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Generic Name: 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


Special Alerts:

[Posted 07/09/2015]

AUDIENCE: Health Professional, Consumer

ISSUE: FDA is strengthening an existing label warning that non-aspirin nonsteroidal anti-inflammatory drugs (NSAIDs) increase the chance of a heart attack or stroke. Based on FDAs comprehensive review of new safety information, FDA is requiring updates to the drug labels of all prescription NSAIDs. As is the case with current prescription NSAID labels, the Drug Facts labels of over-the-counter (OTC) non-aspirin NSAIDs already contain information on heart attack and stroke risk. FDA will also request updates to the OTC non-aspirin NSAID Drug Facts labels. See the FDA Drug Safety Communication (Table 1) at: for a list of non-aspirin nonsteroidal anti-inflammatory drug products.

Prescription NSAID labels will be revised to reflect the following information:

  • The risk of heart attack or stroke can occur as early as the first weeks of using an NSAID. The risk may increase with longer use of the NSAID.

  • The risk appears greater at higher doses.

  • It was previously thought that all NSAIDs may have a similar risk. Newer information makes it less clear that the risk for heart attack or stroke is similar for all NSAIDs; however, this newer information is not sufficient for us to determine that the risk of any particular NSAID is definitely higher or lower than that of any other particular NSAID.

  • NSAIDs can increase the risk of heart attack or stroke in patients with or without heart disease or risk factors for heart disease. A large number of studies support this finding, with varying estimates of how much the risk is increased, depending on the drugs and the doses studied.

  • In general, patients with heart disease or risk factors for it have a greater likelihood of heart attack or stroke following NSAID use than patients without these risk factors because they have a higher risk at baseline.

  • Patients treated with NSAIDs following a first heart attack were more likely to die in the first year after the heart attack compared to patients who were not treated with NSAIDs after their first heart attack.

  • There is an increased risk of heart failure with NSAID use.

BACKGROUND: The risk of heart attack and stroke with NSAIDs, either of which can lead to death, was first described in 2005 in the Boxed Warning and Warnings and Precautions sections of the prescription drug labels. Since then, FDA reviewed a variety of new safety information on prescription and OTC NSAIDs, including observational studies, a large combined analysis of clinical trials, and other scientific publications. These studies were also discussed at a joint meeting of the Arthritis Advisory Committee and Drug Safety and Risk Management Advisory Committee held on February 10-11, 2014.

RECOMMENDATION: Patients and health care professionals should remain alert for heart-related side effects the entire time that NSAIDs are being taken. Patients taking NSAIDs should seek medical attention immediately if they experience symptoms such as chest pain, shortness of breath or trouble breathing, weakness in one part or side of their body, or slurred speech.

For more information visit the FDA website at: and .


  • Cardiovascular Risk
  • Possible increased risk of serious (sometimes fatal) cardiovascular thrombotic events (e.g., MI, stroke).240 Risk may increase with duration of use.240 Individuals with cardiovascular disease or risk factors for cardiovascular disease may be at increased risk.240 (See Cardiovascular Effects under Cautions.)

  • Contraindicated for the treatment of pain in the setting of CABG surgery.240

  • 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.)


Prototypical NSAIA; pyrrole acetic acid derivative. a

Uses for Tolectin

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

Tolectin 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 Tolectin


Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

  • 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

  • Treatment of perioperative pain in the setting of CABG surgery.240



Cardiovascular Effects

Selective COX-2 inhibitors have been associated with increased risk of cardiovascular events (e.g., MI, stroke) in certain situations.241 Several prototypical NSAIAs also have been associated with increased risk of cardiovascular events.244 245 246 Current data insufficient to assess risk associated with tolmetin.244 245 246

Use NSAIAs with caution and careful monitoring (e.g., monitor for development of cardiovascular events), and at the lowest effective dose for the shortest duration necessary.240

Short-term use to relieve acute pain, especially at low dosages, does not appear to be associated with increased risk of serious cardiovascular events (except immediately following CABG surgery).241

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

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 certain diuretics may occur.240 (See Specific Drugs and Laboratory Tests under Interactions.)

Fluid retention and edema reported.240 Caution in patients with fluid retention or heart failure.240

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

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 Tolectin

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




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

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

Tolectin 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

Pending revision, the material in this section should be considered in light of more recently available information in the MedWatch notification at the beginning of this monograph.

  • 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 with long-term use.240

  • 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 notifying clinician if signs and symptoms of a cardiovascular event (chest pain, dyspnea, weakness, slurred speech) occur.240

  • 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

  • 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 2017, Selected Revisions August 27, 2015. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

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


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