ADVERSE REACTIONS SECTION.

ADVERSE REACTIONSIn two well-controlled clinical trials, the following reversible adverse experiences characteristic of salicylates were most commonly reported with salsalate (n-280 pts; listed in descending order of frequency): tinnitus, nausea, hearing impairment, rash, and vertigo. These common symptoms of salicylates, i.e., tinnitus or reversible hearing impairment, are often used as guide to therapy.Although cause-and-effect relationships have not been established, spontaneous reports over ten-year period have included the following additional medically significant adverse experiences: abdominal pain, abnormal hepatic function, anaphylactic shock, angioedema, bronchospasm, decreased creatinine clearance, diarrhea, G.I. bleeding, hepatitis, hypotension, nephritis and urticaria.

BOXED WARNING SECTION.

Cardiovascular RiskNSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk. (See WARNINGS and CLINICAL TRIALS). Salsalate Tablets is contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS). Gastrointestinal Risk NSAIDs cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal events. (See WARNINGS). NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk. (See WARNINGS and CLINICAL TRIALS). Salsalate Tablets is contraindicated for the treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS). Gastrointestinal Risk NSAIDs cause an increased risk of serious gastrointestinal adverse events including bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal events. (See WARNINGS).

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY SECTION.

CarcinogenesisNo long-term animal studies have been performed with salsalate to evaluate its carcinogenic potential.

CLINICAL PHARMACOLOGY SECTION.

CLINICAL PHARMACOLOGYSalsalate is insoluble in acid gastric fluids (<0.1 mg/mL at pH 1.0), but readily soluble in the small intestine where it is partially hydrolyzed to two molecules of salicylic acid. significant portion of the parent compound is absorbed unchanged and undergoes rapid esterase hydrolysis in the body: its half-life is about one hour. About 13% is excreted through the kidneys as glucuronide conjugate of the parent compound, the remainder as salicylic acid and its metabolites. Thus, the amount of salicylic acid available from salsalate is about 15% less than from aspirin, when the two drugs are administered on salicylic acid molar equivalent basis (3.6 salsalate/5 aspirin). Salicylic acid 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. Thus, dosing with salsalate twice day will satisfactorily maintain blood 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 weak inhibitor of prostaglandin synthesis in vitro, salsalate appears to selectively inhibit prostaglandin synthesis in vivo 1, providing anti-inflammatory activity equivalent to aspirin 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.

CONTRAINDICATIONS SECTION.

CONTRAINDICATIONS. CONTRAINDICATIONSSALSALATE TABLETS is contraindicated in patients with known hypersensitivity to salsalate. SALSALATE TABLETS should not be given to patients who have experienced asthma, urticaria, or allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients (see WARNINGS Anaphylactoid Reactions, and PRECAUTIONS Preexisting Asthma). Salsalate Tablets is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS).

DESCRIPTION SECTION.

DESCRIPTIONSALSALATE TABLETS contain the active ingredient Salsalate, which is nonsteroidal anti-inflammatory agent for oral administration. Chemically, salsalate (salicylsalicylic acid or 2-hydroxy-benzoic acid, 2-carboxyphenyl ester) is dimer of salicylic acid; its structural formula is shown below.Chemical Structure:Inactive Ingredients: Microcrystalline Cellulose, Silicon Dioxide, Sodium Starch Glycolate, Stearic Acid, Talc, and Coating (Hypromellose, Polyethylene Glycol, Polysorbate 80, Titanium Dioxide) ChemStruc.

DOSAGE & ADMINISTRATION SECTION.

DOSAGE AND ADMINISTRATIONCarefully consider the potential benefits and risks of SALSALATE TABLETS and other treatment options before deciding to use SALSALATE TABLETS. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS). After observing the response to initial therapy with SALSALATE TABLETS, the dose and frequency should be adjusted to suit an individual patients needs. Salsalate is indicated for relief of the signs and symptoms of rheumatoid arthritis, osteoarthritis and related rheumatic disorder.Adults: The usual dosage is 3000 mg daily, given in divided doses as follows: 1) two doses of two 750 mg tablets; 2) two doses of three 500 mg tablets; or 3) three doses of two 500 mg tablets. Some patients, e.g., the elderly, may require lower dosage to achieve therapeutic blood concentrations and to avoid the more common side effects such as auditory.Alleviation of symptoms is gradual, and full benefit may not be evident for to 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 greater rate of salicyluric acid production and excretion, with 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.

