Tolmetin

Tolmetin is an Analgesic belonging to Non-Steroidal anti-inflammatory agent

Tolmetin is used in the treatment of Juvenile rheumatoid arthritis and Rheumatoid arthritis, decrease’s bioavailability of tolmetin. Tolmetin penetrates synovial fluid and enters breast milk (very small amounts). Plasma protein binding: >99%, to albumin and get Metabolized in the liver via oxidation and conjugation.

and get excreted Mainly via urine (as inactive metabolites/conjugates and unchanged drug). Elimination half-life: Biphasic 1-2 hours (rapid); approx 5 hours (slow).

The onset of action of Tolmetin was within 1 to 2 hours

The Duration of time for Tolmetin was within 12 hours.

The Tmax of Tolmetin is approximately 30 to 60 minutes

Tolmetin shows common side effects like burning. stinging. increased nasal discharge. dryness inside the nose. sneezing. nervousness. nausea. dizziness.

Tolmetin is available in the form of tablets and capsules

Tolmetin is available in India, Germany, Canada, Italy, USA.

Reversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes, which results in decreased formation of prostaglandin precursors; has antipyretic, analgesic, and anti-inflammatory properties.

Tolmetin is available in the form of tablets and capsules.

Tolmetin is used in the treatment of Juvenile rheumatoid arthritis and Rheumatoid/Osteoarthritis.

Tolmetin is a nonsteroidal anti-inflammatory agent. Studies in animals have shown tolmetin to possess anti-inflammatory, analgesic and antipyretic activity. In the rat, tolmetin prevents the development of experimentally induced polyarthritis and also decreases established inflammation. In patients with either rheumatoid arthritis or osteaoarthritis, tolmetin is as effective as aspirin and indomethacin in controlling disease activity, but the frequency of the milder gastrointestinal adverse effects and tinnitus was less than in aspirin-treated patients, and the incidence of central nervous system adverse effects was less than in indomethacin-treated patients. In patients with juvenile rheumatoid arthritis, tolmetin is as effective as aspirin in controlling disease activity, with a similar incidence of adverse reactions.

Tolmetin is approved for use in the following clinical indications

Juvenile rheumatoid arthritis: Treatment of juvenile rheumatoid arthritis (JRA) in pediatric patients ≥2 years.

Rheumatoid/Osteoarthritis: Relief of signs and symptoms of rheumatoid and osteoarthritis, including acute flares and the long-term management of the chronic disease.

Osteoarthritis, rheumatoid arthritis: Oral: Initial: 400 mg 3 times daily; adjust dose according to patient response after 1 to 2 weeks; Maintenance: 600 mg to 1,800 mg/day in 3 divided doses (maximum: 1,800 mg/day).

Tolmetin is available in various strengths as 200 mg, 400 mg, 600 mg.

Tolmetin is available in the form of tablets and capsules.

Hypersensitivity to salicylates (e.g. aspirin) or other NSAIDs. Aspirin-sensitive asthma. Treatment of peri-operative pain in CABG surgery. Pregnancy (late stage).

Concerns related to adverse effects:

• Anaphylactoid reactions: Even in patients without prior exposure anaphylactoid reactions may occur; patients with "aspirin triad" (bronchial asthma, aspirin intolerance, rhinitis) may be at increased risk. Do not use in patients who experience bronchospasm, asthma, rhinitis, or urticaria with nonsteroidal anti-inflammatory drug (NSAID) or aspirin therapy.

• Cardiovascular events: : NSAIDs are associated with an increased risk of adverse cardiovascular thrombotic events, including MI and stroke. Risk may be increased with duration of use or pre-existing cardiovascular risk factors or disease. Carefully evaluate individual cardiovascular risk profiles prior to prescribing. Use caution with fluid retention. Avoid use in heart failure. Concurrent administration of ibuprofen, and potentially other nonselective NSAIDs, may interfere with aspirin’s cardioprotective effect. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of cardiovascular events; alternate therapies should be considered for patients at high risk.

• CNS effects: May cause drowsiness, dizziness, blurred vision, and other neurologic effects which may impair physical or mental abilities; patients must be cautioned about performing tasks which require mental alertness (eg, operating machinery or driving).

• Drug reaction with eosinophilia and systemic symptoms: Potentially serious, sometimes fatal, drug reaction with eosinophilia and systemic symptoms (DRESS), also known as multiorgan hypersensitivity reactions, has been reported with NSAIDs. Monitor for signs and symptoms (eg, fever, rash, lymphadenopathy, eosinophilia) in association with other organ system involvement (eg, hepatitis, nephritis, hematological abnormalities, myocarditis, myositis). Early symptoms of hypersensitivity reaction (eg, lymphadenopathy, fever) may occur without rash; discontinue therapy and further evaluate if DRESS is suspected.

• GI events: : NSAIDs may increase risk of GI irritation, inflammation, ulceration, bleeding, and perforation. These events may occur at any time during therapy and without warning. Use caution with a history of GI disease (bleeding or ulcers), concurrent therapy with aspirin, anticoagulants and/or corticosteroids, smoking, use of alcohol, the elderly or debilitated patients. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of GI adverse events; alternate therapies should be considered for patients at high risk. When used concomitantly with aspirin, a substantial increase in the risk of GI complications (eg, ulcer) occurs; concomitant gastroprotective therapy (eg, proton pump inhibitors) is recommended . In patients with a history of acute lower GI bleeding, avoid use of non-aspirin NSAIDs, especially if due to angioectasia or diverticulosis .

