elbasvir/grazoprevir (Rx)

Brand and Other Names:Zepatier
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

elbasvir/grazoprevir

tablet

  • 50mg/100mg

Chronic Hepatitis C Virus (HCV) Infection

Indicated for chronic hepatitis C virus (HCV) genotype 1 or 4 infection in adults or for use with ribavirin in certain patient populations

1 tablet PO qDay; treatment duration and whether to take with or without ribavirin are dependent on genotypes and other patient variable

Treatment regimen and duration of therapy

  • Patients with or without cirrhosis
  • Genotypes 1a
    • Treatment-naïve or PegIFN/RBV-experienced without baseline NS5A polymorphisms: elbasvir/grazoprevir for 12 wk
    • Treatment-naïve or PegIFN/RBV-experienced WITH baseline NS5A polymorphisms: elbasvir/grazoprevir plus weight-based ribavirin for 16 wk
  • Genotype 1b
    • Treatment-naïve or PegIFN/RBV-experienced: elbasvir/grazoprevir for 12 wk
  • Genotypes 1a or 1b
    • PegIFN/RBV/PI-experienced: elbasvir/grazoprevir plus weight-based ribavirin for 12 wk
  • Genotype 4
    • Treatment-naïve: elbasvir/grazoprevir for 12 wk
    • Peg/IFN/RBV-experienced: elbasvir/grazoprevir plus weight-based ribavirin for 16 wk

Dosage Modifications

Renal impairment

  • No dosage adjustment is required for patients with any degree of renal impairment including patients on hemodialysis
  • Refer to the ribavirin prescribing information for dose in patients with CrCl ≤50 mL/min

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

Testing prior to initiation

  • Test for NS5A resistance in HCV genotype 1a infected patients to determine dosage regimen and duration
  • In clinical trials, patients with genotype 1a who received elbasvir/grazoprevir for 12 weeks showed a lower sustained virologic response (SVR12) rate with ≥1 baseline NS5A resistance-associated polymorphisms at amino acid positions 28, 30, 31, or 93
  • Obtain hepatic laboratory testing prior to and during treatment
  • Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with HCV direct acting antivirals (DDAs)

Safety and efficacy not established

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Interactions

Interaction Checker

and elbasvir/grazoprevir

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            Contraindicated (25)

            • atazanavir

              atazanavir increases levels of elbasvir/grazoprevir by Other (see comment). Contraindicated. Comment: Coadministration with strong OATP1B1/3 inhibitors may increase the risk of ALT elevations owing to a significant increase in grazoprevir plasma concentrations.

            • carbamazepine

              carbamazepine will decrease the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. The therapeutic effect of elbasvir/grazoprevir may be reduced if coadministered with strong CYP3A inducers and is therefore contraindicated.

            • cyclosporine

              cyclosporine increases levels of elbasvir/grazoprevir by Other (see comment). Contraindicated. Comment: Coadministration with strong OATP1B1/3 inhibitors may increase the risk of ALT elevations owing to a significant increase in grazoprevir plasma concentrations.

            • dabrafenib

              dabrafenib will decrease the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. The therapeutic effect of elbasvir/grazoprevir may be reduced if coadministered with strong CYP3A inducers and is therefore contraindicated.

            • darunavir

              darunavir increases levels of elbasvir/grazoprevir by Other (see comment). Contraindicated. Comment: Coadministration with strong OATP1B1/3 inhibitors may increase the risk of ALT elevations owing to a significant increase in grazoprevir plasma concentrations.

            • dexamethasone

              dexamethasone will decrease the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. The therapeutic effect of elbasvir/grazoprevir may be reduced if coadministered with strong CYP3A inducers and is therefore contraindicated.

            • efavirenz

              efavirenz will decrease the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. The therapeutic effect of elbasvir/grazoprevir may be reduced if coadministered with strong CYP3A inducers and is therefore contraindicated.

            • enzalutamide

              enzalutamide will decrease the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. The therapeutic effect of elbasvir/grazoprevir may be reduced if coadministered with strong CYP3A inducers and is therefore contraindicated.

