Glecaprevir-Pibrentasvir

Glecaprevir-Pibrentasvir is a combination of prescription medicines used for treating the symptoms of chronic hepatitis C.

• Glecaprevir-Pibrentasvir is available under the following different brand names: Mavyret

Adult and pediatric dosage

Tablet

• 100mg/40mg

Chronic Hepatitis C

Adult dosage

• 3 tablets (ie, 300 mg/120 mg total dose) orally every day

Pediatric dosage

• Children below 3 years: Safety and efficacy not established
• Children between 3-11 years
  • Weighing below 20 kg: 150 mg/60 mg orally every day (3 packets of oral pellets)
  • Weighing between 20 to 29 kg: 200 mg/80 mg orally every day (4 packets of oral pellets)
  • Weighing between 30 to 44 kg: 250 mg/120 mg orally every day (5 packets of oral pellets)
• Children above 12 years or weight above 45 kg
  • 300 mg/120 mg (3 tablets) orally every day OR
  • Unable to swallow tablets: 300 mg/120 mg orally every day (6 packets of oral pellets)

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

Common side effects of the Glecaprevir-Pibrentasvir include:

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

Serious side effects of the Glecaprevir-Pibrentasvir include:

• 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 the skin or eyes.

Rare side effects of the Glecaprevir-Pibrentasvir include:

• none 

This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Glecaprevir-Pibrentasvir has severe interactions with the following drugs:
  • elagolix
  • rifampin
• Glecaprevir-Pibrentasvir has serious interactions with at least 28 other drugs.
• Glecaprevir-Pibrentasvir has moderate interactions with at least 200 other drugs.
• Glecaprevir-Pibrentasvir has minor interactions with the following drugs:
  • ribociclib
  • voclosporin

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions or concerns.

Contraindications

• Moderate or severe hepatic impairment (Child-Pugh B or C)
• History of prior hepatic decompensation
• Coadministration with atazanavir or rifampin

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Glecaprevir-Pibrentasvir?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Glecaprevir-Pibrentasvir?”

Cautions

• Hepatitis B virus reactivation in patients coinfected with HCV/HBV may occur
• Postmarketing cases of hepatic decompensation/failure, including those with fatal outcomes, have been reported
• No dosage adjustment of required in people who inject drugs (PWID) or those who are on medication-assisted treatment (MAT) for opioid use disorder; safety and efficacy are reported to be similar to those not reporting a history of injection drug use
• Hepatitis B Virus reactivation in HCV and HBV coinfection
  • In patients with resolved HBV infection reappearance of HBsAg can occur
  • Reactivation of HBV replication may be accompanied by hepatitis, ie, an 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
  • In patients with serologic evidence of HBV infection, monitor for clinical and laboratory signs of hepatitis flare or HBV reactivation during HCV treatment and during post-treatment follow-up; initiate appropriate patient management for HBV infection as clinically indicated
• Hepatic decompensation
  • The majority of patients with severe outcomes had evidence of advanced liver disease with moderate or severe hepatic impairment (Child-Pugh B or C) before initiating therapy, 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)
  • 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 in patients who develop evidence of hepatic decompensation/failure
• Drug interaction overview
  • Effects of glecaprevir-Pibrentasvir on other drugs
    • Glecaprevir and pibrentasvir: Inhibit P-gp, BCRP, OATP1B1, and OATP1B3; coadministration of glecaprevir-Pibrentasvir may increase plasma concentrations of substrates of these transporters
    • Glecaprevir and pibrentasvir: Weak inhibitors of CYP3A, CYP1A2, and UGT1A1; significant interactions are not expected when glecaprevir-Pibrentasvir is coadministered with substrates of CYP3A, CYP1A2, CYP2C9, CYP2C19, CYP2D6, UGT1A1, or UGT1A4
  • Effects of other drugs on glecaprevir-Pibrentasvir
    • Glecaprevir and pibrentasvir: Substrates of P-gp and/or BCRP
    • Glecaprevir: Substrate of OATP1B1, OATP1B3, and CYP3A (secondary)
    • Coadministration of glecaprevir-Pibrentasvir with drugs that inhibit hepatic P-gp, BCRP, or OATP1B1/3 may increase the plasma concentrations of glecaprevir and/or pibrentasvir
    • Coadministration of glecaprevir-Pibrentasvir with drugs that induce P-gp/CYP3A may significantly decrease glecaprevir and pibrentasvir plasma concentrations, leading to a reduced therapeutic effect
    • Coadministration is contraindicated with rifampin or atazanavir
    • Coadministration is not recommended with carbamazepine, efavirenz, or St John’s wort

Pregnancy and Lactation

• No adequate human data are available to establish whether or not glecaprevir-Pibrentasvir poses a risk to pregnancy outcomes
• Lactation
  • Unknown if distributed in human breast milk
  • When administered to lactating rodents, glecaprevir and pibrentasvir were present in milk, without effect on growth and development observed in the nursing pups
  • Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or the underlying maternal condition