glecaprevir/pibrentasvir

glek-A-pre-vir/pi-BRENT-as-vir

Therapeutic Classification: antivirals

Pharmacologic Classification: NS5A inhibitors, protease inhibitors

REMS

Chronic hepatitis C virus (HCV) genotypes 1, 2, 3, 4, 5, or 6 infection without cirrhosis or with compensated cirrhosis.
Chronic HCV genotype 1 infection in patients who have previously received treatment with a regimen containing an HCV NS5A inhibitor or an NS3/4A protease inhibitor, but not both.

Glecaprevir: inhibits the HCV NS3/4A protease, resulting in inhibition of viral replication; Pibrentasvir: inhibits the HCV NS5A protein, resulting in inhibition of viral replication.

Therapeutic effects:

Decreased levels of HCV with sustained virologic response and lessened sequelae of chronic HCV infection.

Glecaprevir

Absorption: Well absorbed following oral administration; absorption ↑ by high-fat meal.

Distribution: Unknown.

Protein Binding: 97.5%.

Metabolism/Excretion: Partially metabolized by the liver via the CYP3A4 isoenzyme; 92% excreted in feces and <1% eliminated in urine.

Half-Life: 6 hr.

Pibrentasvir

Absorption: Well absorbed following oral administration.

Distribution: Unknown.

Protein Binding: >99.9%.

Metabolism/Excretion: Not metabolized; 97% excreted in feces.

Half-Life: 13 hr.

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
glecaprevir (PO)	unknown	5 hr	24 hr
pibrentasvir (PO)	unknown	5 hr	24 hr

Contraindicated in:

Moderate or severe hepatic impairment or any prior history of hepatic decompensation (↑ risk of hepatic decompensation/failure);
Concurrent use of atazanavir or rifampin.

Use Cautiously in:

Receiving immunosuppressant or chemotherapy medications (↑ risk of hepatitis B virus [HBV] reactivation);
OB: Safety not established in pregnancy;
Lactation: Safety not established in breastfeeding;
Pedi: Children 3 yr (safety and effectiveness not established).

Derm: pruritus

GI: diarrhea, HBV reactivation, hyperbilirubinemia, nausea

Neuro: fatigue, headache

Drug-drug:

Atazanavir may ↑ levels of glecaprevir/pibrentasvir and ↑ risk of liver enzyme elevation; concurrent use contraindicated.
Rifampin may ↓ levels/effectiveness of glecaprevir/pibrentasvir; concurrent use contraindicated.
Strong CYP3A inducers, including carbamazepine or efavirenz may ↓ levels and effectiveness of glecaprevir/pibrentasvir; concurrent use not recommended.
Darunavir, lopinavir, or ritonavir may ↑ levels and risk of toxicity of glecaprevir/pibrentasvir; concurrent use not recommended.
May ↑ levels and risk of toxicity of atorvastatin, fluvastatin, lovastatin, pitavastatin, pravastatin, rosuvastatin, and simvastatin and ↑ risk of myopathy; concurrent use with atorvastatin, lovastatin, and simvastatin not recommended; ↓ dose of pravastatin by 50%; do not exceed rosuvastatin dose of 10 mg/day; use lowest possible dose of fluvastatin or pitavastatin.
May ↑ dabigatran levels and risk of bleeding; avoid concurrent use.
May ↑ digoxin levels and risk of toxicity; ↓ digoxin dose by 50% when initiating glecaprevir/pibrentasvir therapy.
Concurrent use with ethinyl estradiol-containing oral contraceptives may ↑ risk of liver enzyme elevation; concurrent use not recommended.
Cyclosporine may ↑ levels and risk of toxicity of glecaprevir/pibrentasvir; concurrent use not recommended if patients require cyclosporine dose >100 mg/day.
May cause fluctuations in INR when used with warfarin; closely monitor INR.
↑risk of hypoglycemia with use of certain antidiabetic agents.

Drug-Natural Products:

St. John's wort may ↓ levels and effectiveness of glecaprevir/pibrentasvir; concurrent use not recommended.