            • eslicarbazepine acetate

              eslicarbazepine acetate will decrease the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. The therapeutic effect of elbasvir/grazoprevir may be reduced if coadministered with strong CYP3A inducers and is therefore contraindicated.

            • fosphenytoin

              fosphenytoin will decrease the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. The therapeutic effect of elbasvir/grazoprevir may be reduced if coadministered with strong CYP3A inducers and is therefore contraindicated.

            • lopinavir

              lopinavir increases levels of elbasvir/grazoprevir by Other (see comment). Contraindicated. Comment: Coadministration with strong OATP1B1/3 inhibitors may increase the risk of ALT elevations owing to a significant increase in grazoprevir plasma concentrations.

            • lumacaftor/ivacaftor

              lumacaftor/ivacaftor will decrease the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. The therapeutic effect of elbasvir/grazoprevir may be reduced if coadministered with strong CYP3A inducers and is therefore contraindicated.

            • mitotane

              mitotane will decrease the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. The therapeutic effect of elbasvir/grazoprevir may be reduced if coadministered with strong CYP3A inducers and is therefore contraindicated.

            • nevirapine

              nevirapine will decrease the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. The therapeutic effect of elbasvir/grazoprevir may be reduced if coadministered with strong CYP3A inducers and is therefore contraindicated.

            • oxcarbazepine

              oxcarbazepine will decrease the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. The therapeutic effect of elbasvir/grazoprevir may be reduced if coadministered with strong CYP3A inducers and is therefore contraindicated.

            • pentobarbital

              pentobarbital will decrease the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. The therapeutic effect of elbasvir/grazoprevir may be reduced if coadministered with strong CYP3A inducers and is therefore contraindicated.

            • phenobarbital

              phenobarbital will decrease the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. The therapeutic effect of elbasvir/grazoprevir may be reduced if coadministered with strong CYP3A inducers and is therefore contraindicated.

            • phenytoin

              phenytoin will decrease the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. The therapeutic effect of elbasvir/grazoprevir may be reduced if coadministered with strong CYP3A inducers and is therefore contraindicated.

            • primidone

              primidone will decrease the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. The therapeutic effect of elbasvir/grazoprevir may be reduced if coadministered with strong CYP3A inducers and is therefore contraindicated.

            • rifabutin

              rifabutin will decrease the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. The therapeutic effect of elbasvir/grazoprevir may be reduced if coadministered with strong CYP3A inducers and is therefore contraindicated.

            • rifampin

              rifampin will decrease the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. The therapeutic effect of elbasvir/grazoprevir may be reduced if coadministered with strong CYP3A inducers and is therefore contraindicated.

            • rifapentine

              rifapentine will decrease the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. The therapeutic effect of elbasvir/grazoprevir may be reduced if coadministered with strong CYP3A inducers and is therefore contraindicated.

            • saquinavir

              saquinavir increases levels of elbasvir/grazoprevir by Other (see comment). Contraindicated. Comment: Coadministration with strong OATP1B1/3 inhibitors may increase the risk of ALT elevations owing to a significant increase in grazoprevir plasma concentrations.

            • St John's Wort

              St John's Wort will decrease the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated. The therapeutic effect of elbasvir/grazoprevir may be reduced if coadministered with strong CYP3A inducers and is therefore contraindicated.

            • tipranavir

              tipranavir increases levels of elbasvir/grazoprevir by Other (see comment). Contraindicated. Comment: Coadministration with strong OATP1B1/3 inhibitors may increase the risk of ALT elevations owing to a significant increase in grazoprevir plasma concentrations.

            Serious - Use Alternative (34)

            • abametapir

              abametapir will increase the level or effect of elbasvir/grazoprevir 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.

            • amobarbital

              amobarbital will decrease the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • apalutamide

              apalutamide will decrease the level or effect of elbasvir/grazoprevir 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.

            • armodafinil

              armodafinil will decrease the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The therapeutic effect of elbasvir/grazoprevir may be reduced if coadministered with moderate CYP3A inducers and should be avoided.

