Glecaprevir and Pibrentasvir

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

Pharmacology

Mechanism of Action

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.

Pharmacokinetics/Pharmacodynamics

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%

Use in Specific Populations

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.

Dosage and Administration

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.

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.

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: Reduce afatinib by 10 mg if not tolerated. Some non-US labeling recommends avoiding combination if possible. If used, administer the P-gp inhibitor simultaneously with or after the dose of afatinib. Consider therapy modification

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

ARIPiprazole: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ARIPiprazole. Management: Monitor for increased aripiprazole pharmacologic effects. Aripiprazole dose adjustments may or may not be required based on concomitant therapy and/or indication. Consult full interaction monograph for specific recommendations. 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 the adult betrixaban dose to an initial single dose of 80 mg followed by 40 mg once daily if combined with a P-glycoprotein inhibitor. Consider therapy modification

Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Management: Consider alternatives when possible; bilastine should be avoided in patients with moderate to severe renal insufficiency who are receiving p-glycoprotein inhibitors. Consider therapy modification

Brentuximab Vedotin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Brentuximab Vedotin. Specifically, concentrations of the active monomethyl auristatin E (MMAE) component may be increased. Monitor therapy

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-glycoprotein inhibitor. In those with normal renal and hepatic function, reduce colchicine dose as directed. See full 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

Digoxin: Glecaprevir and Pibrentasvir may increase the serum concentration of Digoxin. Management: Measure serum digoxin concentrations before initiating glecaprevir/pibrentasvir. Reduce digoxin concentrations by decreasing the digoxin dose by approximately 50% or by modifying the dosing frequency; continue monitoring during concomitant therapy. 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). Management: Seek alternatives to P-glycoprotein inhibitors in patients treated with doxorubicin whenever possible. One U.S. manufacturer (Pfizer Inc.) recommends that these combinations be avoided. Consider therapy modification

Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Management: See full monograph for details. Reduced doses are recommended for patients receiving edoxaban for venous thromboembolism in combination with certain P-gp inhibitors. Similar dose adjustment is not recommended for edoxaban use in atrial fibrillation. Consider therapy modification

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

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

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

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

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

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

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 Inducers: May decrease the serum concentration of Glecaprevir and Pibrentasvir. Monitor therapy

P-glycoprotein/ABCB1 Substrates: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Exceptions: Loperamide. Monitor therapy

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

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

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

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

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

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. Management: These listed exceptions are discussed in detail in separate interaction monographs. 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

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. Consider therapy modification

Tolvaptan: May increase the serum concentration of BCRP/ABCG2 Substrates. 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 (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: Consider a venetoclax dose reduction by at least 50% in patients requiring concomitant treatment with P-glycoprotein (P-gp) inhibitors. 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%:

Central nervous system: Headache (6% to 17%), fatigue (adults: 8% to 15%; adolescents: 6%)

Gastrointestinal: Nausea (6% to 12%)

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: Acute hepatic failure (FDA Safety Alert, August 28, 2019), angioedema, severe hepatic disease (FDA Safety Alert, August 28, 2019)

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.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustments, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

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).

Pregnancy

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

Frequently reported side effects of this drug

• Headache
• Loss of strength and energy
• Nausea
• Diarrhea

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Liver problems like dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin.
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of 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 brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.