Salsalat

151.3 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

153.86 Ų [M+H]+ [CCS Type: TW; Method: calibrated with polyalanine and drug standards]

Warning

H302 (87.2%): Harmful if swallowed [Warning Acute toxicity, oral]

P261, P264, P264+P265, P270, P271, P273, P280, P301+P317, P302+P352, P304+P340, P305+P351+P338, P319, P321, P330, P332+P317, P337+P317, P362+P364, P391, P403+P233, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 47 reports by companies from 6 notifications to the ECHA C&L Inventory. Each notification may be associated with multiple companies.

Prospective studies show that a proportion of patients taking salsalate experience at least transient serum aminotransferase elevations particularly when it is given in higher doses. These abnormalities may resolve even with drug continuation or after dose reduction. Marked aminotransferase elevations (>10 fold elevated) occur rarely except with use of higher doses (4 g daily or more) in a manner similar to aspirin. Clinically apparent liver injury with jaundice from salsalate has not been reported and must be very rare. Salsalate is probably capable of inducing Reye syndrome in a susceptible child or adolescent and, like aspirin, should be avoided in those age groups.

Drug Induced Liver Injury Rank (DILIrank 2.0)

Salsalate

vLess-DILI-concern

3

Warnings & precautions

DOI:10.1016/j.drudis.2016.02.015

N - Nervous system

QN - Nervous system

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.

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.

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.