Ombitasvir// plus (Viekira PakTM)

UTILIZATION MANAGEMENT CRITERIA

DRUG CLASS: NS5A inhibitor, NS3/4A protease inhibitor, CYP3A inhibitor, and Nonnucleoside NS5B palm polymerase inhibitor

BRAND (generic) NAME: Viekira Pak (, paritaprevir, ritonavir 12.5/75/50 mg) two tablets once daily and (dasabuvir 250 mg) one tablet twice daily

FDA-APPROVED INDICATIONS: Viekira Pak with or without is indicated for the treatment of patients with genotype 1 chronic C virus (HCV) including those with compensated cirrhosis. Viekera Pak includes ombitasvir, a virus NS5A inhibitor, paritaprevir, a NS3/4A protease inhibitor, ritonavir, a CYP3A inhibitor and dasabuvir, a hepatitis C virus non-nucleoside NS5B palm polymerase inhibitor.

COVERAGE AUTHORIZATION CRITERIA Viekira Pak may be eligible for coverage when the following criteria are met:

1. The patient has a diagnosis of chronic hepatitis C (CHC) infection with confirmed genotype 1a or 1b (medical record documentation required); AND 2. If the patient has confirmed CHC genotype 1a, the provider has documented that the patient will be treated with ribavirin in addition to Viekira Pak; AND 3. The patient has not attempted a previous course of therapy with a protease inhibitor (i.e. , , or ); AND 4. The patient has not attempted a previous course of therapy with a -based regimen (i.e. Sovaldi or Harvoni); AND 5. The patient is treatment-naïve or treatment experienced without cirrhosis; AND  Has F2 or higher on the IASL, Batts-Ludwig, or Metavir fibrosis staging scales (medical record documentation required); OR  Has F3 or higher on the Ishak fibrosis staging scale (medical record documentation required); OR 6. The patient is treatment naïve or treatment experienced and has cirrhosis secondary to CHC [Metavir F4, Ishak F5-6, or radiographic evidence of portal hypertension, esophageal varices, ascites (medical record documentation required)], AND  If the patient has confirmed CHC with cirrhosis, the provider has documented that the patient will be treated with ribavirin in addition to Viekira Pak; AND 7. Viekira Pak is prescribed by or in consultation with a physician with expertise and experience in the management of infectious hepatitis; AND 8. Viekira Pak will not be used in combination with other protease inhibitors used to treat CHC (i.e. boceprevir, simeprevir, or telaprevir); AND 9. The patient does not have hepatocellular carcinoma (see Sovaldi coverage criteria); AND 10. The patient does not have any FDA labeled contraindications to Viekira Pak.

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Duration of Approval Table 1

Genotype 1a: Treatment Naïve or Treatment experienced, without cirrhosis AND  F2 or higher on the IASL, Batts-Ludwig, or 12 weeks WITH ribavirin Metavir fibrosis staging scales OR  F3 or higher on the Ishak fibrosis staging scale Genotype 1b: Treatment Naïve or Treatment experienced, without cirrhosis AND  F2 or higher on the IASL, Batts-Ludwig, or 12 weeks Metavir fibrosis staging scales OR  F3 or higher on the Ishak fibrosis staging scale Genotype 1a: Treatment Naïve or Treatment experienced, AND 24 weeks WITH ribavirin  Has cirrhosis secondary to CHC Genotype 1b: Treatment Naïve or Treatment experienced, AND 12 weeks WITH ribavirin  Has cirrhosis secondary to CHC *HCV/HIV-1 co-infection: For patients with HCV/HIV-1 co-infection, follow the dosage recommendations in the table above.

DOSAGE AND ADMINISTRATION Two ombitasvir, paritaprevir, ritonavir 12.5/75/50 mg tablets once daily (in the morning) and one dasabuvir 250 mg tablet twice daily (morning and evening) with a meal without regard to fat or calorie content. The recommended regimen and treatment duration for Viekira Pak combination therapy is provided in Table 1. When administered with Viekira Pak, the recommended dosage of ribavirin is based on weight: 1000 mg for subjects ≤75 kg and 1200 mg/day for those >75 kg, divided and administered twice-daily with food. For ribavirin dosage modifications, refer to the ribavirin prescribing information.

CONTRAINDICATIONS  If Viekira Pak is administered with ribavirin, the contraindications to ribavirin also apply to this combination regimen.  Patients with severe hepatic impairment.  Co-administration with drugs that are: highly dependent on CYP3A for clearance; strong inducers of CYP3A and CYP2C8; and strong inhibitors of CYP2C8. Refer to Table 2.  Known hypersensitivity to ritonavir (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome).