DRUG ABUSE AND DEPENDENCE SECTION.

DRUG ABUSE AND DEPENDENCEDrug abuse and dependence have not been reported with salsalate.

OVERDOSAGE SECTION.

OVERDOSAGEDeath has followed ingestion of 10 to 30 of salicylates in adults, but much larger amounts have been ingested without fatal outcome.Symptoms: The usual symptoms of salicylism 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. 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.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL 750 mg bottle label. SALSALATE 750 MG TABLETS Rx only. 43063577 Label.

PEDIATRIC USE SECTION.

Pediatric UseSafety and effectiveness of salsalate use in children have not been established.(See WARNINGS section.).

PRECAUTIONS SECTION.

PRECAUTIONS GeneralPatients on treatment with salsalate should be warned not to take other salicylates so as to avoid potentially toxic concentrations. Great care should be exercised when salsalate is prescribed in the presence of chronic renal insufficiency or peptic ulcer disease. Protein binding of salicylic acid can be influenced by nutritional status, competitive binding of other drugs, and fluctuations in serum proteins caused by disease (rheumatoid arthritis, etc.).Although cross reactivity, including bronchospasm, has been reported occasionally with non-acetylated salicylates, including salsalate, in aspirin-sensitive patients 8,9, salsalate is less likely than aspirin to induce asthma in such patients 10. SALSALATE TABLETS cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if decision 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 EffectsBorderline 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 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 EffectsAnemia 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 AsthmaPatients 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.

DRUG INTERACTIONS SECTION.

ACE-inhibitorsReports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. This interaction should be given consideration in patients taking NSAIDs concomitantly with ACE-inhibitors.AspirinSalicylates antagonize the uricosuric action of drugs used to treat gout. ASPIRIN AND OTHER SALICYLATE DRUGS WILL BE ADDITIVE TO SALSALATE AND MAY INCREASE PLASMA CONCENTRATIONS OF SALICYLIC ACID TO TOXIC LEVELS. Drugs and foods that raise urine pH will increase renal clearance and urinary excretion of salicylic acid, thus lowering plasma levels: acidifying drugs or foods will decrease urinary excretion and increase plasma levels. Salicylates given concomitantly with anticoagulant drugs may predispose to systemic bleeding. Salicylates may enhance the hypoglycemic effect of oral antidiabetic drugs of the sulfonylurea class. Salicylate competes with number of drugs for protein binding sites, notably penicillin, thiopental, thyroxine, triiodothyronine, phenytoin, sulfinpyrazone, 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. FurosemideClinical 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. LithiumNSAIDs have produced an elevation of plasma lithium levels and 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.MethotrexateNSAIDs 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.WarfarinThe effcts of warfarin and NSAIDs on GI bleeding are synergistic, such that users of both drugs together have 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 depressed plasma 4 value in some patients; thyroid function and basal metabolismare unaffected.

GENERAL PRECAUTIONS SECTION.

GeneralPatients on treatment with salsalate should be warned not to take other salicylates so as to avoid potentially toxic concentrations. Great care should be exercised when salsalate is prescribed in the presence of chronic renal insufficiency or peptic ulcer disease. Protein binding of salicylic acid can be influenced by nutritional status, competitive binding of other drugs, and fluctuations in serum proteins caused by disease (rheumatoid arthritis, etc.).Although cross reactivity, including bronchospasm, has been reported occasionally with non-acetylated salicylates, including salsalate, in aspirin-sensitive patients 8,9, salsalate is less likely than aspirin to induce asthma in such patients 10. SALSALATE TABLETS cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if decision 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 EffectsBorderline 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 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 EffectsAnemia 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 AsthmaPatients 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.

GERIATRIC USE SECTION.

Geriatric UseAs with any NSAIDs, caution should be exercised in treating the elderly (65 years and older).

HOW SUPPLIED SECTION.

HOW SUPPLIED750mg Tablets: Supplied in bottles of 30ct (NDC 43063-577-30); white, capsule-shaped tablets, debossed with Syntho on one side, and 113 on the other.Dispense contents with child-resistant closure (as required) and in tight container as defined in the USP.

INDICATIONS & USAGE SECTION.

INDICATIONS AND USAGE. INDICATIONS AND USAGECarefully consider the potential benefits and risks of SALSALATE TABLETS and other treatment options before deciding to use SALSALATE TABLETS. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS). Salsalate is indicated for relief of the signs and symptoms of rheumatoid arthritis, osteoarthritis and related rheumatic disorder.

