indication

For the relief of signs and symptoms of rheumatoid arthritis and osteoarthritis, including the treatment of acute flares long-term management. Also for treatment of juvenile rheumatoid arthritis.

pharmacology

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.

mechanism of action

The mode of action of tolmetin is not known. However, studies in laboratory animals and man have demonstrated that the anti-inflammatory action of tolmetin is not due to pituitary-adrenal stimulation. Tolmetin inhibits prostaglandin synthetase in vitro and lowers the plasma level of prostaglandin E in man. This reduction in prostaglandin synthesis may be responsible for the anti-inflammatory action. Tolmetin does not appear to alter the course of the underlying disease in man.

toxicity

Symptoms of overdose include lethargy, drowsiness, nausea, vomiting, and epigastric pain.

biotransformation

Essentially all of the administered dose is recovered in the urine in 24 hours either as an inactive oxidative metabolite or as conjugates of tolmetin.

absorption

Rapidly and almost completely absorbed with peak plasma levels being reached within 30-60 minutes after an oral therapeutic dose.

half life

Biphasic elimination from the plasma consisting of a rapid phase with a half-life of one to 2 hours followed by a slower phase with a half-life of about 5 hours.

drug interactions

Acenocoumarol: Increased risk of bleeding. Monitor for signs and symptoms of bleeding.

Acetylsalicylic acid: Additive adverse effects increase the risk of gastrointestinal bleeding. Possible decrease in the cardioprotective effect of acetylsalicylic acid. Monitor for increased bleeding risk during concomitant therapy.

Aminosalicylic Acid: Additive effects increase the risk of GI bleeding. Monitor for increased bleeding risk during concomitant therapy.

Cholestyramine: Cholestyramine may decrease the absorption of Tolmetin. Monitor for changes in the therapeutic and adverse effects of Tolmetin if Cholestyramine is initiated, discontinued or dose changed. Spacing administration by at least 2 hours may reduce the risk of interaction.

Citalopram: Increased antiplatelet effects may enhance the risk of bleeding. Alternate therapy may be considered or monitor for inreased bleeding during concomitant therapy.

Colesevelam: Colesevelam may decrease the absorption of Tolmetin. Monitor for changes in the therapeutic and adverse effects of Tolmetin if Colesevelam is initiated, discontinued or dose changed. Spacing administration by at least 2 hours may reduce the risk of interaction.

Colestipol: Colestipol may decrease the absorption of Tolmetin. Monitor for changes in the therapeutic and adverse effects of Tolmetin if Colestipol is initiated, discontinued or dose changed. Spacing administration by at least 2 hours may reduce the risk of interaction.

Cyclosporine: Tolmetin may increase the serum concentration of cyclosporine and/or increase the nephrotoxicity of cyclosporine. Consider alternate therapy or monitor for increased cyclosporine serum concentration and nephrotoxicity during concomitant therapy.

Drotrecogin alfa: Increased risk of bleeding. Monitor for increased bleeding during concomitant therapy.

Escitalopram: Increased antiplatelet effects may enhance the risk of bleeding. Alternate therapy may be considered or monitor for inreased bleeding during concomitant therapy.

Fluoxetine: Increased antiplatelet effects may enhance the risk of bleeding. Alternate therapy may be considered or monitor for inreased bleeding during concomitant therapy.

Fluvoxamine: Increased antiplatelet effects may enhance the risk of bleeding. Alternate therapy may be considered or monitor for inreased bleeding during concomitant therapy.

Ginkgo biloba: Increased risk of bleeding due to additive antiplatelet properties of the two agents. Concomitant therapy should be avoided or monitored carefully for bleeding, bruising and altered mental status, which may be caused by CNS bleeds.

Ginseng: Increased risk of bleeding due to additive antiplatelet properties of the two agents. Concomitant therapy should be avoided or monitored carefully for bleeding, bruising and altered mental status, which may be caused by CNS bleeds.

Ketorolac: Risk of adverse NSAID toxic effects (e.g. GI bleeding, renal dysfunction). Concomitant therapy is contraindicated.

Lithium: Tolmetin may increase the risk of Lithium toxicity by decreasing the renal elminiation of Lithium. A dose adjustment of Lithium may be required. Monitor for changes in Lithium therapeutic and adverse effects if Tolmetin is initiated, discontinued or dose changed.

Methotrexate: Tolmetin may decrease the renal excretion of Methotrexate. Alternate therapy should be considered. Otherwise, monitor for hemotologic and renal toxicities.

Paroxetine: Increased antiplatelet effects may enhance the risk of bleeding. Alternate therapy may be considered or monitor for inreased bleeding during concomitant therapy.

Pemetrexed: Tolmetin may decrease the renal excretion of Pemetrexed in patients with decreased creatinine clearance. Tolmetin may be withheld in these patients from 2 days before to 2 days after Pemetrexed administration.

Salsalate: Additive effects increase the risk of GI bleeding. Monitor for increased bleeding risk during concomitant therapy.

Sertraline: Increased antiplatelet effects may enhance the risk of bleeding. Alternate therapy may be considered or monitor for inreased bleeding during concomitant therapy.

Telmisartan: Concomitant use of Telmisartan and Tolmetin may increase the risk of acute renal failure and hyperkalemia. Monitor renal function at the beginning and during treatment.

Timolol: The NSAID, Tolmetin, may antagonize the antihypertensive effect of Timolol.

Trandolapril: The NSAID, Tolmetin, may reduce the antihypertensive effect of Trandolapril. Consider alternate therapy or monitor for changes in Trandolapril efficacy if Tolmetin is initiated, discontinued or dose changed.

Treprostinil: The prostacyclin analogue, Treprostinil, may increase the risk of bleeding when combined with the NSAID, Tolmetin. Monitor for increased bleeding during concomitant thearpy.

Warfarin: The antiplatelet effects of tolmetin may increase the bleed risk associated with warfarin. Consider alternate therapy or monitor for signs and symptoms of bleeding during concomitant therapy.