Nonsteroidal Anti-inflammatory Drugs (NSAIDs) (CPhA Monograph) https://myrxtx.ca/print/new/documents/MONOGRAPH/en/NSAIDsCPhA Health Canada Advisories New safety information for prescription-strength ibuprofen: Risk of heart attack and stroke at high doses. (2015-04) Nonsteroidal Anti-inflammatory Drugs (NSAIDs) ASA—celecoxib—diclofenac diethylamine—diclofenac potassium—diclofenac sodium—diflunisal—etodolac—floctafenine—flurbiprofen —ibuprofen—indomethacin—ketoprofen—ketorolac tromethamine—mefenamic acid—meloxicam—nabumetone—naproxen—naproxen sodium —nepafenac—piroxicam—sulindac—tenoxicam—tiaprofenic acid Anti-inflammatory—Analgesic—Antipyretic—Platelet Aggregation Inhibitor CPhA Monograph Date of Revision: October 2014 This monograph has been compiled by CPhA and reviewed by experts. It may contain information different from that found in Health Canada– Approved Product Monographs. The reader is referred to the CPS Editorial Policy for more information. For additional information regarding acetylsalicylic acid (ASA) please consult the ASA monograph. Summary Product Information Drug Route of Administration Dosage Form Strength Celecoxib Oral Capsule 100 mg, 200 mg Diclofenac diethylamine[a] Topical Gel 1.16% (11.6 mg/g), 2.32% (23.2 mg/g) Diclofenac potassium Oral Tablet 50 mg Powder for oral solution 50 mg/packet Diclofenac sodium[b] Ophthalmic Solution 0.1% Oral Enteric-coated tablet 25 mg, 50 mg Sustained-release tablet 75 mg, 100 mg Rectal Suppository 50 mg, 100 mg Topical Solution 1.5% Diflunisal Oral Tablet 250 mg, 500 mg Etodolac Oral Capsule 200 mg, 300 mg Floctafenine Oral Tablet 200 mg, 400 mg Flurbiprofen Oral Tablet 50 mg, 100 mg Ibuprofen[b] Intravenous Solution 100 mg/mL[c] Oral Capsule 200 mg,[a] 400 mg[a] Suspension 100 mg/5 mL[a] Suspension (drops) 200 mg/5 mL[a] Tablet 200 mg,[a] 300 mg,[a] 400 mg,[a] 600 mg 1 of 17 2020-03-17, 8:32 a.m. Nonsteroidal Anti-inflammatory Drugs (NSAIDs) (CPhA Monograph) https://myrxtx.ca/print/new/documents/MONOGRAPH/en/NSAIDsCPhA Drug Route of Administration Dosage Form Strength Tablet (chewable) 50 mg,[a] 100 mg[a] Indomethacin Oral Capsule 25 mg, 50 mg Rectal Suppository 50 mg, 100 mg Ketoprofen Oral Capsule 50 mg Enteric-coated tablet 50 mg, 100 mg Sustained-release tablet 200 mg Ketorolac tromethamine Ophthalmic Solution 0.4%, 0.45%, 0.5% Oral Tablet 10 mg Parenteral (im) Solution 10 mg/mL, 30 mg/mL Mefenamic acid Oral Capsule 250 mg Meloxicam Oral Tablet 7.5 mg, 15 mg Nabumetone Oral Tablet 500 mg Naproxen[b] Oral Tablet 125 mg, 250 mg, 375 mg, 500 mg Enteric-coated tablet 250 mg, 375 mg, 500 mg Sustained-release tablet 750 mg Suspension 25 mg/mL Rectal Suppository 500 mg Naproxen sodium Oral Capsule 220 mg[a] Tablet 220 mg,[a] 275 mg, 550 mg Nepafenac Ophthalmic Suspension 0.1%, 0.3% Piroxicam Oral Capsule 10 mg, 20 mg Sulindac Oral Tablet 150 mg, 200 mg Tenoxicam Oral Tablet 20 mg Tiaprofenic acid Oral Tablet 200 mg, 300 mg [a] Available without a prescription. [b] Also available in combination products. Consult Health Canada's Drug Product Database [webprod5.hc-sc.gc.ca/dpd-bdpp/index-eng.jsp]. [c] Does not require a prescription but is generally prescribed by a medical practitioner. Indications and Clinical Use As anti-inflammatory, analgesic and antipyretic agents, NSAIDs provide symptomatic relief but do not cure the underlying disease. No NSAID has been proven superior for symptom relief. The choice of drug depends on individual risk factors such as NSAID toxicity, individual patient response, compliance potential, dosage forms, cost and available evidence. For compliance, drugs with a long half-life or available in dosage forms that allow once-daily dosing are preferred (diclofenac, ketoprofen, meloxicam, nabumetone, naproxen, tenoxicam). Health Canada-approved Indications Chronic treatment of inflammatory disorders including rheumatoid arthritis, osteoarthritis and ankylosing spondylitis. 2 of 17 2020-03-17, 8:32 a.m. Nonsteroidal Anti-inflammatory Drugs (NSAIDs) (CPhA Monograph) https://myrxtx.ca/print/new/documents/MONOGRAPH/en/NSAIDsCPhA Short-term treatment of mild to moderate pain associated with inflammation. NSAIDs are effective for musculoskeletal pain, such as muscle and joint pain, dental pain, post-operative pain, muscle strains and headache. For rapid pain relief, NSAIDs with a fast onset are preferred, while enteric-coated and sustained-release products are less suitable (see Table 7). Short-term treatment of pain due to dysmenorrhea. No NSAID has been shown to have superior efficacy in primary dysmenorrhea [Cochrane Database Syst Rev 2010;(1):CD001751]. Short-term treatment of fever. Agents with a fast onset are preferred (see Table 7). Diclofenac powder for oral solution is approved for treatment of acute migraine attacks with or