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Glecaprevir and Pibrentasvir

Medically reviewed by Drugs.com. Last updated on Jun 1, 2020.

Pronunciation

(glek A pre vir & pi BRENT as vir)

Index Terms

  • ABT-493 and ABT-530
  • Pibrentasvir and Glecaprevir

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Mavyret: Glecaprevir 100 mg and pibrentasvir 40 mg

Brand Names: U.S.

  • Mavyret

Pharmacologic Category

  • Antihepaciviral, NS3/4A Protease Inhibitor (Anti-HCV)
  • Antihepaciviral, NS5A Inhibitor
  • NS3/4A Inhibitor
  • NS5A Inhibitor

Pharmacology

Glecaprevir is an inhibitor of hepatitis C virus (HCV) NS3/4A protease, necessary for the proteolytic cleavage of the HCV-encoded polyprotein (into mature forms of the NS3, NS4A, NS4B, NS5A, and NS5B proteins) and is essential for viral replication.

Pibrentasvir is an inhibitor of HCV NS5A, essential for viral RNA replication and virion assembly.

Metabolism

Glecaprevir: Secondary to CYP3A

Excretion

Glecaprevir: Feces (92.1%), urine (0.7%); Pibrentasvir: Feces (96.6%)

Time to Peak

5 hours

Half-Life Elimination

Glecaprevir: 6 hours; Pibrentasvir: 13 hours

Protein Binding

Glecaprevir: 97.5%; Pibrentasvir: >99.9%

Special Populations: Hepatic Function Impairment

Glecaprevir AUC was 100% higher in Child-Pugh class B patients, and increased to 11-fold in Child-Pugh class C patients. Pibrentasvir AUC was 26% higher in Child-Pugh class B patients, and 114% higher in Child-Pugh class C patients.

Use: Labeled Indications

Chronic hepatitis C: Treatment of chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5, or 6 infection in adults and pediatric patients ≥12 years of age or weighing ≥45 kg, without cirrhosis or with compensated cirrhosis (Child-Pugh class A); HCV genotype 1 infection in adults and pediatric patients ≥12 years of age or weighing ≥45 kg, previously treated with a regimen containing an HCV NS5A inhibitor or an NS3/4A protease inhibitor, but not both.

Contraindications

Moderate or severe hepatic impairment (Child-Pugh class B or C); history of hepatic decompensation; coadministration with atazanavir or rifampin.

Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to glecaprevir, pibrentasvir, or any component of the formulation; coadministration with atorvastatin, dabigatran, ethinyl estradiol, or simvastatin.

Dosing: Adult

Chronic hepatitis C (HCV monoinfected or HCV/HIV co-infected patients): Without cirrhosis or with compensated cirrhosis (Child-Pugh class A): Oral:

Treatment-naive patients:

Genotype 1, 2, 3, 4, 5, or 6: Three tablets once daily for 8 weeks.

Treatment-experienced patients:

Genotype 1:

Peginterferon/ribavirin-experienced patients: Three tablets once daily for 8 weeks (without cirrhosis) or 12 weeks (with compensated cirrhosis [Child-Pugh class A]) (AASLD/IDSA 2018).

Peginterferon/ribavirin + NS3 protease inhibitor treatment-experienced patients: Three tablets once daily for 12 weeks (AASLD/IDSA 2018).

Non-NS5A inhibitor, sofosbuvir-containing regimen-experienced patients: Three tablets once daily for 12 weeks (AASLD/IDSA 2018).

NS5A inhibitor-experienced patients (without prior concomitant treatment with an NS3/4 protease inhibitor) (alternative agent): Three tablets once daily for 16 weeks (AASLD/IDSA 2018).

Genotype 2:

Peginterferon/ribavirin-experienced patients: Three tablets once daily for 8 weeks (without cirrhosis) or 12 weeks (with compensated cirrhosis [Child-Pugh class A]) (AASLD/IDSA 2018).

Sofosbuvir + ribavirin-experienced patients: Three tablets once daily for 12 weeks (AASLD/IDSA 2018).

Genotype 3: Peginterferon/ribavirin-experienced patients (alternative agent): Three tablets once daily for 16 weeks (AASLD/IDSA 2018).

