in 80 subjects aged 3 to less than 12 years without cirrhosis treated with weight-based MAVYRET oral pellets in packets for 8, 12 or 16 weeks (DORA-Part 2). The adverse reactions observed in subjects 3 years to less than 12 years of age were consistent with those observed in clinical trials of MAVYRET in adults with the exception of vomiting (occurring at 8%), rash, and abdominal pain upper (each occurring at 4%) which were observed more frequently in pediatric subjects less than 12 years of age compared to adults. Other adverse reactions observed in greater than or equal to 5% of subjects receiving MAVYRET in DORA-Part 2 include fatigue and headache, each occurring at 8%. One subject discontinued treatment due to an adverse reaction of erythematous rash (Grade 3). All other adverse reactions were Grade 1 or 2 and no subjects interrupted treatment due to an adverse reaction [see Use in Specific Populations (8.4), Clinical Studies (14.10)].
Elevations of total bilirubin at least 2 times the ULN occurred in 3.5% of adult subjects treated with MAVYRET versus 0% in placebo; these elevations were observed in 1.2% of adult subjects across the Phase 2 and 3 trials.
In adult subjects with compensated cirrhosis (Child-Pugh A), 17% experienced early, transient post-baseline elevations of bilirubin above the ULN. These bilirubin elevations were typically less than 2 × ULN, generally occurred within the first 2 weeks of treatment and resolved with continued treatment. The subjects with compensated cirrhosis and bilirubin elevations did not have concurrent increases in ALT or AST, or signs of liver decompensation or failure, and these laboratory events did not lead to treatment discontinuation. MAVYRET inhibits OATP1B1/3 and is a weak inhibitor of UGT1A1 and may have the potential to impact bilirubin transport and metabolism, including direct and indirect bilirubin. Few subjects experienced jaundice or ocular icterus and total bilirubin levels decreased after completing MAVYRET.
Liver tests in subjects with acute HCV infectionElevations of total bilirubin at least 2 times ULN occurred in 2.8% of subjects treated with MAVYRET. Subjects with total bilirubin elevations did not have concurrent increases in ALT or AST, or signs of liver decompensation or failure, and these laboratory events did not lead to treatment discontinuation. All subjects with baseline ALT > 3 × ULN improved from baseline by the final treatment visit.
The following adverse reactions have been identified during post-approval use of MAVYRET. Because these reactions 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.
Skin and Subcutaneous Tissue Disorders: Angioedema
Hepatobiliary Disorders: Hepatic decompensation, hepatic failure [see Warnings and Precautions (5.2)].
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.
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)].
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. Increased statin concentrations may increase the risk of myopathy, including rhabdomyolysis. Rosuvastatin may be administered with MAVYRET at a dose that does not exceed 10 mg. |
| Fluvastatin Pitavastatin | ↑ fluvastatin ↑ pitavastatin | Coadministration may increase the concentrations of fluvastatin and pitavastatin. Increased statin concentrations may increase the risk of myopathy, including rhabdomyolysis. Use the lowest approved dose of fluvastatin or pitavastatin. If higher doses are needed, use the lowest necessary statin dose based on a risk/benefit assessment. |
| Immunosuppressants: | ||
| Cyclosporine | ↑ glecaprevir ↑ pibrentasvir | MAVYRET is not recommended for use in patients requiring stable cyclosporine doses > 100 mg per day. |
| See Clinical Pharmacology, Tables 10 and 11. ↑= increase; ↓= decrease; ↔ = no effect |
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No buprenorphine/naloxone or methadone dosage adjustment is required when used concomitantly with MAVYRET. There is insufficient information to make a recommendation regarding the concomitant use of naltrexone with MAVYRET.