PO (Adults and Children ≥12 yr or ≥45 kg): Genotype 1, 2, 3, 4, 5, or 6: Treatment-naive with no cirrhosis or with compensated cirrhosis: Three 100-mg/40-mg tablets once daily for 8 wk or six 50-mg/20-mg pellet packets once daily for 8 wk; Genotype 1: Treatment-experienced with NS5A inhibitor (with no cirrhosis or with compensated cirrhosis): Three 100-mg/40-mg tablets once daily for 16 wk or six 50-mg/20-mg pellet packets once daily for 16 wk; Genotype 1: Treatment-experienced with NS3/4A protease inhibitor (with no cirrhosis or with compensated cirrhosis): Three 100-mg/40-mg tablets once daily for 12 wk or six 50-mg/20-mg pellet packets once daily for 12 wk; Genotype 1, 2, 4, 5, or 6: Treatment-experienced with regimens containing interferon, pegylated interferon, ribavirin, and/or sofosbuvir (no cirrhosis): Three 100-mg/40-mg tablets once daily for 8 wk or six 50-mg/20-mg pellet packets once daily for 8 wk; Genotype 1, 2, 4, 5, or 6: Treatment-experienced with regimens containing interferon, pegylated interferon, ribavirin, and/or sofosbuvir (with compensated cirrhosis): Three 100-mg/40-mg tablets once daily for 12 wk or six 50-mg/20-mg pellet packets once daily for 12 wk; Genotype 3: Treatment-experienced with regimens containing interferon, pegylated interferon, ribavirin, and/or sofosbuvir (with no cirrhosis or with compensated cirrhosis): Three 100-mg/40-mg tablets once daily for 16 wk or six 50-mg/20-mg pellet packets once daily for 16 wk; Liver or kidney transplant recipients: Three 100-mg/40-mg tablets once daily for 12 wk (16 wk for those with Genotype 1 who are treatment experienced with NS5A inhibitor without prior treatment with an NS3/4A protease inhibitor; 16 wk for those with Genotype 3 who are treatment experienced with regimens containing interferon, pegylated interferon, ribavirin, and/or sofosbuvir) or six 50-mg/20-mg pellet packets once daily for 12 wk (16 wk for those with Genotype 1 who are treatment experienced with NS5A inhibitor without prior treatment with an NS3/4A protease inhibitor; 16 wk for those with Genotype 3 who are treatment experienced with regimens containing interferon, pegylated interferon, ribavirin, and/or sofosbuvir).
PO (Children 3–<12 yr and 30–<45 kg): Genotype 1, 2, 3, 4, 5, or 6: Treatment-naive with no cirrhosis or with compensated cirrhosis: Five 50-mg/20-mg pellet packets once daily for 8 wk; Genotype 1: Treatment-experienced with NS5A inhibitor (with no cirrhosis or with compensated cirrhosis): Five 50-mg/20-mg pellet packets once daily for 16 wk; Genotype 1: Treatment-experienced with NS3/4A protease inhibitor (with no cirrhosis or with compensated cirrhosis): Five 50-mg/20-mg pellet packets once daily for 12 wk; Genotype 1, 2, 4, 5, or 6: Treatment-experienced with regimens containing interferon, pegylated interferon, ribavirin, and/or sofosbuvir (no cirrhosis): Five 50-mg/20-mg pellet packets once daily for 8 wk; Genotype 1, 2, 4, 5, or 6: Treatment-experienced with regimens containing interferon, pegylated interferon, ribavirin, and/or sofosbuvir (with compensated cirrhosis): Five 50-mg/20-mg pellet packets once daily for 12 wk; Genotype 3: Treatment-experienced with regimens containing interferon, pegylated interferon, ribavirin, and/or sofosbuvir (with no cirrhosis or with compensated cirrhosis): Five 50-mg/20-mg pellet packets once daily for 16 wk; Liver or kidney transplant recipients: Five 50-mg/20-mg pellet packets once daily for 12 wk (16 wk for those with Genotype 1 who are treatment experienced with NS5A inhibitor without prior treatment with an NS3/4A protease inhibitor; 16 wk for those with Genotype 3 who are treatment experienced with regimens containing interferon, pegylated interferon, ribavirin, and/or sofosbuvir).
PO (Children 3–<12 yr and 20–<30 kg): Genotype 1, 2, 3, 4, 5, or 6: Treatment-naive with no cirrhosis or with compensated cirrhosis: Four 50-mg/20-mg pellet packets once daily for 8 wk; Genotype 1: Treatment-experienced with NS5A inhibitor (with no cirrhosis or with compensated cirrhosis): Four 50-mg/20-mg pellet packets once daily for 16 wk; Genotype 1: Treatment-experienced with NS3/4A protease inhibitor (with no cirrhosis or with compensated cirrhosis): Four 50-mg/20-mg pellet packets once daily for 12 wk; Genotype 1, 2, 4, 5, or 6: Treatment-experienced with regimens containing interferon, pegylated interferon, ribavirin, and/or sofosbuvir (no cirrhosis): Four 50-mg/20-mg pellet packets once daily for 8 wk; Genotype 1, 2, 4, 5, or 6: Treatment-experienced with regimens containing interferon, pegylated interferon, ribavirin, and/or sofosbuvir (with compensated cirrhosis): Four 50-mg/20-mg pellet packets once daily for 12 wk; Genotype 3: Treatment-experienced with regimens containing interferon, pegylated interferon, ribavirin, and/or sofosbuvir (with no cirrhosis or with compensated cirrhosis): Four 50-mg/20-mg pellet packets once daily for 16 wk; Liver or kidney transplant recipients: Four 50-mg/20-mg pellet packets once daily for 12 wk (16 wk for those with Genotype 1 who are treatment experienced with NS5A inhibitor without prior treatment with an NS3/4A protease inhibitor; 16 wk for those with Genotype 3 who are treatment experienced with regimens containing interferon, pegylated interferon, ribavirin, and/or sofosbuvir).
PO (Children 3–<12 yr and <20 kg): Genotype 1, 2, 3, 4, 5, or 6: Treatment-naive with no cirrhosis or with compensated cirrhosis: Three 50-mg/20-mg pellet packets once daily for 8 wk; Genotype 1: Treatment-experienced with NS5A inhibitor (with no cirrhosis or with compensated cirrhosis): Three 50-mg/20-mg pellet packets once daily for 16 wk; Genotype 1: Treatment-experienced with NS3/4A protease inhibitor (with no cirrhosis or with compensated cirrhosis): Three 50-mg/20-mg pellet packets once daily for 12 wk; Genotype 1, 2, 4, 5, or 6: Treatment-experienced with regimens containing interferon, pegylated interferon, ribavirin, and/or sofosbuvir (no cirrhosis): Three 50-mg/20-mg pellet packets once daily for 8 wk; Genotype 1, 2, 4, 5, or 6: Treatment-experienced with regimens containing interferon, pegylated interferon, ribavirin, and/or sofosbuvir (with compensated cirrhosis): Three 50-mg/20-mg pellet packets once daily for 12 wk; Genotype 3: Treatment-experienced with regimens containing interferon, pegylated interferon, ribavirin, and/or sofosbuvir (with no cirrhosis or with compensated cirrhosis): Three 50-mg/20-mg pellet packets once daily for 16 wk; Liver or kidney transplant recipients: Three 50-mg/20-mg pellet packets once daily for 12 wk (16 wk for those with Genotype 1 who are treatment experienced with NS5A inhibitor without prior treatment with an NS3/4A protease inhibitor; 16 wk for those with Genotype 3 who are treatment experienced with regimens containing interferon, pegylated interferon, ribavirin, and/or sofosbuvir).

