HIGHLIGHTS OF PRESCRIBING INFORMATION CONTRAINDICATIONS These highlights do not include all the information needed to use • Patients with moderate to severe hepatic impairment. (4, 5.1, 8.6, 12.3) VIEKIRA XR safely and effectively. See full prescribing information for • If VIEKIRA XR is administered with ribavirin, the contraindications to VIEKIRA XR. ribavirin also apply to this combination regimen. (4) • Co-administration with drugs that are: highly dependent on CYP3A for VIEKIRA XR (dasabuvir, ombitasvir, paritaprevir, and ritonavir) clearance; moderate or strong inducers of CYP3A or strong inducers of extended-release tablets, for oral use CYP2C8; and strong inhibitors of CYP2C8. (4) Initial U.S. Approval: 2014 • Known hypersensitivity to ritonavir (e.g. toxic epidermal necrolysis, Stevens-Johnson syndrome). (4) INDICATIONS AND USAGE VIEKIRA XR includes dasabuvir, a hepatitis C virus non-nucleoside NS5B WARNINGS AND PRECAUTIONS palm polymerase inhibitor, ombitasvir, a hepatitis C virus NS5A inhibitor, • Hepatic Decompensation and Hepatic Failure in Patient with Cirrhosis: paritaprevir, a hepatitis C virus NS3/4A protease inhibitor, and ritonavir, a Hepatic decompensation and hepatic failure, including liver transplantation CYP3A inhibitor and is indicated for the treatment of adult patients with or fatal outcomes, have been reported mostly in patients with advanced chronic hepatitis C virus (HCV): cirrhosis. Monitor for clinical signs and symptoms of hepatic • genotype 1b infection without cirrhosis or with compensated cirrhosis decompensation. (5.1) • genotype 1a infection without cirrhosis or with compensated cirrhosis for • ALT Elevations: Discontinue ethinyl estradiol-containing medications prior use in combination with ribavirin. (1) to starting VIEKIRA XR (alternative contraceptive methods are recommended). Perform hepatic laboratory testing on all patients during the DOSAGE AND ADMINISTRATION first 4 weeks of treatment. For ALT elevations on VIEKIRA XR, monitor Testing Prior to Initiation - Assess for laboratory and clinical evidence of closely and follow recommendations in full prescribing information. (5.2) hepatic decompensation. (2.1) • Risks Associated With Ribavirin Combination Treatment: If VIEKIRA XR Recommended dosage: Three tablets taken once daily. VIEKIRA XR must be is administered with ribavirin, the warnings and precautions for ribavirin taken with a meal because administration under fasting conditions may result also apply to this combination regimen. (5.3) in reduced virologic response and possible development of resistance. (2.2) • Drug Interactions: The concomitant use of VIEKIRA XR and certain other drugs may result in known or potentially significant drug interactions, some Treatment Regimen and Duration by Patient Population of which may lead to loss of therapeutic effect of VIEKIRA XR. (5.4) Patient Population Treatment* Duration Genotype 1a, ADVERSE REACTIONS VIEKIRA XR + ribavirin 12 weeks without cirrhosis In subjects receiving the combination of dasabuvir with ombitasvir, paritaprevir, ritonavir with ribavirin, the most commonly reported adverse Genotype 1a, VIEKIRA XR + ribavirin 24 weeks** reactions (greater than 10% of subjects) were fatigue, nausea, pruritus, other with compensated cirrhosis skin reactions, insomnia and asthenia. In subjects receiving the combination of Genotype 1b, dasabuvir with ombitasvir, paritaprevir, ritonavir without ribavirin, the most with or without compensated VIEKIRA XR 12 weeks commonly reported adverse reactions (greater than or equal to 5% of subjects) cirrhosis were nausea, pruritus and insomnia. (6.1) *Note: Follow the genotype 1a dosing recommendations in patients with an To report SUSPECTED ADVERSE REACTIONS, contact AbbVie Inc. unknown genotype 1 subtype or with mixed genotype 1 infection. at 1-800-633-9110 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. **VIEKIRA XR administered with ribavirin for 12 weeks may be considered for some patients based on prior treatment history [See Clinical Studies DRUG INTERACTIONS (14.3)]. Co-administration of VIEKIRA XR can alter the plasma concentrations of some drugs and some drugs may alter the plasma concentrations of VIEKIRA • HCV/HIV-1 co-infection: For patients with HCV/HIV-1 co-infection, XR. The potential for drug interactions must be considered before and during follow the dosage recommendations in the table above. (2.2) treatment. Consult the full prescribing information prior to and during • Liver Transplant Recipients: In liver transplant recipients with normal treatment for potential drug interactions. (4, 5.4, 7, 12.3) hepatic function and mild fibrosis (Metavir fibrosis score ≤2), the recommended duration of VIEKIRA XR with ribavirin is 24 weeks. (2.4) See 17 for PATIENT