            • atazanavir

              atazanavir will increase the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • bosentan

              bosentan will decrease the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The therapeutic effect of elbasvir/grazoprevir may be reduced if coadministered with moderate CYP3A inducers and should be avoided.

            • chloramphenicol

              chloramphenicol will increase the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • clarithromycin

              clarithromycin will increase the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • clobazam

              clobazam will decrease the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The therapeutic effect of elbasvir/grazoprevir may be reduced if coadministered with moderate CYP3A inducers and should be avoided.

            • cobicistat

              cobicistat will increase the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of elbasvir/grazoprevir with certain strong CYP3A4 inhibitors

            • conivaptan

              conivaptan will increase the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • darunavir

              darunavir will increase the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • elvitegravir/cobicistat/emtricitabine/tenofovir DF

              elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of elbasvir/grazoprevir with certain strong CYP3A4 inhibitors

            • etravirine

              etravirine will decrease the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The therapeutic effect of elbasvir/grazoprevir may be reduced if coadministered with moderate CYP3A inducers and should be avoided.

            • fexinidazole

              fexinidazole will increase the level or effect of elbasvir/grazoprevir 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.

            • fostemsavir

              fostemsavir will increase the level or effect of elbasvir/grazoprevir by Other (see comment). Avoid or Use Alternate Drug. Fostemsavir inhibits OATP1B1/3 transporter. Higher grazoprevir system exposure may increase risk of ALT elevations. Use an alternative HCV regimen if possible.

            • idelalisib

              idelalisib will increase the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • indinavir

              indinavir will increase the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • itraconazole

              itraconazole will increase the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ivosidenib

              ivosidenib will decrease the level or effect of elbasvir/grazoprevir 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.

            • ketoconazole

              ketoconazole will increase the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid coadministration of elbasvir/grazoprevir with certain strong CYP3A4 inhibitors

            • lopinavir

              lopinavir will increase the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • lorlatinib

              lorlatinib will decrease the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • modafinil

              modafinil will decrease the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The therapeutic effect of elbasvir/grazoprevir may be reduced if coadministered with moderate CYP3A inducers and should be avoided.

            • nafcillin

              nafcillin will decrease the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. The therapeutic effect of elbasvir/grazoprevir may be reduced if coadministered with moderate CYP3A inducers and should be avoided.

            • nefazodone

              nefazodone will increase the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • nelfinavir

              nelfinavir will increase the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • posaconazole

              posaconazole will increase the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • ritonavir

              ritonavir will increase the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug.

            • saquinavir

              saquinavir will increase the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • secobarbital

              secobarbital will decrease the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • tipranavir

              tipranavir will increase the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Contraindicated.

            • tucatinib

              tucatinib will increase the level or effect of elbasvir/grazoprevir 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 elbasvir/grazoprevir 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.

            Monitor Closely (25)

            • apalutamide

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

            • atorvastatin

              elbasvir/grazoprevir increases levels of atorvastatin by unknown mechanism. Modify Therapy/Monitor Closely. If coadministered, do not exceed atorvastatin dose of 20 mg/day.

            • belzutifan

              belzutifan will decrease the level or effect of elbasvir/grazoprevir 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.

            • cenobamate

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

            • duvelisib

              duvelisib will increase the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Coadministration with duvelisib increases AUC of a sensitive CYP3A4 substrate which may increase the risk of toxicities of these drugs. Consider reducing the dose of the sensitive CYP3A4 substrate and monitor for signs of toxicities of the coadministered sensitive CYP3A substrate.

            • elagolix

              elagolix will decrease the level or effect of elbasvir/grazoprevir 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.

            • encorafenib

              encorafenib, elbasvir/grazoprevir. 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.

            • fedratinib

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

            • fluvastatin

              elbasvir/grazoprevir increases levels of fluvastatin by unknown mechanism. Modify Therapy/Monitor Closely. If coadministered, use lowest necessary fluvastatin dose.

