Skip to Content

Tolmetin Sodium

Class: Other Nonsteroidal Anti-inflammatory Agents
VA Class: MS120
Chemical Name: Sodium 1-methyl-5-(4-methylbenzoyl)-1H-pyrrole-2-acetate dihydrate
CAS Number: 64490-92-2

Medically reviewed by Last updated on Jan 25, 2019.


    Cardiovascular Risk
  • Increased risk of serious (sometimes fatal) cardiovascular thrombotic events (e.g., MI, stroke).240 500 502 508 Risk may occur early in treatment and may increase with duration of use.500 502 505 506 508 (See Cardiovascular Thrombotic Effects under Cautions.)

  • Contraindicated in the setting of CABG surgery.508

    GI Risk
  • Increased risk of serious (sometimes fatal) GI events (e.g., bleeding, ulceration, perforation of the stomach or intestine).240 Serious GI events can occur at any time and may not be preceded by warning signs and symptoms.240 Geriatric individuals are at greater risk for serious GI events.240 (See GI Effects under Cautions.)


See also: Orencia

Prototypical NSAIA; pyrrole acetic acid derivative. a

Uses for Tolmetin Sodium

Consider potential benefits and risks of tolmetin therapy as well as alternative therapies before initiating therapy with the drug.240 Use lowest possible effective dosage and shortest duration of therapy consistent with patient's treatment goals.240

Inflammatory Diseases

Symptomatic treatment of osteoarthritis and rheumatoid arthritis.240

Management of juvenile rheumatoid arthritis in children ≥2 years of age.240

Has been reported to be effective in the management of ankylosing spondylitis (late stages did not respond as well as early stages); has also been used with some success in the treatment of adhesive capsulitis shoulder (frozen shoulder), radiohumeral bursitis (tennis elbow), and local trauma (e.g., recent sprains).a

Tolmetin Sodium Dosage and Administration


  • Consider potential benefits and risks of tolmetin therapy as well as alternative therapies before initiating therapy with the drug.240


Oral Administration

Administer orally 3 or 4 times daily.240

Administration with antacids (i.e., antacid containing aluminum and magnesium hydroxides) may minimize adverse GI effects.240


Available as tolmetin sodium; dosage expressed in terms of tolmetin.240

To minimize the potential risk of adverse cardiovascular and/or GI events, use lowest effective dosage and shortest duration of therapy consistent with the patient's treatment goals.240 Adjust dosage based on individual requirements and response; attempt to titrate to the lowest effective dosage.240

Pediatric Patients

Inflammatory Diseases
Juvenile Rheumatoid Arthritis

Children ≥2 years of age: Initially, 20 mg/kg daily in 3 or 4 divided doses.240 Adjust dosage based on response and tolerance.240

Usual effective dosage: 15–30 mg/kg daily.240


Inflammatory Diseases
Osteoarthritis or Rheumatoid Arthritis

Initially, 400 mg 3 times daily, preferably including a dose on arising and at bedtime.240 Adjust dosage based on response (after 1 or 2 weeks) and tolerance.a

Usual effective dosage: 600 mg to 1.8 g daily in 3 divided doses.240

Ankylosing Spondylitis

600 mg to 1.6 g daily in divided dose has been used.a

Adhesive Capsulitis Shoulder (frozen shoulder), Radiohumeral Bursitis (tennis elbow), Local Trauma (e.g., recent sprains)

>600 mg or 1.2 g daily in divided doses has been used.a

Prescribing Limits

Pediatric Patients

Inflammatory Diseases
Juvenile Rheumatoid Arthritis

Dosages >30 mg/kg daily have not been studied and are not recommended.240


Inflammatory Diseases
Osteoarthritis or Rheumatoid Arthritis

Dosages >1.8 g daily have not been studied and are not recommended.240

Special Populations

Renal Impairment

Reduce dosage if necessary.240

Geriatric Patients

Select dosage with caution (potential for age-related renal function decline).247