without aura. Indomethacin and sulindac are approved for the treatment of acute attacks of gouty arthritis. Ketorolac is approved for short-term treatment of severe pain following major surgery. Diclofenac, ketorolac and nepafenac ophthalmic drops are approved for relief of pain and inflammation in cataract surgery. Diclofenac and ketorolac are also approved for relief of pain and inflammation in ocular trauma. Pediatrics Only ibuprofen and naproxen are approved for use in children (see Table 1). Treatment of juvenile rheumatoid arthritis. Table 1: Health Canada-approved Indications Anti-inflammatory/Analgesic Antipyretic Moderate to Mild to Severe Moderate Pain Pain Including Accompanied After Rheumatoid Ankylosing by Major Drug Arthritis Osteoarthritis Spondylitis Ophthalmic Dysmenorrhea Inflammation Surgery Fever Celecoxib Yes Yes Yes — — — Yes — Diclofenac ————— Yes—— diethylamine Diclofenac ————— Yes—— potassium Diclofenac Yes Yes — Yes — — — — sodium Diflunisal Yes Yes — — — Yes — — Etodolac Yes Yes — — — — — — Floctafenine — — — — — Yes — — Flurbiprofen Yes Yes Yes — Yes Yes — — Ibuprofen — — — — Yes Yes[a][b] Yes[c] Yes[a] Indomethacin[d] Yes Yes Yes — — Yes — — Ketoprofen Yes Yes Yes — Yes Yes — — Ketorolac ———Yes— —Yes— tromethamine Mefenamic ————YesYes—— acid Meloxicam Yes Yes — — — — — — Nabumetone Yes Yes — — — — — — Naproxen Yes[a] Yes Yes — Yes Yes — — Naproxen Yes[e] Yes[e] ——Yes[b][f] Yes[b][f] — Yes[b][f] sodium 3 of 17 2020-03-17, 8:32 a.m. Nonsteroidal Anti-inflammatory Drugs (NSAIDs) (CPhA Monograph) https://myrxtx.ca/print/new/documents/MONOGRAPH/en/NSAIDsCPhA Anti-inflammatory/Analgesic Antipyretic Moderate to Mild to Severe Moderate Pain Pain Including Accompanied After Rheumatoid Ankylosing by Major Drug Arthritis Osteoarthritis Spondylitis Ophthalmic Dysmenorrhea Inflammation Surgery Fever Nepafenac — — — Yes — — — — Piroxicam Yes Yes Yes — — — — — Sulindac[d] Yes Yes Yes — — Yes — — Tenoxicam Yes Yes Yes — — Yes — — Tiaprofenic Yes Yes — — — — — — acid [a] Approved in children for this indication. [b] Nonprescription product available for self-medication. [c] By iv infusion as adjunct to opioid analgesics. [d] Also approved for gouty arthritis. [e] Only the controlled-release product is approved for this indication. [f] Controlled-release product is not approved for this indication. Uses Without Health Canada Approval Celecoxib may be effective for reducing the number of adenomatous colonic polyps in patients with familial adenomatous polyposis (FAP) [Cochrane Database Syst Rev 2004;(2):CD004079]. Pediatrics Indomethacin is part of the treatment of Bartter syndrome [Pediatr Nephrol 2004;19(8):858-63]. Indomethacin iv has been used in premature neonates to close a patent ductus arteriosus. Indomethacin has also been used as a tocolytic to treat premature labor. There is conflicting evidence whether such use is associated with adverse fetal outcomes including constriction of the ductus arteriosus, impaired renal function and necrotizing enterocolitis [Obstet Gynecol 2005;106(1):173-9]. Ketorolac has been administered by iv injection and has been given im or iv to children 2 years of age and older. Ibuprofen may slow the loss of lung function in children with cystic fibrosis who are ≥6 years and with a forced expiratory volume over 1 minute (FEV1) >60% [Am J Respir Crit Care Med 2007;176(10):957-69], [Cochrane Database Syst Rev 2013;(6):CD001501]. Contraindications Hypersensitivity to the NSAID or to any ingredient in the formulation or component of the container. Perioperative setting of coronary artery bypass graft surgery (CABG) because of the risk of thrombotic events. The exception is low- dose ASA, which is recommended to reduce thrombotic events in the 2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery [Circulation 2011;124(23):2610-42]. History of asthma or allergic-type reactions after taking NSAIDs or ASA including ASA intolerance and the Aspirin Triad (asthma, nasal polyps and ASA intolerance), since fatal anaphylactoid reactions are possible. Cross-reactivity among structurally different nonselective NSAIDs occurs. Third trimester of pregnancy because of possible premature closure of the ductus arteriosus and possible prolonged parturition. Severe uncontrolled heart failure since exacerbations can occur. Active gastric, duodenal or peptic ulcers and inflammatory bowel disease, since NSAIDs (including low-dose ASA) can increase the risk of gastrointestinal irritation, bleeding and ulceration. Cerebrovascular bleeding and other bleeding disorders because NSAIDs can increase bleeding. Severe liver impairment because most NSAIDs are metabolized in the liver. Severe renal impairment (ClCr <30 mL/minute) since NSAIDs can cause renal failure, especially in patients who have