Tablets: glecaprevir 100 mg/pibrentasvir 40 mg
Oral pellets: glecaprevir 50 mg/pibrentasvir 20 mg per pkt

Monitor for signs and symptoms of HBV reactivation or hepatitis (jaundice, dark urine, light colored stools, fatigue, weakness, loss of appetite, nausea, vomiting, stomach pain) during therapy.

Lab Test Considerations:

Test all patients for current or prior HBV infection before starting HCV therapy; may cause HBV reactivation. Measure hepatitis B surface antigen (HBsAg) and hepatitis core antibody (anti-HBc). Monitor for clinical and laboratory signs of hepatitis flare (↑ AST, ALT, bilirubin, liver failure, death) or HBV reactivation (rapid ↑ in serum HBV DNA level) during HCV treatment and post-treatment follow-up.
- Test patient with HCV genotype 1a infection for presence of virus with NS5A resistance-associated polymorphisms prior to starting therapy with Mavyret to determine dose regimen and duration.

PO: Administer once daily with food.
Oral Pellets: Take oral pellets together, with food, once daily. Oral pellets may also be sprinkled on a small amount of soft food with a low water content that will stick to a spoon and should be swallowed without chewing (peanut butter, chocolate hazelnut spread, cream cheese, thick jam, Greek yogurt). Entire mixture of food and oral pellets should be swallowed within 15 min of preparation; DNC: Do not crush or chew oral pellets. Liquids or foods that would drip or slide off the spoon are not recommended as the drug may dissolve quickly and become less effective.

Instruct patient to take medication as directed. Do not skip or miss dose. If dose is missed, take if <18 hr from usual time taken, then take next dose at usual time. If >18 hr from usual time of dose, omit dose and take next dose at usual time. Do not stop medication without consulting health care professional. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
Advise patient to notify health care professional if they have a history of HBV. May cause reactivation.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially St. John's wort.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.

Decreased levels of HCV with sustained virologic response and lessened sequelae of chronic HCV infection.

NDC Code

0074- AbbVie Inc.
- 0074-2625- Mavyret
  - 0074-2625-01- 1 DOSE PACK in 1 CARTON (0074-2625-01) > 3 TABLET, FILM COATED in 1 DOSE PACK

0074- AbbVie Inc.
- 0074-2625- Mavyret
  - 0074-2625-28- 4 CARTON in 1 CARTON (0074-2625-28) > 7 DOSE PACK in 1 CARTON > 3 TABLET, FILM COATED in 1 DOSE PACK

0074- AbbVie Inc.
- 0074-2625- Mavyret
  - 0074-2625-56- 2 CARTON in 1 CARTON (0074-2625-56) > 4 CARTON in 1 CARTON > 7 DOSE PACK in 1 CARTON > 3 TABLET, FILM COATED in 1 DOSE PACK

0074- AbbVie Inc.
- 0074-2625- Mavyret
  - 0074-2625-80- 84 TABLET, FILM COATED in 1 BOTTLE (0074-2625-80)

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