Salsalate
Indications
Salsalate is indicated for relief of the signs and symptoms of rheumatoid arthritis, osteoarthritis and related rheumatic disorders, pain, fever and inflammation.
Pharmacology
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.
Dosage
Adults: The usual dosage is 3000 mg daily, given in divided doses as follows:
Alleviation of symptoms is gradual, and full benefit may not be evident for 3 to 4 days, when plasma salicylate levels have achieved steady state. There is no evidence for development of tissue tolerance (tachyphylaxis) but salicylate therapy may induce increased activity of metabolizing liver enzymes, causing a greater rate of salicyluric acid production and excretion, with a resultant increase in dosage requirement for maintenance of therapeutic serum salicylate levels.
Children: Dosage recommendations and indications for Salsalate use in children have not been established.
- Two doses of two 750 mg tablets
- Two doses of three 500 mg tablets/capsules
- Three doses of two 500 mg tablets/capsules
Alleviation of symptoms is gradual, and full benefit may not be evident for 3 to 4 days, when plasma salicylate levels have achieved steady state. There is no evidence for development of tissue tolerance (tachyphylaxis) but salicylate therapy may induce increased activity of metabolizing liver enzymes, causing a greater rate of salicyluric acid production and excretion, with a resultant increase in dosage requirement for maintenance of therapeutic serum salicylate levels.
Children: Dosage recommendations and indications for Salsalate use in children have not been established.
Administration
Should be taken with food. Take with food or milk.
Interaction
May increase risk of liver damage when used with gold compounds. GI effects may be enhanced with alcohol or concurrent use with corticosteroids. May increase activity of coumarin anticoagulants, sulfonylureas, zafirlukast, methotrexate, phenytoin and valproate. May decrease the activity of probenecid and sulfinpyrazone.
Contraindications
Haemophilia, haemorrhagic disorders, gout, hypersensitivity to aspirin or NSAIDs. Children <12 yr. Pregnancy (3rd trimester) and lactation. Severe renal or hepatic impairment.
Side Effects
GI symptoms, hypersensitivity reactions, skin eruptions, angioedema, weakness, rhinitis and dyspnoea, hypoprothrombinaemia. Hepatotoxicity, renal impairment, iron-deficiency anaemia, occult bleeding. Local irritation (rectally); Reye's syndrome.
Pregnancy & Lactation
Pregnancy Category C. Salsalate and salicylic acid have been shown to be teratogenic and embryocidal in rats when given in doses 4 to 5 times the usual human dose. The effects were not observed at doses twice as great as the usual human dose. There are no adequate and well-controlled studies in pregnantwomen. Salsalate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nursing Mothers: It is not known whether salsalate per se is excreted in human milk; salicylic acid, the primary metabolite of Salsalate , has been shown to appear in human milk in concentrations approximating the maternal blood level. Thus, the infant of a mother on Salsalate therapy might ingest in mother†s milk 30 to 80% as much salicylate per kg body weight as the mother is taking. Accordingly, caution should be exercised when Salsalate is administered to a nursing woman.
Nursing Mothers: It is not known whether salsalate per se is excreted in human milk; salicylic acid, the primary metabolite of Salsalate , has been shown to appear in human milk in concentrations approximating the maternal blood level. Thus, the infant of a mother on Salsalate therapy might ingest in mother†s milk 30 to 80% as much salicylate per kg body weight as the mother is taking. Accordingly, caution should be exercised when Salsalate is administered to a nursing woman.
Precautions & Warnings
Peptic ulcers; asthma, allergic disorders. Impaired hepatic or renal function. Dehydrated patients; uncontrolled hypertension. May cause acute haemolytic anaemia in patients with G6PD deficiency.
Overdose Effects
Symptoms: Tinnitus, vertigo, headache, confusion, drowsiness, sweating, hyperventilation, vomiting and diarrhea will occur. More severe intoxication will lead to disruption of electrolyte balance and blood pH, and hyperthermia and dehydration.
Treatment: Further absorption of Salsalate from the G.I. tract should be prevented by emesis (syrup of ipecac) and if necessary, by gastric lavage. Fluid and electrolyte imbalance should be corrected by the administration of appropriate I.V. therapy. Adequate renal function should be maintained. Hemodialysis or peritoneal dialysis may be required in extreme cases.
Treatment: Further absorption of Salsalate from the G.I. tract should be prevented by emesis (syrup of ipecac) and if necessary, by gastric lavage. Fluid and electrolyte imbalance should be corrected by the administration of appropriate I.V. therapy. Adequate renal function should be maintained. Hemodialysis or peritoneal dialysis may be required in extreme cases.
Therapeutic Class
Drugs for Osteoarthritis, Drugs used for Rheumatoid Arthritis, Non-steroidal Anti-inflammatory Drugs (NSAIDs)