Genotype 4: Peginterferon/ribavirin-experienced patients: Three tablets once daily for 8 weeks (without cirrhosis) or 12 weeks (with compensated cirrhosis [Child-Pugh class A]) (AASLD/IDSA 2018).

Genotype 5 or 6: Peginterferon/ribavirin-experienced patients: Three tablets once daily for 8 weeks (without cirrhosis) or 12 weeks (with compensated cirrhosis [Child-Pugh class A]) (AASLD/IDSA 2018).

Liver or kidney transplant recipients:

Genotypes 1, 2, 3, 4, 5, or 6: Three tablets once daily for 12 weeks (AASLD/IDSA 2018). Note: Manufacturer's labeling recommends a duration of 16 weeks in patients with genotype 1 who are NS5A inhibitor-experienced without prior treatment with an NS3/4A protease inhibitor (PI) and in patients with genotype 3 who have prior treatment experience with regimens containing peginterferon, ribavirin, and/or sofosbuvir, but no prior treatment experience with an NS3/4A PI or NS5A inhibitor.

Missed dose: If <18 hours from the usual dosage time, administer dose as soon as possible, then administer next dose at usual dosage time. If >18 hours from the usual dosage time, skip the missed dose and administer the next dose at usual dosage time.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing.

Dosing: Pediatric

Note: Prior to initiating therapy, test patient for evidence of hepatitis B infection (current or prior).

Chronic hepatitis C infection: Children weighing ≥45 kg or ≥12 years and Adolescents: Oral: Tablet (glecaprevir 100 mg and pibrentasvir 40 mg per tablet): 3 tablets once daily administered at the same time each day; duration dependent on genotype, previous treatment, hepatic compensation, or transplant status (liver, renal); see the following:

Treatment-naive patients (non-transplant): Genotype 1, 2, 3, 4, 5, or 6:

Without cirrhosis: 8 weeks.

With compensated cirrhosis (Child-Pugh class A): 12 weeks.

Treatment-experienced patients:

Genotype 1:

Prior treatment with an NS5A inhibitor containing regimen without an NS3/4A protease inhibitor (with or without cirrhosis): 16 weeks.

Prior treatment with an NS3/4A protease inhibitor containing regimen without an NS5A inhibitor (with or without cirrhosis): 12 weeks.

Genotype 1, 2, 4, 5, or 6: Prior treatment with regimens containing interferon (including pegylated formulations), ribavirin, and/or sofosbuvir, but no prior treatment with an NS3/4A protease inhibitor or NS5A inhibitor:

Without cirrhosis: 8 weeks

With compensated cirrhosis (Child-Pugh class A): 12 weeks.

Genotype 3: Prior treatment with regimens containing interferon (including pegylated formulations), ribavirin, and/or sofosbuvir, but no prior treatment with an NS3/4A protease inhibitor or NS5A inhibitor (with or without cirrhosis): 16 weeks.

Liver or kidney transplant recipient:

Treatment naive: Genotypes 1, 2, 3, 4, 5, or 6 without prior treatment: 12 weeks.

Treatment experienced:

Genotype 1: Prior treatment with an NS5A inhibitor containing regimen without an NS3/4A protease inhibitor: 16 weeks.

Genotype 3: Prior treatment with regimens containing interferon (including pegylated formulations), ribavirin, and/or sofosbuvir, but no prior treatment with an NS3/4A protease inhibitor or NS5A inhibitor: 16 weeks.

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Administration

Oral: Administer with food.

Storage

Store at ≤30°C (86°F).

Drug Interactions

Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Afatinib. Management: If combined, administer the P-gp inhibitor simultaneously with, or after, the dose of afatinib. Monitor closely for signs and symptoms of afatinib toxicity and if the combination is not tolerated, reduce the afatinib dose by 10 mg. Consider therapy modification

Aliskiren: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Aliskiren. Monitor therapy

Alpelisib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Alpelisib. Management: Avoid coadministration of BCRP/ABCG2 inhibitors and alpelisib due to the potential for increased alpelisib concentrations and toxicities. If coadministration cannot be avoided, closely monitor for increased alpelisib adverse reactions. Consider therapy modification