INFORMATION FOR PATIENTS SECTION.

INFORMATION FOR PATIENTS. INFORMATION FOR PATIENTSPatients should be informed of the following information before initiating therapy with an NSAID and periodically during the course of ongoing therapy. Patients should also be encouraged to read the NSAID Medication Guide that accompanies each prescription dispensed.SALSALATE TABLETS, like other NSAIDs, may cause serious CV side effects, such as MI or stroke, which may result in hospitalization and even death. Although serious CV events can occur without warning symptoms, patients should be alert for the signs and symptoms of chest pain, shortness of breath, weakness, slurring of speech, and should ask for medical advice when observing any indicative sign or symptoms. Patients should be apprised of the importance of this follow-up (see WARNINGS, Cardiovascular Effects). SALSALATE TABLETS, like other NSAIDs, can cause GI discomfort and, rarely, serious GI side effects, such as ulcers and bleeding, which may result in hospitalization and 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.. SALSALATE TABLETS, like other NSAIDs, may cause serious CV side effects, such as MI or stroke, which may result in hospitalization and even death. Although serious CV events can occur without warning symptoms, patients should be alert for the signs and symptoms of chest pain, shortness of breath, weakness, slurring of speech, and should ask for medical advice when observing any indicative sign or symptoms. Patients should be apprised of the importance of this follow-up (see WARNINGS, Cardiovascular Effects). SALSALATE TABLETS, like other NSAIDs, can cause GI discomfort and, rarely, serious GI side effects, such as ulcers and bleeding, which may result in hospitalization and 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.

LABOR & DELIVERY SECTION.

Labor and DeliveryThere exist no adequate and well-controlled studies in pregnant women. Although adverse effects on mother or infant have not been reported with salsalate use during labor, caution is advised when anti-inflammatory dosage is involved. However, other salicylates have been associated with prolonged gestation and labor, maternal and neonatal bleeding sequelae, potentiation of narcotic and barbiturate effects (respiratory or cardiac arrest in the 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.

LABORATORY TESTS SECTION.

LABORATORY TESTSPlasma salicylic acid concentrations should be periodically monitored during long-term treatment with salsalate to aid maintenance of therapeutically effective levels: 10 to 30 mg/100 ml. Toxic manifestations are not usually seen until plasma concentrations exceed 30 mg/100 ml (see OVERDOSAGE). Urinary pH should also be regularly monitored: sudden acidification, as from pH 6.5 to 5.5, can double the plasma level, resulting in toxicity. Because serious GI tract ulcerations and bleeding can occur without warning symptoms, physicians should monitor for signs or symptoms of GI bleeding. Patients on long-term treatment with NSAIDs, should have their CBC and chemistry profile checked periodically. If clinical signs and symptoms consistent with liver or renal disease develop, systemic manifestations occur (e.g., eosinophilia, rash, etc.) or if abnormal liver tests persist or worsen, SALSALATE TABLETS should be discontinued.

NONTERATOGENIC EFFECTS SECTION.

Nonteratogenic EffectsBecause of the known effects of nonsteroidal anti-inflammatory drugs on the fetal cardiovascular system (closure of ductus arteriosus), use during pregnancy (particularly late pregnancy) should be avoided.

NURSING MOTHERS SECTION.

Nursing MothersIt 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 mother on salsalate therapy might ingest in mothers 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 nursing woman.

PREGNANCY SECTION.

PregnancyIn late pregnancy, as with other NSAIDs, SALSALATE TABLETS should be avoided because it may cause premature closure of the ductus arteriosus.

REFERENCES SECTION.

