glecaprevir/pibrentasvir (Rx)

Brand and Other Names:Mavyret

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

glecaprevir/pibrentasvir

tablet

  • 100mg/40mg

Chronic Hepatitis C

Indicated for patients with genotypes 1-6 without cirrhosis or with compensated cirrhosis

Treatment-experienced patients with genotype 1 previously treated with a regimen containing NS5A inhibitor or an NS3/4A protease inhibitor, but not both

3 tablets (ie, 300 mg/120 mg total dose) PO qDay

Treatment duration, treatment-naïve

  • Genotypes 1-6, no cirrhosis or compensated cirrhosis (Child-Pugh A): 8 weeks

Treatment duration, treatment-experienced

  • No cirrhosis
    • Genotype 1 and NS5A inhibitor without prior treatment with an NS3/4A protease inhibitor (PI): 16 weeks
    • Genotype 1 and NS3/4A PI without prior treatment with an NS5A inhibitor: 12 weeks
    • Genotypes 1, 2, 4, 5, or 6 (prior treatment with simeprevir and sofosbuvir, or simeprevir, boceprevir, or telaprevir with pegylated interferon and ribavirin): 8 weeks
    • Genotype 3 (prior treatment with simeprevir and sofosbuvir, or simeprevir, boceprevir, or telaprevir with pegylated interferon and ribavirin): 16 weeks
  • Compensated cirrhosis (Child-Pugh A)
    • Genotype 1 and NS5A inhibitor without prior treatment with an NS3/4A protease inhibitor (PI): 16 weeks
    • Genotype 1 and NS3/4A PI without prior treatment with an NS5A inhibitor: 12 weeks
    • Genotypes 1, 2, 4, 5, or 6 (prior treatment with simeprevir and sofosbuvir, or simeprevir, boceprevir, or telaprevir with pegylated interferon and ribavirin): 12 weeks
    • Genotype 3 (prior treatment with simeprevir and sofosbuvir, or simeprevir, boceprevir, or telaprevir with pegylated interferon and ribavirin): 16 weeks
  • Liver or kidney transplant recipients
    • Treatment duration is 12 weeks
    • 16-week treatment duration recommended for genotype 1 (NS5A inhibitor-experienced without prior treatment with an NS3/4A protease inhibitor) or genotype 3 (treatment-experience with regimens containing [peg]interferon, ribavirin, and/or sofosbuvir, but no prior treatment experience with an HCV NS3/4A PI or NS5A inhibitor)

Dosage Modifications

Renal impairment

  • Mild, moderate, or severe, including patients on dialysis: No dosage adjustment required

Hepatic impairment

  • Mild (Child-Pugh A): No dosage adjustment required
  • Moderate-to-severe (Child-Pugh B or C): Contraindicated
  • Patients with any history of prior hepatic decompensation: Contraindicated

Dosing Considerations

Test for evidence of current or prior hepatitis B virus (HBV) infection by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) before initiating HCV treatment

Dosage Forms & Strengths

glecaprevir/pibrentasvir

tablet

  • 100mg/40mg

oral pellets

  • 50mg/20mg

Chronic Hepatitis C

Indicated for treatment-naïve children aged ≥3 years with chronic hepatitis C virus (HCV) genotypes 1-6 without cirrhosis or with compensated cirrhosis

Also indicated for treatment-experienced children aged ≥3 years with HCV genotype 1 who have been previously treated with a regimen containing either an NS5A inhibitor or an NS3/4A protease inhibitor, but not both

<3 years: Safety and efficacy not established

3-11 years

  • <20 kg: 150 mg/60 mg PO qDay (3 packets of oral pellets)
  • 20 to <30 kg: 200 mg/80 mg PO qDay (4 packets of oral pellets)
  • 30 to <45 kg: 250 mg/120 mg PO qDay (5 packets of oral pellets)

≥12 years or weight ≥45 kg

  • 300 mg/120 mg (3 tablets) PO qDay OR
  • Unable to swallow tablets: 300 mg/120 mg PO qDay (6 packets of oral pellets)

Treatment duration, treatment-naïve

  • Genotypes 1-6, no cirrhosis or compensated cirrhosis (Child-Pugh A): 8 weeks

Treatment duration, treatment-experienced

  • No cirrhosis
    • Genotype 1 and NS5A inhibitor without prior treatment with an NS3/4A protease inhibitor (PI): 16 weeks
    • Genotype 1 and NS3/4A PI without prior treatment with an NS5A inhibitor: 12 weeks
    • Genotypes 1, 2, 4, 5, or 6 (prior treatment with simeprevir and sofosbuvir, or simeprevir, boceprevir, or telaprevir with pegylated interferon and ribavirin): 8 weeks
    • Genotype 3 (prior treatment with simeprevir and sofosbuvir, or simeprevir, boceprevir, or telaprevir with pegylated interferon and ribavirin): 16 weeks
  • Compensated cirrhosis (Child-Pugh A)
    • Genotype 1 and NS5A inhibitor without prior treatment with an NS3/4A protease inhibitor (PI): 16 weeks
    • Genotype 1 and NS3/4A PI without prior treatment with an NS5A inhibitor: 12 weeks
    • Genotypes 1, 2, 4, 5, or 6 (prior treatment with simeprevir and sofosbuvir, or simeprevir, boceprevir, or telaprevir with pegylated interferon and ribavirin): 12 weeks
    • Genotype 3 (prior treatment with simeprevir and sofosbuvir, or simeprevir, boceprevir, or telaprevir with pegylated interferon and ribavirin): 16 weeks
  • Liver or kidney transplant recipients
    • Treatment duration is 12 weeks
    • 16-week treatment duration recommended for genotype 1 (NS5A inhibitor-experienced without prior treatment with an NS3/4A protease inhibitor) or genotype 3 (treatment-experience with regimens containing [peg]interferon, ribavirin, and/or sofosbuvir, but no prior treatment experience with an HCV NS3/4A PI or NS5A inhibitor)

Dosage Modifications

Renal impairment

  • Mild, moderate, or severe, including patients on dialysis: No dosage adjustment required

Hepatic impairment

  • Mild (Child-Pugh A): No dosage adjustment required
  • Moderate-to-severe (Child-Pugh B or C): Contraindicated
  • Patients with any history of prior hepatic decompensation: Contraindicated

Dosing Considerations

Test for evidence of current or prior hepatitis B virus (HBV) infection by measuring hepatitis B surface antigen (HBsAg) and hepatitis B core antibody (anti-HBc) before initiating HCV treatment

Next:

Interactions

Interaction Checker

and glecaprevir/pibrentasvir

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            Contraindicated (2)

            • elagolix

              glecaprevir/pibrentasvir will increase the level or effect of elagolix by Other (see comment). Contraindicated. Concomitant use of elagolix and strong OATP1B1 inhibitors is contraindicated.

            • rifampin

              rifampin will decrease the level or effect of glecaprevir/pibrentasvir by increasing metabolism. Contraindicated. Coadministration of rifampin (a strong CYP3A4 and P-gp inducer) with glecaprevir/pibrentasvir significantly decreased glecaprevir/pibrentasvir plasma concentrations and AUC. Potential for loss of therapeutic effect.

            Serious - Use Alternative (33)

            • abametapir

              abametapir will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. For 2 weeks after abametapir application, avoid taking drugs that are CYP3A4 substrates. If not feasible, avoid use of abametapir.