Antidiabetic Agents: Direct Acting Antiviral Agents (HCV) may enhance the hypoglycemic effect of Antidiabetic Agents. Monitor therapy

Asunaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Asunaprevir. Avoid combination

Atazanavir: May increase the serum concentration of Glecaprevir and Pibrentasvir. Avoid combination

AtorvaSTATin: Glecaprevir and Pibrentasvir may increase the serum concentration of AtorvaSTATin. Avoid combination

Betrixaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Betrixaban. Management: Decrease adult betrixaban dose to an initial single dose of 80 mg followed by 40 mg once daily if combined with a P-gp inhibitor. Avoid concomitant use of betrixaban and P-gp inhibitors in patients with severe renal impairment (CrCL less than 30 mL/min). Consider therapy modification

Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Avoid combination

CarBAMazepine: May decrease the serum concentration of Glecaprevir and Pibrentasvir. Avoid combination

Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol. Monitor therapy

Cladribine: BCRP/ABCG2 Inhibitors may increase the serum concentration of Cladribine. Management: Avoid concomitant use of BCRP inhibitors during the 4 to 5 day oral cladribine treatment cycles whenever possible. If combined, consider dose reduction of the BCRP inhibitor and separation in the timing of administration. Consider therapy modification

CloZAPine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of CloZAPine. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Monitor therapy

Cobicistat: May increase the serum concentration of Glecaprevir and Pibrentasvir. Monitor therapy

Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: Colchicine is contraindicated in patients with impaired renal or hepatic function who are also receiving a P-gp inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. See interaction monograph for details. Consider therapy modification

CycloSPORINE (Systemic): May increase the serum concentration of Glecaprevir and Pibrentasvir. Avoid combination

CYP3A4 Inducers (Moderate): May decrease the serum concentration of Glecaprevir and Pibrentasvir. Monitor therapy

CYP3A4 Inducers (Strong): May decrease the serum concentration of Glecaprevir and Pibrentasvir. Monitor therapy

Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Monitor therapy

Darunavir: May increase the serum concentration of Glecaprevir and Pibrentasvir. Avoid combination

Digitoxin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Digitoxin. Monitor therapy

Digoxin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Digoxin. Management: Measure digoxin serum concentrations before initiating treatment with these P-glycoprotein (P-gp) inhibitors. Reduce digoxin concentrations by either reducing the digoxin dose by 15% to 30% or by modifying the dosing frequency. Consider therapy modification

Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Monitor therapy

DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Avoid combination

Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Management: Exceptions to this monograph are discussed in separate Lexi-Interact monographs. Monitor therapy

Efavirenz: May decrease the serum concentration of Glecaprevir and Pibrentasvir. Avoid combination

Elagolix: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix. Avoid combination

Elagolix, Estradiol, and Norethindrone: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix, Estradiol, and Norethindrone. Specifically, concentrations of elagolix may be increased. Avoid combination

Eltrombopag: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. Monitor therapy

Eltrombopag: May increase the serum concentration of BCRP/ABCG2 Substrates. Monitor therapy

Eluxadoline: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Eluxadoline. Management: Decrease the eluxadoline dose to 75 mg twice daily if combined with OATP1B1/1B3 inhibitors and monitor patients for increased eluxadoline effects/toxicities. Consider therapy modification

Ethinyl Estradiol: May enhance the adverse/toxic effect of Glecaprevir and Pibrentasvir. Specifically, the risk for ALT elevation may be increased with this combination. Avoid combination

Etoposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide. Monitor therapy

Etoposide Phosphate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide Phosphate. Monitor therapy

Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Monitor therapy

Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Monitor therapy

Fosphenytoin-Phenytoin: May decrease the serum concentration of Glecaprevir and Pibrentasvir. Avoid combination

Gemfibrozil: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. See separate drug interaction monographs for agents listed as exceptions. Monitor therapy

Grazoprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Grazoprevir. Avoid combination

HMG-CoA Reductase Inhibitors (Statins): Glecaprevir and Pibrentasvir may increase the serum concentration of HMG-CoA Reductase Inhibitors (Statins). Management: Use the lowest statin dose possible if combined with glecaprevir/pibrentasvir and monitor for increased statin effects/toxicities. Avoid concomitant use with atorva-, simva-, or lovastatin. Limit rosuvastatin to 10 mg daily and reduce pravastatin dose 50% Consider therapy modification