Cautions for Tolmetin Sodium


  • Known hypersensitivity to tolmetin or any ingredient in the formulation.240

  • History of asthma, urticaria, or other sensitivity reaction precipitated by aspirin or other NSAIAs.240

  • In the setting of CABG surgery.508



Cardiovascular Thrombotic Effects

NSAIAs (selective COX-2 inhibitors, prototypical NSAIAs) increase the risk of serious adverse cardiovascular thrombotic events (e.g., MI, stroke) in patients with or without cardiovascular disease or risk factors for cardiovascular disease.500 502 508

Findings of FDA review of observational studies, meta-analysis of randomized controlled trials, and other published information500 501 502 indicate that NSAIAs may increase the risk of such events by 10–50% or more, depending on the drugs and dosages studied.500

Relative increase in risk appears to be similar in patients with or without known underlying cardiovascular disease or risk factors for cardiovascular disease, but the absolute incidence of serious NSAIA-associated cardiovascular thrombotic events is higher in those with cardiovascular disease or risk factors for cardiovascular disease because of their elevated baseline risk.500 502 506 508

Increased risk may occur early (within the first weeks) following initiation of therapy and may increase with higher dosages and longer durations of use.500 502 505 506 508

In controlled studies, increased risk of MI and stroke observed in patients receiving a selective COX-2 inhibitor for analgesia in first 10–14 days following CABG surgery.508

In patients receiving NSAIAs following MI, increased risk of reinfarction and death observed beginning in the first week of treatment.505 508

Increased 1-year mortality rate observed in patients receiving NSAIAs following MI;500 508 511 absolute mortality rate declined somewhat after the first post-MI year, but the increased relative risk of death persisted over at least the next 4 years.508 511

Some systematic reviews of controlled observational studies and meta-analyses of randomized studies suggest naproxen may be associated with lower risk of cardiovascular thrombotic events compared with other NSAIAs.244 245 246 248 500 501 502 503 506 FDA states that limitations of these studies and indirect comparisons preclude definitive conclusions regarding relative risks of NSAIAs.500

Use NSAIAs with caution and careful monitoring (e.g., monitor for development of cardiovascular events throughout therapy, even in those without prior cardiovascular symptoms) and at the lowest effective dose for the shortest duration necessary.240 500 508

Some clinicians suggest that it may be prudent to avoid NSAIA use, whenever possible, in patients with cardiovascular disease.505 511 512 516 Avoid use in patients with recent MI unless benefits of therapy are expected to outweigh risk of recurrent cardiovascular thrombotic events; if used, monitor for cardiac ischemia.508 Contraindicated in the setting of CABG surgery.508

No consistent evidence that concomitant use of low-dose aspirin mitigates the increased risk of serious adverse cardiovascular events associated with NSAIAs.240 502 508 (See Specific Drugs and Laboratory Tests under Interactions.)

GI Effects

Serious GI toxicity (e.g., bleeding, ulceration, perforation) can occur with or without warning symptoms; increased risk in those with a history of GI bleeding or ulceration, geriatric patients, smokers, those with alcohol dependence, and those in poor general health.200 201 212 240 227 230 237

For patients at high risk for complications from NSAIA-induced GI ulceration (e.g., bleeding, perforation), consider concomitant use of misoprostol;203 227 228 229 alternatively, consider concomitant use of a proton-pump inhibitor (e.g., omeprazole)203 227 228 or use of an NSAIA that is a selective inhibitor of COX-2 (e.g., celecoxib).228


Hypertension and worsening of preexisting hypertension reported; either event may contribute to the increased incidence of cardiovascular events.240 Use with caution in patients with hypertension; monitor BP.240

Impaired response to ACE inhibitors, angiotensin II receptor antagonists, β-blockers, and certain diuretics may occur.240 508 509 (See Specific Drugs and Laboratory Tests under Interactions.)

