Mavyret is a regimen used to treat patients with chronic hepatitis C or HIV and chronic hepatitis C co-infected patients. It is a combination of direct-acting agents of NS5A inhibitor pibrentasvir and NS3/4A protease inhibitor glecaprevir.
Mavyret (Glecaprevir and pibrentasvir) Uses:
-
Chronic hepatitis C: In adults and children >12 years or weight ≥45 kg
- It is indicated in the treatment of patients with chronic hepatitis HCV genotype 1-6, without cirrhosis or with compensated cirrhosis (Child-Pugh class A)
- HCV genotype 1 infection: Previously treated with HCV NS5A inhibitor or an NS3/4A protease inhibitor, but not both.
Mavyret (Glecaprevir and pibrentasvir) Dose in Adults
Mavyret (Glecaprevir and pibrentasvir) Dose in the treatment of chronic hepatitis C (HCV mono-infected or HCV/HIV co-infected patients):
-
Without cirrhosis or with compensated cirrhosis (Child-Pugh class A): Oral:
-
Treatment-naive patients:
- Genotype 1-6:
- 3 tablets once a day for 8 weeks without cirrhosis or 12 weeks with compensated cirrhosis (Child-Pugh class A).
- Genotype 1-6:
-
Treatment-experienced patients:
- Genotype 1: Previously treated with an NS5A inhibitor-containing regimen without an NS3/4A protease inhibitor:
- 3 tablets once a day for 16 weeks
- Genotype 1: Previously treated with an NS3/4A protease inhibitor-containing regimen without an NS5A inhibitor:
- 3 tablets once a day for 12 weeks
- Genotype 1, 2, 4, 5, or 6: Previously treated with interferons (including pegylated formulations) and/or ribavirin but no prior treatment with an NS3/4A or NS5A inhibitor:
- 3 tablets once a day for 8 weeks without cirrhosis or 12 weeks with compensated cirrhosis (Child-Pugh class A)
- Genotype 1 or 2: Previously treated with sofosbuvir, but no prior treatment with an NS3/4A or NS5A inhibitor:
- 3 tablets once a day for 12 weeks without cirrhosis or with compensated cirrhosis (Child-Pugh class A)
- Genotype 3: Previously treated with interferon (including pegylated formulations), ribavirin, and/or sofosbuvir, but no prior treatment with an NS3/4A or NS5A inhibitor:
- 3 tablets once a day for 16 weeks
- Genotype 1: Previously treated with an NS5A inhibitor-containing regimen without an NS3/4A protease inhibitor:
-
Liver or kidney transplant recipients:
- Genotypes 1-6: Treatment-naive:
- 3 tablets once a day for 12 weeks
- Genotype 1: Previously treated with an NS5A inhibitor without an NS3/4A protease inhibitor:
- 3 tablets once a day for 16 weeks
- Genotype 1: Previously treated with an NS3/4A protease inhibitor without an NS5A inhibitor:
- 3 tablets once a day for 12 weeks
- Genotype 1, 2, 4, 5, or 6: Previously treated with interferon (including pegylated formulations), ribavirin, and/or sofosbuvir but no prior treatment with an NS3/4A or NS5A inhibitor:
- 3 tablets once a day for 12 weeks.
- Genotype 3: Previously treated with interferon (including pegylated formulations), ribavirin, and/or sofosbuvir, but no prior treatment with an NS3/4A or NS5A inhibitor:
- 3 tablets once a day for 16 weeks
- Genotypes 1-6: Treatment-naive:
-
Missed dose:
- If less than18 hours from the usual dose time, take the dose as soon as possible, then next doses according to schedule
- If more than18 hours from the usual dose time, skip the missed dose and take the next doses according to schedule
-
Use in Children:
Not indicated.
Mavyret (Glecaprevir and pibrentasvir) Pregnancy Category: N
- Studies on animal reproduction have not shown adverse effects of glecaprevir and pibrentasvir, as individuals.
- Hepatitis C treatment during pregnancy is not recommended at the moment.
- If HCV detected during pregnancy, postpone treatment until after delivery
- Postpone pregnancy for non-pregnant women until you have received complete treatment to lower the risk of HCV transmission
Use of pibrentasvir and glecaprevir during breastfeeding
- It is unknown whether breastmilk contains glecaprevir and pibrentasvir. It is important to consider the risks of infant exposure as well as the benefits for the mother.