Irinotecan Products: UGT1A1 Inhibitors may increase serum concentrations of the active metabolite(s) of Irinotecan Products. Specifically, concentrations of SN-38 may be increased. UGT1A1 Inhibitors may increase the serum concentration of Irinotecan Products. Avoid combination

Lapatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Lapatinib. Monitor therapy

Larotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Larotrectinib. Monitor therapy

Lasmiditan: May increase the serum concentration of BCRP/ABCG2 Substrates. Avoid combination

Lefamulin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Lefamulin. Management: Avoid concomitant use of lefamulin tablets with P-glycoprotein/ABCB1 inhibitors. If concomitant use is required, monitor for lefamulin adverse effects. Consider therapy modification

Lemborexant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lemborexant. Management: The maximum recommended dosage of lemborexant is 5 mg, no more than once per night, when coadministered with weak CYP3A4 inhibitors. Consider therapy modification

Lomitapide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lomitapide. Management: Patients on lomitapide 5 mg/day may continue that dose. Patients taking lomitapide 10 mg/day or more should decrease the lomitapide dose by half. The lomitapide dose may then be titrated up to a max adult dose of 30 mg/day. Consider therapy modification

Lopinavir: May increase the serum concentration of Glecaprevir and Pibrentasvir. Avoid combination

Lovastatin: Glecaprevir and Pibrentasvir may increase the serum concentration of Lovastatin. Avoid combination

Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Morphine (Systemic). Monitor therapy

Nadolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Nadolol. Monitor therapy

Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naldemedine. Monitor therapy

Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Monitor therapy

NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Monitor therapy

Osimertinib: May increase the serum concentration of BCRP/ABCG2 Substrates. Monitor therapy

Ozanimod: BCRP/ABCG2 Inhibitors may increase serum concentrations of the active metabolite(s) of Ozanimod. Avoid combination

PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Avoid combination

PAZOPanib: BCRP/ABCG2 Inhibitors may increase the serum concentration of PAZOPanib. Avoid combination

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of Glecaprevir and Pibrentasvir. Exceptions: CycloSPORINE (Systemic); Ritonavir. Monitor therapy

Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Avoid combination

Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine. Monitor therapy

Regorafenib: May increase the serum concentration of BCRP/ABCG2 Substrates. Monitor therapy

Revefenacin: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentrations of the active metabolite(s) of Revefenacin. Avoid combination

RifAMPin: May decrease the serum concentration of Glecaprevir and Pibrentasvir. RifAMPin may increase the serum concentration of Glecaprevir and Pibrentasvir. Specifically, a single dose of rifampin may increase glecaprevir/pibrentasvir concentrations, while chronic daily use of rifampin may decrease glecaprevir/pibrentasvir concentrations. Avoid combination

RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Monitor therapy

Rimegepant: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Rimegepant. Avoid combination

Rimegepant: BCRP/ABCG2 Inhibitors may increase the serum concentration of Rimegepant. Avoid combination

RisperiDONE: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RisperiDONE. Monitor therapy

Ritonavir: May increase the serum concentration of Glecaprevir and Pibrentasvir. Avoid combination

Rolapitant: May increase the serum concentration of BCRP/ABCG2 Substrates. Management: Monitor patients receiving rolapitant for increased exposure to and/or effects of BCRP/ABCG2 substrates. Use the lowest effective rosuvastatin dose when used in combination with rolapitant. Monitor therapy

RomiDEPsin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RomiDEPsin. Monitor therapy

Sacituzumab Govitecan: UGT1A1 Inhibitors may increase serum concentrations of the active metabolite(s) of Sacituzumab Govitecan. Specifically, concentrations of SN-38 may be increased. Avoid combination

Saquinavir: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Saquinavir. Monitor therapy

Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Monitor therapy

Simvastatin: Glecaprevir and Pibrentasvir may increase the serum concentration of Simvastatin. Avoid combination

Sirolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Sirolimus. Management: Avoid concurrent use of sirolimus with P-glycoprotein (P-gp) inhibitors when possible and alternative agents with lesser interaction potential with sirolimus should be considered. Monitor for increased sirolimus concentrations/toxicity if combined. Consider therapy modification

St John's Wort: May decrease the serum concentration of Glecaprevir and Pibrentasvir. Avoid combination

Tacrolimus (Systemic): Glecaprevir and Pibrentasvir may increase the serum concentration of Tacrolimus (Systemic). Monitor therapy

Tafamidis: May increase the serum concentration of BCRP/ABCG2 Substrates. Monitor therapy

Talazoparib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Talazoparib. Monitor therapy

Talazoparib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Talazoparib. Monitor therapy

Tedizolid: May increase the serum concentration of BCRP/ABCG2 Substrates. Monitor therapy

Tegaserod: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod. Monitor therapy

Teniposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Teniposide. Monitor therapy

Teriflunomide: May increase the serum concentration of BCRP/ABCG2 Substrates. Monitor therapy

Teriflunomide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. Monitor therapy

Theophylline Derivatives: CYP1A2 Inhibitors (Weak) may increase the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. Monitor therapy

TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use is necessary, initiate tizanidine at an adult dose of 2 mg and increase in 2 to 4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Consider therapy modification

Tolvaptan: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates. Management: Avoid concomitant use of OATP1B1/1B3 substrates in patients receiving the Jynarque brand of tolvaptant. Concentrations and effects of the OATP1B1/1B3 substrate would be expected to increase with combined use. Consider therapy modification

Tolvaptan: May increase the serum concentration of BCRP/ABCG2 Substrates. Management: Avoid concomitant use of BCRP/ABCG2 substrates in patients receiving the Jynarque brand of tolvaptan. Concentrations and effects of the BCRP/ABCG2 substrate would be expected to increase with combined use. Consider therapy modification

Topotecan: BCRP/ABCG2 Inhibitors may increase the serum concentration of Topotecan. Avoid combination

Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Avoid combination

Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Management: Consider triazolam dose reduction in patients receiving concomitant weak CYP3A4 inhibitors. Consider therapy modification

Ubrogepant: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ubrogepant. Management: In patients taking weak CYP3A4 inhibitors, the initial and second dose (given at least 2 hours later if needed) of ubrogepant should be limited to 50 mg. Consider therapy modification

Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Venetoclax. Management: Reduce the venetoclax dose by at least 50% in patients requiring concomitant treatment with P-glycoprotein (P-gp) inhibitors. Resume the previous venetoclax dose 2 to 3 days after discontinuation of a P-gp inhibitor. Consider therapy modification

VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Avoid combination

Vitamin K Antagonists (eg, warfarin): Direct Acting Antiviral Agents (HCV) may diminish the anticoagulant effect of Vitamin K Antagonists. Monitor therapy

Voxilaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Voxilaprevir. Avoid combination

Voxilaprevir: May increase the serum concentration of BCRP/ABCG2 Substrates. Avoid combination

Adverse Reactions

As reported in adults, unless otherwise noted.

>10%:

Gastrointestinal: Nausea (6% to 12%)

Nervous system: Fatigue (adults: 8% to 15%; adolescents: 6%), headache (6% to 17%)

1% to 10%:

Dermatologic: Pruritus (6% to 7%)

Gastrointestinal: Diarrhea (3% to 7%)

Hepatic: Increased serum bilirubin (≥2 x ULN: 4%)

Frequency not defined: Infection: Reactivation of HBV

Postmarketing:

Hepatic: Acute hepatic failure (FDA Safety Alert, August 28, 2019), decompensated liver disease, severe hepatic disease (FDA Safety Alert, August 28, 2019)

Hypersensitivity: Angioedema

ALERT: U.S. Boxed Warning

Hepatitis B virus reactivation:

Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with glecaprevir and pibrentasvir. HBV reactivation has been reported in hepatitis C virus (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 co-infected 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.

Warnings/Precautions

Disease-related concerns:

• Diabetes: Rapid reduction in hepatitis C viral load during direct-acting antiviral (DAA) therapy for hepatitis C may lead to improvement in glucose metabolism in patients with diabetes, potentially resulting in symptomatic hypoglycemia if antidiabetic agents are continued at the same dose. Monitor for changes in glucose tolerance and inform patients of the risk of hypoglycemia during DAA therapy, particularly within the first 3 months. Modification of antidiabetic may be necessary (Ciancio 2018; Dawood 2017; Hum 2017).

