PRODUCT MONOGRAPH PrCELEBREX® (celecoxib) Capsules, 100 mg and 200 mg ATC Code: M01AH01 Anti-inflammatory and anti-rheumatic products, non-steroids Upjohn Canada ULC Date of Revision: 17300, Trans-Canada Highway May 11, 2020 Kirkland, Quebec H9J 2M5 Submission Control No: 236661 ® G.D. Searle LLC Upjohn Canada ULC, Licensee © Upjohn Canada ULC, 2020 TABLE OF CONTENTS PART I: HEALTH PROFESSIONAL INFORMATION .........................................................3 SUMMARY PRODUCT INFORMATION .....................................................................3 INDICATIONS AND CLINICAL USE ...........................................................................3 CONTRAINDICATIONS .................................................................................................4 WARNINGS AND PRECAUTIONS ...............................................................................5 ADVERSE REACTIONS ................................................................................................16 DRUG INTERACTIONS ................................................................................................24 DOSAGE AND ADMINISTRATION ...........................................................................27 OVERDOSAGE ...............................................................................................................29 ACTION AND CLINICAL PHARMACOLOGY ........................................................29 STORAGE AND STABILITY........................................................................................31 DOSAGE FORMS, COMPOSITION AND PACKAGING ........................................31 PART II: SCIENTIFIC INFORMATION ................................................................................33 PHARMACEUTICAL INFORMATION ......................................................................33 CLINICAL TRIALS ........................................................................................................34 DETAILED PHARMACOLOGY ..................................................................................44 TOXICOLOGY................................................................................................................46 REFERENCES .................................................................................................................50 PART III: CONSUMER INFORMATION...............................................................................54 CELEBREX (celecoxib) – Product Monograph Page 2 of 57 PrCELEBREX® (celecoxib) PART I: HEALTH PROFESSIONAL INFORMATION SUMMARY PRODUCT INFORMATION Route of Dosage Form / All Nonmedicinal Ingredients Administration Strength Oral Capsules, 100 mg and croscarmellose sodium, gelatin, lactose 200 mg monohydrate, magnesium stearate, povidone, sodium lauryl sulfate, titanium dioxide (E171) and edible inks (ferric oxide (E172) for 200 mg capsules and indigotine (E132) for 100 mg capsules). INDICATIONS AND CLINICAL USE CELEBREX (celecoxib) is indicated for relief of symptoms associated with: • Osteoarthritis, • Adult Rheumatoid Arthritis, and • Ankylosing Spondylitis CELEBREX is also indicated for the short-term (≤7 days) management of moderate to severe acute pain in adults in conditions such as the following: • Musculoskeletal and/or soft tissue trauma including sprains, • Postoperative orthopaedic, and • Pain following dental extraction CELEBREX, particularly at doses higher than 200 mg per day, is associated with an increased risk of serious cardiovascular related adverse events (such as myocardial infarction, stroke or thrombotic events), which can be fatal. Doses of CELEBREX >200 mg/day should NOT be used in patients with ischemic heart disease, cerebrovascular disease, patients with congestive heart failure (NYHA II-IV) or patients with risk factors for cardiovascular disease. For patients with an increased risk of developing cardiovascular adverse events, other management strategies that do NOT include the use of NSAIDs, particularly celecoxib, diclofenac, or ibuprofen, should be considered first (see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS). For patients with an increased risk of developing gastrointestinal adverse events, other management strategies that do NOT include the use of NSAIDs, including CELEBREX, CELEBREX (celecoxib) – Product Monograph Page 3 of 57 should be considered first (see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS). Use of CELEBREX should be limited to the lowest effective dose for the shortest possible duration of treatment in order to minimize the potential risk for cardiovascular or gastrointestinal adverse events (see CONTRAINDICATIONS and WARNINGS AND PRECAUTIONS). CELEBREX, as a NSAID, does NOT treat clinical disease or prevent its progression. CELEBREX, as a