Dosing & Uses
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)
Chronic Hepatitis C Virus (HCV) Infection
Indicated for treatment of chronic hepatitis C virus (HCV) genotype 1 or 4 infection in adult and pediatric patients aged ≥12 years or weighing ≥30 kg
Also, indicated 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 variables
Treatment regimen and duration of therapy in 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)
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
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 (38)
- 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
- leniolisib
leniolisib will increase the level or effect of elbasvir/grazoprevir by Other (see comment). Avoid or Use Alternate Drug. Leniolisib, an OATP1B1 and OATP1B3 inhibitor, may increase systemic exposure of these substrates
- levoketoconazole
levoketoconazole 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.
- 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.
- nirmatrelvir
nirmatrelvir will increase the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Increased grazoprevir concentrations can result in ALT elevations.
- nirmatrelvir/ritonavir
nirmatrelvir/ritonavir will increase the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Increased grazoprevir concentrations can result in ALT elevations.
- 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.
- trofinetide
trofinetide will increase the level or effect of elbasvir/grazoprevir 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 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 (26)
- 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.
- ceritinib
ceritinib will increase the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.
- 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.
encorafenib will increase the level or effect of elbasvir/grazoprevir 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. - 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.
- lenacapavir
lenacapavir will increase the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir (a moderate CYP3A4 inhibitor) 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.
- 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.
Minor (5)
- acetazolamide
acetazolamide will increase the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- anastrozole
anastrozole will increase the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- cyclophosphamide
cyclophosphamide will increase the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- larotrectinib
larotrectinib will increase the level or effect of elbasvir/grazoprevir by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Minor/Significance Unknown.
- 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.
Adverse Effects
>10%
Adults
- Fatigue, treatment-naïve (5-11%)
- Headache, treatment-naïve (10-11%)
Pediatric patients
- Headache (14%)
1-10%
Adults
-
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%)
Pediatric patients
- Nausea (9%)
Postmarketing Reports
Skin and SC tissue disorders: Angioedema
Hepatobiliary disorders: Hepatic decompensation, hepatic failure
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
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.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
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)
Images
| BRAND | FORM. | UNIT PRICE | PILL IMAGE |
|---|---|---|---|
| Zepatier oral - | 50-100 mg tablet |  |
Copyright © 2010 First DataBank, Inc.
Formulary
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