Version July 2025
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.
Chronic hepatitis C:
Children 3 to <12 years:
<20 kg: Oral pellets: Oral: Glecaprevir 150 mg/pibrentasvir 60 mg once daily.
20 to <30 kg: Oral pellets: Oral: Glecaprevir 200 mg/pibrentasvir 80 mg once daily.
30 to <45 kg: Oral pellets: Oral: Glecaprevir 250 mg/pibrentasvir 100 mg once daily.
≥45 kg: Tablets, Oral pellets: Oral: Glecaprevir 300 mg/pibrentasvir 120 mg once daily.
Children ≥12 years and Adolescents: Tablets, Oral pellets: Oral: Glecaprevir 300 mg/pibrentasvir 120 mg once daily.
Duration of therapy: Dependent on genotype, previous treatment, hepatic compensation, or transplant status (liver, renal):
Treatment-naive patients (non-transplant) without or with compensated cirrhosis: Genotype 1, 2, 3, 4, 5, or 6: 8 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.
Children ≥3 years and Adolescents:
Any degree of renal impairment: No dosage adjustment necessary.
Dialysis: No dosage adjustment necessary.
Children ≥3 years and Adolescents:
Mild impairment: No dosage adjustment necessary.
Moderate or severe impairment: Use is contraindicated.
History of prior hepatic decompensation: Use is contraindicated.
(For additional information see "Glecaprevir and pibrentasvir: Drug information")
Chronic hepatitis C, treatment:
Note: Compensated cirrhosis is defined as Child-Pugh class A (Ref).
Treatment-naive patients without cirrhosis or with compensated cirrhosis:
Genotype 1, 2, 3, 4, 5, or 6: Oral: 3 tablets (glecaprevir 100 mg/pibrentasvir 40 mg per tablet) once daily for 8 weeks (Ref). Note: For HIV/hepatitis C virus (HCV)-coinfected patients with genotype 4 and compensated cirrhosis, a duration of 12 weeks is recommended (Ref).
Treatment-experienced patients (all genotypes) without cirrhosis or with compensated cirrhosis:
Glecaprevir/Pibrentasvir treatment failures: Oral: 3 tablets (glecaprevir 100 mg/pibrentasvir 40 mg per tablet) once daily in combination with sofosbuvir and weight-based ribavirin for 16 weeks (Ref).
Multiple direct-acting antiviral treatment failures, including sofosbuvir/velpatasvir/voxilaprevir or sofosbuvir plus glecaprevir/pibrentasvir: Oral: 3 tablets (glecaprevir 100 mg/pibrentasvir 40 mg per tablet) once daily in combination with sofosbuvir and weight-based ribavirin for 16 weeks; may extend treatment to 24 weeks in difficult cases (eg, genotype 3 with cirrhosis or failure following sofosbuvir plus glecaprevir/pibrentasvir) (Ref).
Sofosbuvir-based treatment failures (alternative agent): Oral: 3 tablets (glecaprevir 100 mg/pibrentasvir 40 mg per tablet) once daily for 16 weeks. Note: Not recommended for patients with prior exposure to an NS5A inhibitor plus NS3/4 protease inhibitor regimen (eg, elbasvir/grazoprevir) or for genotype 3 infection with sofosbuvir/NS5A inhibitor experience (Ref).
Hepatitis C, chronic, posttransplant (kidney, liver):
Note: Not recommended for use in direct-acting antiviral (DAA) treatment–experienced kidney or liver transplant recipients.
Oral: 3 tablets (glecaprevir 100 mg/pibrentasvir 40 mg per tablet) once daily for 12 weeks (Ref).
Hepatitis C virus–uninfected recipients of organs from hepatitis C virus–viremic donors (off-label use):
Note: For patients without HCV who are recipients of organs from donors with HCV. Initiate therapy as soon as possible for nonliver transplant recipients and within 2 weeks for liver transplant recipients (Ref).
Oral: 3 tablets (glecaprevir 100 mg/pibrentasvir 40 mg per tablet) once daily for 8 weeks (nonliver organs) or 12 weeks (liver allografts); if treatment initiation is delayed beyond the first week posttransplant of nonliver organs, extend treatment to 12 weeks or for recipients of liver allografts (Ref).
