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OLYSIO (Simeprevir) Capsules, for Oral Use Ribavirin May Cause Birth Defects and Fetal Death and Animal Studies Initial U.S

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OLYSIO (Simeprevir) Capsules, for Oral Use Ribavirin May Cause Birth Defects and Fetal Death and Animal Studies Initial U.S • Because ribavirin may cause birth defects and fetal death, OLYSIO in HIGHLIGHTS OF PRESCRIBING INFORMATION combination with peginterferon alfa and ribavirin is contraindicated in These highlights do not include all the information needed to use pregnant women and in men whose female partners are pregnant. (4) OLYSIOTM safely and effectively. See full prescribing information for OLYSIO. ------------------------WARNINGS AND PRECAUTIONS----------------------­ • Embryofetal Toxicity (Use with Ribavirin and Peginterferon Alfa): OLYSIO (simeprevir) capsules, for oral use Ribavirin may cause birth defects and fetal death and animal studies Initial U.S. Approval – 2013 have shown interferons have abortifacient effects; avoid pregnancy in female patients and female partners of male patients. Patients must have ----------------------------INDICATIONS AND USAGE---------------------------­ a negative pregnancy test prior to initiating therapy, use at least OLYSIO is a hepatitis C virus (HCV) NS3/4A protease inhibitor indicated for two effective methods of contraception during treatment, and undergo the treatment of chronic hepatitis C (CHC) infection as a component of a monthly pregnancy tests. (5.1) combination antiviral treatment regimen. (1) • Photosensitivity: Serious photosensitivity reactions have been observed • OLYSIO efficacy has been established in combination with during combination therapy with OLYSIO, peginterferon alfa and peginterferon alfa and ribavirin in HCV genotype 1 infected subjects ribavirin. Use sun protection measures and limit sun exposure. Consider with compensated liver disease (including cirrhosis). (1, 14) discontinuation if a photosensitivity reaction occurs. (5.2) • OLYSIO must not be used as monotherapy. (1) • Rash: Rash has been observed during combination therapy with • Screening patients with HCV genotype 1a infection for the presence of OLYSIO, peginterferon alfa and ribavirin. Discontinue OLYSIO if virus with the NS3 Q80K polymorphism at baseline is strongly severe rash occurs. (5.3) recommended. Alternative therapy should be considered for patients infected with HCV genotype 1a containing the Q80K polymorphism. (1, ------------------------------ADVERSE REACTIONS------------------------------­ 12, 14) The most common reported adverse reactions (greater than 20% of subjects) in subjects receiving the combination of OLYSIO with peginterferon and -----------------------DOSAGE AND ADMINISTRATION----------------------­ ribavirin and occurring with at least 3% higher frequency compared to • One 150 mg capsule taken once daily with food. (2.1) subjects receiving placebo in combination with peginterferon alfa and • OLYSIO should be administered with both peginterferon alfa and ribavirin during the first 12 weeks of treatment were: rash (including ribavirin. The recommended treatment duration of OLYSIO with photosensitivity), pruritus and nausea. (6.1) peginterferon alfa and ribavirin is 12 weeks, followed by either 12 or 36 additional weeks of peginterferon alfa and ribavirin depending on To report SUSPECTED ADVERSE REACTIONS, contact Janssen prior response status. (2.1) Products, LP at 1-800-JANSSEN (1-800-526-7736) or FDA at • For specific dosage instructions for peginterferon alfa and ribavirin, see 1-800-FDA-1088 or www.fda.gov/medwatch. their respective prescribing information. (2.1) -------------------------------DRUG INTERACTIONS------------------------------­ • A dose recommendation cannot be made for patients of East Asian Co-administration of OLYSIO with drugs that are moderate or strong inducers ancestry. (2.5, 8.6) or inhibitors of CYP3A may significantly affect the plasma concentrations of • A dose recommendation cannot be made for patients with moderate to simeprevir. The potential for drug-drug interactions must be considered prior severe hepatic impairment. (2.4, 8.8) to and during treatment. (5.6, 7, 12.3) ----------------------DOSAGE FORMS AND STRENGTHS--------------------­ See 17 for PATIENT COUNSELING INFORMATION and FDA- Capsule: 150 mg (3) approved patient labeling. Revised: 12/2013 -------------------------------CONTRAINDICATIONS------------------------------­ • All contraindications to peginterferon alfa and ribavirin also apply to OLYSIO combination treatment with peginterferon alfa and ribavirin. (4) FULL PRESCRIBING INFORMATION: CONTENTS* 8.3 Nursing Mothers 8.4 Pediatric Use 1 INDICATIONS AND USAGE 8.5 Geriatric Use 2 DOSAGE AND ADMINISTRATION 8.6 Race 2.1 OLYSIO/Peginterferon alfa/Ribavirin Combination 8.7 Renal Impairment Treatment 8.8 Hepatic Impairment 2.2 Discontinuation of Dosing 8.9 Other HCV Genotypes 2.3 Dosage