Salsalate is used for anti-inflammatory and analgesic effects in the symptomatic treatment of rheumatoid arthritis, osteoarthritis, and related inflammatory conditions.
There are few controlled comparative studies of salsalate and aspirin, but the anti-inflammatory and analgesic effects of salsalate are generally considered to be comparable to those of aspirin. In one study, the anti-inflammatory and analgesic effects of salsalate (1 g 3 times daily) in the treatment of rheumatoid arthritis were about equal to those of indomethacin (25 mg 3 times daily). Further comparative studies of salsalate in the treatment of rheumatoid arthritis or osteoarthritis are needed to determine the relative efficacy of the drug. Salsalate may be particularly useful in patients with GI intolerance to aspirin or in patients in whom interference with normal platelet function by aspirin or other NSAIAs is considered undesirable.
There is insufficient evidence that salsalate has antipyretic activity. Since salsalate does not inhibit platelet aggregation, the drug should not be substituted for aspirin in the prophylaxis of thrombosis.
Dosage and Administration
Salsalate is administered orally. The drug should usually be administered with food or a large quantity (240 mL) of water or milk.
For the symptomatic treatment of rheumatoid arthritis, osteoarthritis, or related inflammatory conditions, the usual initial adult dosage of salsalate is 3 g daily, given in 2 or 3 divided doses. Dosage should be adjusted according to the patient's response, tolerance, and serum salicylate concentration. The usual maintenance dosage of salsalate is 2-4 g daily.
Patients should be advised that salsalate, like other NSAIAs, is not free of potential adverse effects, including some that can cause discomfort, and that, rarely, more serious effects (e.g., myocardial infarction, stroke, GI bleeding), which may require hospitalization and may even be fatal, can occur. Selective COX-2 inhibitors have been associated with an increased risk of serious adverse cardiovascular thrombotic events in certain situations. Several prototypical NSAIAs also have been associated with an increased risk of cardiovascular events. (See Cautions: Cardiovascular Effects, in Celecoxib 28:08.04.08.) The risk of potentially serious adverse GI effects should be considered in patients receiving salsalate, particularly in patients receiving chronic therapy with the drug. (See Cautions: GI Effects, in Naproxen 28:08.04.92.) NSAIAs are contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery. Patients should be advised to read the medication guide for NSAIAs that is provided to the patient each time the drug is dispensed.
For additional information on cautions, precautions, and contraindications associated with the use of salsalate, .
Safety and efficacy of salsalate in children have not been established.
For information on the absorption, distribution, and elimination of salicylate, .
Salsalate is completely absorbed from the GI tract following oral administration. The drug is practically insoluble in acidic gastric fluids and is probably not absorbed from the stomach. Salsalate is absorbed principally from the small intestine and is partially hydrolyzed to salicylate during absorption and on first pass through the liver. The relative amount of an oral dose of salsalate that reaches the systemic circulation as unhydrolyzed drug has not been established.
In one study in fasting healthy adults who received a single 1-g oral dose of salsalate (as two 500-mg tablets), average peak plasma salsalate concentrations of 21 mcg/mL occurred at 1.5 hours and average peak plasma salicylate concentrations of 54 mcg/mL occurred within 2-4 hours. Following oral administration of a single 2-g dose of salsalate (as four 500-mg tablets) in fasting healthy adults in another study, average peak blood salicylate concentrations of 117 mcg/mL were attained within 4 hours. Food delays the absorption of salsalate and decreases peak serum salicylate concentrations. Following oral administration of a single 1-g dose of salsalate (as two 500-mg capsules [no longer commercially available in the US]) in healthy adults in one study, average peak serum salicylate concentrations of 108 mcg/mL were attained in 3 hours during fasting conditions, and average peak serum salicylate concentrations of 75 mcg/mL were attained in 5 hours during nonfasting conditions.
Salsalate is rapidly and widely distributed, apparently into most body tissues and fluids. The apparent volume of distribution of salsalate is approximately the same as that of aspirin and is generally 0.15-0.2 L/kg in adults.
It is not known if unhydrolyzed salsalate is distributed into milk.
The plasma elimination half-life of salsalate is about 1 hour in patients with normal renal and hepatic function.
Salsalate is rapidly and extensively hydrolyzed to 2 molecules of salicylate by esterases in the GI mucosa, liver, plasma, blood, and other tissues and fluids. Negligible amounts of the drug are apparently hydrolyzed in the lumen of the small intestine. Salsalate is hydrolyzed more slowly than aspirin, and hydrolysis occurs more slowly in whole blood than in plasma. Unlike salicylate, unhydrolyzed salsalate does not undergo capacity-limited metabolism and does not accumulate in plasma following multiple doses. In healthy individuals, about 7-13% of a single oral dose of salsalate is conjugated with glucuronic acid and is not hydrolyzed to salicylate. Therefore, the amount of salicylate derived from salsalate is up to about 15% less than the amount derived from aspirin when the drugs are given in doses that theoretically provide equivalent amounts of salicylate.
In healthy adults, a single oral dose of salsalate is almost completely excreted in the urine, with about 7-13% excreted as salsalate glucuronide, less than 1% as unhydrolyzed salsalate, and the remainder as salicylate and its metabolites.