Missed dose
Note: Missed dosing recommendations apply only to those individuals who are DAA naive and are eligible for simplified regimens; all other patients situations warrant a consult with an infectious disease and/or hepatology hepatitis C expert to determine appropriate testing and therapy decisions if nonadherence is identified (Ref).
Interruption in direct-acting antiviral therapy occurring at <28 days
If ≤7 days missed: Restart DAA immediately and complete therapy based on originally planned duration (eg, 8 or 12 weeks).
If ≥8 days missed: Restart DAA therapy immediately and obtain an HCV RNA test, preferably the same day as restarting DAA therapy. If HCV RNA is undetectable, complete original course as planned (eg, 8 or 12 weeks); if patient has compensated cirrhosis or genotype 3, or if HCV RNA cannot be obtained or is positive (>25 IU/L), extend original treatment course by an additional 4 weeks (Ref).
Interruption in direct-acting antiviral therapy occurring at ≥28 days
If ≤7 days missed: Restart DAA immediately and complete therapy based on originally planned duration (eg, 8 or 12 weeks).
If 8 to 20 days missed: Restart DAA therapy immediately and obtain an HCV RNA test, preferably the same day as restarting DAA therapy. If HCV RNA is undetectable, complete original course as planned (eg, 8 or 12 weeks); if patient has compensated cirrhosis or genotype 3, extend original treatment course by an additional 4 weeks. If HCV RNA cannot be obtained or is positive (>25 units/L), STOP therapy and retreat.
If ≥21 days missed: Stop DAA treatment and assess for 12 week sustained viral response (SVR); if SVR is not achieved, stop therapy and retreat (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment necessary.
Preexisting hepatic impairment:
Mild impairment (Child-Pugh class A): No dosage adjustment necessary.
Moderate or severe impairment (Child-Pugh class B or C): Use is contraindicated.
History of prior hepatic decompensation: Use is contraindicated.
Hepatotoxicity during treatment:
Asymptomatic increases in ALT <10-fold: Closely monitor with repeat testing every 2 weeks. If persistent elevation remains, consider stopping therapy (Ref).
<10-fold increase in ALT from baseline with weakness, nausea, vomiting, jaundice, or significantly increased bilirubin, alkaline phosphatase, or INR: Discontinue direct-acting antiviral (Ref).
≥10-fold increase in ALT from baseline at any time during treatment: Discontinue direct-acting antiviral therapy, especially with signs and symptoms of liver inflammation or increasing conjugated bilirubin, alkaline phosphatase, or INR (Ref).
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. As reported in adults, unless otherwise noted.
>10%:
Gastrointestinal: Nausea (6% to 12%)
Nervous system: Fatigue (children, adolescents, and adults: 6% to 15%), headache (6% to 17%)
1% to 10%:
Dermatologic: Pruritus (6% to 7%), skin rash (children: 4%)
Gastrointestinal: Diarrhea (3% to 7%), upper abdominal pain (children: 4%), vomiting (children: 8%)
Hepatic: Increased serum bilirubin (≥2 × ULN: 4%)
Frequency not defined: Dermatologic: Erythematous rash
Postmarketing:
Gastrointestinal: Decompensated liver disease
Hepatic: Acute hepatic failure (FDA 2019), severe hepatic disease (FDA 2019)
Hypersensitivity: Angioedema
Infection: Reactivation of HBV
Moderate or severe hepatic impairment (Child-Pugh class B or C); history of hepatic decompensation; coadministration with atazanavir or rifampin.
Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Canadian labeling: Additional contraindications (not in US labeling): Hypersensitivity to glecaprevir, pibrentasvir, or any component of the formulation; coadministration with atorvastatin, dabigatran, ethinyl estradiol (products containing >20 mcg), or simvastatin.
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.