            • apalutamide

              apalutamide will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of apalutamide, a strong CYP3A4 inducer, with drugs that are CYP3A4 substrates can result in lower exposure to these medications. Avoid or substitute another drug for these medications when possible. Evaluate for loss of therapeutic effect if medication must be coadministered. Adjust dose according to prescribing information if needed.

            • atazanavir

              atazanavir will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. In clinical trials, coadministration of atazanavir (an inhibitor of CYP3A4 and OATP1B1) with glecaprevir (a CYP3A4 and OATP1B1 substrate) increased risk for ALT elevations.

            • atorvastatin

              glecaprevir/pibrentasvir increases levels of atorvastatin by Other (see comment). Avoid or Use Alternate Drug. Comment: Increased statin concentrations resulting from OATP1B1 inhibition may increase risk of myopathy, including rhabdomyolysis. Coadministration of glecaprevir/pibrentasvir with atorvastatin is not recommended.

            • carbamazepine

              carbamazepine will decrease the level or effect of glecaprevir/pibrentasvir by increasing metabolism. Avoid or Use Alternate Drug. Coadministration of carbamazepine (a strong CYP3A4 and P-gp inducer) with glecaprevir/pibrentasvir may significantly decrease glecaprevir/pibrentasvir plasma concentrations and AUC. Potential for loss of therapeutic effect.

              carbamazepine will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • colchicine

              glecaprevir/pibrentasvir will increase the level or effect of colchicine by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Avoid use of colchicine with P-gp inhibitors. If coadministration is necessary, decrease colchicine dose or frequency as recommended in prescribing information. Use of any colchicine product in conjunction with P-gp inhibitors is contraindicated in patients with renal or hepatic impairment.

            • cyclosporine

              cyclosporine will increase the level or effect of glecaprevir/pibrentasvir by decreasing metabolism. Avoid or Use Alternate Drug. Coadministration of cyclosporine (a moderate CYP3A4 inhibitor and P-gp inhibitor) with glecaprevir (CYP3A4 and P-gp substrate) and pibrentasvir (P-gp substrate) is not recommended if cyclosporine dose exceeds 100 mg/day.

            • darunavir

              darunavir will increase the level or effect of glecaprevir/pibrentasvir by decreasing metabolism. Avoid or Use Alternate Drug. Avoid coadministration of glecaprevir/pibrentasvir with darunavir (P-gp and a strong CYP3A4 inhibitor).

            • efavirenz

              efavirenz will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of efavirenz (a strong CYP3A4 inducer) with glecaprevir/pibrentasvir may significantly decrease glecaprevir/pibrentasvir plasma concentrations and AUC. Potential for loss of therapeutic effect.

            • enzalutamide

              enzalutamide will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of drugs that induce CYP3A4 with glecaprevir/pibrentasvir may decrease glecaprevir/pibrentasvir plasma concentrations. Potential for loss of therapeutic effect.

            • fexinidazole

              fexinidazole will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Fexinidazole inhibits CYP3A4. Coadministration may increase risk for adverse effects of CYP3A4 substrates.

            • ivosidenib

              ivosidenib will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of sensitive CYP3A4 substrates with ivosidenib or replace with alternate therapies. If coadministration is unavoidable, monitor patients for loss of therapeutic effect of these drugs.

            • lasmiditan

              lasmiditan increases levels of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            • leniolisib

              leniolisib will increase the level or effect of glecaprevir/pibrentasvir by Other (see comment). Avoid or Use Alternate Drug. Leniolisib, an OATP1B1 and OATP1B3 inhibitor, may increase systemic exposure of these substrates

            • lopinavir

              lopinavir will increase the level or effect of glecaprevir/pibrentasvir by decreasing metabolism. Avoid or Use Alternate Drug. Avoid coadministration of glecaprevir/pibrentasvir with lopinavir (P-gp and a strong CYP3A4 inhibitor).

            • lovastatin

              glecaprevir/pibrentasvir increases levels of lovastatin by Other (see comment). Avoid or Use Alternate Drug. Comment: Increased statin concentrations resulting from OATP1B1 inhibition may increase risk of myopathy, including rhabdomyolysis. Coadministration of glecaprevir/pibrentasvir with lovastatin is not recommended.

            • nirmatrelvir

              nirmatrelvir will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Glecaprevir/pibrentasvir serum concentrations may be increased owing to P-gp, BCRP and OATP1B inhibition by ritonavir.

            • nirmatrelvir/ritonavir

              nirmatrelvir/ritonavir will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. Glecaprevir/pibrentasvir serum concentrations may be increased owing to P-gp, BCRP and OATP1B inhibition by ritonavir.

            • phenytoin

              phenytoin will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • primidone

              primidone will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • revefenacin

              glecaprevir/pibrentasvir increases levels of revefenacin by Other (see comment). Avoid or Use Alternate Drug. Comment: OATP1B1 and OATP1B3 transport inhibitors may increase systemic exposure of revefenacin's active metabolite. Coadministration not recommended.

            • rifampin

              rifampin will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • rimegepant

              glecaprevir/pibrentasvir will increase the level or effect of rimegepant by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.

            • ritonavir

              ritonavir will increase the level or effect of glecaprevir/pibrentasvir by decreasing metabolism. Avoid or Use Alternate Drug. Avoid coadministration of glecaprevir/pibrentasvir with ritonavir (P-gp and a strong CYP3A4 inhibitor).

            • simvastatin

              glecaprevir/pibrentasvir increases levels of simvastatin by Other (see comment). Avoid or Use Alternate Drug. Comment: Increased statin concentrations resulting from OATP1B1 inhibition may increase risk of myopathy, including rhabdomyolysis. Coadministration of glecaprevir/pibrentasvir with simvastatin is not recommended.

            • sotorasib

              sotorasib will decrease the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If use is unavoidable, refer to the prescribing information of the P-gp substrate for dosage modifications.

            • St John's Wort

              St John's Wort will decrease the level or effect of glecaprevir/pibrentasvir by increasing metabolism. Avoid or Use Alternate Drug. Coadministration of St John's wort (a strong CYP3A4 and P-gp inducer) with glecaprevir/pibrentasvir may significantly decrease glecaprevir/pibrentasvir plasma concentrations and AUC. Potential for loss of therapeutic effect.

            • sulbactam/durlobactam

              glecaprevir/pibrentasvir will increase the level or effect of sulbactam/durlobactam by Other (see comment). Avoid or Use Alternate Drug. Sulbactam is predicted to have active secretion by OATP1 as a significant portion of total clearance; therefore, inhibition of OAT1 may increase sulbactam plasma concentrations

            • tepotinib

              tepotinib will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If concomitant use unavoidable, reduce the P-gp substrate dosage if recommended in its approved product labeling.

            • trofinetide

              trofinetide will increase the level or effect of glecaprevir/pibrentasvir by Other (see comment). Avoid or Use Alternate Drug. Trofinetide (an OATP131 and OATP13B inhibitor) may increase plasma levels of OATP131 or OATP13B substrates. Avoid coadministration with sensitive substrates.

            • tucatinib

              tucatinib will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.

            • voxelotor

              voxelotor will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.

            • zavegepant intranasal

              glecaprevir/pibrentasvir will increase the level or effect of zavegepant intranasal by Other (see comment). Avoid or Use Alternate Drug. OATP1B3 inhibitors may result in a significant increase in systemic exposure of zavegepant (an OATP1B3 substrate).