REFERENCES Morris HG, Sherman NULL, McQuain C, et al: Effects of Salsalate (Non-Acetylated Salicylate) and Aspirin (ASA) on Serum Prostaglandins in Humans. Ther. Drug Monit. 7:435-438, 1985.April PA, Curran NJ, Ekohlm BP, et al: Multicenter Comparative Study of Salsalate (SSA) vs Aspirin (ASA) in Rheumatoid Arthritis (RA), Arthritis Rheumatism 30 (4 supplement):S93, 1987.Deodhar SD, McLeod MM, Dick WC, et al: Short-Term Comparative Trial of Salsalate and Indomethacin in Rheumatoid Arthritis. Curr. Med. Res. Opin., 5:185-188,1977.Estes D, Kaplan K: Lack of Platelet Effect With the Aspirin Analog, Salsalate, Arthritis and Rheumatism, 23:1303-1307, 1980.Dick C, Dick PH, Nuki G, et al: Effect of Anti-inflammatory Drug Therapy on Clearance of 133Xe from Knee Joints of Patients with Rheumatoid Arthritis. British Med. J. 3:278-280, 1969.Dick WC, Grayson MF, Woodburn A, et al: Indices of Inflammatory Activity. Ann. of the Rheum. Dis. 29:643-648, 1970.Cohen A:Fecal Blood Loss and Plasma Salicylate Study of Salicylsalicylic Acid and Aspirin. J. Clin. Pharmacol. 19:242-247, 1979.Chudwin DS, Strub M. Golden HE, et al: Sensitivity to Non-Acetylated Salicylates in Patient with Asthma, Nasal Polyps, and Rheumatoid Arthritis. Annals of Allergy 57:133-134, 1986.Spector SL, Wangaard CH, Farr RS: Aspirin and Concomitant Idiosyncrasies in Adult Asthmatic Patients. J. Allergy Clin. Immunol 64:500-506, 1979.Stevenson DD, Schrank PJ, Hougham AJ, et al: Salsalate Cross Sensitivity in Aspirin-Sensitive Asthmatics. J. Allergy Clin. Immunol 81:181, 1988.. Morris HG, Sherman NULL, McQuain C, et al: Effects of Salsalate (Non-Acetylated Salicylate) and Aspirin (ASA) on Serum Prostaglandins in Humans. Ther. Drug Monit. 7:435-438, 1985.. April PA, Curran NJ, Ekohlm BP, et al: Multicenter Comparative Study of Salsalate (SSA) vs Aspirin (ASA) in Rheumatoid Arthritis (RA), Arthritis Rheumatism 30 (4 supplement):S93, 1987.. Deodhar SD, McLeod MM, Dick WC, et al: Short-Term Comparative Trial of Salsalate and Indomethacin in Rheumatoid Arthritis. Curr. Med. Res. Opin., 5:185-188,1977.. Estes D, Kaplan K: Lack of Platelet Effect With the Aspirin Analog, Salsalate, Arthritis and Rheumatism, 23:1303-1307, 1980.. Dick C, Dick PH, Nuki G, et al: Effect of Anti-inflammatory Drug Therapy on Clearance of 133Xe from Knee Joints of Patients with Rheumatoid Arthritis. British Med. J. 3:278-280, 1969.. Dick WC, Grayson MF, Woodburn A, et al: Indices of Inflammatory Activity. Ann. of the Rheum. Dis. 29:643-648, 1970.. Cohen A:Fecal Blood Loss and Plasma Salicylate Study of Salicylsalicylic Acid and Aspirin. J. Clin. Pharmacol. 19:242-247, 1979.. Chudwin DS, Strub M. Golden HE, et al: Sensitivity to Non-Acetylated Salicylates in Patient with Asthma, Nasal Polyps, and Rheumatoid Arthritis. Annals of Allergy 57:133-134, 1986.. Spector SL, Wangaard CH, Farr RS: Aspirin and Concomitant Idiosyncrasies in Adult Asthmatic Patients. J. Allergy Clin. Immunol 64:500-506, 1979.. Stevenson DD, Schrank PJ, Hougham AJ, et al: Salsalate Cross Sensitivity in Aspirin-Sensitive Asthmatics. J. Allergy Clin. Immunol 81:181, 1988.

STORAGE AND HANDLING SECTION.

Store at 20C 25C (68F 77F); excursions permitted to 15C 30C (59F 86F). [See USP Controlled Room Temperature]. Rx only.

TERATOGENIC EFFECTS SECTION.

Teratogenic EffectsReproductive studies conducted in rats and rabbits have not demonstrated evidence of developmental abnormalities. However, animal reproduction studies are not always predictive of human response. There are no adequate and well-controlled studies in pregnant women.

WARNINGS SECTION.

WARNINGSReyes Syndrome may develop in individuals who have chicken pox, influenza, or flu symptoms. Some studies suggest possible association between the development of Reyes Syndrome and the use of medicines containing salicylate or aspirin. Salsalate contains salicylate and therefore is not recommended for use in patients with chicken pox, influenza, or flu symptoms.