Rash may be more common in pediatric patients compared to adults; in initial trials, 4% of pediatric patients <12 years of age developed a rash, including a case of grade 3 erythematous rash which resulted in treatment discontinuation. Vomiting was also reported more frequently (8%) compared to adults.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Packet, Oral:
Mavyret: Glecaprevir 50 mg and pibrentasvir 20 mg (28 ea) [gluten free]
Tablet, Oral:
Mavyret: Glecaprevir 100 mg and pibrentasvir 40 mg
No
Pack (Mavyret Oral)
50-20 mg (per each): $113.15
Tablets (Mavyret Oral)
100-40 mg (per each): $188.57
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Packet, Oral:
Maviret: Glecaprevir 50 mg and pibrentasvir 20 mg (28 ea)
Tablet, Oral:
Maviret: Glecaprevir 100 mg and pibrentasvir 40 mg
Oral: Administer orally with food at the same time daily.
Oral pellets: Determine appropriate number of oral pellet packets for patient-specific dose; do not open until ready to use. Pour a small amount of soft food into a bowl; soft food should have a low water content, should stick to a spoon, and should be able to be swallowed without chewing (eg, peanut butter, chocolate hazelnut spread, cream cheese, thick jam, Greek yogurt); food should not be heated. Sprinkle oral pellets over food and mix thoroughly, without crushing pellets. Administer entire mixture; if needed, add more soft food to bowl to ensure all pellets are consumed. Mixing with liquids is not recommended as drug may dissolve quickly and result in decreased efficacy; water can be administered after dose is consumed. Swallow oral pellet and food mixture within 15 minutes of preparation; to improve palatability, administer within 5 minutes (a bitter taste starts at ~5 minutes). Do not crush or chew oral pellets.
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.
Partial dose: Oral pellets: If patient does not finish the entire dose, do not try to administer remaining amount at a later time and do not re-dose. Contact health care provider for instructions.
Oral: Administer with food.
Store at ≤30°C (86°F).
Treatment of chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5, or 6 infection in patients without cirrhosis or with compensated cirrhosis (Child-Pugh class A); treatment of chronic HCV genotype 1 infection in patients previously treated with a regimen containing an HCV NS5A inhibitor or an NS3/4A protease inhibitor, but not both (All indications: FDA approved in ages ≥3 years and adults).
Substrate of BCRP, CYP3A4 (Major with inducers), CYP3A4 (Minor with inhibitors), OATP1B1/1B3, P-glycoprotein (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits BCRP, CYP1A2 (Weak), CYP3A4 (Weak), OATP1B1/1B3, P-glycoprotein, UGT1A1;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program
Afatinib: P-glycoprotein/ABCB1 Inhibitors may increase 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. Risk D: Consider Therapy Modification
Aliskiren: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Aliskiren. Risk C: Monitor
Alpelisib: BCRP/ABCG2 Inhibitors may increase 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. Risk D: Consider Therapy Modification
ALPRAZolam: CYP3A4 Inhibitors (Weak) may increase serum concentration of ALPRAZolam. Risk C: Monitor
Antidiabetic Agents: Direct Acting Antiviral Agents (HCV) may increase hypoglycemic effects of Antidiabetic Agents. Risk C: Monitor
Asciminib: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Atazanavir: May increase serum concentration of Glecaprevir and Pibrentasvir. Risk X: Avoid
Atogepant: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Atogepant. Management: For episodic migraine, the recommended atogepant dose is 10 mg or 30 mg once daily if given with OATP1B1/1B3 inhibitors. For chronic migraine, the recommended atogepant dose is 30 mg once daily with OATP1B1/1B3 inhibitors. Risk D: Consider Therapy Modification
Atorvastatin: Glecaprevir and Pibrentasvir may increase serum concentration of Atorvastatin. Risk X: Avoid
Atrasentan: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Atrasentan. Risk X: Avoid
Belinostat: UGT1A1 Inhibitors may increase serum concentration of Belinostat. Management: Avoid if possible; when required decrease belinostat dose by 25% if receiving a dose of 1,000 m/m2 or 750 mg/m2. If receiving 500 mg/m2, interrupt belinostat therapy during UGT1A1 inhibitor treatment. Risk D: Consider Therapy Modification
Belumosudil: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Management: Avoid coadministration of belumosudil with these substrates of BCRP for which minimal concentration increases can cause serious adverse effects. If coadministration is required, dose reductions of the BCRP substrate may be required. Risk D: Consider Therapy Modification