No dose adjustment is required when MAVYRET is coadministered with the following medications: abacavir, amlodipine, caffeine, dextromethorphan, dolutegravir, elvitegravir/cobicistat, emtricitabine, ethinyl estradiol of 20 mcg or less, felodipine, lamivudine, lamotrigine, losartan, midazolam, norethindrone or other progestin-only contraceptives, omeprazole, raltegravir, rilpivirine, sofosbuvir, tacrolimus, tenofovir alafenamide, tenofovir disoproxil fumarate, tolbutamide, and valsartan.
Included as part of the PRECAUTIONS section.
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.
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)].
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.
Glecaprevir and pibrentasvir were not genotoxic in a battery of in vitro or in vivo assays, including bacterial mutagenicity, chromosome aberration using human peripheral blood lymphocytes and in vivo rodent micronucleus assays.
Carcinogenicity studies with glecaprevir and pibrentasvir have not been conducted.
No effects on mating, female or male fertility, or early embryonic development were observed in rodents at up to the highest dose tested. Systemic exposures (AUC) to glecaprevir and pibrentasvir were approximately 63 and 102 times higher, respectively, than the exposure in humans at the recommended dose.
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.
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)].
The effect of doses up to glecaprevir 600 mg (2 times the recommended dosage) with doses up to pibrentasvir 240 mg (2 times the recommended dosage) on QTc interval was evaluated in an active-controlled (moxifloxacin 400 mg) thorough QT study. At 20-fold of glecaprevir and 5fold of pibrentasvir therapeutic concentrations, the glecaprevir and pibrentasvir combination does not prolong the QTc interval to any clinically relevant extent.
The pharmacokinetic properties of the components of MAVYRET in healthy subjects are provided in Table 7. The steady-state pharmacokinetic parameters of glecaprevir and pibrentasvir in subjects with chronic HCV infection without cirrhosis are provided in Table 8. For pellets relative to tablets in healthy adult subjects under non-fasting conditions, geometric mean ratios (GMRs) of glecaprevir and pibrentasvir Cmax were 0.664 and 1.137, AUCinf were 0.795 and 1.219, and C24 (concentrations at 24 hours post-dose) were 0.917 and 1.174. These differences were not considered clinically significant.
Table 7. Pharmacokinetic Properties of the Components of MAVYRET in Healthy Subjects
| Glecaprevir | Pibrentasvir | |
| Absorption | ||
| Tmax (h)a of tablets | 5.0 | 5.0 |
| Tmax (h)a of oral pellets | 3.0 | 5.0 |
| Effect of meal (relative to fasting)b on tablets | ↑ 83-163% | ↑ 40-53% |
| Effect of meal (relative to fasting)b on oral pellets | ↑ 131-167% | ↑ 56-114% |
| Distribution | ||
| % Bound to human plasma proteins | 97.5 | >99.9 |
| Blood-to-plasma ratio | 0.57 | 0.62 |
| Elimination | ||
| t1/2 (h) | 6 | 13 |
| Metabolism | secondary, CYP3A | None |
| Major route of excretion | biliary-fecal | biliary-fecal |
| % of dose excreted in urinec | 0.7 | 0 |
| % of dose excreted in fecesc | 92.1 | 96.6 |
| a. Median Tmax following single doses of glecaprevir and pibrentasvir in healthy subjects. b. Mean systemic exposures with low/moderate to high fat meals. c. Single dose administration of radiolabeled glecaprevir or pibrentasvir in mass balance studies. |
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Table 8. Steady-State Pharmacokinetic Parameters of Glecaprevir and Pibrentasvir
Following Administration of MAVYRET in Subjects with Chronic HCV Infection without Cirrhosis
| Pharmacokinetic Parameter | Glecaprevirb | Pibrentasvirc |
| Cmax (ng/mL)a | 597 (114) | 110 (49) |
| AUC24,ss (ng•h/mL)a | 4800 (122) | 1430 (57) |
| Ctrough,ss (ng/mL)a | 13.0 (334) | 18.9 (92) |
| a Geometric mean (%CV) of individual-estimated Cmax, AUC24,ss and Ctrough,ss values b Relative to healthy subjects, glecaprevir Cmax was 51% lower, AUC24,ss was similar (10% difference), and Ctrough,ss was 157% higher in subjects without cirrhosis with chronic HCV infection c Relative to healthy subjects, pibrentasvir Cmax was 63% lower, AUC24,ss was 34% lower, and Ctrough,ss was 37% lower in subjects without cirrhosis with chronic HCV infection |
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No clinically meaningful differences in glecaprevir and pibrentasvir exposures are expected among adult patients with acute HCV infection and adult patients with chronic HCV infection.