COUNSELING INFORMATION and Medication Guide. DOSAGE FORMS AND STRENGTHS Extended-release tablets: 200 mg dasabuvir, 8.33 mg ombitasvir, 50 mg Revised: 7/2016 paritaprevir, and 33.33 mg ritonavir (3) FULL PRESCRIBING INFORMATION: CONTENTS* 7.1 Potential for VIEKIRA XR to Affect Other Drugs 1 INDICATIONS AND USAGE 7.2 Potential for Other Drugs to Affect One or More Components of 2 DOSAGE AND ADMINISTRATION VIEKIRA XR 2.1 Testing Prior to Initiation of VIEKIRA XR 7.3 Established and Other Potential Drug Interactions 2.2 Recommended Dosage in Adults 7.4 Drugs without Clinically Significant Interactions with VIEKIRA XR 2.3 Use in Liver Transplant Recipients 8 USE IN SPECIFIC POPULATIONS 2.4 Hepatic Impairment 8.1 Pregnancy 3 DOSAGE FORMS AND STRENGTHS 8.2 Lactation 4 CONTRAINDICATIONS 8.3 Females and Males of Reproductive Potential 5 WARNINGS AND PRECAUTIONS 8.4 Pediatric Use 5.1 Risk of Hepatic Decompensation and Hepatic Failure in Patients with 8.5 Geriatric Use Cirrhosis 8.6 Hepatic Impairment 5.2 Increased Risk of ALT Elevations 8.7 Renal Impairment 5.3 Risks Associated With Ribavirin Combination Treatment 10 OVERDOSAGE 5.4 Risk of Adverse Reactions or Reduced Therapeutic Effect Due to Drug 11 DESCRIPTION Interactions 12 CLINICAL PHARMACOLOGY 5.5 Risk of HIV-1 Protease Inhibitor Drug Resistance in HCV/HIV-1 Co­ 12.1 Mechanism of Action infected Patients 12.2 Pharmacodynamics 6 ADVERSE REACTIONS 12.3 Pharmacokinetics 6.1 Clinical Trials Experience 12.4 Microbiology 6.2 Postmarketing Experience 13 NONCLINICAL TOXICOLOGY 7 DRUG INTERACTIONS 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Reference ID: 3962663 14 CLINICAL STUDIES 14.6 Clinical Trial in Subjects with HCV/HIV-1 Co-infection 14.1 Description of Clinical Trials (TURQUOISE-I) 14.2 Clinical Trial Results in Adults with Chronic HCV Genotype 1a and 1b 14.7 Durability of Response Infection without Cirrhosis 16 HOW SUPPLIED/STORAGE AND HANDLING 14.3 Clinical Trial Results in Adults with Chronic HCV Genotype 1a and 1b 17 PATIENT COUNSELING INFORMATION Infection and Compensated Cirrhosis 14.4 Effect of Ribavirin Dose Reductions on SVR12 *Sections or subsections omitted from the full prescribing information are not 14.5 Clinical Trial of Selected Liver Transplant Recipients (CORAL-I) listed. Reference ID: 3962663 FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE VIEKIRA XR is indicated for the treatment of adult patients with chronic hepatitis C virus (HCV) [see Dosage and Administration (2.2) and Clinical Studies (14)]: genotype 1b infection without cirrhosis or with compensated cirrhosis genotype 1a infection without cirrhosis or with compensated cirrhosis for use in combination with ribavirin. 2 DOSAGE AND ADMINISTRATION 2.1 Testing Prior to Initiation of VIEKIRA XR Prior to initiation of VIEKIRA XR, assess for laboratory and clinical evidence of hepatic decompensation [see Warnings and Precautions (5.1 and 5.2)]. 2.2 Recommended Dosage in Adults VIEKIRA XR is a 4-drug fixed-dose combination, extended-release tablet containing 200 mg of dasabuvir, 8.33 mg of ombitasvir, 50 mg of paritaprevir, and 33.33 mg of ritonavir. The recommended dosage of VIEKIRA XR is three tablets taken orally once daily. VIEKIRA XR must be taken with a meal because administration under fasting conditions may result in reduced virologic response and possible development of resistance [see Clinical Pharmacology (12.3)]. Swallow tablets whole. Splitting, crushing, or chewing tablets may compromise the extended-release performance, efficacy, and/or safety of VIEKIRA XR. For optimal release of dasabuvir, alcohol should not be consumed within 4 hours of taking VIEKIRA XR. VIEKIRA XR is used in combination with ribavirin (RBV) in certain patient populations (see Table 1). When administered with VIEKIRA XR, the recommended dosage of RBV is based on weight: 1000 mg/day for subjects <75 kg and 1200 mg/day for those ≥75 kg, divided and administered twice-daily with food. The starting dosage and on-treatment dosage of RBV can be decreased based on changes in hemoglobin levels and/or creatinine clearance. For ribavirin dosage modifications, refer to the ribavirin prescribing information. For patients with HCV/HIV-1 co-infection, follow the dosage recommendations in Table 1. Refer to Drug Interactions (7) for dosage recommendations for concomitant HIV-1 antiviral drugs. Table 1 shows the recommended VIEKIRA XR treatment regimen and duration based on patient population. Reference ID: 3962663 Table 1. Treatment Regimen and Duration by Patient Population (Treatment-Naïve or Interferon-Experienced) Patient Population Treatment* Duration Genotype 1a, VIEKIRA XR + ribavirin 12 weeks without cirrhosis Genotype 1a, with compensated cirrhosis VIEKIRA XR + ribavirin 24 weeks** (Child-Pugh A) Genotype