            Monitor Closely (200)

            • abiraterone

              abiraterone will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • afatinib

              afatinib will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              glecaprevir/pibrentasvir will increase the level or effect of afatinib by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely.

            • aliskiren

              glecaprevir/pibrentasvir will increase the level or effect of aliskiren by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely.

            • alvimopan

              glecaprevir/pibrentasvir will increase the level or effect of alvimopan by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely.

            • ambrisentan

              glecaprevir/pibrentasvir will increase the level or effect of ambrisentan by Other (see comment). Use Caution/Monitor. Coadministration with glecaprevir/pibrentasvir may increase plasma concentration of drugs that are substrates of OATP1B1 or OATP1B3

              glecaprevir/pibrentasvir will increase the level or effect of ambrisentan by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely.

            • amiodarone

              amiodarone will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              glecaprevir/pibrentasvir will increase the level or effect of amiodarone by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely.

            • amitriptyline

              glecaprevir/pibrentasvir will increase the level or effect of amitriptyline by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely.

            • amobarbital

              amobarbital will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of drugs that induce CYP3A4 with glecaprevir/pibrentasvir may decrease glecaprevir/pibrentasvir plasma concentrations. Potential for loss of therapeutic effect.

            • apalutamide

              apalutamide will decrease the level or effect of glecaprevir/pibrentasvir by increasing elimination. Use Caution/Monitor. Apalutamide weakly induces OATP1B1 and may decrease systemic exposure of drugs that are OATP1B1 substrates.

            • apixaban

              glecaprevir/pibrentasvir will increase the level or effect of apixaban by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely.

            • atogepant

              glecaprevir/pibrentasvir will increase the level or effect of atogepant by Other (see comment). Modify Therapy/Monitor Closely. Recommended dosage of atogepant (an OATP1B1 substrate) with concomitant use of OATP inhibitors is 10 mg or 30 mg qDay.

            • azithromycin

              azithromycin will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • belzutifan

              belzutifan will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. If unable to avoid coadministration of belzutifan with sensitive CYP3A4 substrates, consider increasing the sensitive CYP3A4 substrate dose in accordance with its prescribing information.

            • bendamustine

              glecaprevir/pibrentasvir will increase the level or effect of bendamustine by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely.

            • berotralstat

              glecaprevir/pibrentasvir increases levels of berotralstat by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Reduced berotralstat dose to 110 mg/day when coadministered with P-gp inhibitors.

              berotralstat will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor or titrate P-gp substrate dose if coadministered.

            • bosentan

              bosentan will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of drugs that induce CYP3A4 with glecaprevir/pibrentasvir may decrease glecaprevir/pibrentasvir plasma concentrations. Potential for loss of therapeutic effect.

              glecaprevir/pibrentasvir will increase the level or effect of bosentan by Other (see comment). Use Caution/Monitor. Coadministration with glecaprevir/pibrentasvir may increase plasma concentration of drugs that are substrates of OATP1B1 or OATP1B3

            • budesonide

              glecaprevir/pibrentasvir will increase the level or effect of budesonide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • butabarbital

              butabarbital will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of drugs that induce CYP3A4 with glecaprevir/pibrentasvir may decrease glecaprevir/pibrentasvir plasma concentrations. Potential for loss of therapeutic effect.

            • butalbital

              butalbital will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of drugs that induce CYP3A4 with glecaprevir/pibrentasvir may decrease glecaprevir/pibrentasvir plasma concentrations. Potential for loss of therapeutic effect.

            • carfilzomib

              glecaprevir/pibrentasvir will increase the level or effect of carfilzomib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • carvedilol

              carvedilol will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              glecaprevir/pibrentasvir will increase the level or effect of carvedilol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • caspofungin

              caspofungin will increase the level or effect of glecaprevir/pibrentasvir by decreasing metabolism. Use Caution/Monitor. Caution when coadministering glecaprevir/pibrentasvir with OATP1B1/OATP1B3 inhibitors

            • cenobamate

              cenobamate will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Increase dose of CYP3A4 substrate, as needed, when coadministered with cenobamate.

            • cetirizine

              glecaprevir/pibrentasvir will increase the level or effect of cetirizine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • cimetidine

              glecaprevir/pibrentasvir will increase the level or effect of cimetidine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • ciprofloxacin

              glecaprevir/pibrentasvir will increase the level or effect of ciprofloxacin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • clarithromycin

              clarithromycin will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • clotrimazole

              clotrimazole will increase the level or effect of glecaprevir/pibrentasvir by decreasing metabolism. Use Caution/Monitor. Caution when coadministering glecaprevir/pibrentasvir with OATP1B1/OATP1B3 inhibitors

            • cobicistat

              cobicistat will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • conivaptan

              conivaptan will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • crizotinib

              crizotinib will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • dabigatran

              glecaprevir/pibrentasvir will increase the level or effect of dabigatran by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • dabrafenib

              dabrafenib will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of drugs that induce CYP3A4 with glecaprevir/pibrentasvir may decrease glecaprevir/pibrentasvir plasma concentrations. Potential for loss of therapeutic effect.

              glecaprevir/pibrentasvir will increase the level or effect of dabrafenib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • dasabuvir

              glecaprevir/pibrentasvir will increase the level or effect of dasabuvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • daunorubicin

              glecaprevir/pibrentasvir will increase the level or effect of daunorubicin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              glecaprevir/pibrentasvir will increase the level or effect of daunorubicin by decreasing metabolism. Use Caution/Monitor. Glecaprevir/pibrentasvir may increase plasma concentration of BCRP substrates.

            • desloratadine

              glecaprevir/pibrentasvir will increase the level or effect of desloratadine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • dexamethasone

              dexamethasone will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of drugs that induce CYP3A4 with glecaprevir/pibrentasvir may decrease glecaprevir/pibrentasvir plasma concentrations. Potential for loss of therapeutic effect.

              glecaprevir/pibrentasvir will increase the level or effect of dexamethasone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • digoxin

              glecaprevir/pibrentasvir will increase the level or effect of digoxin by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Measure serum digoxin concentrations before initiating glecaprevir/pibrentasvir. To reduce digoxin concentrations, decrease the dose by ~50% or by modifying the dosing frequency and continue monitoring.

            • diltiazem

              glecaprevir/pibrentasvir will increase the level or effect of diltiazem by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • dipyridamole

              dipyridamole will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              dipyridamole will increase the level or effect of glecaprevir/pibrentasvir by decreasing metabolism. Use Caution/Monitor. Caution when coadministering glecaprevir/pibrentasvir with BCRP inhibitors.

              glecaprevir/pibrentasvir will increase the level or effect of dipyridamole by decreasing metabolism. Use Caution/Monitor. Glecaprevir/pibrentasvir may increase plasma concentration of BCRP substrates.

            • docetaxel

              glecaprevir/pibrentasvir will increase the level or effect of docetaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • doxorubicin

              glecaprevir/pibrentasvir will increase the level or effect of doxorubicin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              glecaprevir/pibrentasvir will increase the level or effect of doxorubicin by decreasing metabolism. Use Caution/Monitor. Glecaprevir/pibrentasvir may increase plasma concentration of BCRP substrates.

            • dronedarone

              dronedarone will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • duvelisib

              glecaprevir/pibrentasvir will increase the level or effect of duvelisib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • edoxaban

              glecaprevir/pibrentasvir will increase the level or effect of edoxaban by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • elagolix

              elagolix will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              elagolix decreases levels of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Elagolix is a weak-to-moderate CYP3A4 inducer. Monitor CYP3A substrates if coadministered. Consider increasing CYP3A substrate dose if needed.