Pediatric Patients
The pharmacokinetics of glecaprevir and pibrentasvir were determined in pediatric subjects with chronic HCV infection who were 3 years of age and older receiving a daily dose of MAVYRET as described below in Table 9. GMRs of glecaprevir and pibrentasvir Cmax and AUC24 in pediatrics vs. adults with chronic HCV infection ranged from 1.58-2.68 and 0.965-1.64, respectively. GMRs of glecaprevir Ctrough ranged from 0.292-0.954 and GMRs of pibrentasvir Ctrough ranged from 0.794-1.93. All pediatric glecaprevir and pibrentasvir PK parameter values fell within the range observed in adult subjects. These differences were not considered clinically significant.
No clinically meaningful differences in glecaprevir and pibrentasvir exposures are expected among pediatric patients with acute HCV infection and pediatric patients with chronic HCV infection.
The pharmacokinetics of glecaprevir and pibrentasvir have not been established in children less than 3 years of age.
Table 9. Pharmacokinetic Parameters of Glecaprevir (GLE) and Pibrentasvir (PIB) in Pediatric Subjects with Chronic HCV Infection
| Age and Weight (kg) | N | Total Daily Dose of GLE/PIB (mg) | PK Parameter | Geometric Mean (%CV) | |
| GLE | PIB | ||||
| 12 to < 18 years, ≥ 45 kg |
14 | 300/120 | AUC24 (ng•h/mL) | 4790 (72) | 1380 (40) |
| Cmax (ng/mL) | 1040 (86) | 174 (36) | |||
| Ctrough (ng/mL) | 3.79 (82) | 15.0 (61) | |||
| 9 to < 12 years, 30 to < 45 kg |
13 | 250/100 | AUC24 (ng•h/mL) | 7870 (209) | 2200 (99) |
| Cmax (ng/mL) | 1370 (169) | 225 (72) | |||
| Ctrough (ng/mL) | 12.4 (856) | 36.5 (164) | |||
| 6 to < 9 years, 20 to < 30 kg |
13 | 200/80 | AUC24 (ng•h/mL) | 6860 (142) | 1640 (63) |
| Cmax (ng/mL) | 1600 (155) | 197 (52) | |||
| Ctrough (ng/mL) | 7.44 (383) | 19.4 (103) | |||
| 3 to < 6 years, 12 to < 20 kg |
12 | 150/60 | AUC24 (ng•h/mL) | 7520 (205) | 1790 (58) |
| Cmax (ng/mL) | 1530 (280) | 233 (48) | |||
| Ctrough(ng/mL) | 6.58 (318) | 17.9 (119) | |||
Subjects with Renal Impairment
Glecaprevir and pibrentasvir AUC were increased ≤ 56% in non-HCV infected subjects with mild, moderate, severe, or end-stage renal impairment (GFR estimated using Modification of Diet in Renal Disease) not on dialysis compared to subjects with normal renal function. Glecaprevir and pibrentasvir AUC were similar with and without dialysis (≤ 18% difference) in dialysis-dependent non-HCV infected subjects. In subjects with chronic HCV infection, 86% higher glecaprevir and 54% higher pibrentasvir AUC were observed for subjects with end stage renal disease, with or without dialysis, compared to subjects with normal renal function.
Subjects with Hepatic Impairment
Following administration of MAVYRET in subjects with chronic HCV infection and compensated cirrhosis (Child-Pugh A), exposure of glecaprevir was approximately 2-fold and pibrentasvir exposure was similar to non-cirrhotic subjects with chronic HCV infection.
