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
- 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.)
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
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
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
Juvenile Rheumatoid ArthritisOral
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
Osteoarthritis or Rheumatoid ArthritisOral
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
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)Oral
>600 mg or 1.2 g daily in divided doses has been used.a
Juvenile Rheumatoid ArthritisOral
Dosages >30 mg/kg daily have not been studied and are not recommended.240
Osteoarthritis or Rheumatoid ArthritisOral
Dosages >1.8 g daily have not been studied and are not recommended.240
Reduce dosage if necessary.240
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.)
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
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.)
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
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
Ocular and Otic Effects
Visual disturbances reported; ophthalmic evaluation recommended if visual changes occur.240
Tinnitus reported; deterioration in hearing reported rarely.a
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
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
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
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
Safety and efficacy not established in children <2 years of age.240
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
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
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
Reduced BP response to the ACE inhibitor240
Angiotensin II receptor antagonists
Reduced BP response to angiotensin II receptor antagonist247
Possible bleeding complications240
Increased PT and bleeding reported rarelya
Caution advised 240
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
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
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
400 mg (of tolmetin)*
Tolmetin Sodium Capsules
200 mg (of tolmetin)*
Tolmetin Sodium Tablets
600 mg (of tolmetin)*
Tolmetin Sodium Tablets
AHFS DI Essentials. © Copyright 2017, Selected Revisions January 25, 2017. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
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