Heart Failure and Edema

Fluid retention and edema reported.240 508

NSAIAs (selective COX-2 inhibitors, prototypical NSAIAs) may increase morbidity and mortality in patients with heart failure.500 501 504 507 508

NSAIAs may diminish cardiovascular effects of diuretics, ACE inhibitors, or angiotensin II receptor antagonists used to treat heart failure or edema.508 (See Specific Drugs and Laboratory Tests under Interactions.)

Manufacturer recommends avoiding use in patients with severe heart failure unless benefits of therapy are expected to outweigh risk of worsening heart failure; if used, monitor for worsening heart failure.508

Some experts recommend avoiding use, whenever possible, in patients with reduced left ventricular ejection fraction and current or prior symptoms of heart failure.507

Renal Effects

Direct renal injury, including renal papillary necrosis, reported in patients receiving long-term NSAIA therapy.240

Potential for overt renal decompensation.204 240 Increased risk of renal toxicity in patients with renal or hepatic impairment or heart failure, in geriatric patients, in patients with volume depletion, and in those receiving a diuretic, ACE inhibitor, or angiotensin II receptor antagonist.204 240 243 247 (See Renal Impairment under Cautions.)

Sensitivity Reactions

Hypersensitivity Reactions

Anaphylactoid reactions reported. 240

Immediate medical intervention and discontinuance for anaphylaxis.240

Avoid in patients with aspirin triad (aspirin sensitivity, asthma, nasal polyps); caution in patients with asthma.240

Dermatologic Reactions

Serious skin reactions (e.g., exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis) reported; can occur without warning.240 Discontinue at first appearance of rash or any other sign of hypersensitivity (e.g., blisters, fever, pruritus).240

General Precautions

Ocular and Otic Effects

Visual disturbances reported; ophthalmic evaluation recommended if visual changes occur.240

Tinnitus reported; deterioration in hearing reported rarely.a

Hepatic Effects

Severe reactions including jaundice, fatal fulminant hepatitis, liver necrosis, and hepatic failure (sometimes fatal) reported rarely with NSAIAs. 240

Elevations of serum ALT or AST reported.240 Elevations of serum alkaline phosphatase also reported.a

Monitor for symptoms and/or signs suggesting liver dysfunction; monitor abnormal liver function test results.240 Discontinue if signs or symptoms of liver disease or systemic manifestations (e.g., eosinophilia, rash) occur or if liver function test abnormalities persist or worsen.240

Hematologic Effects

Anemia reported rarely.240 Determine hemoglobin concentration or hematocrit in patients receiving long-term therapy if signs or symptoms of anemia occur.240

Small and transient decreases in hemoglobin concentration or hematocrit (not associated with GI bleeding), leukopenia (including granulocytopenia), thrombocytopenia, and hemolytic anemia reported.a One case of fatal agranulocytosis reported. a

May inhibit platelet aggregation and prolong bleeding time.240

Other Precautions

Not a substitute for corticosteroid therapy; not effective in the management of adrenal insufficiency.240

May mask certain signs of infection.240

Obtain CBC and chemistry profile periodically during long-term use.240

Specific Populations


Category C.240 Avoid use in third trimester because of possible premature closure of the ductus arteriosus.240


Distributed into milk in humans.240 Discontinue nursing or the drug.240

Pediatric Use

Safety and efficacy not established in children <2 years of age.240

Geriatric Use

Caution advised.240 Geriatric adults appear to tolerate NSAIA-induced adverse effects less well than younger individuals.247 Fatal adverse GI effects reported more frequently in geriatric patients than younger adults.240

Hepatic Impairment

Monitor closely.240

Renal Impairment

Use not recommended in patients with advanced renal disease; close monitoring of renal function advised if used.240

Common Adverse Effects

Nausea, dyspepsia, GI distress, diarrhea, abdominal pain, flatulence, vomiting, dizziness, headache, asthenia, elevated BP, edema, weight change.240

Interactions for Tolmetin Sodium

Protein-bound Drugs

Potential for tolmetin to be displaced from binding sites by, or to displace from binding sites, other protein-bound drugs.a Observe for adverse effects.a