Adjustment or Interruption 8.10 Liver Transplantation 2.4 Hepatic Impairment 10 OVERDOSAGE 2.5 Race 11 DESCRIPTION 3 DOSAGE FORMS AND STRENGTHS 12 CLINICAL PHARMACOLOGY 4 CONTRAINDICATIONS 12.1 Mechanism of Action 5 WARNINGS AND PRECAUTIONS 12.2 Pharmacodynamics 5.1 Embryo-Fetal Toxicity (Use with Ribavirin and 12.3 Pharmacokinetics Peginterferon alfa) 12.4 Microbiology 5.2 Photosensitivity 12.5 Pharmacogenomics 5.3 Rash 13 NONCLINICAL TOXICOLOGY 5.4 Sulfa Allergy 13.1 Carcinogenesis, Mutagenesis, Impairment of 5.5 Use with Peginterferon alfa and Ribavirin Fertility 5.6 Drug Interactions 13.2 Animal Toxicology and/or Pharmacology 6 ADVERSE REACTIONS 14 CLINICAL STUDIES 6.1 Clinical Studies Experience 14.1 Treatment-Naïve Adult Subjects with HCV 7 DRUG INTERACTIONS Genotype 1 Infection 7.1 Potential for OLYSIO to Affect Other Drugs 14.2 Adult Subjects with HCV Genotype 1 Infection 7.2 Potential for Other Drugs to Affect OLYSIO who Failed Prior Therapy 7.3 Established and Other Potentially Significant 16 HOW SUPPLIED/STORAGE AND HANDLING Drug Interactions 17 PATIENT COUNSELING INFORMATION 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnancy *Sections or subsections omitted from the full prescribing information are not listed 1 Reference ID: 3417522 2 Reference ID: 3417522 FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE OLYSIOTM is a hepatitis C virus (HCV) NS3/4A protease inhibitor indicated for the treatment of chronic hepatitis C (CHC) infection as a component of a combination antiviral treatment regimen. • OLYSIO efficacy has been established in combination with peginterferon alfa and ribavirin, in HCV genotype 1 infected subjects with compensated liver disease (including cirrhosis) [see Clinical Studies (14)]. The following points should be considered when initiating OLYSIO for treatment of chronic hepatitis C infection: • OLYSIO must not be used as monotherapy [see Warning and Precautions (5.5)]. • OLYSIO efficacy in combination with peginterferon alfa and ribavirin is influenced by baseline host and viral factors [see Clinical Pharmacology (12.5) and Clinical Studies (14)]. • OLYSIO efficacy in combination with peginterferon alfa and ribavirin is substantially reduced in patients infected with HCV genotype 1a with an NS3 Q80K polymorphism at baseline compared to patients infected with hepatitis C virus (HCV) genotype 1a without the Q80K polymorphism [see Microbiology (12.4) and Clinical Studies (14)]. Screening patients with HCV genotype 1a infection for the presence of virus with the NS3 Q80K polymorphism at baseline is strongly recommended. Alternative therapy should be considered for patients infected with HCV genotype 1a containing the Q80K polymorphism. • OLYSIO efficacy has not been studied in patients who have previously failed therapy with a treatment regimen that includes OLYSIO or other HCV protease inhibitors [see Microbiology (12.4)]. 2 DOSAGE AND ADMINISTRATION 2.1 OLYSIO/Peginterferon alfa/Ribavirin Combination Treatment The recommended dose of OLYSIO is one capsule of 150 mg taken orally once daily with food. The type of food does not affect exposure to simeprevir [see Clinical Pharmacology (12.3)]. The capsule should be swallowed as a whole. OLYSIO should be used in combination with peginterferon alfa and ribavirin. For peginterferon alfa and ribavirin specific dosage instructions, refer to their respective prescribing information. 3 Reference ID: 3417522 Duration of Treatment The recommended duration of treatment with OLYSIO is 12 weeks in combination with peginterferon alfa and ribavirin. In all patients, treatment with OLYSIO should be initiated in combination with peginterferon alfa and ribavirin and should be administered for 12 weeks. All treatment-naïve and prior relapser patients, including those with cirrhosis, should receive an additional 12 weeks of peginterferon alfa and ribavirin after completing 12 weeks of treatment with OLYSIO, peginterferon alfa and ribavirin (total treatment duration of 24 weeks). All prior non-responder patients (including partial and null-responders), including those with cirrhosis, should receive an additional 36 weeks of peginterferon alfa and ribavirin after completing 12 weeks of treatment with OLYSIO, peginterferon alfa and ribavirin (total treatment duration of 48 weeks). The recommended duration of treatment with OLYSIO, peginterferon alfa and ribavirin is also presented in Table 1. Refer to Table 2 for treatment stopping rules. Table 1: Duration of Treatment with OLYSIO, Peginterferon Alfa and Ribavirin Treatment with Treatment with Total OLYSIO, Peginterferon alfa Treatment * Peginterferon alfa and and Ribavirin* Duration Ribavirin* † Treatment-naïve and prior relapser patients First 12 weeks Additional 12 weeks 24 weeks including those with cirrhosis ‡ Prior non-responder patients (including First 12 weeks Additional 36 weeks 48 weeks partial and null responders) including those with cirrhosis
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