            • elbasvir/grazoprevir

              glecaprevir/pibrentasvir will increase the level or effect of elbasvir/grazoprevir by Other (see comment). Use Caution/Monitor. Coadministration with glecaprevir/pibrentasvir may increase plasma concentration of drugs that are substrates of OATP1B1 or OATP1B3

            • eletriptan

              glecaprevir/pibrentasvir will increase the level or effect of eletriptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • eliglustat

              eliglustat will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • eltrombopag

              eltrombopag will increase the level or effect of glecaprevir/pibrentasvir by decreasing metabolism. Use Caution/Monitor. Monitor for glecaprevir/pibrentasvir adverse effects if coadministered with drugs that are OATP1B1 and BCRP inhibitor

            • eluxadoline

              eluxadoline will increase the level or effect of glecaprevir/pibrentasvir by Other (see comment). Use Caution/Monitor. Glecaprevir/pibrentasvir is an OATP1B1 inhibitor, BCRP substrate and inhibitor, and glecaprevir is a OAT1B1/3 substrate. Eluxadoline is an OATP1B1 substrate and BCRP inhibitor. Glecaprevir/pibrentasvir may decrease the therapeutic effects of eluxadoline. Eluxadoline may increase the plasma levels of glecaprevir/pibrentasvir.

            • enalapril

              glecaprevir/pibrentasvir will increase the level or effect of enalapril by Other (see comment). Use Caution/Monitor. Coadministration with glecaprevir/pibrentasvir may increase plasma concentration of drugs that are substrates of OATP1B1 or OATP1B3

            • encorafenib

              encorafenib, glecaprevir/pibrentasvir. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Encorafenib both inhibits and induces CYP3A4 at clinically relevant plasma concentrations. Coadministration of encorafenib with sensitive CYP3A4 substrates may result in increased toxicity or decreased efficacy of these agents.

              encorafenib will increase the level or effect of glecaprevir/pibrentasvir by Other (see comment). Modify Therapy/Monitor Closely. Encorafenib (a OATP1B1 and OATP1B3 inhibitor) may increase the concentration and toxicities of OATP1B1 and OATP1B3 substrates. Closely monitor for signs and symptoms of increased exposure and consider adjusting the dose of these substrates.

            • erythromycin base

              erythromycin base will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              glecaprevir/pibrentasvir will increase the level or effect of erythromycin base by Other (see comment). Use Caution/Monitor. Coadministration with glecaprevir/pibrentasvir may increase plasma concentration of drugs that are substrates of OATP1B1 or OATP1B3

              glecaprevir/pibrentasvir will increase the level or effect of erythromycin base by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • eslicarbazepine acetate

              eslicarbazepine acetate will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of drugs that induce CYP3A4 with glecaprevir/pibrentasvir may decrease glecaprevir/pibrentasvir plasma concentrations. Potential for loss of therapeutic effect.

            • estradiol

              glecaprevir/pibrentasvir will increase the level or effect of estradiol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • etoposide

              glecaprevir/pibrentasvir will increase the level or effect of etoposide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • etravirine

              etravirine will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of drugs that induce CYP3A4 with glecaprevir/pibrentasvir may decrease glecaprevir/pibrentasvir plasma concentrations. Potential for loss of therapeutic effect.

              etravirine will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • everolimus

              glecaprevir/pibrentasvir will increase the level or effect of everolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • ezetimibe

              glecaprevir/pibrentasvir will increase the level or effect of ezetimibe by Other (see comment). Use Caution/Monitor. Coadministration with glecaprevir/pibrentasvir may increase plasma concentration of drugs that are substrates of OATP1B1 or OATP1B3

            • fedratinib

              fedratinib will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Adjust dose of drugs that are CYP3A4 substrates as necessary.

            • fentanyl

              glecaprevir/pibrentasvir will increase the level or effect of fentanyl by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • fexofenadine

              glecaprevir/pibrentasvir will increase the level or effect of fexofenadine by Other (see comment). Use Caution/Monitor. Coadministration with glecaprevir/pibrentasvir may increase plasma concentration of drugs that are substrates of OATP1B1 or OATP1B3

              glecaprevir/pibrentasvir will increase the level or effect of fexofenadine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • flibanserin

              flibanserin will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • fluvastatin

              glecaprevir/pibrentasvir increases levels of fluvastatin by Other (see comment). Modify Therapy/Monitor Closely. Comment: Increased statin concentrations resulting from OATP1B1 inhibition may increase risk of myopathy, including rhabdomyolysis. Use lowest approved dose of fluvastatin. If a higher dose is needed, use the lowest necessary statin dose based on a risk/benefit assessment.

            • fosamprenavir

              fosamprenavir will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fosphenytoin

              fosphenytoin will decrease the level or effect of glecaprevir/pibrentasvir by increasing metabolism. Use Caution/Monitor. Coadministration of drugs that induce CYP3A4 and P-gp with glecaprevir/pibrentasvir may decrease glecaprevir/pibrentasvir plasma concentrations. Potential for loss of therapeutic effect.

              fosphenytoin will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • fostamatinib

              fostamatinib will increase the level or effect of glecaprevir/pibrentasvir by Other (see comment). Use Caution/Monitor. Concomitant use of fostamatinib may increase concentrations of P-gp/BCRP substrate drugs. Monitor for toxicities of P-gp/BCRP substrate drug that may require dosage reduction when given concurrently with fostamatinib.

            • fostemsavir

              fostemsavir will increase the level or effect of glecaprevir/pibrentasvir by Other (see comment). Modify Therapy/Monitor Closely. Fostemsavir inhibits OATP1B1/3 transporter. If possible, avoid coadministration or modify dose of OATP1B1/3 substrates coadministered with fostemsavir.

            • gefitinib

              gefitinib will increase the level or effect of glecaprevir/pibrentasvir by decreasing metabolism. Use Caution/Monitor. Caution when coadministering glecaprevir/pibrentasvir with BCRP inhibitors.

            • gemfibrozil

              gemfibrozil will increase the level or effect of glecaprevir/pibrentasvir by decreasing metabolism. Use Caution/Monitor. Caution when coadministering glecaprevir/pibrentasvir with OATP1B1/OATP1B3 inhibitors

            • glyburide

              glyburide will increase the level or effect of glecaprevir/pibrentasvir by decreasing metabolism. Use Caution/Monitor. Caution when coadministering glecaprevir/pibrentasvir with OATP1B1/OATP1B3 inhibitors

              glecaprevir/pibrentasvir will increase the level or effect of glyburide by Other (see comment). Use Caution/Monitor. Glecaprevir/pibrentasvir may increase plasma concentration of P-gp and BCRP substrates.

            • grapefruit

              grapefruit will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • hydrocortisone

              glecaprevir/pibrentasvir will increase the level or effect of hydrocortisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • ibrutinib

              ibrutinib will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • idarubicin

              glecaprevir/pibrentasvir will increase the level or effect of idarubicin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • idelalisib

              idelalisib will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • imatinib

              imatinib will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              glecaprevir/pibrentasvir will increase the level or effect of imatinib by Other (see comment). Use Caution/Monitor. Glecaprevir/pibrentasvir may increase plasma concentration of OATP1B1/OATP1B3, P-gp and BCRP substrates.