Specific Drugs and Laboratory Tests

Drug or Test



ACE inhibitors

Reduced BP response to the ACE inhibitor240

Monitor BP240

Angiotensin II receptor antagonists

Reduced BP response to angiotensin II receptor antagonist247

Monitor BP247

Anticoagulants (warfarin)

Possible bleeding complications240

Increased PT and bleeding reported rarelya

Caution advised 240

Antidiabetic agents

Administration with insulin or sulfonylureas does not appear to alter the clinical effects of the NSAIA or the antidiabetic agenta 240

Diuretics (furosemide, thiazides)

Reduced natriuretic effects 240

Monitor for diuretic efficacy and renal failure240


Increase plasma lithium concentrations240

Monitor for lithium toxicity240


Possible increased and prolonged blood concentrations of methotrexate205 206 207 208 209 210 211

Use with caution240


NSAIAs including aspirin: Increased risk of GI ulceration or other complications 240

Aspirin: No consistent evidence that low-dose aspirin mitigates the increased risk of serious cardiovascular events associated with NSAIAs240 502 508

Concomitant use not recommended240

Tests for urinary protein

False-positive results with tests that use sulfosalicylic acid reagent240

Use dye-impregnated reagent strips (e.g., Albustix, Uristix)240

Tolmetin Sodium Pharmacokinetics



Well absorbed following oral administration.a


Bioavailability reduced 16% when administered immediately after food or with milk. a 240 Peak plasma concentrations reduced 50% when administered immediately after food.a 240



Distributed into human milk.240

Crosses the blood-brain barrier and placenta in animals.a

Plasma Protein Binding




Oxidized in liver to an inactive dicarboxylic acid metabolite.a

Elimination Route

Excreted in the urine within 24 hours as the dicarboxylic acid metabolite (60%), unchanged tolmetin (20%), and tolmetin conjugates (20%).a


Approximately 1 hour in healthy males.a

Special Populations

Patients with rheumatoid arthritis: Pharmacokinetic values generally similar to values in healthy individuals; however, increase in renal clearance of tolmetin and its metabolites reported in one study.a




Capsules and Tablets

Tight, light-resistant containers at 15–30°C.240


  • Inhibits cyclooxygenase-1 (COX-1) and COX-2.221 222 223 224 225 226

  • Pharmacologic actions similar to those of other prototypical NSAIAs; exhibits anti-inflammatory, analgesic, and antipyretic activity.a

Advice to Patients

  • Importance of reading the medication guide for NSAIAs that is provided to the patient each time the drug is dispensed.240

  • Risk of serious cardiovascular events (e.g., MI, stroke).240 500 508

  • Risk of GI bleeding and ulceration.240

  • Risk of serious skin reactions.240 Risk of anaphylactoid and other sensitivity reactions.240

  • Risk of hepatotoxicity.240

  • Importance of seeking immediate medical attention if signs and symptoms of a cardiovascular event (chest pain, dyspnea, weakness, slurred speech) occur.240 500 508

  • Importance of notifying clinician if signs and symptoms of GI ulceration or bleeding, unexplained weight gain, or edema develops.240

  • Importance of discontinuing tolmetin and contacting clinician if rash or other signs of hypersensitivity (blisters, fever, pruritus) develop.240 Importance of seeking immediate medical attention if an anaphylactic reaction occurs.240

  • Importance of discontinuing therapy and contacting clinician immediately if signs and symptoms of hepatotoxicity (nausea, fatigue, lethargy, pruritus, jaundice, upper right quadrant tenderness, flu-like symptoms) occur.240

  • Risk of heart failure or edema; importance of reporting dyspnea, unexplained weight gain, or edema.508

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.240 Importance of avoiding tolmetin in late pregnancy (third trimester).240

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant diseases.240

  • Importance of informing patients of other important precautionary information.240 (See Cautions.)


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Tolmetin Sodium


Dosage Forms


Brand Names




400 mg (of tolmetin)*

Tolmetin Sodium Capsules


200 mg (of tolmetin)*

Tolmetin Sodium Tablets

Tablets, film-coated

600 mg (of tolmetin)*

Tolmetin Sodium Tablets

AHFS DI Essentials™. © Copyright 2019, Selected Revisions January 25, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.


