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, 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. Note: For HIV/hepatitis C virus (HCV)-coinfected patients with genotype 1, 2, 3, or 4 and compensated cirrhosis or genotype 5 or 6 (without cirrhosis or with 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 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.
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: 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.
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).
Refer to adult dosing.
(For additional information see "Glecaprevir and pibrentasvir: Pediatric drug information")
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 (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.
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, 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 with food.
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.
Hepatitis C, chronic, treatment: Treatment of chronic hepatitis C virus (HCV) genotype 1, 2, 3, 4, 5, or 6 infection in adults and pediatric patients ≥3 years of age, without cirrhosis or with compensated cirrhosis (Child-Pugh class A); HCV genotype 1 infection in adults and pediatric patients ≥3 years of age, previously treated with a regimen containing an HCV NS5A inhibitor or an NS3/4A protease inhibitor, but not both.
Hepatitis C virus–uninfected recipients of organs from hepatitis C virus–viremic donors
Substrate of BCRP/ABCG2, CYP3A4 (major), OATP1B1/1B3 (SLCO1B1/1B3), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential; Inhibits BCRP/ABCG2, CYP1A2 (weak), CYP3A4 (weak), OATP1B1/1B3 (SLCO1B1/1B3), P-glycoprotein/ABCB1, 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 Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
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. Risk D: Consider therapy modification
Aliskiren: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Aliskiren. Risk C: 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. Risk D: Consider therapy modification
ALPRAZolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of ALPRAZolam. Risk C: Monitor therapy
Antidiabetic Agents: Direct Acting Antiviral Agents (HCV) may enhance the hypoglycemic effect of Antidiabetic Agents. Risk C: Monitor therapy
Asciminib: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Asunaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Asunaprevir. Risk X: Avoid combination
Atazanavir: May increase the serum concentration of Glecaprevir and Pibrentasvir. Risk X: Avoid combination
Atogepant: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the 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 the serum concentration of Atorvastatin. Risk X: Avoid combination
Belinostat: UGT1A1 Inhibitors may increase the serum concentration of Belinostat. Risk X: Avoid combination
Berotralstat: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Berotralstat. Management: Decrease the berotralstat dose to 110 mg daily when combined with P-glycoprotein (P-gp) inhibitors. Risk D: Consider therapy modification
Bilastine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Bilastine. Risk X: Avoid combination
Brincidofovir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the 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
CarBAMazepine: May decrease the serum concentration of Glecaprevir and Pibrentasvir. Risk X: Avoid combination
Celiprolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Celiprolol. Risk C: 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. Risk D: Consider therapy modification
CloZAPine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of CloZAPine. Risk C: Monitor therapy
Cobicistat: May increase the serum concentration of Glecaprevir and Pibrentasvir. Risk C: 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: 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 the 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 the serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor therapy
Dabigatran Etexilate: P-glycoprotein/ABCB1 Inhibitors may increase serum concentrations of the active metabolite(s) of Dabigatran Etexilate. Risk C: Monitor therapy
Darolutamide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Darunavir: May increase the serum concentration of Glecaprevir and Pibrentasvir. Risk X: Avoid combination
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. Risk D: Consider therapy modification
Dofetilide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Dofetilide. Risk C: Monitor therapy
DOXOrubicin (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Conventional). Risk X: Avoid combination
DOXOrubicin (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of DOXOrubicin (Liposomal). Risk C: Monitor therapy
Edoxaban: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Edoxaban. Risk C: Monitor therapy
Efavirenz: May decrease the serum concentration of Glecaprevir and Pibrentasvir. Risk X: Avoid combination
Elacestrant: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Elagolix: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elagolix. Risk X: 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. Risk X: Avoid combination
Elbasvir and Grazoprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Elbasvir and Grazoprevir. Risk X: Avoid combination
Eltrombopag: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Eltrombopag: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: 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. Risk D: Consider therapy modification
Ethinyl Estradiol-Containing Products: May enhance the hepatotoxic effect of Glecaprevir and Pibrentasvir. Glecaprevir and Pibrentasvir may increase the serum concentration of Ethinyl Estradiol-Containing Products. Management: Use of glecaprevir/pibrentasvir and products containing more than 20 mcg of ethinyl estradiol is not recommended. Lower dose ethinyl estradiol-containing products may be used. Risk D: Consider therapy modification
Etoposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide. Risk C: Monitor therapy
Etoposide Phosphate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Etoposide Phosphate. Risk C: Monitor therapy
Everolimus: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Everolimus. Risk C: Monitor therapy
Fezolinetant: CYP1A2 Inhibitors (Weak) may increase the serum concentration of Fezolinetant. Risk X: Avoid combination
Finerenone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Finerenone. Risk C: Monitor therapy
Flibanserin: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Flibanserin. Risk C: Monitor therapy
Fosphenytoin-Phenytoin: May decrease the serum concentration of Glecaprevir and Pibrentasvir. Risk X: Avoid combination
Futibatinib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Gemfibrozil: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Gilteritinib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
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% Risk D: 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. Risk X: Avoid combination
Ixabepilone: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Ixabepilone. Risk C: Monitor therapy
Lapatinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Lapatinib. Risk C: Monitor therapy
Larotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Larotrectinib. Risk C: Monitor therapy
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. Risk D: Consider therapy modification
Leflunomide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
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. Risk D: Consider therapy modification
Leniolisib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
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. Risk D: Consider therapy modification
Lonafarnib: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Lonafarnib. Management: Avoid concurrent use of lonafarnib with weak CYP3A4 inhibitors. If concurrent use is unavoidable, reduce the lonafarnib dose to or continue at a dose of 115 mg/square meter. Monitor for evidence of arrhythmia, syncope, palpitations, or similar effects. Risk D: Consider therapy modification
Lopinavir: May increase the serum concentration of Glecaprevir and Pibrentasvir. Risk X: Avoid combination
Lovastatin: Glecaprevir and Pibrentasvir may increase the serum concentration of Lovastatin. Risk X: Avoid combination
Midazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Midazolam. Risk C: Monitor therapy
Momelotinib: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Momelotinib. Risk C: Monitor therapy
Morphine (Systemic): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Morphine (Systemic). Risk C: Monitor therapy
Nadolol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Nadolol. Risk C: Monitor therapy
Naldemedine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naldemedine. Risk C: Monitor therapy
Naloxegol: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Naloxegol. Risk C: Monitor therapy
NiMODipine: CYP3A4 Inhibitors (Weak) may increase the serum concentration of NiMODipine. Risk C: Monitor therapy
Nirmatrelvir and Ritonavir: May increase the serum concentration of Glecaprevir and Pibrentasvir. Risk X: Avoid combination
Osimertinib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Oteseconazole: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Pacritinib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
PAZOPanib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of PAZOPanib. Risk X: Avoid combination
PAZOPanib: BCRP/ABCG2 Inhibitors may increase the serum concentration of PAZOPanib. Risk X: Avoid combination
P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor therapy
P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of Glecaprevir and Pibrentasvir. Risk C: Monitor therapy
Pimozide: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Pimozide. Risk X: Avoid combination
Pralsetinib: P-glycoprotein/ABCB1 Inhibitors may increase the 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
Pretomanid: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Ranolazine: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Ranolazine. Risk C: Monitor therapy
Red Yeast Rice: Glecaprevir and Pibrentasvir may increase the serum concentration of Red Yeast Rice. Risk X: Avoid combination
Regorafenib: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Relugolix: P-glycoprotein/ABCB1 Inhibitors may increase the 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
Relugolix, Estradiol, and Norethindrone: P-glycoprotein/ABCB1 Inhibitors may increase the 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
Repotrectinib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Repotrectinib. Risk X: Avoid combination
Revefenacin: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase serum concentrations of the active metabolite(s) of Revefenacin. Risk X: 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. Risk X: Avoid combination
RifAXIMin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RifAXIMin. Risk C: Monitor therapy
Rimegepant: P-glycoprotein/ABCB1 Inhibitors may increase the 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 the serum concentration of RisperiDONE. Risk C: Monitor therapy
Ritonavir: May increase the serum concentration of Glecaprevir and Pibrentasvir. Risk X: Avoid combination
Rolapitant: May increase the 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 therapy
RomiDEPsin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of RomiDEPsin. Risk C: 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. Risk X: Avoid combination
Saquinavir: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Saquinavir. Risk C: Monitor therapy
Silodosin: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Silodosin. Risk C: Monitor therapy
Simvastatin: Glecaprevir and Pibrentasvir may increase the serum concentration of Simvastatin. Risk X: Avoid combination