            • indinavir

              indinavir will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              glecaprevir/pibrentasvir will increase the level or effect of indinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • irinotecan

              glecaprevir/pibrentasvir will increase the level or effect of irinotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              glecaprevir/pibrentasvir will increase the level or effect of irinotecan by decreasing metabolism. Use Caution/Monitor. Glecaprevir/pibrentasvir may increase plasma concentration of BCRP substrates.

            • irinotecan liposomal

              glecaprevir/pibrentasvir will increase the level or effect of irinotecan liposomal by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • isavuconazonium sulfate

              isavuconazonium sulfate will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • isoniazid

              isoniazid will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • istradefylline

              istradefylline will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of CYP3A4 substrates in clinical trials. This effect was not observed with istradefylline 20 mg/day. Consider dose reduction of sensitive CYP3A4 substrates.

              istradefylline will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Istradefylline 40 mg/day increased peak levels and AUC of P-gp substrates in clinical trials. Consider dose reduction of sensitive P-gp substrates.

            • itraconazole

              itraconazole will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              itraconazole will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • ivacaftor

              ivacaftor will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Ivacaftor and its M1 metabolite has the potential to inhibit P-gp; may significantly increase systemic exposure to sensitive P-gp substrates with a narrow therapeutic index.

            • ivermectin

              glecaprevir/pibrentasvir will increase the level or effect of ivermectin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • ketoconazole

              ketoconazole will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lapatinib

              lapatinib will increase the level or effect of glecaprevir/pibrentasvir by decreasing metabolism. Use Caution/Monitor. Caution when coadministering glecaprevir/pibrentasvir with P-gp/BCRP inhibitors.

              glecaprevir/pibrentasvir will increase the level or effect of lapatinib by Other (see comment). Use Caution/Monitor. Glecaprevir/pibrentasvir may increase plasma concentration of P-gp and BCRP substrates.

            • ledipasvir/sofosbuvir

              ledipasvir/sofosbuvir will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              glecaprevir/pibrentasvir will increase the level or effect of ledipasvir/sofosbuvir by Other (see comment). Use Caution/Monitor. Glecaprevir/pibrentasvir may increase plasma concentration of P-gp and BCRP substrates.

            • leflunomide

              glecaprevir/pibrentasvir will increase the level or effect of leflunomide by decreasing metabolism. Use Caution/Monitor. Glecaprevir/pibrentasvir may increase plasma concentration of BCRP substrates.

            • lenacapavir

              lenacapavir will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.

            • lenvatinib

              glecaprevir/pibrentasvir will increase the level or effect of lenvatinib by Other (see comment). Use Caution/Monitor. Glecaprevir/pibrentasvir may increase plasma concentration of P-gp and BCRP substrates.

            • letermovir

              glecaprevir/pibrentasvir increases levels of letermovir by decreasing metabolism. Use Caution/Monitor. Coadminstration of letermovir, an OATP1B1/3 substrate, with OATP1B1/3 inhibitors may increase letermovir plasma concentrations.

              letermovir increases levels of glecaprevir/pibrentasvir by Other (see comment). Use Caution/Monitor. Comment: Letermovir, an OATP1B1/3 inhibitor may increase plasma concentrations of coadministered OATP1B1/3 substrates.

            • levoketoconazole

              levoketoconazole will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lidocaine

              glecaprevir/pibrentasvir will increase the level or effect of lidocaine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • linagliptin

              glecaprevir/pibrentasvir will increase the level or effect of linagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • lomitapide

              lomitapide will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • lonafarnib

              lonafarnib will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Lonafarnib is a weak P-gp inhibitor. Monitor for adverse reactions if coadministered with P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities. Reduce P-gp substrate dose if needed.

            • loperamide

              glecaprevir/pibrentasvir will increase the level or effect of loperamide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • lorlatinib

              lorlatinib will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • lovastatin

              glecaprevir/pibrentasvir will increase the level or effect of lovastatin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • lumacaftor/ivacaftor

              lumacaftor/ivacaftor will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of drugs that induce CYP3A4 with glecaprevir/pibrentasvir may decrease glecaprevir/pibrentasvir plasma concentrations. Potential for loss of therapeutic effect.

            • maraviroc

              glecaprevir/pibrentasvir will increase the level or effect of maraviroc by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • mefloquine

              mefloquine will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              glecaprevir/pibrentasvir will increase the level or effect of mefloquine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • methotrexate

              glecaprevir/pibrentasvir will increase the level or effect of methotrexate by Other (see comment). Use Caution/Monitor. Glecaprevir/pibrentasvir may increase plasma concentration of OATP1B1/OATP1B3, P-gp and BCRP substrates.

            • methylprednisolone

              glecaprevir/pibrentasvir will increase the level or effect of methylprednisolone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • metyrapone

              metyrapone will increase the level or effect of glecaprevir/pibrentasvir by decreasing metabolism. Use Caution/Monitor. Caution when coadministering glecaprevir/pibrentasvir with OATP1B1/OATP1B3 inhibitors

            • mifepristone

              mifepristone will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • mitomycin

              glecaprevir/pibrentasvir will increase the level or effect of mitomycin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • mitotane

              mitotane will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of drugs that induce CYP3A4 with glecaprevir/pibrentasvir may decrease glecaprevir/pibrentasvir plasma concentrations. Potential for loss of therapeutic effect.

            • mitoxantrone

              glecaprevir/pibrentasvir will increase the level or effect of mitoxantrone by decreasing metabolism. Use Caution/Monitor. Glecaprevir/pibrentasvir may increase plasma concentration of BCRP substrates.

            • morphine

              glecaprevir/pibrentasvir will increase the level or effect of morphine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • nadolol

              glecaprevir/pibrentasvir will increase the level or effect of nadolol by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • nafcillin

              nafcillin will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of drugs that induce CYP3A4 with glecaprevir/pibrentasvir may decrease glecaprevir/pibrentasvir plasma concentrations. Potential for loss of therapeutic effect.

            • naldemedine

              glecaprevir/pibrentasvir will increase the level or effect of naldemedine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • nefazodone

              nefazodone will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • nelfinavir

              nelfinavir will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              nelfinavir will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              glecaprevir/pibrentasvir will increase the level or effect of nelfinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • nevirapine

              nevirapine will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of drugs that induce CYP3A4 with glecaprevir/pibrentasvir may decrease glecaprevir/pibrentasvir plasma concentrations. Potential for loss of therapeutic effect.

            • nicardipine

              nicardipine will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              glecaprevir/pibrentasvir will increase the level or effect of nicardipine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • nilotinib

              nilotinib will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              glecaprevir/pibrentasvir will increase the level or effect of nilotinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • nintedanib

              glecaprevir/pibrentasvir will increase the level or effect of nintedanib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • nitrofurantoin

              glecaprevir/pibrentasvir will increase the level or effect of nitrofurantoin by decreasing metabolism. Use Caution/Monitor. Glecaprevir/pibrentasvir may increase plasma concentration of BCRP substrates.