• Hematologic effects: Platelet adhesion and aggregation may be decreased; may prolong bleeding time; patients with coagulation disorders or who are receiving anticoagulants should be monitored closely. Anemia may occur; patients on long-term NSAID therapy should be monitored for anemia. Rarely, NSAID use has been associated with potentially severe blood dyscrasias (eg, agranulocytosis, thrombocytopenia, aplastic anemia).

• Hepatic effects: Notable elevations of ALT or AST (eg, >3 x ULN) have been reported. Severe hepatic reactions (eg, jaundice, fulminant hepatitis, liver necrosis, liver failure) have occurred with NSAID use, some with fatal outcomes; discontinue if clinical signs or symptoms of liver disease develop, or if systemic manifestations occur (eg, eosinophilia, rash).

• Hyperkalemia: NSAID use may increase the risk of hyperkalemia, particularly in the elderly, diabetics, renal disease, and with concomitant use of other agents capable of inducing hyperkalemia (eg, ACE-inhibitors). Monitor potassium closely.

• Renal effects: NSAID use may compromise existing renal function; dose-dependent decreases in prostaglandin synthesis may result from NSAID use, reducing renal blood flow, which may cause renal decompensation. Patients with impaired renal function, dehydration, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly are at greater risk of renal toxicity. Rehydrate patient before starting therapy; monitor renal function closely. Long-term NSAID use may result in renal papillary necrosis and other renal injury.

• Skin reactions: NSAIDs may cause potentially fatal serious skin adverse events including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN); discontinue use at first sign of skin rash or hypersensitivity.

• Take with or without food. Food (or milk) can decrease oral bioavailability by 16%. Tolmetin may be taken with food to reduce gastrointestinal upset, but it may reduce tolmetin serum levels by 50%.

• Common Adverse effects:

Hyperkalemia, elevated ALT/AST levels, hypertension, edema, peptic ulcer, jaundice, weight changes (gain/loss); renal papillary necrosis, acute interstitial nephritis, nephrotic syndrome (long-term use).

• Less Common Adverse effects:

Abdominal pain, diarrhoea, dyspepsia, flatulence, gastrointestinal distress, nausea, vomiting, constipation, gastritis.

• Rare Common Adverse effects:

Exfoliative dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis, MI, stroke, gastrointestinal bleeding, ulceration, and perforation, severe blood dyscrasias (e.g. agranulocytosis, thrombocytopenia, aplastic anemia), hepatic failure, liver necrosis, fulminant hepatitis.

Increased risk of bleeding with anticoagulants, corticosteroids, salicylates (e.g. aspirin) and other NSAIDs. May decrease the antihypertensive effect of ACE inhibitors or angiotensin receptor blockers. Increases the plasma concentration of lithium. May reduce the natriuretic effects of furosemide or thiazide diuretics. May enhance methotrexate toxicity.

The common side effects of Tolmetin include the following Dermal ulcer, Weight loss, Abdominal pain, decreased appetite, diarrhea, nausea, vomiting, Increased liver enzymes, Fatigue.

Symptoms: Nasopharyngitis, gastrointestinal symptoms, increased liver enzymes.

Management: Supportive treatment.

Pharmacodynamic

Tolmetin is a nonsteroidal anti-inflammatory agent. Studies in animals have shown tolmetin to possess anti-inflammatory, analgesic and antipyretic activity. In the rat, tolmetin prevents the development of experimentally induced polyarthritis and also decreases established inflammation. In patients with either rheumatoid arthritis or osteaoarthritis, tolmetin is as effective as aspirin and indomethacin in controlling disease activity, but the frequency of the milder gastrointestinal adverse effects and tinnitus was less than in aspirin-treated patients, and the incidence of central nervous system adverse effects was less than in indomethacin-treated patients. In patients with juvenile rheumatoid arthritis, tolmetin is as effective as aspirin in controlling disease activity, with a similar incidence of adverse reactions. tolmetin has produced additional therapeutic benefit when added to a regimen of gold salts and, to a lesser extent, with corticosteroids. Tolmetin should not be used in conjunction with salicylates since greater benefit from the combination is not likely, but the potential for adverse reactions is increased.

Pharmacokinetics

• Absorption: Rapidly and well absorbed from the gastrointestinal tract. Food and milk decreases bioavailability. Time to peak plasma concentration: Approx 30-60 minutes.

• Distribution: Penetrates synovial fluid and enters breast milk (very small amounts). Plasma protein binding: >99%, to albumin.

• Metabolism: Metabolized in the liver via oxidation and conjugation.

• Excretion: Mainly via urine (as inactive metabolites/conjugates and unchanged drug). Elimination half-life: Biphasic 1-2 hours (rapid); approx 5 hours (slow).

• https://www.rxlist.com/dopram-drug.html
• https://www.mims.com/india/drug/info/Tolmetin?type=full&mtype=generic
• https://go.drugbank.com/drugs/DB00561
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7003846/