ZEPATIER®▼ (elbasvir/grazoprevir)

DDIs and dosing simplicity

Prescribing Information (Great Britain) & Prescribing Information (Northern Ireland) [External links]

ZEPATIER can be used with the following drugs without clinically significant interactions or dose adjustments^2,3

Opiate substitution therapy

(methadone, buprenorphine/naloxone)

Antipsychotics

(amisulpride, clozapine, flupentixol, haloperidol, olanzapine, paliperidone, trifluoperazine, zuclopentixol)

Oral contraception

(ethinyloestradiol/levonorgestrel)

Other categories without clinically significant interactions or dose adjustments include: antiarrhythmics (digoxin), antidepressants*, beta blockers, gastric acid suppressants (H2-receptor antagonist (famotidine), Proton Pump Inhibitor (pantoprazole), antacids), HBV and HIV NRTIs, HIV NNRTIs (rilpivirine), HIV integrase inhibitors (raltegravir and dolutegravir), HCV antivirals (sofosbuvir and ribavirin), immunosuppressants (prednisone, mycophenolate mofetil), phosphate binders (calcium acetate, sevelamer carbonate) and statins^† (pitavastatin, pravastatin).

Please consult the ZEPATIER SmPC before prescribing.²

*Potential interaction likely to be of weak intensity. Additional action/monitoring or dosage adjustment is unlikely to be required³

^†Other statins (HMG-CoA reductase inhibitors) – use low dose when concomitantly given with ZEPATIER²

Glucose levels of diabetic patients initiating DAA therapy should be closely monitored, particularly within the first 3 months, and their diabetic medication modified when necessary

Contraindications

Co-administration with inhibitors of organic anion transporting polypeptide 1B (OATP1B), such as rifampicin, atazanavir, darunavir, lopinavir, saquinavir, tipranavir, cobicistat or ciclosporin.

Co-administration with inducers of cytochrome P450 3A (CYP3A) or P-glycoprotein (P-gp), such as efavirenz, phenytoin, carbamazepine, bosentan, etravirine, modafinil or St. John’s wort (Hypericum perforatum).

Dosing simplicity²

One tablet once daily²
With or without food²
Blister pack with named days²
12 weeks without ribavirin for the majority of G1 + G4 patients²

*Not actual size*

Recommended ZEPATIER therapy for treatment of chronic hepatitis C infection in patients with or without compensated cirrhosis (Child-Pugh A only)²

Genotype 1a, 1b & 4: 12 weeks. For Genotype 1a or 4 with NS5A baseline resistance or high viral load: 16 weeks + RBV

Adapted from ZEPATIER Summary of Product Characteristics²

In the clinical studies, the dose of ribavirin was weight-based (<66 kg = 800 mg/day, 66 to 80 kg = 1,000 mg/day, 81 to 105 kg = 1,200 mg/day, >105 kg = 1,400 mg/day) administered in two divided doses with food.²

Consider 16-week ZEPATIER treatment with ribavirin for G1a patients with baseline HCV RNA level >800,000 IU/ml and/or the presence of specific NS5A polymorphisms causing at least a 5-fold reduction in activity of elbasvir to minimise the risk of treatment failure²
ZEPATIER for 16 weeks plus RBV should be considered in G4 patients with baseline HCV RNA level >800,000 IU/ml to minimise the risk of treatment failure²
For specific dosage instructions for ribavirin, including dose modification, refer to the ribavirin Summary of Product Characteristics

Cure defined as cure of HCV infection = sustained virologic response (SVR), the primary endpoint in all studies, was defined as hepatitis C virus (HCV) ribonucleic acid (RNA) less than the lower limit of quantification (LLOQ) (≤15 IU/ml) at 12 weeks after the cessation of treatment.⁴

References

Höner zu Siederdissen C, Maasoumy B, Marra F, et al. Drug-drug interactions with novel all oral interferon-free antiviral agents in a large real-world cohort. Clin Infect Dis. 2016;62:561–567.
ZEPATIER Summary of Product Characteristics.
Liverpool Drug Interactions Group, University of Liverpool. https://www.hep-druginteractions.org/view_all_interactions/582987.
European Association for the Study of Liver. J Hepatol. 2018;69;461-511.

Supporting documentation

Prescribing Information (Great Britain) & Prescribing Information (Northern Ireland)
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