Beta-Acetyldigoxin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Beta-Acetyldigoxin. Risk C: Monitor
Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Bilastine. Risk X: Avoid
Brincidofovir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Brincidofovir. Management: Consider alternatives to OATP1B/1B3 inhibitors in patients treated with brincidofovir. If coadministration is required, administer OATP1B1/1B3 inhibitors at least 3 hours after brincidofovir and increase monitoring for brincidofovir adverse reactions. Risk D: Consider Therapy Modification
Bulevirtide: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Management: Coadministration of bulevirtide with OATP1B1/1B3 (also known as SLCO1B1/1B3) substrates should be avoided when possible. If used together, close clinical monitoring is recommended. Risk D: Consider Therapy Modification
CarBAMazepine: May decrease serum concentration of Glecaprevir and Pibrentasvir. Risk X: Avoid
Ceftobiprole Medocaril: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid
Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Celiprolol. Risk C: Monitor
Cladribine: BCRP/ABCG2 Inhibitors may increase 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. Risk D: Consider Therapy Modification
CloZAPine: CYP1A2 Inhibitors (Weak) may increase serum concentration of CloZAPine. Risk C: Monitor
Cobicistat: May increase serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor
Colchicine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Colchicine. Colchicine distribution into certain tissues (e.g., brain) may also be increased. Management: This combination is often contraindicated, but combined use may be permitted with dose adjustment and monitoring. Recommendations vary based on brand, indication, use of CYP3A4 inhibitors, and hepatic/renal function. See interaction monograph for details. Risk D: Consider Therapy Modification
CycloSPORINE (Systemic): May increase serum concentration of Glecaprevir and Pibrentasvir. Management: Glecaprevir/pibrentasvir is not recommended for use in patients requiring stable doses of cyclosporine greater than 100 mg per day. If combined with lower doses of cyclosporine, monitor for increased glecaprevir/pibrentasvir toxicities. Risk D: Consider Therapy Modification
CYP3A4 Inducers (Moderate): May decrease serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor
CYP3A4 Inducers (Strong): May decrease serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase active metabolite exposure of Dabigatran Etexilate. Risk C: Monitor
Darolutamide: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Darunavir: May increase serum concentration of Glecaprevir and Pibrentasvir. Risk X: Avoid
Digitoxin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Digitoxin. Risk C: Monitor
Digoxin: P-glycoprotein/ABCB1 Inhibitors may increase 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. Risk D: Consider Therapy Modification
Dofetilide: CYP3A4 Inhibitors (Weak) may increase serum concentration of Dofetilide. Risk C: Monitor
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of DOXOrubicin (Conventional). Risk X: Avoid
DOXOrubicin (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of DOXOrubicin (Liposomal). Risk C: Monitor
Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Edoxaban. Risk C: Monitor
Efavirenz: May decrease serum concentration of Glecaprevir and Pibrentasvir. Risk X: Avoid
Elacestrant: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Elagolix, Estradiol, and Norethindrone: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Elagolix, Estradiol, and Norethindrone. Specifically, concentrations of elagolix may be increased. Risk X: Avoid
Elagolix: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Elagolix. Risk X: Avoid
Elbasvir and Grazoprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid
Eltrombopag: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Eltrombopag: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Eluxadoline: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase 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. Risk D: Consider Therapy Modification
Ensartinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Ensartinib. Risk X: Avoid
Ethinyl Estradiol-Containing Products: May increase hepatotoxic effects of Glecaprevir and Pibrentasvir. Glecaprevir and Pibrentasvir may increase serum concentration of Ethinyl Estradiol-Containing Products. Management: Use of glecaprevir/pibrentasvir and products containing 20 mcg of ethinyl estradiol or more is not recommended. Lower dose ethinyl estradiol-containing products may be used. Risk D: Consider Therapy Modification
