Drug Detail:Glecaprevir and pibrentasvir (Glecaprevir and pibrentasvir [ glec-a-pre-vir-and-pi-brent-as-vir ])
Drug Class: Antiviral combinations
Usual Adult Dose for Chronic Hepatitis C
Glecaprevir 300 mg-pibrentasvir 120 mg (3 tablets) orally once a day
Duration of Therapy:
THERAPY-NAIVE PATIENTS:
HCV genotype 1, 2, 3, 4, 5, or 6:
- No cirrhosis: 8 weeks
- Compensated cirrhosis (Child-Pugh A): 8 weeks
THERAPY-EXPERIENCED PATIENTS:
HCV genotype 1 (prior therapy with regimen containing an NS5A inhibitor without prior therapy with an NS3/4A protease inhibitor):
- No cirrhosis: 16 weeks
- Compensated cirrhosis (Child-Pugh A): 16 weeks
HCV genotype 1 (prior therapy with regimen containing an NS3/4A protease inhibitor without prior therapy with an NS5A inhibitor):
- No cirrhosis: 12 weeks
- Compensated cirrhosis (Child-Pugh A): 12 weeks
HCV genotype 1, 2, 4, 5, or 6 (prior therapy with regimen containing PRS):
- No cirrhosis: 8 weeks
- Compensated cirrhosis (Child-Pugh A): 12 weeks
HCV genotype 3 (prior therapy with regimen containing PRS):
- No cirrhosis: 16 weeks
- Compensated cirrhosis (Child-Pugh A): 16 weeks
LIVER OR KIDNEY TRANSPLANT RECIPIENTS: 12 weeks
- HCV genotype 1 (NS5A inhibitor-experienced without prior therapy with an NS3/4A protease inhibitor) or HCV genotype 3 (PRS therapy-experienced): 16 weeks
Comments:
- Each fixed-dose combination tablet contains glecaprevir 100 mg and pibrentasvir 40 mg.
- Recommended for HCV monoinfected and HCV/HIV-1-coinfected patients with compensated liver disease (with or without cirrhosis); the manufacturer product information should be consulted regarding dose recommendations for coadministered HIV-1 antiviral agents (if applicable).
- NS5A: Nonstructural protein 5A; NS3/4A: Nonstructural protein 3/4A
- In clinical trials, patients with prior NS5A inhibitor experience were treated with regimens containing ledipasvir-sofosbuvir or daclatasvir with (peg)interferon and ribavirin.
- In clinical trials, patients with prior NS3/4A protease inhibitor experience were treated with regimens containing simeprevir with sofosbuvir, or simeprevir, boceprevir, or telaprevir with (peg)interferon and ribavirin.
- PRS: Prior treatment experience with regimens containing (peg)interferon, ribavirin, and/or sofosbuvir without prior treatment experience with an HCV NS3/4A protease inhibitor or NS5A inhibitor
Uses:
- For the treatment of patients with chronic HCV genotype 1, 2, 3, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis (Child-Pugh A)
- For the treatment of HCV genotype 1-infected patients with prior treatment using a regimen containing an HCV NS5A inhibitor or an NS3/4A protease inhibitor, but not both
Usual Pediatric Dose for Chronic Hepatitis C
3 to less than 12 years:
- Weight less than 20 kg: Glecaprevir 150 mg-pibrentasvir 60 mg (3 packets of oral pellets) orally once a day
- Weight 20 to less than 30 kg: Glecaprevir 200 mg-pibrentasvir 80 mg (4 packets of oral pellets) orally once a day
- Weight 30 to less than 45 kg: Glecaprevir 250 mg-pibrentasvir 100 mg (5 packets of oral pellets) orally once a day
- Weight at least 45 kg: Glecaprevir 300 mg-pibrentasvir 120 mg (3 tablets) orally once a day
12 years or older: Glecaprevir 300 mg-pibrentasvir 120 mg (3 tablets) orally once a day
Duration of Therapy:
THERAPY-NAIVE PATIENTS:
HCV genotype 1, 2, 3, 4, 5, or 6:
- No cirrhosis: 8 weeks
- Compensated cirrhosis (Child-Pugh A): 8 weeks
THERAPY-EXPERIENCED PATIENTS:
HCV genotype 1 (prior therapy with regimen containing an NS5A inhibitor without prior therapy with an NS3/4A protease inhibitor):
- No cirrhosis: 16 weeks
- Compensated cirrhosis (Child-Pugh A): 16 weeks
HCV genotype 1 (prior therapy with regimen containing an NS3/4A protease inhibitor without prior therapy with an NS5A inhibitor):
- No cirrhosis: 12 weeks
- Compensated cirrhosis (Child-Pugh A): 12 weeks
HCV genotype 1, 2, 4, 5, or 6 (prior therapy with regimen containing PRS):
- No cirrhosis: 8 weeks
- Compensated cirrhosis (Child-Pugh A): 12 weeks
HCV genotype 3 (prior therapy with regimen containing PRS):
- No cirrhosis: 16 weeks
- Compensated cirrhosis (Child-Pugh A): 16 weeks
LIVER OR KIDNEY TRANSPLANT RECIPIENTS: 12 weeks
- HCV genotype 1 (NS5A inhibitor-experienced without prior therapy with an NS3/4A protease inhibitor) or HCV genotype 3 (PRS therapy-experienced): 16 weeks
Comments:
- Each packet of oral pellets (a fixed-dose combination product) contains glecaprevir 50 mg and pibrentasvir 20 mg.