Sirolimus (Conventional): P-glycoprotein/ABCB1 Inhibitors may increase the 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 the serum concentration of Sirolimus (Protein Bound). Risk X: Avoid combination
Sparsentan: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
St John's Wort: May decrease the serum concentration of Glecaprevir and Pibrentasvir. Risk X: Avoid combination
Tacrolimus (Systemic): Direct Acting Antiviral Agents (HCV) may decrease the serum concentration of Tacrolimus (Systemic). Direct Acting Antiviral Agents (HCV) may increase the serum concentration of Tacrolimus (Systemic). Risk C: Monitor therapy
Tafamidis: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Talazoparib: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Talazoparib. Risk C: Monitor therapy
Talazoparib: BCRP/ABCG2 Inhibitors may increase the serum concentration of Talazoparib. Risk C: Monitor therapy
Taurursodiol: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Taurursodiol. Risk X: Avoid combination
Taurursodiol: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Tedizolid: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Tegaserod (Withdrawn from US Market): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tegaserod (Withdrawn from US Market). Risk C: Monitor therapy
Teniposide: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Teniposide. Risk C: Monitor therapy
Tenofovir Disoproxil Fumarate: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Tenofovir Disoproxil Fumarate. Risk C: Monitor therapy
Teriflunomide: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Theophylline Derivatives: CYP1A2 Inhibitors (Weak) may increase the serum concentration of Theophylline Derivatives. Risk C: 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. Risk D: Consider therapy modification
Topotecan: BCRP/ABCG2 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination
Topotecan: P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of Topotecan. Risk X: Avoid combination
Triazolam: CYP3A4 Inhibitors (Weak) may increase the serum concentration of Triazolam. Risk C: Monitor therapy
Trofinetide: May increase the 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 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. Risk D: 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. Risk D: Consider therapy modification
VinCRIStine (Liposomal): P-glycoprotein/ABCB1 Inhibitors may increase the serum concentration of VinCRIStine (Liposomal). Risk X: Avoid combination
Vitamin K Antagonists (eg, warfarin): Direct Acting Antiviral Agents (HCV) may diminish the anticoagulant effect of Vitamin K Antagonists. Risk C: Monitor therapy
Voclosporin: May increase the serum concentration of OATP1B1/1B3 (SLCO1B1/1B3) Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
Voxilaprevir: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Voxilaprevir. Risk X: Avoid combination
Voxilaprevir: May increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk X: Avoid combination
Zavegepant: OATP1B1/1B3 (SLCO1B1/1B3) Inhibitors may increase the serum concentration of Zavegepant. Risk X: Avoid combination
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 2021).
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 2021; SMFM [Dotters-Katz 2021]).
It is not known if glecaprevir or pibrentasvir are present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and benefits of treatment to the mother. Breastfeeding is not linked to the spread of hepatitis C virus; however, if nipples are cracked or bleeding, breastfeeding is not recommended (milk should be expressed and discarded) (AASLD/IDSA 2021; SMFM [Dotters-Katz 2021]).
Pretreatment assessment: Evaluate for advanced hepatic fibrosis and hepatocellular carcinoma. Confirm vaccination against hepatitis A and B (AASLD/IDSA 2021). Assess for potential drug-drug interaction and patient’s potential readiness for adherence.
Laboratory tests recommended at any time before starting therapy:
Quantitative hepatitis C virus (HCV) RNA (HCV viral load), HIV antigen/antibody (AASLD/IDSA 2021).
Assessment for active hepatitis B virus coinfection: HBV surface antigen (HBsAg); HBV core antibody (anti-HBc) and HBV surface antibody (anti-HBs); if evidence of hepatitis B viral coinfection, HBV DNA level should be drawn. HBsAg-positive patients should be assessed for whether they meet criteria for treatment of HBV. For HBsAg-positive patients who do not meet HBV suppressive therapy treatment criteria should be either: initiated on prophylactic HBV antiviral therapy (for those with low or undetectable HBV DNA levels), which should be continued until 12 weeks after completion of HCV therapy OR monitor HBV DNA levels monthly during and immediately after HCV therapy (AASLD/IDSA 2021).
Laboratory tests recommended within 6 months prior to starting therapy: CBC, INR, hepatic function panel (serum albumin, total and direct bilirubin, ALT, AST, alkaline phosphatase), eGFR (AASLD/IDSA 2021).
Laboratory tests immediately prior to starting therapy:
Serum pregnancy test for patients of childbearing potential.
Consider NS5A RAS testing for genotype 1a-infected, treatment-experienced patients with or without cirrhosis prior to treatment (AASLD/IDSA 2021).
On-treatment monitoring:
Periodic monitoring of LFTs and assessment for presence of symptoms of liver dysfunction (eg, weakness, nausea, vomiting, jaundice, or significantly elevated bilirubin, alkaline phosphase, or INR) (AASLD/IDSA 2021).
In patients with diabetes, monitor blood glucose and for signs/symptoms of hypoglycemia (AASLD/IDSA 2021; Ciancio 2018; Dawood 2017; Hum 2017); in patients taking warfarin, monitor INR during and post therapy (AASLD/IDSA 2021).
Posttreatment assessment of cure: Quantitative HCV viral load testing ≥12 weeks after completion of therapy to document sustained virologic response and liver transaminases (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.
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