At the clinical dose, compared to non-HCV infected subjects with normal hepatic function, glecaprevir AUC was 100% higher in Child-Pugh B subjects, and increased 11-fold in Child-Pugh C subjects. Pibrentasvir AUC was 26% higher in Child-Pugh B subjects, and 114% higher in Child-Pugh C subjects.
Age/Gender/Race/Body Weight
No clinically significant differences in the pharmacokinetics of glecaprevir or pibrentasvir were observed based on age (12-88 years), sex, race/ethnicity or body weight (45 kg or greater). Patients under the age of 12 and weighing less than 45 kg are dosed based on body weight [see Dosage and Administration (2.4)].
Drug interaction studies were performed with glecaprevir/pibrentasvir and other drugs that are likely to be coadministered and with drugs commonly used as probes for pharmacokinetic interactions. Tables 10 and 11 summarize the pharmacokinetic effects when glecaprevir/pibrentasvir was coadministered with other drugs which showed potentially clinically relevant changes. Significant interactions are not expected when MAVYRET is coadministered with substrates of CYP3A, CYP1A2, CYP2C9, CYP2C19, CYP2D6, UGT1A1, or UGT1A4.
Table 10. Drug Interactions: Changes in Pharmacokinetic Parameters of Glecaprevir (GLE) or Pibrentasvir (PIB) in the Presence of Coadministered Drug
| Co- administered Drug | Regimen of Co- administered Drug (mg) | Regimen of GLE/PIB (mg) | N | DAA | Central Value Ratio (90% CI) | ||
| Cmax | AUC | Cmin | |||||
| Atazanavir + ritonavir | 300 + 100 once daily | 300/120 once dailya | 12 | GLE | ≥4.06 (3.15, 5.23) | ≥6.53 (5.24, 8.14) | ≥14.3 (9.85, 20.7) |
| PIB | ≥1.29 (1.15, 1.45) | ≥1.64 (1.48, 1.82) | ≥2.29 (1.95, 2.68) | ||||
| Carbamazepine | 200 twice daily | 300/120 single dose | 10 | GLE | 0.33 (0.27, 0.41) | 0.34 (0.28, 0.40) | -- |
| PIB | 0.50 (0.42, 0.59) | 0.49 (0.43, 0.55) | -- | ||||
| Cyclosporine | 100 single dose | 300/120 once daily | 12 | GLEb | 1.30 (0.95, 1.78) | 1.37 (1.13, 1.66) | 1.34 (1.12, 1.60) |
| PIB | ↔ | ↔ | 1.26 (1.15, 1.37) | ||||
| 400 single dose | 300/120 single dose | 11 | GLE | 4.51 (3.63, 6.05) | 5.08 (4.11, 6.29) | -- | |
| PIB | ↔ | 1.93 (1.78, 2.09) | -- | ||||
| Darunavir + ritonavir | 800 + 100 once daily | 300/120 once daily | 8 | GLE | 3.09 (2.26, 4.20) | 4.97 (3.62, 6.84) | 8.24 (4.40, 15.4) |
| PIB | ↔ | ↔ | 1.66 (1.25, 2.21) | ||||
| Elvitegravir/ cobicistat/ emtricitabine/ tenofovir alafenamide | 150/150/ 200/10 once daily | 300/120 once daily | 11 | GLE | 2.50 (2.08, 3.00) | 3.05 (2.55, 3.64) | 4.58 (3.15,6.65) |
| PIB | ↔ | 1.57 (1.39, 1.76) | 1.89 (1.63, 2.19) | ||||
| Omeprazole | 20 once daily | 300/120 single dose | 9 | GLE | 0.78 (0.60, 1.00) | 0.71 (0.58, 0.86) | -- |