            • glecaprevir/pibrentasvir

              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

            • istradefylline

              istradefylline will increase the level or effect of elbasvir/grazoprevir 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.

            • letermovir

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

            • lovastatin

              elbasvir/grazoprevir increases levels of lovastatin by unknown mechanism. Modify Therapy/Monitor Closely. If coadministered, use lowest necessary lovastatin dose.

            • mifepristone

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

            • ribociclib

              ribociclib will increase the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.

            • rosuvastatin

              elbasvir/grazoprevir increases levels of rosuvastatin by unknown mechanism. Modify Therapy/Monitor Closely. If coadministered, do not exceed rosuvastatin dose of 10 mg/day.

            • rucaparib

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

            • simvastatin

              elbasvir/grazoprevir increases levels of simvastatin by unknown mechanism. Modify Therapy/Monitor Closely. If coadministered, use lowest necessary simvastatin dose.

            • sofosbuvir/velpatasvir

              sofosbuvir/velpatasvir increases levels of elbasvir/grazoprevir by Other (see comment). Use Caution/Monitor. Comment: Velpatasvir inhibits OATP1B1, OATP1B3, and OATP2B1 transporters. .

            • stiripentol

              stiripentol, elbasvir/grazoprevir. 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.

            • tacrolimus

              elbasvir/grazoprevir increases levels of tacrolimus by unknown mechanism. Modify Therapy/Monitor Closely. Frequently monitor tacrolimus whole blood concentrations, renal function, and tacrolimus-associated adverse events if coadministered with elbasvir/grazoprevir.

            • tazemetostat

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

            • tecovirimat

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

            • voriconazole

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

            • warfarin

              elbasvir/grazoprevir increases toxicity of warfarin by anticoagulation. Use Caution/Monitor. Fluctuations in INR values may occur in patients receiving warfarin concomitant with HCV treatment; frequent monitoring of INR values recommended during treatment and post-treatment follow-up.

            Minor (1)

            • voclosporin

              voclosporin will increase the level or effect of elbasvir/grazoprevir 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%

            Fatigue, treatment-naïve (11%)

            1-10%

            Headache, treatment-naïve (10%)

            Treatment-experienced

            • Fatigue (5%)
            • Abdominal pain (2%)
            • Diarrhea (2%)
            • Irritability (1%)
            • Depression (1%)

            Treatment-experienced plus ribavirin

            • Anemia (8%)
            • Headache (6%)
            • Fatigue (4%)
            • Dyspnea (4%)
            • Rash or pruritus (4%)
            • Irritability (3%)
            • Abdominal pain (2%)
            • Depression (2%)
            • Arthralgia (2%)
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            Warnings

            Black Box Warnings

            Test all patients for evidence of current or prior hepatitis B virus (HBV) infection before initiating treatment with HCV direct acting antivirals (DDAs)

            HBV reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with DDAs 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 post-treatment follow-up

            Initiate appropriate patient management for HBV infection as clinically indicated

            Contraindications

            Patients with moderate or severe hepatic impairment (Child-Pugh B or C) or those with any history of hepatic decompensation due to the risk of hepatic decompensation

            If administered with ribavirin, the contraindications to ribavirin also apply to this combination regimen (refer to ribavirin prescribing information)

            Coadministration with OATP1B1/3 inhibitors

            • Not a comprehensive list
            • May increase the risk of ALT elevations owing to a significant increase in grazoprevir plasma concentrations caused by OATP1B1/3 inhibition
            • HIV medications: atazanavir, darunavir, lopinavir, saquinavir, tipranavir
            • Immunosuppressants: cyclosporine

            Coadministration with strong CYP3A inducers

            • Not a comprehensive list May lead to loss of virologic response to elbasvir/grazoprevir owing to significant decreases in elbasvir and grazoprevir plasma concentrations caused by strong CYP3A induction
            • Anticonvulsants: carbamazepine, phenytoin
            • Antimycobacterials: rifampin
            • Herbals: St John’s wort
            • HIV medications: efavirenz