200. Palmer JF. Letter sent to Siegfried J. of McNeil Pharmaceuticals regarding labeling revisions about gastrointestinal adverse reactions to Tolectin (tolmetin). Rockville, MD: Food and Drug Administration, Division of Oncology and Radiopharmaceutical Drug Products; 1988 Sep.

201. Food and Drug Administration. Labeling revisions for NSAIDs. FDA Drug Bull. 1989; 19:3-4.

202. Searle. Cytotec (misoprostol) prescribing information. 1989 Jan.

203. Anon. Drugs for rheumatoid arthritis. Med Lett Drugs Ther. 2000; 42:57-64.

204. McNeil. Tolectin (tolmetin tablets and capsules) prescribing information. Spring House, PA; 1997 Jun

205. Thyss A, Milano G, Kubar J et al. Clinical and pharmacokinetic evidence of a life-threatening interaction between methotrexate and ketoprofen. Lancet. 1986; 1:256-8.

206. Ellison NM, Servi RJ. Acute renal failure and death following sequential intermediate-dose methotrexate and 5-FU: a possible adverse effect due to concomitant indomethacin administration. Cancer Treat Rep. 1985; 69:342-3.

207. Singh RR, Malaviya AN, Pandey JN et al. Fatal interaction between methotrexate and naproxen. Lancet. 1986; 1:1390.

208. Day RO, Graham GG, Champion GD et al. Anti-rheumatic drug interactions. Clin Rheum Dis. 1984; 10:251-75.

209. Daly HM, Scott GL, Boyle J et al. Methotrexate toxicity precipitated by azapropazone. Br J Dermatol. 1986; 114:733-5.

210. Hansten PD, Horn JR. Methotrexate interactions: ketoprofen (Orudis). Drug Interact Newsl. 1986; 6(Updates):U5-6.

211. Maiche AG. Acute renal failure due to concomitant action of methotrexate and indomethacin. Lancet. 1986; 1:1390.

212. Soll AH, Weinstein WM, Kurata J et al. Nonsteroidal anti-inflammatory drugs and peptic ulcer disease. Ann Intern Med. 1991; 114:307-19.

213. Ciba Geigy, Ardsley, NY: Personal communication on diclofenac 28:08.04.

214. Reviewers’ comments (personal observations) on diclofenac 28:08.04.

215. Corticosteroid interactions: nonsteroidal anti-inflammatory drugs (NSAIDs). In: Hansten PD, Horn JR. Drug interactions and updates. Vancouver, WA: Applied Therapeutics, Inc; 1993:562.

216. Garcia Rodriguez LA, Jick H. Risk of upper gastrointestinal bleeding and perforation associated with individual non-steroidal anti-inflammatory drugs. Lancet. 1994; 343:769-72.

217. Hollander D. Gastrointestinal complications of nonsteroidal anti-inflammatory drugs: prophylactic and therapeutic strategies. Am J Med. 1994; 96:274-81.

218. Schubert TT, Bologna SD, Yawer N et al. Ulcer risk factors: interaction between Helicobacter pylori infection, nonsteroidal use, and age. Am J Med. 1993; 94:413-7.

219. Piper JM, Ray WA, Daugherty JR et al. Corticosteroid use and peptic ulcer disease: role of nonsteroidal anti-inflammatory drugs. Ann Intern Med. 1991; 114:735-40.

220. Bateman DN, Kennedy JG. Non-steroidal anti-inflammatory drugs and elderly patients: the medicine may be worse than the disease. BMJ. 1995; 310:817-8.

221. Hawkey CJ. COX-2 inhibitors. Lancet. 1999; 353:307-14.

222. Kurumbail RG, Stevens AM, Gierse JK et al. Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents. Nature. 1996; 384:644-8.