| PIB | ↔ | ↔ | -- | ||||
| 40 once daily (1 hour before GLE/PIB) | 300/120 single dose | 12 | GLE | 0.36 (0.21, 0.59) | 0.49 (0.35, 0.68) | -- | |
| PIB | ↔ | ↔ | -- | ||||
| Rifampin | 600 (first dose) | 300/120 single dose | 12 | GLE | 6.52 (5.06, 8.41) | 8.55 (7.01, 10.4) | -- |
| PIB | ↔ | ↔ | -- | ||||
| 600 once daily | 300/120 single dosec | 12 | GLE | 0.14 (0.11, 0.19) | 0.12 (0.09, 0.15) | -- | |
| PIB | 0.17 (0.14, 0.20) | 0.13 (0.11, 0.15) | -- | ||||
| Lopinavir/ ritonavir | 400/100 twice daily | 300/120 once daily | 9 | GLE | 2.55 (1.84, 3.52) | 4.38 (3.02, 6.36) | 18.6 (10.4, 33.5) |
| PIB | 1.40 (1.17, 1.67) | 2.46 (2.07, 2.92) | 5.24 (4.18, 6.58) | ||||
| ↔ = No change (central value ratio 0.80 to 1.25) a. Effect of atazanavir and ritonavir on the first dose of glecaprevir and pibrentasvir is reported. b. HCV-infected transplant recipients who received cyclosporine dose of 100 mg or less per day had mean glecaprevir exposures 2.4-fold of those not receiving cyclosporine. c. Effect of rifampin on glecaprevir and pibrentasvir 24 hours after final rifampin dose. |
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Table 11. Drug Interactions: Changes in Pharmacokinetic Parameters for Coadministered Drug in the Presence of Combination of Glecaprevir/Pibrentasvir (GLE/PIB)
| Co- administered Drug | Regimen of Co- administered Drug (mg) | Regimen of GLE/PIB (mg) | N | Central Value Ratio (90% CI) | ||
| Cmax | AUC | Cmin | ||||
| Abacavir | ABC/DTG/3TC 600/50/300 once daily | 300/120 once daily | 12 | ↔ | ↔ | 1.31 (1.05, 1.63) |
| Atorvastatin | 10 once daily | 400/120 once daily | 11 | 22.0 (16.4, 29.6) | 8.28 (6.06, 11.3) | -- |
| Caffeine | 100 single dose | 300/120 once daily | 12 | ↔ | 1.35 (1.23, 1.48) | -- |
| Dabigatran | Dabigatran etexilate 150 single dose | 300/120 once daily | 11 | 2.05 (1.72, 2.44) | 2.38 (2.11, 2.70) | -- |
|
Darunavir |
DRV + RTV 800 + 100 once daily | 300/120 once daily | 12 | 1.30 (1.21, 1.40) | 1.29 (1.18, 1.42) | ↔ |
| Ritonavir | 2.03 (1.78, 2.32) | 1.87 (1.74, 2.02) | ↔ | |||
| Dextro- methorphan | Dextromethorphan hydrobromide 30 single dose | 300/120 once daily | 12 | 0.70 (0.61, 0.81) | 0.75 (0.66, 0.85) | -- |
| Digoxin | 0.5 single dose | 400/120 once daily | 12 | 1.72 (1.45, 2.04) | 1.48 (1.40, 1.57) | -- |
| Ethinyl estradiol (EE) | EE/ Norgestimate 35 µg/250 µg once daily | 300/120 once daily | 11 | 1.31 (1.24, 1.38) | 1.28 (1.23, 1.32) | 1.38 (1.25, 1.52) |
| Norgestrel | 1.54 (1.34, 1.76) | 1.63 (1.50, 1.76) | 1.75 (1.62, 1.89) | |||
| Norgestromin | ↔ | 1.44 (1.34, 1.54) | 1.45 (1.33, 1.58) | |||
| Ethinyl estradiol | EE/ Levonorgestrel 20 µg/100 µg once daily | 300/120 once daily | 12 | 1.30 (1.18, 1.44) | 1.40 (1.33, 1.48) | 1.56 (1.41, 1.72) |