- Each fixed-dose combination tablet contains glecaprevir 100 mg and pibrentasvir 40 mg.
- Pediatric patients weighing at least 45 kg who are unable to swallow tablets may be administered 6 packets of oral pellets once a day; dosing with the oral pellets has not been studied in pediatric patients weighing more than 45 kg.
- Recommended for HCV monoinfected and HCV/HIV-1-coinfected patients with compensated liver disease (with or without cirrhosis); the manufacturer product information should be consulted regarding dose recommendations for coadministered HIV-1 antiviral agents (if applicable).
- NS5A: Nonstructural protein 5A; NS3/4A: Nonstructural protein 3/4A
- In clinical trials, patients with prior NS5A inhibitor experience were treated with regimens containing ledipasvir-sofosbuvir or daclatasvir with (peg)interferon and ribavirin.
- In clinical trials, patients with prior NS3/4A protease inhibitor experience were treated with regimens containing simeprevir with sofosbuvir, or simeprevir, boceprevir, or telaprevir with (peg)interferon and ribavirin.
- PRS: Prior treatment experience with regimens containing (peg)interferon, ribavirin, and/or sofosbuvir without prior treatment experience with an HCV NS3/4A protease inhibitor or NS5A inhibitor
Uses:
- For the treatment of patients with chronic HCV genotype 1, 2, 3, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis (Child-Pugh A)
- For the treatment of HCV genotype 1-infected patients with prior treatment using a regimen containing an HCV NS5A inhibitor or an NS3/4A protease inhibitor, but not both
Renal Dose Adjustments
Mild, moderate, or severe renal dysfunction: No adjustment recommended.
Liver Dose Adjustments
Mild liver dysfunction (Child-Pugh A): No adjustment recommended.
Moderate or severe liver dysfunction (Child-Pugh B or C) or any history of hepatic decompensation: Contraindicated
Comments:
- This drug has not been evaluated in HCV-infected patients with moderate or severe liver dysfunction or in those with any history of hepatic decompensation.
- Higher exposures of both components in subjects with severe liver dysfunction.
Precautions
US BOXED WARNING:
- RISK OF HBV REACTIVATION IN PATIENTS COINFECTED WITH HCV AND HBV: All patients should be tested for evidence of current/prior HBV infection before starting this drug. HBV reactivation has been reported during or after completion of HCV direct-acting antiviral therapy in HCV/HBV-coinfected patients who were not receiving HBV antiviral therapy; some cases resulted in fulminant hepatitis, hepatic failure, and death. HCV/HBV-coinfected patients should be monitored for hepatitis flare or HBV reactivation during HCV therapy and posttherapy follow-up; appropriate patient management for HBV infection should be started as clinically indicated.
CONTRAINDICATIONS:
- Moderate or severe liver dysfunction (Child-Pugh B or C) or any history of hepatic decompensation
- Coadministration with atazanavir or rifampin
Safety and efficacy have not been established in patients younger than 3 years.
Consult WARNINGS section for additional precautions.
Dialysis
No adjustment recommended.
Other Comments
Administration advice:
- Before starting this drug, test all patients for evidence of current/prior HBV infection; measure hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc).
- Administer with food.
- Oral pellets: Consult the manufacturer product information (Instructions for Use) for details regarding administration.
- Administer the oral pellets together once a day with food; sprinkle the oral pellets for the total daily dose on a small amount of soft food with a low water content that will stick to a spoon (e.g., peanut butter, chocolate hazelnut spread, cream cheese, thick jam, Greek yogurt) and swallow without chewing.
- Swallow the entire mixture of food and oral pellets within 15 minutes of preparation; do not crush or chew the oral pellets.
- Do not use liquids or foods that would drip or slide off the spoon as the drug may dissolve quickly and become less effective.
- Tablets: It is important to administer all 3 tablets at the same time once a day with food.
- Consult the manufacturer product information regarding missed doses.
Storage requirements:
- Store at or below 30C (86F).
Reconstitution/preparation techniques:
- Oral pellets: The manufacturer product information (Instructions for Use) should be consulted.
General:
- Each fixed-dose combination tablet contains glecaprevir 100 mg and pibrentasvir 40 mg.
- Each packet of oral pellets (a fixed-dose combination product) contains glecaprevir 50 mg and pibrentasvir 20 mg.
Monitoring:
- General: For clinical and laboratory signs of hepatitis flare or HBV reactivation in patients with serological proof of HBV infection (during HCV therapy with this drug and during posttreatment follow-up)
- Hepatic: Hepatic laboratory testing in patients with compensated cirrhosis or proof of advanced liver disease (as clinically indicated); for signs/symptoms of hepatic decompensation
Patient advice:
- Read the US FDA-approved patient information (Patient Information and Instructions for Use).
- Seek medical evaluation at once for symptoms of worsening liver problems (e.g., nausea, tiredness, yellowing of the skin/white part of the eyes, bleeding/bruising more easily than normal, confusion, loss of appetite, diarrhea, dark/brown urine, dark/bloody stool, swelling of the stomach area [abdomen]/pain in the upper right side of the stomach area, sleepiness, vomiting of blood).
- Avoid missing doses and complete the entire course of therapy.
- Oral pellets: Read and follow the Instructions for Use for preparing the correct dose.
- Tablets: It is important to take all 3 tablets at the same time once a day with food.
Frequently asked questions
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