NSAID, only relieves symptoms and decreases inflammation for as long as the patient continues to take it. Geriatrics (>65 years of age): Evidence from clinical studies and postmarket experience suggests that use in geriatric population is associated with differences in safety (see WARNINGS AND PRECAUTIONS – Special Populations - Geriatrics). Paediatrics (<18 years of age): Safety and Efficacy have not been established in the paediatric population (see CONTRAINDICATIONS). CONTRAINDICATIONS CELEBREX (celecoxib) is contraindicated in: • The peri-operative setting of Coronary Artery Bypass Graft Surgery (CABG). Although CELEBREX has NOT been studied in this patient population, a selective COX-2 inhibitor NSAID studied in such a setting has led to an increased incidence of cardiovascular/thromboembolic events, deep surgical infections and sternal wound complications (see CLINICAL TRIALS – Cardiovascular Safety). • The third trimester of pregnancy, because of risk of premature closure of the ductus arteriosus and prolonged parturition. • Women who are breastfeeding, because of the potential for serious adverse reactions in nursing infants. • Severe uncontrolled heart failure. • Known hypersensitivity to celecoxib or to any of the components/excipients. • Demonstrated allergic-type reactions to sulfonamides. • History of asthma, urticaria, or allergic-type reactions after taking Acetylsalicylic Acid (ASA) or other NSAIDs (i.e. complete or partial syndrome of ASA-intolerance - rhinosinusitis, urticaria/angioedema, nasal polyps, asthma). Fatal anaphylactoid reactions have occurred in such individuals. Individuals with the above medical problems are at risk of a severe reaction even if they have taken NSAIDs in the past without any adverse reaction. The potential for cross-reactivity between different NSAIDs must be kept in CELEBREX (celecoxib) – Product Monograph Page 4 of 57 mind (see WARNINGS AND PRECAUTIONS - Hypersensitivity Reactions - Anaphylactoid Reactions). • Active gastric / duodenal / peptic ulcer, active gastrointestinal bleeding. • Cerebrovascular bleedings. • Inflammatory bowel disease. • Severe liver impairment or active liver disease. • Severe renal impairment (creatinine clearance <30 mL/min or 0.5 mL/sec) or deteriorating renal disease (individuals with lesser degrees of renal impairment are at risk of deterioration of their renal function when prescribed NSAIDs and must be monitored) (see WARNINGS AND PRECAUTIONS - Renal). • Known hyperkalemia (see WARNINGS AND PRECAUTIONS - Renal - Fluid and Electrolyte Balance). • Safety and efficacy of CELEBREX have not been established in the paediatric population under 18 years of age. WARNINGS AND PRECAUTIONS Serious Warnings and Precautions • Risk of Cardiovascular (CV) Adverse Events: Ischemic Heart Disease, Cerebrovascular Disease, Congestive Heart Failure (NYHA II-IV) (see WARNINGS AND PRECAUTIONS – Cardiovascular and CLINICAL TRIALS – Cardiovascular Safety). CELEBREX (celecoxib) is a non-steroidal anti-inflammatory drug (NSAID). CELEBREX (celecoxib), particularly at doses higher than 200 mg per day, is associated with an increased incidence of serious cardiovascular (CV) thrombotic events (such as myocardial infarction and stroke), which can be fatal. This increased risk is comparable to that with high doses of diclofenac (≥150 mg per day) or ibuprofen (≥2400 mg per day). Doses of CELEBREX >200 mg/day should NOT be used in patients with ischemic heart disease (including but NOT limited to acute myocardial infarction, history of myocardial infarction and/or angina), cerebrovascular disease (including but NOT limited to stroke, cerebrovascular accident, transient ischemic attacks and/or amaurosis fugax), congestive heart failure (NYHA II-IV), and/or risk factors for cardiovascular disease. A meta-analysis of randomized clinical trials comparing several different NSAIDs, concluded that CELEBREX is associated with higher cardiovascular risk when compared with placebo. Large population-based observational studies also support these findings. An increased risk of CV thrombotic events may occur early in the treatment and become higher with the duration of treatment. Patients with CV disease or risk factors for CV disease may be at greater risk (See Cardiovascular in WARNINGS AND PRECAUTIONS). To minimize the potential for an adverse cardiovascular event, the CELEBREX (celecoxib) – Product Monograph Page 5 of 57 lowest effective dose should be used for the shortest possible duration. For patients with a high risk of developing an adverse cardiovascular event, other management strategies that do NOT include NSAIDs, particularly celecoxib, diclofenac, or ibuprofen, should be considered first. Use of NSAIDs, such as CELEBREX, can promote sodium retention in a dose-dependent