• Hepatic effects: Hepatic decompensation and hepatic failure (including fatal cases) have been reported. Typically occurs within the first 4 weeks of treatment initiation. Most patients with severe outcomes had either advanced liver disease with moderate or severe hepatic impairment prior to treatment initiation, or compensated cirrhosis with mild liver impairment at baseline but with a prior decompensation event (eg, history of ascites, variceal bleeding, encephalopathy). Additionally, rare cases have been reported in patients without cirrhosis or with compensated cirrhosis (often with evidence of portal hypertension), with concomitant use of medications that are not recommended, or in patients with other confounding factors (eg, serious liver-related medical or surgical comorbidities). In patients with compensated cirrhosis (Child-Pugh class A), transient elevations in bilirubin (<2 ULN) without concurrent elevations in ALT/AST, may occur early in treatment (generally within the first 2 weeks); usually resolves with continued treatment. Monitor LFTs as clinically indicated in patients with compensated cirrhosis (Child Pugh class A) or with evidence of advance liver disease (eg, portal hypertension). Discontinue treatment in patients who develop signs/symptoms of hepatic decompensation/failure.

• Hepatitis B virus reactivation: [US Boxed Warning]: Hepatitis B virus (HBV) reactivation has been reported in hepatitis C virus (HCV)/HBV coinfected patients who were receiving 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. Test all patients for evidence of current or prior HBV infection prior to initiation of treatment; monitor HCV/HBV co-infected patients for hepatitis flare or HBV reactivation during treatment and post-treatment follow-up. Initiate treatment for HBV infection as clinically indicated. HBV reactivation has been reported in HBsAg positive patients and in patients with serologic evidence of resolved HBV infection (ie, HBsAg negative and anti-HBc positive) and is characterized by an abrupt increase in HBV replication manifested as a rapid increase in serum HBV DNA level; reappearance of HBsAg may occur in patients with resolved HBV infection. Risk of HBV reactivation may be increased in patients receiving certain immunosuppressants or chemotherapeutic agents.

Monitoring Parameters

Baseline (within 12 weeks prior to starting antiviral therapy) CBC, INR, hepatic function panel (albumin, total and direct bilirubin, ALT, AST, and alkaline phosphatase), and calculated GFR; repeat CBC, serum creatinine, calculated GFR, and hepatic function panel after 4 weeks of therapy and as clinically indicated; baseline (at any time prior to starting therapy) hepatitis C virus (HCV) genotype and subtype and quantitative HCV viral load; repeat quantitative HCV viral load testing (after 4 weeks of therapy and at 12 weeks after completion of therapy). If quantitative HCV viral load is detectable at treatment week 4, repeat testing is recommended after 2 additional weeks of treatment (treatment week 6) (AASLD/IDSA 2018). Hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) prior to initiation; in patients with serologic evidence of hepatitis B virus (HBV) infection, monitor for clinical and laboratory signs of hepatitis flare or HBV reactivation during treatment and during post-treatment follow-up. In patients with diabetes, monitor blood glucose and for signs/symptoms of hypoglycemia (Ciancio 2018; Dawood 2017; Hum 2017).

Reproductive Considerations

HCV-infected females of childbearing potential should consider postponing pregnancy until therapy is complete to reduce the risk of HCV transmission (AASLD/IDSA 2018).

Pregnancy Considerations

Adverse events were not observed in animal reproduction studies with glecaprevir or pibrentasvir as individual agents.

Treatment of hepatitis C is not currently recommended to treat maternal infection or to decrease the risk of mother-to-child transmission during pregnancy (Tran 2016). When HCV infection is detected during pregnancy, treatment should be deferred until after delivery. Direct-acting antiviral medications should not be used in pregnant females outside of clinical trials until safety and efficacy information is available (SMFM [Hughes 2017]).

Patient Education

What is this drug used for?

• It is used to treat hepatitis C infection.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Headache

• Loss of strength and energy

• Nausea

• Diarrhea

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

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