            Cautions

            Hepatitis B virus (HBV) reactivation has been reported in HCV/HBV coinfected patients who were undergoing or had completed treatment with HCV DDAs, and who were not receiving HBV antiviral therapy; HBV reactivation is characterized as an abrupt increase in HBV replication manifesting as a rapid increase in serum HBV DNA level (see Black Box Warnings and Dosing Considerations)

            May increase ALT levels; measure liver enzymes prior to therapy, at treatment week 8, and as clinically indicated; for patients receiving 16 weeks of therapy, additional hepatic laboratory testing should be performed at treatment week 12

            Postmarketing cases of hepatic decompensation/failure, including those with fatal outcomes, reported; in patients with compensated cirrhosis (Child-Pugh A) or evidence of advanced liver disease, such as portal hypertension, more frequent hepatic laboratory testing may be warranted; patients should be monitored for signs and symptoms of hepatic decompensation such as the presence of jaundice, ascites, hepatic encephalopathy, and variceal hemorrhage; discontinue therapy in patients who develop evidence of hepatic decompensation/failure

            Warnings and precautions (including pregnancy) for ribavirin apply if coadministered

            Risk of adverse reactions or reduced therapeutic effect caused by drug interactions (see Contraindications and Drug Interactions)

            Drug interaction overview

            • Grazoprevir is an OATP1B1/3 substrate, CYP3A4 substrate, and P-gp substrate
            • Elbasvir is a CYP3A4 and P-gp substrate
            • Coadministration with OATP1B1/3 inhibitors that are known or expected to significantly increase grazoprevir plasma concentrations is contraindicated
            • Intestinal P-gp in the absorption of elbasvir and grazoprevir appears to be minimal
            • Coadministration with moderate or strong CYP3A4 inducers may decrease elbasvir and grazoprevir plasma concentrations, leading to reduced therapeutic effect of elbasvir/grazoprevir
            • Coadministration with strong CYP3A inducers or efavirenz is contraindicated
            • Coadministration with moderate CYP3A inducers is not recommended
            • Coadministration with strong CYP3A inhibitors may increase elbasvir and grazoprevir concentrations and is not recommended
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            Pregnancy

            Pregnancy

            No adequate human data are available

            In animal reproduction studies, no evidence of adverse developmental outcomes was observed with elbasvir or grazoprevir at exposures greater than those in humans at the recommended human dose

            Note: Ribavirin is contraindicated in pregnant women and men whose female partners are pregnant

            Lactation

            Unknown if distributed in human breast milk

            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

            Elbasvir: Inhibitor of HCV NS5A, which is essential for viral RNA replication and virion assembly

            Grazoprevir: Inhibitor of HCV NS3/4A protease, which is 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

            Absorption

            Peak plasma time: 3 hr (elbasvir); 2 hr (grazoprevir)

            Peak plasma concentration: 121 ng/mL (elbasvir); 165 ng/mL (grazoprevir)

            AUC: 1920 ng·hr/mL (elbasvir); 1420 ng·hr/mL (grazoprevir)

            Distribution

            Protein bound: >99.9% (elbasvir); >98.8% (grazoprevir)

            Vd: 680 L (elbasvir); 1250 L (grazoprevir)

            Metabolism

            Elbasvir and grazoprevir are partially eliminated by oxidative metabolism, primarily by CYP3A

            No circulating metabolites of either elbasvir or grazoprevir were detected in human plasma

            Elimination

            Excretion: >90% feces; <1% urine

            Half-life: 24 hr (elbasvir); 31 hr (grazoprevir)

            Pharmacogenomics

            In population pharmacokinetic analyses, elbasvir and grazoprevir AUCs are estimated to be 15% and 50% higher, respectively, for Asians compared to Caucasians

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            Administration

            Oral Administration

            May take with or without food

            Storage

            Store at 20-25°C (68-77°F); excursions permitted between 15-30°C (59-86°F)

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            Images

            BRAND FORM. UNIT PRICE PILL IMAGE
            Zepatier oral
            -
            50-100 mg tablet

            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

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
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            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            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.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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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.