| 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. |
| Pharmacodynamics | 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. |
| Absorption | Rapidly and almost completely absorbed with peak plasma levels being reached within 30-60 minutes after an oral therapeutic dose. |
| Volume of distribution | Not Available |
| Protein binding | Not Available |
| Metabolism | 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. |
| Route of elimination | Not Available |
| 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. |
| Clearance | Not Available |
| Toxicity | Symptoms of overdose include lethargy, drowsiness, nausea, vomiting, and epigastric pain. |