Etoposide Phosphate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Etoposide Phosphate. Risk C: Monitor
Etoposide: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Etoposide. Risk C: Monitor
Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Everolimus. Risk C: Monitor
Fezolinetant: CYP1A2 Inhibitors (Weak) may increase serum concentration of Fezolinetant. Risk X: Avoid
Finerenone: CYP3A4 Inhibitors (Weak) may increase serum concentration of Finerenone. Risk C: Monitor
Flibanserin: CYP3A4 Inhibitors (Weak) may increase serum concentration of Flibanserin. Risk C: Monitor
Fluvastatin: Glecaprevir and Pibrentasvir may increase serum concentration of Fluvastatin. Management: Initiate fluvastatin at the lowest dose and monitor for increased statin toxicities (eg, myopathy, rhabdomyolysis) during coadministration with glecaprevir/pibrentasvir. If fluvastatin dose increases are required, use the lowest necessary. Risk D: Consider Therapy Modification
Fosphenytoin-Phenytoin: May decrease serum concentration of Glecaprevir and Pibrentasvir. Risk X: Avoid
Futibatinib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Gemfibrozil: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Gilteritinib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Irinotecan Products: UGT1A1 Inhibitors may increase active metabolite exposure of Irinotecan Products. Specifically, concentrations of SN-38 may be increased. UGT1A1 Inhibitors may increase serum concentration of Irinotecan Products. Risk X: Avoid
Ixabepilone: CYP3A4 Inhibitors (Weak) may increase serum concentration of Ixabepilone. Risk C: Monitor
Lapatinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Lapatinib. Risk C: Monitor
Larotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Larotrectinib. Risk C: Monitor
Lazertinib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Lefamulin: P-glycoprotein/ABCB1 Inhibitors may increase 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. Risk D: Consider Therapy Modification
Leflunomide: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Lemborexant: CYP3A4 Inhibitors (Weak) may increase 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. Risk D: Consider Therapy Modification
Leniolisib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid
Lomitapide: CYP3A4 Inhibitors (Weak) may increase 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. Risk D: Consider Therapy Modification
Lopinavir: May increase serum concentration of Glecaprevir and Pibrentasvir. Risk X: Avoid
Lovastatin: Glecaprevir and Pibrentasvir may increase serum concentration of Lovastatin. Risk X: Avoid
Mavorixafor: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Mavorixafor. Risk C: Monitor
Midazolam: CYP3A4 Inhibitors (Weak) may increase serum concentration of Midazolam. Risk C: Monitor
Momelotinib: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Momelotinib. Risk C: Monitor
Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Morphine (Systemic). Risk C: Monitor
Nadolol: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Nadolol. Risk C: Monitor
Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Naldemedine. Risk C: Monitor
Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Naloxegol. Risk C: Monitor
NiMODipine: CYP3A4 Inhibitors (Weak) may increase serum concentration of NiMODipine. Risk C: Monitor
Nirmatrelvir and Ritonavir: May increase serum concentration of Glecaprevir and Pibrentasvir. Risk X: Avoid
Osimertinib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Oteseconazole: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
P-glycoprotein/ABCB1 Inducers: May decrease serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor
P-glycoprotein/ABCB1 Inhibitors: May increase serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor
PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of PAZOPanib. Risk X: Avoid
Pimozide: CYP3A4 Inhibitors (Weak) may increase serum concentration of Pimozide. Risk X: Avoid
Pitavastatin: Glecaprevir and Pibrentasvir may increase serum concentration of Pitavastatin. Management: Initiate pitavastatin at the lowest dose and monitor for increased statin toxicities (eg, myopathy, rhabdomyolysis) during coadministration with glecaprevir/pibrentasvir. If pitavastatin dose increases are required, use the lowest necessary. Risk D: Consider Therapy Modification
Pralsetinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Pralsetinib. Management: If this combo cannot be avoided, decrease pralsetinib dose from 400 mg daily to 300 mg daily; from 300 mg daily to 200 mg daily; and from 200 mg daily to 100 mg daily. Risk D: Consider Therapy Modification