- Breastfeeding is not associated with the spread of HCV. However, breastfeeding is not recommended if the nipples become cracked or bleeding.
- It is not recommended that you breastfeed HIV co-infection patients.
Dose in Kidney disease:
No dose adjustment required.
Dose in Liver disease:
- Mild impairment (Child-Pugh class A):
- No dose adjustment required.
- Moderate impairment (Child-Pugh class B):
- Not recommended.
- Severe impairment (Child-Pugh class C):
- Contraindicated.
Common Side Effects of Mavyret (Glecaprevir and pibrentasvir):
-
Central nervous system:
- Headache
- Fatigue
-
Gastrointestinal:
- Nausea
Less Common Side Effects of Mavyret (Glecaprevir and pibrentasvir):
-
Dermatologic:
- Pruritus
-
Gastrointestinal:
- Diarrhea
-
Hepatic:
- Increased serum bilirubin
-
Infection:
- Reactivation of HBV
Contraindications to Mavyret (Glecaprevir and pibrentasvir):
- Severe hepatic impairment (Child Puugh class C).
- Use atazanavir and rifampin in combination
Additional contraindications for Canadian labeling (not US labeling)
- Hypersensitivity to pibrentasvir or glecaprevir
- Coadministration with atorvastatin, dabigatran, Ethinyl estradiol, or simvastatin.
Warnings and precautions
-
Diabetes:
- Diabetes patients may experience hypoglycemia after receiving direct-acting antiviral therapy (DAA) for hepatitis C.
- This is due to an improvement in glucose metabolism following rapid reductions in viral load.
- Monitor blood sugar levels, especially in the first three months.
-
Hepatic impairment
- Avoid moderate impairment (Childugh class B).
- In severe impairment (Child Puugh class C), contraindicated
-
Hepatitis B virus activation: [US-Boxed Warning]
- Patients infected by HCV/HBV while receiving HCV DAA (directly-acting antivirals), but not receiving antiviral treatment for hepatitis B, may develop fulminant liver disease, hepatic failure and even death.
- Before starting treatment, test for HBV infection.
- Monitor for HBV reactivation or hepatitis flare in HBV coinfected patients during treatment. Followup
- If HBV infection is diagnosed clinically, start treatment immediately.
- HBV reactivation was also reported.
Glecaprevir and pibrentasvir: Drug Interaction
|
Risk Factor C (Monitor therapy) |
|
|
Antidiabetic Agents |
Direct Acting Antiviral Agents (HCV) may enhance the hypoglycemic effect of Antidiabetic Agents. |
|
ARIPiprazole |
CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. |
|
Brentuximab Vedotin |
P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. |
|
Celiprolol |
P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol. |
|
CloZAPine |
CYP1A2 Inhibitors (Weak) may increase the serum concentration of CloZAPine. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. |
|
Cobicistat |
May increase the serum concentration of Glecaprevir and Pibrentasvir. |
|
CYP3A4 Inducers (Moderate) |
May decrease the serum concentration of Glecaprevir and Pibrentasvir. |
|
CYP3A4 Inducers (Strong) |
May decrease the serum concentration of Glecaprevir and Pibrentasvir. |
|
Dofetilide |
CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. |
|
Eltrombopag |
May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. |
|
Eltrombopag |
May increase the serum concentration of BCRP/ABCG2 Substrates. |
|
Everolimus |
P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. |
|
Flibanserin |
CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. |
|
Gemfibrozil |
May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. See separate drug interaction monographs for agents listed as exceptions. |
|
Larotrectinib |
P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Larotrectinib. |
|
Naldemedine |
P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naldemedine. |
|
Naloxegol |
P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. |
|
NiMODipine |
CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. |
|
Osimertinib |
May increase the serum concentration of BCRP/ABCG2 Substrates. |
|
P-glycoprotein/ABCB1 Inducers |
: May decrease the serum concentration of Glecaprevir and Pibrentasvir. |
|
P-glycoprotein/ABCB1 Substrates |
P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Exceptions: Loperamide. |
|
Prucalopride |
P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Prucalopride. |
|
Ranolazine |
P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine. |
|
Regorafenib |
May increase the serum concentration of BCRP/ABCG2 Substrates. |
|
RifAXIMin |
P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. |
|
Rolapitant |
May increase the serum concentration of BCRP/ABCG2 Substrates. Management: Monitor patients receiving rolapitant for increased exposure to and/or effects of BCRP/ABCG2 substrates. Use the lowest effective rosuvastatin dose when used in combination with rolapitant. |
|
Silodosin |
P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. |
|
Tacrolimus (Systemic) |
Glecaprevir and Pibrentasvir may increase the serum concentration of Tacrolimus (Systemic). |
|
Talazoparib |
P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Talazoparib. Management: These listed exceptions are discussed in detail in separate interaction monographs. |
|
Talazoparib |
BCRP/ABCG2 Inhibitors may increase the serum concentration of Talazoparib. |
|
Tedizolid |
May increase the serum concentration of BCRP/ABCG2 Substrates. |
|
Teriflunomide |
May increase the serum concentration of BCRP/ABCG2 Substrates. |
|
Teriflunomide |
May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. |
|
Risk Factor D (Consider therapy modification) |
|
|
Afatinib |
P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: Per US labeling: reduce afatinib by 10mg if not tolerated. Per Canadian labeling: avoid combination if possible; if used, administer the P-gp inhibitor simultaneously with or after the dose of afatinib. |
|
Betrixaban |
P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Betrixaban. Management: Decrease the betrixaban dose to an initial single dose of 80 mg followed by 40 mg once daily if combined with a P-glycoprotein inhibitor. |
|
Bilastine |
P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Management: Consider alternatives when possible; bilastine should be avoided in patients with moderate to severe renal insufficiency who are receiving p-glycoprotein inhibitors. |
|
Cladribine |
BCRP/ABCG2 Inhibitors may increase the serum concentration of Cladribine. Management: Avoid concomitant use of BCRP inhibitors during the 4 to 5 day oral cladribine treatment cycles whenever possible. If combined, consider dose reduction of the BCRP inhibitor and separation in the timing of administration. |
|
Colchicine |
P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a p-glycoprotein inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. See full monograph for details. |
|
Dabigatran Etexilate |
P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Management: Dabigatran dose reductions may be needed. Specific recommendations vary considerably according to US vs Canadian labeling, specific P-gp inhibitor, renal function, and indication for dabigatran treatment. Refer to full monograph or dabigatran labeling. |
|
Digoxin |
Glecaprevir and Pibrentasvir may increase the serum concentration of Digoxin. Management: Measure serum digoxin concentrations before initiating glecaprevir/pibrentasvir. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 50% or by modifying the dosing frequency; continue monitoring during concomitant therapy. |
|
DOXOrubicin (Conventional) |
P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Management: Seek alternatives to P-glycoprotein inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. |
|
Edoxaban |
P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Management: See full monograph for details. Reduced doses are recommended for patients receiving edoxaban for venous thromboembolism in combination with certain P-gp inhibitors. Similar dose adjustment is not recommended for edoxaban use in atrial fibrillation. |
|
HMG-CoA Reductase Inhibitors (Statins) |
Glecaprevir and Pibrentasvir may increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Management: Use the lowest statin dose possible if combined with glecaprevir/pibrentasvir and monitor for increased statin effects/toxicities. Avoid concomitant use with atorva-, simva-, or lovastatin. Limit rosuvastatin to 10 mg daily and reduce pravastatin dose 50% |
|
Lomitapide |
CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. |
|
TiZANidine |
CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use is necessary, initiate tizanidine at an adult dose of 2 mg and increase in 2 to 4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. |
|
Tolvaptan |
May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. |
|
Tolvaptan |
May increase the serum concentration of BCRP/ABCG2 Substrates. |
|
Venetoclax |
P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Consider a venetoclax dose reduction by at least 50% in patients requiring concomitant treatment with P-glycoprotein (P-gp) inhibitors. |
|
Risk Factor X (Avoid combination) |
|
|
Asunaprevir |
OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Asunaprevir. |
|
Atazanavir |
May increase the serum concentration of Glecaprevir and Pibrentasvir. |
|
AtorvaSTATin |
Glecaprevir and Pibrentasvir may increase the serum concentration of AtorvaSTATin. |
|
CarBAMazepine |
May decrease the serum concentration of Glecaprevir and Pibrentasvir. |
|
CycloSPORINE (Systemic) |
May increase the serum concentration of Glecaprevir and Pibrentasvir. |
|
Darunavir |
May increase the serum concentration of Glecaprevir and Pibrentasvir. |
|
Efavirenz |
May decrease the serum concentration of Glecaprevir and Pibrentasvir. |
|
Elagolix |
OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix. |
|
Ethinyl Estradiol |
May enhance the adverse/toxic effect of Glecaprevir and Pibrentasvir. Specifically, the risk for ALT elevation may be increased with this combination. |
|
Fosphenytoin-Phenytoin |
May decrease the serum concentration of Glecaprevir and Pibrentasvir. |
|
Grazoprevir |
OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Grazoprevir. |
|
Irinotecan Products |
UGT1A1 Inhibitors may increase serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, concentrations of SN-38 may be increased. UGT1A1 Inhibitors may increase the serum concentration of Irinotecan Products. |
|
Lopinavir |
May increase the serum concentration of Glecaprevir and Pibrentasvir. |
|
Lovastatin |
Glecaprevir and Pibrentasvir may increase the serum concentration of Lovastatin. |
|
PAZOPanib |
P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. |
|
PAZOPanib |
BCRP/ABCG2 Inhibitors may increase the serum concentration of PAZOPanib. |
|
Pimozide |
CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. |
|
Revefenacin |
OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentrations of the active metabolite(s) of Revefenacin. |
|
RifAMPin |
May decrease the serum concentration of Glecaprevir and Pibrentasvir. RifAMPin may increase the serum concentration of Glecaprevir and Pibrentasvir. Specifically, a single dose of rifampin may increase glecaprevir/pibrentasvir concentrations, while chronic daily use of rifampin may decrease glecaprevir/pibrentasvir concentrations. |
|
Simvastatin |
Glecaprevir and Pibrentasvir may increase the serum concentration of Simvastatin. |
|
St John's Wort |
May decrease the serum concentration of Glecaprevir and Pibrentasvir. |
|
Topotecan |
BCRP/ABCG2 Inhibitors may increase the serum concentration of Topotecan. |
|
Topotecan |
P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. |
|
VinCRIStine ( |
P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). |
|
Liposomal) |
OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Voxilaprevir. |
|
Voxilaprevir |
May increase the serum concentration of BCRP/ABCG2 Substrates. |
Monitoring parameters:
- Baseline (within 12 weeks before starting therapy):
- CBC, INR, hepatic function panel (albumin, total and direct bilirubin, ALT, AST, and alkaline phosphatase), and calculated GFR. Repeat these test after 4 weeks or according to clinical indications
- HCV - genotype and subtype and quantitative HCV viral load before starting the therapy repeat quantitative viral load after 4 weeks of therapy and at 12 weeks after completion of therapy.
- If the quantitative viral load is detectable at treatment week 4, repeat testing after 2 additional weeks of treatment (treatment week 6)
- HBsAg and anti-HBc before starting therapy:
- If the patient has serologic evidence of hepatitis B virus infection, monitor for clinical and laboratory signs of hepatitis flare or HBV reactivation during treatment and follow-up
- Monitor blood sugar level in diabetics ( to avoid the risk of symptomatic hypoglycemia).
How to administer Mavyret (Glecaprevir and pibrentasvir)?
Oral: can be taken with food.
Mechanism of action of Mavyret (Glecaprevir and pibrentasvir):
Glecaprevir
- It inhibits HCV NS3/4A protease, which is necessary for the proteolytic cleavage (into mature forms the NS4A and NS4B, NS5A and NS5A proteins) and is vital for viral replication.
Pibrentasvir:
- It blocks HCV NS5A, which is essential for viral RNA replication.
Protein binding:
- Glecaprevir: 97.5%
- Pibrentasvir: >99.9%
Metabolism:
- Glecaprevir: Secondary to CYP3A
Half-life elimination:
- Glecaprevir: 6 hours
- Pibrentasvir: 13 hours
Time to peak: 5 hours Excretion:
- Glecaprevir: Feces (92.1%), urine (0.7%)
- Pibrentasvir: Feces (96.6%)
International Brand Names of Glecaprevir and pibrentasvir:
- Mavyret
Glecaprevir and pibrentasvir Brand Names in Paksitan:
No Brands Available in Pakistan.
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