glecaprevir/pibrentasvir (glek-a

 Indications

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.

Action

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.

Pharmacokinetics

Glevaprevir

Absorption: Well absorbed following oral administration;

absorptionqby high-fat meal.

Distribution: Unknown.

Protein Binding: 97.5%.

Metabolism and Excretion: Partially metabolized

by CYP3A4; 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 and Excretion: Not metabolized;

97% excreted in feces.

Half-life: 13 hr.

TIME/ACTION PROFILE (blood levels)

ROUTE ONSET PEAK DURATION

glecaprevir

(PO)

unknown 5 hr 24 hr

pibrentasvir

(PO)

unknown 5 hr 24 hr

Contraindications/Precautions

Contraindicated in: Severe hepatic impairment

(Child-Pugh C); Concurrent use of atazanavir, carbamazepine,

dabigatran, darunavir, efavirenz, lopinavir,

oral contraceptives containing ethinyl estradiol, rifampin,

ritonavir, or St. John’s wort.

Use Cautiously in: Receiving immunosuppressant

or chemotherapy medications (qrisk of hepatitis B virus

reactivation); Moderate hepatic impairment (safety

and effectiveness not established); OB: Safety not established;

Lactation: Weigh benefits of breast feeding

against possible adverse effects; Pedi: Safety and effectiveness

not established.

Adverse Reactions/Side Effects

CNS: fatigue, headache. Derm: pruritus. GI: diarrhea,

hyperbilirubinemia, nausea. Misc: hepatitis B virus

reactivation.

Interactions

Drug-Drug: Atazanavir mayqlevels of glecaprevir/

pibrentasvir andqrisk of liver enzyme elevation; concurrent

use contraindicated. Rifampin mayplevels/effectiveness

of glecaprevir/pibrentasvir; concurrent use

contraindicated. Strong CYP3A inducers, including

carbamazepine or efavirenz mayplevels/effectiveness

of glecaprevir/pibrentasvir; concurrent use not

recommended. Darunavir, lopinavir, or ritonavir

mayqlevels of glecaprevir/pibrentasvir; concurrent use

not recommended. Mayqlevels of atorvastatin, fluvastatin,

lovastatin, pitavastatin, pravastatin, rosuvastatin,

and simvastatin andqrisk of myopathy;

concurrent use with atorvastatin, lovastatin, and simvastatin

not recommended;pdose of pravastatin by 50%;

do not exceed rosuvastatin dose of 10 mg/day; use lowest

possible dose of fluvastatin or pitavastatin. Mayq

dabigatran levels; avoid concurrent use. Mayqdigoxin

levels;pdigoxin dose by 50% when initiating

glecaprevir/pibrentasvir therapy. Concurrent use with

ethinyl estradiol-containing oral contraceptives

mayqrisk of liver enzyme elevation; concurrent use

not recommended. Cyclosporine mayqlevels/toxicity

of glecaprevir/pibrentasvir; concurrent use not recommended

if patients require cyclosporine dose 100

mg/day.

Drug-Natural Products: St. John’s wort mayp

levels/effectiveness of glecaprevir/pibrentasvir; concurrent

use not recommended.

Route/Dosage

PO (Adults): Genotype 1, 2, 3, 4, 5, or 6: Treatmentnaı

¨ve with no cirrhosis—3 tablets (glecaprevir 300

mg/pibrentasvir 120 mg) once daily for 8 wk; Genotype

1, 2, 3, 4, 5, or 6: Treatment-naı¨ve with compensated

cirrhosis (Child–Pugh A)—3 tablets (glecaprevir

300 mg/pibrentasvir 120 mg) once daily for

12 wk; Genotype 1: Treatment-experienced with

NS5A inhibitor (with no cirrhosis or with compensated

cirrhosis [Child–Pugh A])—3 tablets (glecaprevir

300 mg/pibrentasvir 120 mg) once daily for 16

wk; Genotype 1: Treatment-experienced with NS3/4A

protease inhibitor (with no cirrhosis or with compensated

cirrhosis [Child–Pugh A])—3 tablets (glecaprevir

300 mg/pibrentasvir 120 mg) 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)—3 tablets (glecaprevir 300 mg/pibrentasvir

120 mg) 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 [Child–

Pugh A])—3 tablets (glecaprevir 300 mg/pibrentasvir

120 mg) 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 [Child–Pugh A])—3 tablets (glecaprevir

300 mg/pibrentasvir 120 mg) once daily for 16 wk.

Availability

Tablets: glecaprevir 100 mg/pibrentasvir 40 mg.