Crohn’s Disease Recommended Maintenance Adult Subcutaneous Dosage HIGHLIGHTS OF PRESCRIBING INFORMATION (2.3): These highlights do not include all the information needed to use ® A subcutaneous 90 mg dose 8 weeks after the initial intravenous dose, then STELARA safely and effectively. See full prescribing information for every 8 weeks thereafter. STELARA®. ----------------------DOSAGE FORMS AND STRENGTHS--------------------- STELARA® (ustekinumab) injection, for subcutaneous or intravenous use Subcutaneous Injection Initial U.S. Approval: 2009 • Injection: 45 mg/0.5 mL or 90 mg/mL in a single-dose prefilled syringe (3) --------------------------RECENT MAJOR CHANGES---------------------------- • Injection: 45 mg/0.5 mL in a single-dose vial (3) Indications and Usage, Crohn’s Disease (1.3) 09/2016 Dosage and Administration (2.3) 09/2016 Intravenous Infusion Dosage and Administration (2.6) 09/2016 • Injection: 130 mg/26 mL (5 mg/mL) solution in a single-dose vial (3) -----------------------------INDICATIONS AND USAGE--------------------------- ® -----------------------------CONTRAINDICATIONS--------------------------------- STELARA is a human interleukin-12 and -23 antagonist indicated for the Clinically significant hypersensitivity to ustekinumab or to any of the treatment of adult patients with: excipients. (4) • moderate to severe plaque psoriasis (Ps) who are candidates for phototherapy or systemic therapy. (1.1) -------------------------WARNINGS AND PRECAUTIONS---------------------- ® • active psoriatic arthritis (PsA), alone or in combination with • Infections: Serious infections have occurred. Do not start STELARA methotrexate. (1.2) during any clinically important active infection. If a serious infection or • clinically significant infection develops, consider discontinuing moderately to severely active Crohn’s disease (CD) who have ® • failed or were intolerant to treatment with immunomodulators or STELARA until the infection resolves. (5.1) corticosteroids, but never failed a tumor necrosis factor (TNF) • Theoretical Risk for Particular Infections: Serious infections from blocker or mycobacteria, salmonella and Bacillus Calmette-Guerin (BCG) • failed or were intolerant to treatment with one or more TNF vaccinations have been reported in patients genetically deficient in IL- blockers. (1.3) 12/IL-23. Diagnostic tests for these infections should be considered as dictated by clinical circumstances. (5.2) ------------------------DOSAGE AND ADMINISTRATION----------------------- • Tuberculosis (TB): Evaluate patients for TB prior to initiating treatment Psoriasis Recommended Adult Subcutaneous Dosage (2.1): with STELARA®. Initiate treatment of latent TB before administering ® Weight Range (kilogram) Dosage Regimen STELARA . (5.3) ® less than or equal to 100 kg 45 mg administered subcutaneously • Malignancies: STELARA may increase risk of malignancy. The safety ® initially and 4 weeks later, followed by of STELARA in patients with a history of or a known malignancy has 45 mg administered subcutaneously every not been evaluated. (5.4) 12 weeks • Hypersensitivity Reactions: Anaphylaxis or other clinically significant greater than 100 kg 90 mg administered subcutaneously hypersensitivity reactions may occur. (5.5) initially and 4 weeks later, followed by • Reversible Posterior Leukoencephalopathy Syndrome (RPLS): One case 90 mg administered subcutaneously every was reported. If suspected, treat promptly and discontinue STELARA®. 12 weeks (5.6) Psoriatic Arthritis Recommended Adult Subcutaneous Dosage (2.2): ------------------------------ADVERSE REACTIONS------------------------------- • The recommended dosage is 45 mg administered subcutaneously Most common adverse reactions are: initially and 4 weeks later, followed by 45 mg administered • Psoriasis (≥3%): nasopharyngitis, upper respiratory tract infection, subcutaneously every 12 weeks. headache, and fatigue. (6.1) • For patients with co-existent moderate-to-severe plaque psoriasis • Crohn’s Disease, induction (≥3%): vomiting. (6.1) weighing greater than 100 kg, the recommended dosage is 90 mg • Crohn’s Disease, maintenance (≥3%): nasopharyngitis, injection site administered subcutaneously initially and 4 weeks later, followed by erythema, vulvovaginal candidiasis/mycotic infection, bronchitis, 90 mg administered subcutaneously every 12 weeks. pruritus, urinary tract infection, and sinusitis. (6.1) Crohn’s Disease Recommended Initial Adult Intravenous Dosage (2.3): To report SUSPECTED ADVERSE REACTIONS, contact Janssen A single intravenous infusion using weight-based dosing: Biotech, Inc. at 1-800-JANSSEN (1-800-526-7736) or FDA at 1-800-FDA- 1088 or www.fda.gov/medwatch. Weight Range (kilogram) Recommended Dosage Up to 55 kg 260 mg (2 