            • olmesartan

              glecaprevir/pibrentasvir will increase the level or effect of olmesartan by Other (see comment). Use Caution/Monitor. Coadministration with glecaprevir/pibrentasvir may increase plasma concentration of drugs that are substrates of OATP1B1 or OATP1B3

            • ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC)

              glecaprevir/pibrentasvir will increase the level or effect of ombitasvir/paritaprevir/ritonavir & dasabuvir (DSC) by Other (see comment). Use Caution/Monitor. Coadministration with glecaprevir/pibrentasvir may increase plasma concentration of drugs that are substrates of OATP1B1 or OATP1B3

            • ondansetron

              glecaprevir/pibrentasvir will increase the level or effect of ondansetron by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • osimertinib

              osimertinib will increase the level or effect of glecaprevir/pibrentasvir by decreasing metabolism. Use Caution/Monitor. Caution when coadministering glecaprevir/pibrentasvir with BCRP inhibitors.

              glecaprevir/pibrentasvir will increase the level or effect of osimertinib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              glecaprevir/pibrentasvir will increase the level or effect of osimertinib by decreasing metabolism. Use Caution/Monitor. Glecaprevir/pibrentasvir may increase plasma concentration of BCRP substrates.

            • oxcarbazepine

              oxcarbazepine will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of drugs that induce CYP3A4 with glecaprevir/pibrentasvir may decrease glecaprevir/pibrentasvir plasma concentrations. Potential for loss of therapeutic effect.

            • paclitaxel

              paclitaxel will increase the level or effect of glecaprevir/pibrentasvir by decreasing metabolism. Use Caution/Monitor. Caution when coadministering glecaprevir/pibrentasvir with OATP1B1/OATP1B3 inhibitors

              glecaprevir/pibrentasvir will increase the level or effect of paclitaxel by Other (see comment). Use Caution/Monitor. Coadministration with glecaprevir/pibrentasvir may increase plasma concentration of drugs that are substrates of OATP1B1 or OATP1B3

              glecaprevir/pibrentasvir will increase the level or effect of paclitaxel by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • paclitaxel protein bound

              glecaprevir/pibrentasvir will increase the level or effect of paclitaxel protein bound by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • paliperidone

              paliperidone will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              glecaprevir/pibrentasvir will increase the level or effect of paliperidone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • pantoprazole

              pantoprazole will increase the level or effect of glecaprevir/pibrentasvir by decreasing metabolism. Use Caution/Monitor. Caution when coadministering glecaprevir/pibrentasvir with P-gp/BCRP inhibitors.

              glecaprevir/pibrentasvir will increase the level or effect of pantoprazole by Other (see comment). Use Caution/Monitor. Glecaprevir/pibrentasvir may increase plasma concentration of P-gp and BCRP substrates.

            • pazopanib

              pazopanib will increase the level or effect of glecaprevir/pibrentasvir by decreasing metabolism. Use Caution/Monitor. Caution when coadministering glecaprevir/pibrentasvir with OATP1B1/OATP1B3 inhibitors

              glecaprevir/pibrentasvir will increase the level or effect of pazopanib by Other (see comment). Use Caution/Monitor. Glecaprevir/pibrentasvir may increase plasma concentration of P-gp and BCRP substrates.

            • pentobarbital

              pentobarbital will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of drugs that induce CYP3A4 with glecaprevir/pibrentasvir may decrease glecaprevir/pibrentasvir plasma concentrations. Potential for loss of therapeutic effect.

            • phenobarbital

              phenobarbital will decrease the level or effect of glecaprevir/pibrentasvir by increasing metabolism. Use Caution/Monitor. Coadministration of drugs that induce CYP3A4 and P-gp with glecaprevir/pibrentasvir may decrease glecaprevir/pibrentasvir plasma concentrations. Potential for loss of therapeutic effect.

              phenobarbital will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • pioglitazone

              pioglitazone will increase the level or effect of glecaprevir/pibrentasvir by decreasing metabolism. Use Caution/Monitor. Caution when coadministering glecaprevir/pibrentasvir with OATP1B1/OATP1B3 inhibitors

            • pitavastatin

              glecaprevir/pibrentasvir increases levels of pitavastatin by Other (see comment). Modify Therapy/Monitor Closely. Comment: Increased statin concentrations resulting from OATP1B1 inhibition may increase risk of myopathy, including rhabdomyolysis. Use lowest approved dose of pitavastatin. If a higher dose is needed, use the lowest necessary statin dose based on a risk/benefit assessment.

            • pomalidomide

              glecaprevir/pibrentasvir will increase the level or effect of pomalidomide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • ponatinib

              ponatinib will increase the level or effect of glecaprevir/pibrentasvir by decreasing metabolism. Use Caution/Monitor. Caution when coadministering glecaprevir/pibrentasvir with P-gp/BCRP inhibitors.

            • posaconazole

              posaconazole will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              glecaprevir/pibrentasvir will increase the level or effect of posaconazole by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • pravastatin

              glecaprevir/pibrentasvir increases levels of pravastatin by Other (see comment). Modify Therapy/Monitor Closely. Comment: Increased statin concentrations resulting from OATP1B1 inhibition may increase risk of myopathy, including rhabdomyolysis. If coadministered, reduce pravastatin dose by 50%.

            • prazosin

              glecaprevir/pibrentasvir will increase the level or effect of prazosin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • prednisone

              glecaprevir/pibrentasvir will decrease the level or effect of prednisone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • progesterone, natural

              progesterone, natural will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • propafenone

              propafenone will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • propranolol

              propranolol will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • quinidine

              quinidine will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              glecaprevir/pibrentasvir will increase the level or effect of quinidine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • quinine

              quinine will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              glecaprevir/pibrentasvir will increase the level or effect of quinine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • ranolazine

              ranolazine will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              glecaprevir/pibrentasvir will increase the level or effect of ranolazine by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • regorafenib

              regorafenib will increase the level or effect of glecaprevir/pibrentasvir by decreasing metabolism. Use Caution/Monitor. Caution when coadministering glecaprevir/pibrentasvir with BCRP inhibitors.

            • repaglinide

              repaglinide will increase the level or effect of glecaprevir/pibrentasvir by decreasing metabolism. Use Caution/Monitor. Caution when coadministering glecaprevir/pibrentasvir with OATP1B1/OATP1B3 inhibitors

              glecaprevir/pibrentasvir will increase the level or effect of repaglinide by Other (see comment). Use Caution/Monitor. Coadministration with glecaprevir/pibrentasvir may increase plasma concentration of drugs that are substrates of OATP1B1 or OATP1B3

            • rifabutin

              rifabutin will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of drugs that induce CYP3A4 with glecaprevir/pibrentasvir may decrease glecaprevir/pibrentasvir plasma concentrations. Potential for loss of therapeutic effect.

            • rifapentine

              rifapentine will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of drugs that induce CYP3A4 with glecaprevir/pibrentasvir may decrease glecaprevir/pibrentasvir plasma concentrations. Potential for loss of therapeutic effect.

            • rifaximin

              glecaprevir/pibrentasvir will increase the level or effect of rifaximin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • riociguat

              glecaprevir/pibrentasvir will increase the level or effect of riociguat by Other (see comment). Use Caution/Monitor. Glecaprevir/pibrentasvir may increase plasma concentration of P-gp and BCRP substrates.

            • risperidone

              glecaprevir/pibrentasvir will increase the level or effect of risperidone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • ritonavir

              glecaprevir/pibrentasvir will increase the level or effect of ritonavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • rolapitant

              rolapitant will increase the level or effect of glecaprevir/pibrentasvir by decreasing metabolism. Use Caution/Monitor. Caution when coadministering glecaprevir/pibrentasvir with P-gp/BCRP inhibitors.