223. Riendeau D, Charleson S, Cromlish W et al. Comparison of the cyclooxygenase-1 inhibitory properties of nonsteroidal anti-inflammatory drugs (NSAIDs) and selective COX-2 inhibitors, using sensitive microsomal and platelet assays. Can J Physiol Pharmacol. 1997; 75:1088-95.

224. DeWitt DL, Bhattacharyya D, Lecomte M et al. The differential susceptibility of prostaglandin endoperoxide H synthases-1 and -2 to nonsteroidal anti-inflammatory drugs: aspirin derivatives as selective inhibitors. Med Chem Res. 1995; 5:325-43.

225. Cryer B, Dubois A. The advent of highly selective inhibitors of cyclooxygenase—a review. Prostaglandins Other Lipid Mediators. 1998; 56:341-61.

226. Simon LS. Role and regulation of cyclooxygenase-2 during inflammation. Am J Med. 1999; 106(Suppl 5B):37-42S.

227. Wolfe MM, Lichtenstein DR, Singh G. Gastrointestinal toxicity of nonsteroidal antiinflammatory drugs. N Engl J Med. 1999; 340:1888-99.

228. American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis: 2002 update. Arthritis Rheum. 2002;46:328-46.

229. Lanza FL, and the members of the Ad Hoc Committee on Practice Parameters of the American College of Gastroenterology. A guideline for the treatment and prevention of NSAID-induced ulcers. Am J Gastroenterol. 1998; 93:2037-46.

230. Singh G, Triadafilopoulos G. Epidemiology of NSAID induced gastrointestinal complications. J Rheumatol. 1999; 26(suppl 56):18-24.

231. in’t Veld BA, Ruitenberg A, Hofman A et al. Nonsteroidal antiinflammatory drugs and the risk of Alzheimer’s disease. N Engl J Med. 2001; 345:1515-21.

232. Breitner JCS, Zandi PP. Do nonsteroidal antiinflammatory drugs reduce the risk of Alzheimer’s disease? N Engl J Med. 2001; 345:1567-8. Editorial.

233. McGeer PL, Schulzer M, McGeer EG. Arthritis and anti-inflammatory agents as possible protective factors for Alzheimer’s disease: a review of 17 epidemiologic studies. Neurology. 1996; 47:425-32.

234. Beard CM, Waring SC, O’sBrien PC et al. Nonsteroidal anti-inflammatory drug use and Alzheimer’s disease: a case-control study in Rochester, Minnesota, 1980 through 1984. Mayo Clin Proc. 1998; 73:951-5.

235. in’t Veld BA, Launer LJ, Hoes AW et al. NSAIDs and incident Alzheimer’s disease: the Rotterdam Study. Neurobiol Aging. 1998; 19:607-11.

236. Stewart WF, Kawas C, Corrada M et al. Risk of Alzheimer’s disease and duration of NSAID use. Neurology. 1997; 48:626-32.

237. Pharmacia. Daypro (oxaprozin) caplets prescribing information. Chicago, IL; 2002 May.

238. Chan FKL, Hung LCT, Suen BY et al. Celecoxib versus diclofenac and omeprazole in reducing the risk of recurrent ulcer bleeding in patients with arthritis. N Engl J Med. 2002; 347:2104-10.

239. Graham DY. NSAIDs, Helicobacter pylori, and Pandora’s box. N Engl J Med. 2002; 347:2162-4.

240. Ortho-McNeil Pharmaceuticals. Tolectin DS (tolmetin sodium) capsules and Tolectin 600 (tolmetin sodium) tablets prescribing information. Raritan, NJ; 2006 Feb.

241. Food and Drug Administration. Analysis and recommendations for agency action regarding non-steroidal anti-inflammatory drugs and cardiovascular risk. 2005 Apr 6.

242. Cush JJ. The safety of COX-2 inhibitors: deliberations from the February 16-18, 2005, FDA meeting. From the American College of Rheumatology website ( Accessed 2005 Oct 12.

243. Novartis Pharmaceuticals. Diovan (valsartan) capsules prescribing information (dated 1997 Apr). In: Physicians’ desk reference. 53rd ed. Montvale, NJ: Medical Economics Company Inc; 1999:2013-5.