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Table 2: Drugs that are Contraindicated with Viekira Pak Drug Class Drugs Within Class Clinical Comments Alpha1- Alfuzosin HCL Potential for hypotension. adrenoreceptor antagonist Anticonvulsants Carbamazepine, Ombitasvir, paritaprevir, ritonavir and phenytoin, dasabuvir exposures may decrease leading to a phenobarbital potential loss of therapeutic activity. Antihyperlipidemic Gemfibrozil Increase in dasabuvir exposures by 10-fold, agent increasing the risk of QT prolongation. Antimycobacterial Rifampin Ombitasvir, paritaprevir, ritonavir and dasabuvir exposures may decrease leading to a potential loss of therapeutic activity. Ergot derivatives Ergotamine, dihydroergotamine, Acute ergot toxicity characterized by ergonovine, methylergonovine vasospasm and tissue ischemia has been associated with co-administration of ritonavir and ergonovine, ergotamine, dihydroergotamine, or methylergonovine. Ethinyl estradiol- Ethinyl estradiol-containing Potential for ALT elevations containing such as combined products oral contraceptives Herbal Product St. John’s Wort (Hypericum Ombitasvir, paritaprevir, ritonavir and perforatum) dasabuvir exposures may decrease leading to a potential loss of therapeutic activity. HMG-CoA Lovastatin, simvastatin Potential for myopathy including rhabdomyolysis. Reductase Sedatives/hypnotics Triazolam, Orally administered Coadministration may cause large increases in midazolam the concentration of these benzodiazepines. The potential exists for serious and/or life threatening events such as prolonged or increased sedation or respiratory depression.

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DRUG-DRUG INTERACTIONS

Table 3: Potentially Significant Drug Interactions Drug Class Drugs Within Class Clinical Comments Antiarrhythmics Amiodarone, bepridil, Caution is warranted and therapeutic disopyramide, flecainide, lidocaine concentration monitoring is (systemic), mexiletine, recommended for antiarrhythmics when propafenone, quinidine coadministered with Viekira Pak. Antifungals Ketoconazole, Voriconazole When co-administered with ketoconazole, the maximum daily dose of ketoconazole should be limited to 200 mg per day. Co-administration of with voriconazole is not recommended. Calcium Channel Amlodipine Consider dose reduction for amlodipine. Blockers Clinical monitoring is recommended. Corticosteroids Fluticasone Concomitant use with inhaled or nasal (Inhaled/Nasal) fluticasone may reduce serum cortisol concentrations. Alternative corticosteroids should be considered, particularly for long term use. Diuretics Furosemide Increased concentrations of furosemide may occur. Clinical monitoring of patients is recommended. HIV-Antiviral Agents Atazanavir/ritonavir, When coadministered with Viekira Pak, darunavir/ritonavir, atazanavir 300 mg (without ritonavir) should only lopinavir/ritonavir, rilpivirine be given in the morning. Co-administration with darunavir/ritonavir is not recommended. Co-administration with lopinavir/ritonavir is not recommended. Co-administration with rilpivirine once daily is not recommended due to potential for QT interval prolongation with higher concentrations of rilpivirine. HMG-CoA Rosuvastatin, pravastatin When co-administered with rosuvastatin, the Reductase dose of rosuvastatin should not exceed 10 mg per day. When co-administered with pravastatin, the dose of pravastatin should not exceed 40 mg per day. Immunosuppressants Cyclosporine, Tacrolimus When initiating therapy with Viekira Pak, reduce cyclosporine dose to 1/5th of the patient’s current cyclosporine dose. Frequent assessment of renal function and cyclosporine- related side effects is recommended. When initiating therapy with Viekira Pak, the dose of tacrolimus needs to be reduced. Proton Pump Omeprazole Monitor patients for decreased efficacy of Inhibitors omeprazole.

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REFERENCES American Association for the Study of Liver Diseases and Infectious Disease Society of America. Recommendations for Testing, Managing, and Treating Hepatitis C. When and in Whom to Initiate HCV Therapy. http://www.hcvguidelines.org/full-report/when-and-whom-initiate-hcv-therapy. 2014

Viekira Pak (Ombitasvir/Paritaprevir/Ritonavir plus Dasabuvir) product labeling. Abbvie, Inc. North Chicago, IL. December 2014

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