            • rosiglitazone

              rosiglitazone will increase the level or effect of glecaprevir/pibrentasvir by decreasing metabolism. Use Caution/Monitor. Caution when coadministering glecaprevir/pibrentasvir with OATP1B1/OATP1B3 inhibitors

            • rosuvastatin

              glecaprevir/pibrentasvir increases levels of rosuvastatin by Other (see comment). Modify Therapy/Monitor Closely. Comment: Increased statin concentrations resulting from OATP1B1 inhibition may increase risk of myopathy, including rhabdomyolysis. If coadministered, do not exceed 10 mg/day of rosuvastatin.

            • rucaparib

              rucaparib will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.

            • safinamide

              safinamide will increase the level or effect of glecaprevir/pibrentasvir by decreasing metabolism. Use Caution/Monitor. Caution when coadministering glecaprevir/pibrentasvir with BCRP inhibitors.

            • saquinavir

              saquinavir will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

              saquinavir will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              glecaprevir/pibrentasvir will increase the level or effect of saquinavir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • sarecycline

              sarecycline will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Monitor for toxicities of P-gp substrates that may require dosage reduction when coadministered with P-gp inhibitors.

            • saxagliptin

              glecaprevir/pibrentasvir will increase the level or effect of saxagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • secobarbital

              secobarbital will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Coadministration of drugs that induce CYP3A4 with glecaprevir/pibrentasvir may decrease glecaprevir/pibrentasvir plasma concentrations. Potential for loss of therapeutic effect.

            • selexipag

              glecaprevir/pibrentasvir will increase the level or effect of selexipag by decreasing metabolism. Use Caution/Monitor. Glecaprevir/pibrentasvir may increase plasma concentration of BCRP substrates.

            • silodosin

              glecaprevir/pibrentasvir will increase the level or effect of silodosin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • sirolimus

              glecaprevir/pibrentasvir will increase the level or effect of sirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • sitagliptin

              glecaprevir/pibrentasvir will increase the level or effect of sitagliptin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • stiripentol

              stiripentol, glecaprevir/pibrentasvir. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.

              stiripentol will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely. Consider reducing the dose of P-glycoprotein (P-gp) substrates, if adverse reactions are experienced when administered concomitantly with stiripentol.

            • sulfasalazine

              glecaprevir/pibrentasvir will increase the level or effect of sulfasalazine by decreasing metabolism. Use Caution/Monitor. Glecaprevir/pibrentasvir may increase plasma concentration of BCRP substrates.

            • sunitinib

              sunitinib will increase the level or effect of glecaprevir/pibrentasvir by decreasing metabolism. Use Caution/Monitor. Caution when coadministering glecaprevir/pibrentasvir with P-gp/BCRP inhibitors.

            • suvorexant

              suvorexant will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • tacrolimus

              tacrolimus will increase the level or effect of glecaprevir/pibrentasvir by decreasing metabolism. Use Caution/Monitor. Caution when coadministering glecaprevir/pibrentasvir with OATP1B1/OATP1B3 inhibitors

              glecaprevir/pibrentasvir will increase the level or effect of tacrolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • talazoparib

              glecaprevir/pibrentasvir will increase the level or effect of talazoparib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Talazoparib is a P-glycoprotein (P-gp) substrate; coadministration with P-gp inhibitors may increase talazoparib systemic exposure.

            • tamoxifen

              tamoxifen will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • tazemetostat

              tazemetostat will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tecovirimat

              tecovirimat will decrease the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.

            • telmisartan

              telmisartan will increase the level or effect of glecaprevir/pibrentasvir by decreasing metabolism. Use Caution/Monitor. Caution when coadministering glecaprevir/pibrentasvir with OATP1B1/OATP1B3 inhibitors

              glecaprevir/pibrentasvir will increase the level or effect of telmisartan by Other (see comment). Use Caution/Monitor. Coadministration with glecaprevir/pibrentasvir may increase plasma concentration of drugs that are substrates of OATP1B1 or OATP1B3

            • temsirolimus

              glecaprevir/pibrentasvir will increase the level or effect of temsirolimus by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • teniposide

              glecaprevir/pibrentasvir will increase the level or effect of teniposide by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • tenofovir AF

              glecaprevir/pibrentasvir will increase the level or effect of tenofovir AF by decreasing metabolism. Use Caution/Monitor. Glecaprevir/pibrentasvir may increase plasma concentration of BCRP substrates.

            • tenofovir DF

              glecaprevir/pibrentasvir will increase the level or effect of tenofovir DF by decreasing metabolism. Use Caution/Monitor. Glecaprevir/pibrentasvir may increase plasma concentration of BCRP substrates.

            • testosterone

              glecaprevir/pibrentasvir will increase the level or effect of testosterone by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • tipranavir

              tipranavir will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • tolvaptan

              glecaprevir/pibrentasvir will increase the level or effect of tolvaptan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • topotecan

              glecaprevir/pibrentasvir will increase the level or effect of topotecan by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              glecaprevir/pibrentasvir will increase the level or effect of topotecan by decreasing metabolism. Use Caution/Monitor. Glecaprevir/pibrentasvir may increase plasma concentration of BCRP substrates.

            • trabectedin

              glecaprevir/pibrentasvir will increase the level or effect of trabectedin by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • tucatinib

              tucatinib will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor. Consider reducing the dosage of P-gp substrates, where minimal concentration changes may lead to serious or life-threatening toxicities.

            • ulipristal

              ulipristal will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • vandetanib

              vandetanib will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              vandetanib will increase the level or effect of glecaprevir/pibrentasvir by decreasing metabolism. Use Caution/Monitor. Caution when coadministering glecaprevir/pibrentasvir with BCRP inhibitors.

            • velpatasvir

              glecaprevir/pibrentasvir will increase the level or effect of velpatasvir by Other (see comment). Use Caution/Monitor. Glecaprevir/pibrentasvir may increase plasma concentration of P-gp and BCRP substrates.

            • vemurafenib

              vemurafenib will increase the level or effect of glecaprevir/pibrentasvir by decreasing metabolism. Use Caution/Monitor. Caution when coadministering glecaprevir/pibrentasvir with P-gp/BCRP inhibitors.

              glecaprevir/pibrentasvir will increase the level or effect of vemurafenib by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              glecaprevir/pibrentasvir will increase the level or effect of vemurafenib by decreasing metabolism. Use Caution/Monitor. Glecaprevir/pibrentasvir may increase plasma concentration of BCRP substrates.

            • venetoclax

              venetoclax will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              glecaprevir/pibrentasvir will increase the level or effect of venetoclax by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • verapamil

              verapamil will increase the level or effect of glecaprevir/pibrentasvir by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

              glecaprevir/pibrentasvir will increase the level or effect of verapamil by P-glycoprotein (MDR1) efflux transporter. Use Caution/Monitor.

            • vinblastine

              glecaprevir/pibrentasvir will increase the level or effect of vinblastine by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely.

            • vincristine

              glecaprevir/pibrentasvir will increase the level or effect of vincristine by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely.

            • voriconazole

              voriconazole will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • voxilaprevir

              glecaprevir/pibrentasvir will increase the level or effect of voxilaprevir by P-glycoprotein (MDR1) efflux transporter. Modify Therapy/Monitor Closely.

            Minor (6)

            • acetazolamide

              acetazolamide will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • anastrozole

              anastrozole will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • cyclophosphamide

              cyclophosphamide will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • larotrectinib

              larotrectinib will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • ribociclib

              ribociclib will increase the level or effect of glecaprevir/pibrentasvir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.

