ble. physicians and patients should remain alert for the development of such events, even in the absence of previous cv symptoms. patients should be informed about the signs and/or symptoms of serious cv events and the steps to take if they occur. there is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious cv thrombotic events associated with nsaid use. the concurrent use of aspirin and an nsaid does increase the risk of serious gi events (see gi warnings ). two large, controlled, clinical trials of a cox-2 selective nsaid for the treatment of pain in the first 10 to 14 days following cabg surgery found an increased incidence of myocardial infarction and stroke (see contraindications ). hypertension nsaids, including salsalate tablets, can lead to onset of new hypertension or worsening of pre-existing hypertension, either of which may contribute to the increased incidence of cv events. patients taking thiazides or loop diuretics may have impaired response to these therapies when taking nsaids. nsaids, including salsalate tablets, should be used with caution in patients with hypertension. blood pressure (bp) should be monitored closely during the initiation of nsaid treatment and throughout the course of therapy. congestive heart failure and edema fluid retention and edema have been observed in some patients taking nsaids. salsalate tablets should be used with caution in patients with fluid retention or heart failure. gastrointestinal effects-risk of ulceration, bleeding, and perforation nsaids, including salsalate tablets, can cause serious gastrointestinal (gi) adverse events including inflammation, bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, which can be fatal. these serious adverse events can occur at any time, with or without warning symptoms, in patients treated with nsaids. only one in five patients, who develop a serious upper gi adverse event on nsaid therapy, is symptomatic. upper gi ulcers, gross bleeding, or perforation caused by nsaids occur in approximately 1% of patients treated for 3 to 6 months, and in about 2% to 4% of patients treated for one year. these trends continue with longer duration of use, increasing the likelihood of developing a serious gi event at some time during the course of therapy. however, even short-term therapy is not without risk. nsaids should be prescribed with extreme caution in those with a prior history of ulcer disease or gastrointestinal bleeding. patients with a prior history of peptic ulcer disease and/or gastrointestinal bleeding who use nsaids have a greater than 10-fold increased risk for developing a gi bleed compared to patients with neither of these risk factors. other factors that increase the risk for gi bleeding in patients treated with nsaids include concomitant use of oral corticosteroids or anticoagulants, longer duration of nsaid therapy, smoking, use of alcohol, older age, and poor general health status. most spontaneous reports of fatal gi events are in elderly or debilitated patients and therefore, special care should be taken in treating this population. to minimize the potential risk for an adverse gi event in patients treated with an nsaid, the lowest effective dose should be used for the shortest possible duration. patients and physicians should remain alert for signs and symptoms of gi ulceration and bleeding during nsaid therapy and promptly initiate additional evaluation and treatment if a serious gi adverse event is suspected. this should include discontinuation of the nsaid until a serious gi adverse event is ruled out. for high risk patients, alternate therapies that do not involve nsaids should be considered. renal effects long-term administration of nsaids has resulted in renal papillary necrosis and other renal injury. renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. in these patients, administration of a nonsteroidal anti-inflammatory drug may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ace inhibitors, and the elderly. discontinuation of nsaid therapy is usually followed by recovery to the pretreatment state. advanced renal disease no information is available from controlled clinical studies regarding the use of salsalate tablets in patients with advanced renal disease. therefore, treatment with salsalate tablets are not recommended in these patients with advanced renal disease. if salsalate tablets therapy must be initiated, close monitoring of the patient's renal function is advisable. anaphylactoid reactions fetal toxicity premature closure of fetal ductus arteriosus: avoid use of nsaids, including salsalate, in pregnant women at about 30 weeks gestation and later. nsaids, including salsalate, increase the risk of premature closure of the fetal ductus arteriosus at approximately this gestational age. oligohydramnios/neonatal renal impairment: use of nsaids, including salsalate, at about 20 weeks gestation or later in pregnancy may cause fetal renal dysfunction leading to oligohydramnios and, in some cases, neonatal renal impairment. these adverse outcomes are seen, on average, after days to weeks of treatment, although oligohydramnios has been infrequently reported as soon as 48 hours after nsaid initiation. oligohydramnios is often, but not always, reversible with treatment discontinuation. complications of prolonged oligohydramnios may, for example, include limb contractures and delayed lung maturation. in some postmarketing cases of impaired neonatal renal function, invasive procedures such as exchange transfusion or dialysis were required. if nsaid treatment is necessary between about 20 weeks and 30 weeks gestation, limit salsalate use to the lowest effective dose and shortest duration possible. consider ultrasound monitoring of amniotic fluid if salsalate treatment extends beyond 48 hours. discontinue salsalate if oligohydramnios occurs and follow up according to clinical practice ( see precautions: pregnancy ). inform pregnant women to avoid use of salsalate and other nsaids starting at 30 weeks gestation because of the risk of the premature closing of the fetal ductus arteriosus. if treatment with salsalate is needed for a pregnant woman between about 20 to 30 weeks gestation, advise her that she may need to be monitored for oligohydramnios, if treatment continues for longer than 48 hours (see warnings: fetal toxicity, precautions: pregnancy ) .

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.

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 .