indication

For relief of the signs and symptoms of rheumatoid arthritis, osteoarthritis and related rheumatic disorders.

pharmacology

Salsalate is a nonsteroidal anti-inflammatory agent for oral administration. Salsalate's mode of action as an anti-inflammatory and antirheumatic agent may be due to inhibition of synthesis and release of prostaglandins. The usefulness of salicylic acid, the active in vivo product of salsalate, in the treatment of arthritic disorders has been established. In contrast to aspirin, salsalate causes no greater fecal gastrointestinal blood loss than placebo.

mechanism of action

The mode of anti-inflammatory action of salsalate and other nonsteroidal anti-inflammatory drugs is not fully defined, but appears to be primarily associated with inhibition of prostaglandin synthesis. This inhibition of prostaglandin synthesis is done through the inactivation of cyclooxygenase-1 (COX-1) and COX-2, which are reponsible for catalyzing the formation of prostaglandins in the arachidonic acid pathway. Although salicylic acid (the primary metabolite of salsalate) is a weak inhibitor of prostaglandin synthesis in vitro, salsalate appears to selectively inhibit prostaglandin synthesis in vivo, providing anti-inflammatory activity equivalent to aspirin and indomethacin. Unlike aspirin, salsalate does not inhibit platelet aggregation.

toxicity

Death has followed ingestion of 10 to 30 g of salicylates in adults, but much larger amounts have been ingested without fatal outcome.

biotransformation

Salsalate is readily soluble in the small intestine where it is partially hydrolyzed to two molecules of salicylic acid. A significant portion of the parent compound is absorbed unchanged and undergoes rapid esterase hydrolysis in the body.

absorption

Salsalate is insoluble in acid gastric fluids (< 0.1 mg/ml at pH 1.0), but readily soluble in the small intestine where it is partially hydrolyzed to two molecules of salicylic acid. A significant portion of the parent compound is absorbed unchanged. The amount of salicylic acid available from salsalate is about 15% less than from aspirin, when the two drugs are administered on a salicylic acid molar equivalent basis (3.6 g salsalate/5 g aspirin). Food slows the absorption of all salicylates including salsalate.

half life

The parent compound has an elimination half-life of about 1 hour. Salicylic acid (the active metabolite) biotransformation is saturated at anti-inflammatory doses of salsalate. Such capacity limited biotransformation results in an increase in the half-life of salicylic acid from 3.5 to 16 or more hours.

drug interactions

Betamethasone: The corticosteroid, betamethasone, may decrease the effect of the salicylate, salsalate.

Chlorpropamide: The salicylate, salsalate, increases the effect of the sulfonylurea, chlorpropamide.

Dexamethasone: The corticosteroid, dexamethasone, may decrease the effect of the salicylate, salsalate.

Fludrocortisone: The corticosteroid, fludrocortisone, may decrease the effect of the salicylate, salsalate.

Gliclazide: The salicylate, salsalate, increases the effect of the sulfonylurea, gliclazide.

Glyburide: The salicylate, salsalate, increases the effect of the sulfonylurea, glibenclamide.

Hydrocortisone: The corticosteroid, hydrocortisone, may decrease the effect of the salicylate, salsalate.

Methazolamide: The salicylate, salsalate, at high dose increases the effect of the carbonic anhydrase inhibitor, methazolamide.

Methotrexate: The salicylate, salsalate, increases the effect and toxicity of methotrexate.

Prednisolone: The corticosteroid, prednisolone, may decrease the effect of the salicylate, salsalate.

Prednisone: The corticosteroid, prednisone, may decrease the effect of the salicylate, salsalate.

Probenecid: The salicylate, salsalate, decreases the uricosuric effect of probenecid.

Sulindac: Risk of additive toxicity (e.g. bleed risk). Salsalate may decrease the serum concentration of sulindac. Consider alternate therapy or monitor for changes in the therapeutic effects of sulindac and adverse effects of both agents if the interacting agent is initiated, discontinued or dose changed.

Tiaprofenic acid: Increased risk of gastrointestinal bleeding.

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

Trandolapril: The salicylate, Salsalate, may reduce the efficacy of Trandolapril. Monitor for changes in Trandolapril efficacy if Salsalate is initiated, discontinued or dose changed.

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

Triamcinolone: The corticosteroid, triamcinolone, may decrease the effect of the salicylate, salsalate.