| Norgestrel | 1.37 (1.23, 1.52) | 1.68 (1.57, 1.80) | 1.77 (1.58, 1.98) | |||
| Elvitegravir | EVG/COBI/FTC/ TAF 150/ 150/200/10 once daily | 300/120 once daily | 12 | 1.36 (1.24, 1.49) | 1.47 (1.37, 1.57) | 1.71 (1.50, 1.95) |
| Tenofovir | ↔ | ↔ | ↔ | |||
| Felodipine | 2.5 single dose | 300/120 once daily | 11 | 1.31 (1.05, 1.62) | 1.31 (1.08, 1.58) | -- |
| Losartan | 50 single dose | 300/120 once daily | 12 | 2.51 (2.00, 3.15) | 1.56 (1.28, 1.89) | -- |
| Losartan carboxylic acid | 2.18 (1.88, 2.53) | ↔ | -- | |||
| Lovastatin | Lovastatin 10 once daily | 300/120 once daily | 12 | ↔ | 1.70 (1.40, 2.06) | -- |
| Lovastatin acid | 5.73 (4.65, 7.07) | 4.10 (3.45, 4.87) | -- | |||
| Midazolam | 1 single dose | 300/120 once daily | 12 | ↔ | 1.27 (1.11, 1.45) | -- |
| Omeprazole | 20 single dose | 300/120 once daily | 12 | 0.57 (0.43, 0.75) | 0.79 (0.70, 0.90) | -- |
| Pravastatin | 10 once daily | 400/120 once daily | 12 | 2.23 (1.87, 2.65) | 2.30 (1.91, 2.76) | -- |
| Raltegravir | 400 twice daily | 300/120 once daily | 12 | 1.34 (0.89, 1.98) | 1.47 (1.15, 1.87) | 2.64 (1.42, 4.91) |
| Rilpivirine | 25 once daily | 300/120 once daily | 12 | 2.05 (1.73, 2.43) | 1.84 (1.72, 1.98) | 1.77 (1.59, 1.96) |
| Rosuvastatin | 5 once daily | 400/120 once daily | 11 | 5.62 (4.80, 6.59) | 2.15 (1.88, 2.46) | -- |
| Simvastatin | Simvastatin 5 once daily | 300/120 once daily | 12 | 1.99 (1.60, 2.48) | 2.32 (1.93, 2.79) | -- |
| Simvastatin acid | 10.7 (7.88, 14.6) | 4.48 (3.11, 6.46) | -- | |||
| Sofosbuvir | Sofosbuvir 400 once daily | 400/120 once daily | 8 | 1.66 (1.23, 1.22) | 2.25 (1.86, 2.72) | -- |
| GS-331007 | ↔ | ↔ | 1.85 (1.67, 2.04) | |||
| Tacrolimus | 1 single dose | 300/120 once daily | 10 | 1.50 (1.24, 1.82) | 1.45 (1.24, 1.70) | -- |
| Tenofovir | EFV/FTC/TDF 300/200/300 once daily | 300/120 once daily | 12 | ↔ | 1.29 (1.23, 1.35) | 1.38 (1.31, 1.46) |
| Valsartan | 80 single dose | 300/120 once daily | 12 | 1.36 (1.17, 1.58) | 1.31 (1.16, 1.49) |
-- |
| ↔ = No change (central value ratio 0.80 to 1.25) 3TC – lamivudine; ABC – abacavir; COBI – cobicistat; DRV – darunavir; DTG – dolutegravir; EFV – efavirenz; EVG – elvitegravir; FTC – emtricitabine; RTV – ritonavir; TAF – tenofovir alafenamide; TDF – tenofovir disoproxil fumarate |
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Advise the patient to read the FDA-approved patient labeling (Patient Information).
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)].
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)].
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)].
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:
