Mavyret (glecaprevir and pibrentasvir)

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.

Mavyret is indicated for the treatment of adult and pediatric patients 12 years and older or weighing at least 45 kg with 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 12 years and older or weighing at least 45 kg 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.

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.

Common side effects of Mavyret include:

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

Mavyret is a fixed-dose combination product containing glecaprevir 100 mg and pibrentasvir 40 mg in each tablet.

The recommended oral dosage of Mavyret is 3 tablets taken at the same time once daily with food (total daily dose: glecaprevir 300 mg and pibrentasvir 120 mg).

Liver Or Kidney Transplant Recipients

• Mavyret is recommended for 12 weeks in adult and pediatric patients 12 years and older or weighing at least 45 kg 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.

Hepatic Impairment

• Mavyret is not recommended in patients with moderate hepatic impairment (Child-Pugh B) and is contraindicated in patients with severe hepatic impairment (Child-Pugh C).

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.
• Fluctuations in INR values may occur in patients receiving warfarin concomitant with HCV treatment, including treatment with Mavyret. If Mavyret is coadministered with warfarin, close monitoring of INR values is recommended during treatment and post-treatment follow-up.

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.

Table 5: Potentially Significant Drug Interactions Identified in Drug Interaction Studies

Drugs with No Observed Clinically Significant Interactions with Mavyret

No dose adjustment is required when Mavyret is coadministered with the following medications:

• abacavir,
• amlodipine,
• buprenorphine,
• caffeine,
• dextromethorphan,
• elvitegravir/cobicistat,
• lamivudine,
• lamotrigine,
• losartan,
• methadone,
• midazolam,
• naloxone,
• norethindrone or other progestin-only contraceptives,
• omeprazole, and
• valsartan.

• 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.
• 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.
• 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.
• 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.