244. McGettigan P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of observational studies of selective and nonselective inhibitors of cyclooxygenase 2. JAMA. 2006; 296: 1633-44.

245. Kearney PM, Baigent C, Godwin J et al. Do selective cyclo-oxygenase-2 inhibitors and traditional non-steroidal anti-inflammatory drugs increase the risk of atherothrombosis? Meta-analysis of randomised trials. BMJ. 2006; 332: 1302-5.

246. Graham DJ. COX-2 inhibitors, other NSAIDs, and cardiovascular risk; the seduction of common sense. JAMA. 2006; 296:1653-6.

247. Merck & Co. Clinoril (sulindac) tablets prescribing information. Whitehouse Station, NJ; 2006 Feb.

248. Chou R, Helfand M, Peterson K et al. Comparative effectiveness and safety of analgesics for osteoarthritis. Comparative effectiveness review no. 4. (Prepared by the Oregon evidence-based practice center under contract no. 290-02-0024.) . Rockville, MD: Agency for Healthcare Research and Quality. 2006 Sep. Available at:

500. Food and Drug Administration. Drug safety communication: FDA strengthens warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) can cause heart attacks or strokes. Silver Spring, MD; 2015 Jul 9. From the FDA web site. Accessed 2016 Mar 22.

501. Coxib and traditional NSAID Trialists' (CNT) Collaboration, Bhala N, Emberson J et al. Vascular and upper gastrointestinal effects of non-steroidal anti-inflammatory drugs: meta-analyses of individual participant data from randomised trials. Lancet. 2013; 382:769-79.

502. Food and Drug Administration. FDA briefing document: Joint meeting of the arthritis advisory committee and the drug safety and risk management advisory committee, February 10-11, 2014. From FDA web site

503. Trelle S, Reichenbach S, Wandel S et al. Cardiovascular safety of non-steroidal anti-inflammatory drugs: network meta-analysis. BMJ. 2011; 342:c7086.

504. Gislason GH, Rasmussen JN, Abildstrom SZ et al. Increased mortality and cardiovascular morbidity associated with use of nonsteroidal anti-inflammatory drugs in chronic heart failure. Arch Intern Med. 2009; 169:141-9.

505. Schjerning Olsen AM, Fosbøl EL, Lindhardsen J et al. Duration of treatment with nonsteroidal anti-inflammatory drugs and impact on risk of death and recurrent myocardial infarction in patients with prior myocardial infarction: a nationwide cohort study. Circulation. 2011; 123:2226-35.

506. McGettigan P, Henry D. Cardiovascular risk with non-steroidal anti-inflammatory drugs: systematic review of population-based controlled observational studies. PLoS Med. 2011; 8:e1001098.

507. Yancy CW, Jessup M, Bozkurt B et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013; 62:e147-239.

508. Teva. Tolmetin sodium capsules prescribing information. North Wales, PA; 2015 Jul.

509. Cumberland Pharmaceuticals Inc. Caldolor (ibuprofen) injection prescribing information. Nashville, TN; 2016 Apr.

511. Olsen AM, Fosbøl EL, Lindhardsen J et al. Long-term cardiovascular risk of nonsteroidal anti-inflammatory drug use according to time passed after first-time myocardial infarction: a nationwide cohort study. Circulation. 2012; 126:1955-63.

512. Olsen AM, Fosbøl EL, Lindhardsen J et al. Cause-specific cardiovascular risk associated with nonsteroidal anti-inflammatory drugs among myocardial infarction patients--a nationwide study. PLoS One. 2013; 8:e54309.

516. Bavry AA, Khaliq A, Gong Y et al. Harmful effects of NSAIDs among patients with hypertension and coronary artery disease. Am J Med. 2011; 124:614-20.

a. AHFS Drug Information 2007. McEvoy GK, ed. Tolmetin. Bethesda, MD: American Society of Health-System Pharmacists; 2007: 2118-2122.