Pravastatin: Glecaprevir and Pibrentasvir may increase serum concentration of Pravastatin. Management: Reduce the pravastatin dose by 50% during coadministration with glecaprevir and pibrentasvir. Risk D: Consider Therapy Modification
Pretomanid: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Ranolazine. Risk C: Monitor
Red Yeast Rice: Glecaprevir and Pibrentasvir may increase serum concentration of Red Yeast Rice. Risk X: Avoid
Regorafenib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Relugolix, Estradiol, and Norethindrone: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Relugolix, Estradiol, and Norethindrone. Management: Avoid use of relugolix/estradiol/norethindrone with P-glycoprotein (P-gp) inhibitors. If concomitant use is unavoidable, relugolix/estradiol/norethindrone should be administered at least 6 hours before the P-gp inhibitor. Risk D: Consider Therapy Modification
Relugolix: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Relugolix. Management: Avoid coadministration of relugolix with oral P-gp inhibitors whenever possible. If combined, take relugolix at least 6 hours prior to the P-gp inhibitor and monitor patients more frequently for adverse reactions. Risk D: Consider Therapy Modification
Repotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Repotrectinib. Risk X: Avoid
Resmetirom: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Resmetirom. Risk X: Avoid
Revefenacin: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase active metabolite exposure of Revefenacin. Risk X: Avoid
RifAMPin: May decrease serum concentration of Glecaprevir and Pibrentasvir. RifAMPin may increase 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. Risk X: Avoid
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of RifAXIMin. Risk C: Monitor
Rimegepant: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Rimegepant. Management: Avoid administration of another dose of rimegepant within 48 hours if given concomitantly with a P-glycoprotein (P-gp) inhibitor. Risk D: Consider Therapy Modification
RisperiDONE: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of RisperiDONE. Risk C: Monitor
Ritonavir: May increase serum concentration of Glecaprevir and Pibrentasvir. Risk X: Avoid
Rolapitant: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). 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. Risk C: Monitor
RomiDEPsin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of RomiDEPsin. Risk C: Monitor
Rosuvastatin: Glecaprevir and Pibrentasvir may increase serum concentration of Rosuvastatin. Management: Initiate rosuvastatin at 5 mg or rosuvastatin/ezetimibe at 5 mg/10 mg daily and limit doses to rosuvastatin 10 mg or rosuvastatin/ezetimibe 10 mg/10 mg daily. Risk D: Consider Therapy Modification
Sacituzumab Govitecan: UGT1A1 Inhibitors may increase active metabolite exposure of Sacituzumab Govitecan. Specifically, concentrations of SN-38 may be increased. Risk X: Avoid
Saquinavir: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Saquinavir. Risk C: Monitor
Seladelpar: BCRP/ABCG2 Inhibitors may increase serum concentration of Seladelpar. Risk C: Monitor
Selpercatinib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Silodosin. Risk C: Monitor
Simvastatin: Glecaprevir and Pibrentasvir may increase serum concentration of Simvastatin. Risk X: Avoid
Sirolimus (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Sirolimus (Conventional). 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. Risk D: Consider Therapy Modification
Sirolimus (Protein Bound): P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Sirolimus (Protein Bound). Risk X: Avoid
Sparsentan: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid
St John's Wort: May decrease serum concentration of Glecaprevir and Pibrentasvir. Risk X: Avoid
Tacrolimus (Systemic): Direct Acting Antiviral Agents (HCV) may decrease serum concentration of Tacrolimus (Systemic). Direct Acting Antiviral Agents (HCV) may increase serum concentration of Tacrolimus (Systemic). Risk C: Monitor
Tafamidis: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Talazoparib: BCRP/ABCG2 Inhibitors may increase serum concentration of Talazoparib. Risk C: Monitor
Talazoparib: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Talazoparib. Risk C: Monitor
Taurursodiol: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid
Taurursodiol: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Taurursodiol. Risk X: Avoid
Tedizolid: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Teniposide: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Teniposide. Risk C: Monitor
Tenofovir Disoproxil Fumarate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor
Teriflunomide: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Theophylline Derivatives: CYP1A2 Inhibitors (Weak) may increase serum concentration of Theophylline Derivatives. Risk C: Monitor
TiZANidine: CYP1A2 Inhibitors (Weak) may increase serum concentration of TiZANidine. Management: Avoid the use of tizanidine with weak CYP1A2 inhibitors when possible. If combined, monitor closely for increased tizanidine toxicities (eg, hypotension, bradycardia, drowsiness). Tizanidine dose reduction or discontinuation may be necessary. Risk D: Consider Therapy Modification
Topotecan: BCRP/ABCG2 Inhibitors may increase serum concentration of Topotecan. Risk X: Avoid
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of Topotecan. Risk X: Avoid
Triazolam: CYP3A4 Inhibitors (Weak) may increase serum concentration of Triazolam. Risk C: Monitor
Trofinetide: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Management: Avoid concurrent use with OATP1B1/1B3 substrates for which small changes in exposure may be associated with serious toxicities. Monitor for evidence of an altered response to any OATP1B1/1B3 substrate if used together with trofinetide. Risk D: Consider Therapy Modification
Ubrogepant: CYP3A4 Inhibitors (Weak) may increase 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. Risk D: Consider Therapy Modification
Vadadustat: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Vanzacaftor, Tezacaftor, and Deutivacaftor: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Venetoclax: P-glycoprotein/ABCB1 Inhibitors may increase 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. Risk D: Consider Therapy Modification
Vimseltinib: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Management: Avoid concomitant use of vimseltinib and BCRP substrates when possible. If combined, monitor for increased effects and toxicities of the BCRP substrate and consider dose adjustments. Risk D: Consider Therapy Modification
VinCRIStine: P-glycoprotein/ABCB1 Inhibitors may increase serum concentration of VinCRIStine. Risk X: Avoid
Vitamin K Antagonists: Direct Acting Antiviral Agents (HCV) may decrease anticoagulant effects of Vitamin K Antagonists. Risk C: Monitor
Voclosporin: May increase serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor
Voxilaprevir: May increase serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid
Voxilaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Voxilaprevir. Risk X: Avoid
Zavegepant: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentration of Zavegepant. Risk X: Avoid
Patients with hepatitis C virus (HCV) infection should be treated before considering pregnancy to optimize maternal health and reduce the risk of HCV transmission (AASLD/IDSA 2023).
Adverse events were not observed in animal reproduction studies with glecaprevir or pibrentasvir as individual agents.
Outcome data following maternal use of direct-acting antiviral (DAA) medications during pregnancy are limited. Use of a DAA is not currently recommended for the purpose of reducing mother-to-child transmission of hepatitis C virus due to a lack of safety and efficacy data. The decision to continue treatment in a patient who becomes pregnant while taking a DAA should be individualized after considering the potential benefits and risks of therapy. DAA medications should not be initiated during pregnancy outside of clinical trials until safety and efficacy data are available (AASLD/IDSA 2023; SMFM [Dotters-Katz 2021]).
Management of hepatitis C virus (HCV) infection requires extensive monitoring; refer to current guidelines for additional guidance including response to abnormal laboratory parameters (AASLD/IDSA 2021).
Baseline:
Within 6 months prior to starting antiviral therapy: CBC, INR, hepatic function panel (albumin, total and direct bilirubin, ALT, AST, and alkaline phosphatase), SCr, calculated GFR.
Prior to starting antiviral therapy (no specific time frame): Hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and hepatitis B core antibody (anti-HBc); HIV testing; quantitative HCV viral load (AASLD/IDSA 2021).
During therapy: Liver function tests (as clinically indicated); quantitative HCV viral load testing (≥12 weeks after completion of therapy) (AASLD/IDSA 2021).
In diabetes patients, monitor glucose and signs and symptoms of hypoglycemia. 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 posttreatment follow-up (AASLD/IDSA 2021).
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.
Protein binding: Glecaprevir: 97.5%; Pibrentasvir: >99.9%
Metabolism: Glecaprevir: Secondary to CYP3A
Half-life elimination: Glecaprevir: 6 hours; Pibrentasvir: 13 hours
Time to peak: 5 hours
Excretion: Glecaprevir: Feces (92.1%), urine (0.7%); Pibrentasvir: Feces (96.6%)
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.