vials) See 17 for PATIENT COUNSELING INFORMATION and Medication Greater than 55 kg to 85 kg 390 mg (3 vials) Guide. Greater than 85 kg 520 mg (4 vials) Revised: 09/2016 FULL PRESCRIBING INFORMATION: CONTENTS* 5.1 Infections 1 INDICATIONS AND USAGE 5.2 Theoretical Risk for Vulnerability to Particular 1.1 Psoriasis (Ps) Infections 1.2 Psoriatic Arthritis (PsA) 5.3 Pre-treatment Evaluation for Tuberculosis 1.3 Crohn’s Disease 5.4 Malignancies 2 DOSAGE AND ADMINISTRATION 5.5 Hypersensitivity Reactions 2.1 Psoriasis 5.6 Reversible Posterior Leukoencephalopathy 2.2 Psoriatic Arthritis Syndrome 2.3 Crohn’s Disease 5.7 Immunizations 2.4 General Considerations for Administration 5.8 Concomitant Therapies ® 2.5 Instructions for Administration of STELARA 6 ADVERSE REACTIONS Prefilled Syringes Equipped with Needle Safety 6.1 Clinical Trials Experience Guard 6.2 Immunogenicity ® 2.6 Preparation and Administration of STELARA 6.3 Postmarketing Experience 130 mg/26 mL (5 mg/mL) Vial for Intravenous 7 DRUG INTERACTIONS Infusion (Crohn’s Disease) 7.1 Live Vaccines 3 DOSAGE FORMS AND STRENGTHS 7.2 Concomitant Therapies 4 CONTRAINDICATIONS 7.3 CYP450 Substrates 5 WARNINGS AND PRECAUTIONS 7.4 Allergen Immunotherapy 1 Reference ID: 3990240 8 USE IN SPECIFIC POPULATIONS 13.1 Carcinogenesis, Mutagenesis, Impairment of 8.1 Pregnancy Fertility 8.2 Lactation 13.2 Animal Toxicology and/or Pharmacology 8.4 Pediatric Use 14 CLINICAL STUDIES 8.5 Geriatric Use 14.1 Psoriasis 10 OVERDOSAGE 14.2 Psoriatic Arthritis 11 DESCRIPTION 14.3 Crohn’s Disease 12 CLINICAL PHARMACOLOGY 15 REFERENCES 12.1 Mechanism of Action 16 HOW SUPPLIED/STORAGE AND HANDLING 12.2 Pharmacodynamics 17 PATIENT COUNSELING INFORMATION 12.3 Pharmacokinetics 13 NONCLINICAL TOXICOLOGY *Sections or subsections omitted from the full prescribing information are not listed. 2 Reference ID: 3990240 FULL PRESCRIBING INFORMATION 1 INDICATIONS AND USAGE 1.1 Psoriasis (Ps) STELARA® is indicated for the treatment of adult patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy. 1.2 Psoriatic Arthritis (PsA) STELARA® is indicated for the treatment of adult patients with active psoriatic arthritis. STELARA® can be used alone or in combination with methotrexate (MTX). 1.3 Crohn’s Disease STELARA® is indicated for the treatment of adult patients with moderately to severely active Crohn’s disease who have: • failed or were intolerant to treatment with immunomodulators or corticosteroids, but never failed treatment with a tumor necrosis factor (TNF) blocker or • failed or were intolerant to treatment with one or more TNF blockers. 2 DOSAGE AND ADMINISTRATION 2.1 Psoriasis Subcutaneous Adult Dosage Regimen • For patients weighing 100 kg or less, the recommended dose is 45 mg initially and 4 weeks later, followed by 45 mg every 12 weeks. • For patients weighing more than 100 kg, the recommended dose is 90 mg initially and 4 weeks later, followed by 90 mg every 12 weeks. In subjects weighing more than 100 kg, 45 mg was also shown to be efficacious. However, 90 mg resulted in greater efficacy in these subjects [see Clinical Studies (14)]. 2.2 Psoriatic Arthritis Subcutaneous Adult Dosage Regimen • The recommended dose is 45 mg initially and 4 weeks later, followed by 45 mg every 12 weeks. • For patients with co-existent moderate-to-severe plaque psoriasis weighing more than 100 kg, the recommended dose is 90 mg initially and 4 weeks later, followed by 90 mg every 12 weeks. 3 Reference ID: 3990240 2.3 Crohn’s Disease Intravenous Induction Adult Dosage Regimen A single intravenous infusion dose of STELARA® using the weight-based dosage regimen specified in Table 1 [see Instructions for dilution of STELARA® 130 mg vial for intravenous infusion (2.6)]. Table 1: Initial Intravenous Dosage of STELARA® Body Weight of Patient at the time of Dose Number of 130 mg/26 mL (5 mg/mL) dosing STELARA® vials 55 kg or less 260 mg 2 more than 55 kg to 85 kg 390 mg 3 more than 85 kg 520 mg 4 Subcutaneous Maintenance Adult Dosage Regimen The recommended maintenance dosage is a subcutaneous 90 mg dose administered 8 weeks after the initial intravenous dose, then every 8 weeks thereafter. 2.4 General Considerations for Administration • After proper training in subcutaneous injection technique, a patient may self-inject with STELARA® if a physician determines that it is appropriate. Patients should be instructed to follow the directions provided in the Medication Guide [see Medication Guide]. • The needle cover on the prefilled syringe contains dry natural rubber (a derivative of latex). The needle cover should not be handled by persons sensitive to latex. • It is recommended that each injection be administered at a different anatomic location (such as upper arms, gluteal regions, thighs, or any quadrant