Mavyret

Last reviewed on RxList: 6/16/2021
Mavyret Side Effects Center

Medical Editor: John P. Cunha, DO, FACOEP

What Is Mavyret?

Mavyret (glecaprevir and pibrentasvir) tablets are a fixed-dose combination of a hepatitis C virus (HCV) NS3/4A protease inhibitor and an HCV NS5A inhibitor, indicated for the treatment of patients with chronic HCV genotype (GT) 1, 2, 3, 4, 5 or 6 infection without cirrhosis and with compensated cirrhosis (Child-Pugh A). Mavyret is also indicated for the treatment of adult patients 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.

What Are Side Effects of Mavyret?

Common side effects of Mavyret include:

  • headache,
  • fatigue,
  • nausea,
  • diarrhea, and
  • weakness/lack of energy.

Dosage for Mavyret

All patients are tested for HBV infection prior to initiating therapy with Mavyret by measuring HBsAg and anti-HBc. The recommended dosage of Mavyret is three tablets (total daily dose: glecaprevir 300 mg and pibrentasvir 120 mg) taken orally once daily with food.

What Drugs, Substances, or Supplements Interact with Mavyret?

Mavyret may interact with:

Tell your doctor all medications and supplements you use.

Mavyret During Pregnancy and Breastfeeding

Tell your doctor if you are pregnant or plan to become pregnant before using Mavyret; it is unknown how it would affect a fetus. It is unknown if Mavyret passes into breast milk. Consult your doctor before breastfeeding.

Additional Information

Our Mavyret (glecaprevir and pibrentasvir) Tablets Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

SLIDESHOW

Digestive Disorders: Common Misconceptions See Slideshow
Mavyret Consumer Information

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Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

In rare cases, glecaprevir and pibrentasvir may cause serious liver injury. Tell your doctor right away if you have symptoms such as:

  • right-sided upper stomach pain;
  • nausea, vomiting, loss of appetite;
  • confusion, tiredness, feeling light-headed;
  • easy bruising or bleeding, vomiting blood;
  • diarrhea, black or bloody stools;
  • dark urine; or
  • yellowing of your skin or eyes.

Common side effects may include:

  • headache; or
  • feeling tired.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the entire detailed patient monograph for Mavyret (glecaprevir and pibrentasvir)

Mavyret Professional Information

SIDE EFFECTS

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 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].

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 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.

Adverse Reactions In Subjects 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].

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 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%.

Adverse Reactions In HCV/HIV-1 Co-Infected Subjects

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. Thirtythree 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%).

Adverse Reactions In Subjects With Liver Or Kidney Transplant

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.

Adverse Reactions In People Who Inject Drugs (PWID) And Those On Medication-Assisted Treatment (MAT) For Opioid Use Disorder

The safety of MAVYRET in PWID with 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 and Clinical Studies].

Among 225 subjects reporting concomitant use of MAT for opioid use disorder, adverse reactions observed in greater than or equal to 5% were headache (15%), fatigue (12%), nausea (11%), and diarrhea (6%). Among 4,098 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 and Clinical Studies].

Adverse Reactions In Pediatric Subjects 3 Years And Older

The safety of MAVYRET in HCV GT1, 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, Clinical Studies].

Laboratory Abnormalities

Serum Bilirubin Elevations

Elevations of total bilirubin at least 2 times the upper limit of normal 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 upper limit of normal. These bilirubin elevations were typically less than two times the upper limit of normal, 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.

Postmarketing Experience

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].

DRUG INTERACTIONS

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.

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 and CLINICAL PHARMACOLOGY].

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, WARNINGS AND PRECAUTIONS, and CLINICAL PHARMACOLOGY]. 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].
Ethinyl Estradiol-Containing Products:
Ethinyl estradiolcontaining medications such as combined oral contraceptives ↔ glecaprevir
↔ pibrentasvir
Coadministration of MAVYRET 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].
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

Medication-Assisted Treatment (MAT) For Opioid Use Disorder

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.

Drugs With No Observed Clinically Significant Interactions With MAVYRET

No dose adjustment is required when MAVYRET is coadministered with the following medications: abacavir, amlodipine, caffeine, dextromethorphan, dolutegravir, elvitegravir/cobicistat, emtricitabine, felodipine, lamivudine, lamotrigine, losartan, midazolam, norethindrone or other progestin-only contraceptives, omeprazole, raltegravir, rilpivirine, sofosbuvir, tacrolimus, tenofovir alafenamide, tenofovir disoproxil fumarate, tolbutamide, and valsartan.

Read the entire FDA prescribing information for Mavyret (glecaprevir and pibrentasvir)

© Mavyret Patient Information is supplied by Cerner Multum, Inc. and Mavyret Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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