            • voclosporin

              voclosporin will increase the level or effect of glecaprevir/pibrentasvir by Other (see comment). Minor/Significance Unknown. Information suggests voclosporin (an OATP1B1 inhibitor) may increase in the concentration of OATP1B1 substrates is possible. Monitor for adverse reactions of OATP1B1 substrates when coadministered with voclosporin.

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            Adverse Effects

            >10%

            Headache (9-17%)

            Fatigue (11-14%)

            Nausea (6-12%)

            1-10%

            Diarrhea (3-7%)

            Increased bilirubin, ≥2x ULN (3.5%)

            Pruritus (7%)

            Postmarketing Reports

            Skin and SC tissue disorders: Angioedema

            Hepatobiliary disorders: Hepatic decompensation, hepatic failure

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            Warnings

            Black Box Warnings

            Risk of hepatitis B virus reactivation in patients coinfected with HCV and HBV

            • Test for evidence of current or prior HBV infection by measuring HBsAg and anti-HBc before initiating treatment
            • HBV reactivation has been reported in 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-coinfected patients for hepatitis flare or HBV reactivation during HCV treatment and posttreatment follow up
            • Initiate appropriate patient management for HBV infection as clinically indicated

            Contraindications

            Moderate or severe hepatic impairment (Child-Pugh B or C)

            History of prior hepatic decompensation

            Coadministration with atazanavir or rifampin

            Cautions

            Hepatitis B virus reactivation in patients coinfected with HCV/HBV may occur

            Postmarketing cases of hepatic decompensation/failure, including those with fatal outcomes, have been reported

            No dosage adjustment of required in people who inject drugs (PWID) or those who are on medication-assisted treatment (MAT) for opioid use disorder; safety and efficacy reported to be similar to those not reporting history of injection drug use

            Hepatitis B Virus reactivation in HCV and HBV coinfection

            • In patients with resolved HBV infection reappearance of HBsAg can occur
            • Reactivation of HBV replication may be accompanied by hepatitis, ie, increase in aminotransferase levels and, in severe cases, increases in bilirubin levels, liver failure, and death can occur
            • Test all patients for evidence of current or prior HBV infection by measuring HBsAg and anti-HBc before initiating HCV treatment
            • In patients with serologic evidence of HBV infection, monitor for clinical and laboratory signs of hepatitis flare or HBV reactivation during HCV treatment and during post-treatment follow-up; initiate appropriate patient management for HBV infection as clinically indicated

            Hepatic decompensation

            • Majority of patients with severe outcomes had evidence of advanced liver disease with moderate or severe hepatic impairment (Child-Pugh B or C) prior to initiating therapy, including some patients reported as having compensated cirrhosis with mild liver impairment (Child-Pugh A) at baseline but with a prior decompensation event (i.e., prior history of ascites, variceal bleeding, encephalopathy)
            • Patients with compensated cirrhosis (Child Pugh A) or evidence of advanced liver disease such as portal hypertension, perform hepatic laboratory testing as clinically indicated; and monitor for signs and symptoms of hepatic decompensation such as presence of jaundice, ascites, hepatic encephalopathy, and variceal hemorrhage; discontinue in patients who develop evidence of hepatic decompensation/failure

            Drug interaction overview

            • Effects of glecaprevir/pibrentasvir on other drugs
              • Glecaprevir and pibrentasvir: Inhibit P-gp, BCRP, OATP1B1, and OATP1B3; coadministration of glecaprevir/pibrentasvir may increase plasma concentrations of substrates of these transporters
              • Glecaprevir and pibrentasvir: Weak inhibitors of CYP3A, CYP1A2, and UGT1A1; significant interactions are not expected when glecaprevir/pibrentasvir is coadministered with substrates of CYP3A, CYP1A2, CYP2C9, CYP2C19, CYP2D6, UGT1A1, or UGT1A4
            • Effects of other drugs on glecaprevir/pibrentasvir
              • Glecaprevir and pibrentasvir: Substrates of P-gp and/or BCRP
              • Glecaprevir: Substrate of OATP1B1, OATP1B3, and CYP3A (secondary)
              • Coadministration of glecaprevir/pibrentasvir with drugs that inhibit hepatic P-gp, BCRP, or OATP1B1/3 may increase the plasma concentrations of glecaprevir and/or pibrentasvir
              • Coadministration of glecaprevir/pibrentasvir with drugs that induce P-gp/CYP3A may significantly decrease glecaprevir and pibrentasvir plasma concentrations, leading to reduced therapeutic effect
              • Coadministration is contraindicated with rifampin or atazanavir
              • Coadministration is not recommended with carbamazepine, efavirenz, or St John’s wort
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            Pregnancy

            Pregnancy

            No adequate human data are available to establish whether or not glecaprevir/pibrentasvir poses a risk to pregnancy outcomes

            Animal studies

            • No adverse developmental effects were observed when glecaprevir and pibrentasvir were administered separately during organogenesis at exposures up to 53 times (rats; glecaprevir) or 51 and 1.5 times (mice and rabbits, respectively; pibrentasvir) the human exposures at the recommended dose

            Lactation

            Unknown if distributed in human breast milk

            When administered to lactating rodents, glecaprevir and pibrentasvir were present in milk, without effect on growth and development observed in the nursing pups

            Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

            Pregnancy Categories

            A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA: Information not available.

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            Pharmacology

            Mechanism of Action

            Glecaprevir: HCV NS3/4A protease inhibitor; 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: HCV NS5A inhibitor; essential for viral RNA replication and virion assembly

            Absorption

            Peak plasma time: 5 hr (glecaprevir and pibrentasvir)

            Peak plasma concentration: 597 ng/mL (glecaprevir); 110 ng/mL (pibrentasvir)

            AUC: 4800 ng⋅hr/mL (glecaprevir); 1430 ng⋅hr/mL (pibrentasvir)

            Distribution

            Protein bound: 97.5% (glecaprevir); >99.9% (pibrentasvir)

            Blood-to-plasma ratio: 0.57 (glecaprevir); 0.62 (pibrentasvir)

            Metabolism

            Glecaprevir is metabolized by CYP3A4 (secondary)

            Elimination

            Half-life: 6 hr (glecaprevir); 13 hr (pibrentasvir)

            Excretion

            • Glecaprevir: Feces (92.7%); urine (0.7%)
            • Pibrentasvir: Feces (96.6%)
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            Administration

            Oral Pellet Preparation

            Sprinkle oral pellets for the total daily dose on a small amount of soft food with low water content (eg, peanut butter, chocolate hazelnut spread, cream cheese, thick jam, or Greek yogurt) that will stick to a spoon and can be swallowed without chewing

            Avoid liquids or foods that would drip or slide off the spoon as the drug may dissolve quickly and become less effective

            Oral Administration

            Tablets: Take with food at the same time once daily

            Oral pellets

            • Take together as one dose, with food, once daily
            • Do not crush or chew
            • Swallow within 15 minutes of preparation

            Missed dose

            • <18 hr from usual dosage time: Take dose as soon as possible; take next dose at the usual time
            • >18 hr from usual dosage time: Do not to take missed dose; take next dose at the usual time

            Storage

            Tablets or pellets: Store at or below 30°C (86°F)

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            Images

            BRAND FORM. UNIT PRICE PILL IMAGE
            Mavyret oral
            -
            100-40 mg tablet
            Mavyret oral
            -
            50-20 mg pellet

            Copyright © 2010 First DataBank, Inc.

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            Patient Handout

            A Patient Handout is not currently available for this monograph.
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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.