razone, naproxen, warfarin, methotrexate, and possibly corticosteroids. [when salsalate tablets is administered with aspirin, its protein binding is reduced, although the clearance of free salsalate tablets is not altered. the clinical significance of this interaction is not known; however,] as with other nsaids, concomitant administration of salsalate and aspirin is not generally recommended because of the potential of increased adverse effects. furosemide clinical studies, as well as post marketing observations, have shown that salsalate tablets can reduce the natriuretic effect-of furosemide and thiazides in some patients. this response has been attributed to inhibition of renal prostaglandin synthesis. during concomitant therapy with nsaids, the patient should be observed closely for signs of renal failure (see precautions, renal effects ), as well as to assure diuretic efficacy. lithium nsaids have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance. the mean minimum lithium concentration increased 15% and the renal clearance was decreased by approximately 20%. these effects have been attributed to inhibition of renal prostaglandin synthesis by the nsaid. thus, when nsaids and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity. methotrexate nsaids have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. this may indicate that they could enhance the toxicity of methotrexate. caution should be used when nsaids are administered concomitantly with methotrexate. warfarin the effcts of warfarin and nsaids on gi bleeding are synergistic, such that users of both drugs together have a risk of serious gi bleeding higher than users of either drug alone. drug/laboratory test interactions: salicylate competes with thyroid hormone for binding to plasma proteins, which may be reflected in a depressed plasma t 4 value in some patients; thyroid function and basal metabolismare unaffected.

sion is made to discontinue corticosteroids. the pharmacological activity of salsalate tablets in reducing [fever and] inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions. hepatic effects hepatic effects borderline elevations of one or more liver tests may occur in up to 15% of patients taking nsaids including salsalate tablets. these laboratory abnormalities may progress, may remain unchanged, or may be transient with continuing therapy. notable elevations of alt or ast (approximately three or more times the upper limit of normal) have been reported in approximately 1% of patients in clinical trials with nsaids. in addition, rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis and hepatic failure, some of them with fatal outcomes have been reported. a patient with symptoms and/or signs suggesting liver dysfunction, or in whom an abnormal liver test has occurred, should be evaluated for evidence of the development of a more severe hepatic reaction while on therapy with salsalate tablets. if clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), salsalate tablets should be discontinued. hematological effects hematological effects anemia is sometimes seen in patients receiving nsaids, including salsalate tablets. this may be due to fluid retention, occult or gross gi blood loss, or an incompletely described effect upon erythropoiesis. patients on long-term treatment with nsaids, including salsalate tablets, should have their hemoglobin or hematocrit checked if they exhibit any signs or symptoms of anemia. nsaids inhibit platelet aggregation and have been shown to prolong bleeding time in some patients. unlike aspirin, their effect on platelet function is quantitatively less, of shorter duration, and reversible. patients receiving salsalate tablets, who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants, should be carefully monitored. preexisting asthma preexisting asthma patients with asthma may have aspirin-sensitive asthma. the use of aspirin in patients with aspirin-sensitive asthma has been associated with severe bronchospasm which can be fatal. since cross reactivity, including bronchospasm, between aspirin and other nonsteroidal anti-inflammatory drugs has been reported in such aspirin-sensitive patients, salsalate tablets should not be administered to patients with this form of aspirin sensitivity and should be used with caution in patients with preexisting asthma.

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.

razone, naproxen, warfarin, methotrexate, and possibly corticosteroids. [when salsalate tablets is administered with aspirin, its protein binding is reduced, although the clearance of free salsalate tablets is not altered. the clinical significance of this interaction is not known; however,] as with other nsaids, concomitant administration of salsalate and aspirin is not generally recommended because of the potential of increased adverse effects. furosemide clinical studies, as well as post marketing observations, have shown that salsalate tablets can reduce the natriuretic effect-of furosemide and thiazides in some patients. this response has been attributed to inhibition of renal prostaglandin synthesis. during concomitant therapy with nsaids, the patient should be observed closely for signs of renal failure (see precautions, renal effects ), as well as to assure diuretic efficacy. lithium nsaids have produced an elevation of plasma lithium levels and a reduction in renal lithium clearance. the mean minimum lithium concentration increased 15% and the renal clearance was decreased by approximately 20%. these effects have been attributed to inhibition of renal prostaglandin synthesis by the nsaid. thus, when nsaids and lithium are administered concurrently, subjects should be observed carefully for signs of lithium toxicity. methotrexate nsaids have been reported to competitively inhibit methotrexate accumulation in rabbit kidney slices. this may indicate that they could enhance the toxicity of methotrexate. caution should be used when nsaids are administered concomitantly with methotrexate. warfarin the effcts of warfarin and nsaids on gi bleeding are synergistic, such that users of both drugs together have a risk of serious gi bleeding higher than users of either drug alone. drug/laboratory test interactions: salicylate competes with thyroid hormone for binding to plasma proteins, which may be reflected in a depressed plasma t 4 value in some patients; thyroid function and basal metabolismare unaffected.

mother), delivery problems and stillbirth. in rat studies with nsaids, as with other drugs known to inhibit prostaglandin synthesis, an increased incidence of dystocia, delayed parturition, and decreased pup survival occurred. the effects of salsalate tablets on labor and delivery in pregnant women are unknown. 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. pediatric use safety and effectiveness of salsalate use in children have not been established. (see warnings section.)

levels within the desired therapeutic range (10 to 30 mg/100 ml) throughout the 12-hour intervals. therapeutic blood levels continue for up to 16 hours after the last dose. the parent compound does not show capacity-limited biotransformation, nor does it accumulate in the plasma on multiple dosing. food slows the absorption of all salicylates including salsalate. the mode of anti-inflammatory action of salsalate and other nonsteroidal anti-inflammatory drugs is not fully defined. 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 1 , providing anti-inflammatory activity equivalent to aspirin 2 and indomethacin 3 . unlike aspirin, salsalate does not inhibit platelet aggregation 4 . the usefulness of salicylic acid, the active in vivo product of salsalate, in the treatment of arthritic disorders has been established 5,6 . in contrast to aspirin, salsalate causes no greater fecal gastrointestinal blood loss than placebo 7 .

d even death. although serious gi tract ulcerations and bleeding can occur without warning symptoms, patients should be alert for the signs and symptoms of ulcerations and bleeding, and should ask for medical advice when observing any indicative sign or symptoms including epigastric pain, dyspepsia, melena, and hematemesis. patients should be apprised of the importance of this follow-up (see warnings, gastrointestinal effects: risk of ulceration, bleeding, and perforation ). salsalate tablets like other nsaids, can cause serious skin side effects such as exfoliative dermatitis, sjs, and ten, which may result in hospitalizations and even death. although serious skin reactions may occur without warning, patients should be alert for the signs and symptoms of skin rash and blisters, fever, or other signs of hypersensitivity such as itching, and should ask for medical advice when observing any indicative signs or symptoms. patients should be advised to stop the drug immediately if they develop any type of rash and contact their physicians as soon as possible. patients should promptly report signs or symptoms of unexplained weight gain or edema to their physicians. patients should be informed of the warning signs and symptoms of hepatotoxicity (e.g., nausea, fatigue, lethargy, pruritus, jaundice, right upper quadrant tenderness, and "flu-like" symptoms). if these occur, patients should be instructed to stop therapy and seek immediate medical therapy. patients should be informed of the signs of an anaphylactoid reaction (e.g. difficulty breathing, swelling of the face or throat). if these occur, patients should be instructed to seek immediate emergency help (see warnings ). in late pregnancy, as with other nsaids, salsalate tablets should be avoided because it will cause premature closure of the ductus arteriosus.