Salsalate 750 mg Tablet, 500-count — NDC 65162-513-50 (Billing 65162-0513-50)

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

CARDIOVASCULAR EFFECTS Cardiovascular Thrombotic Events Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular (CV) thrombotic events, myocardial infarction, and stroke, which can be fatal. All NSAIDs, both COX-2 selective and nonselective, may have a similar risk. Patients with known CV disease or risk factors for CV disease may be at greater risk.

To minimize the potential risk for an adverse CV event in patients treated with an NSAID, the lowest effective dose should be used for the shortest duration possible. 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.

Mo… [Excerpted — this section continues on DailyMed.]

ADVERSE REACTIONS In 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 a guide to therapy. Although cause-and-effect relationships have not been established, spontaneous reports over a 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.

To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

PRECAUTIONS General Patients 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 a 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 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 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 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. INFORMATION FOR PATIENTS Patients 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. 1. Salsalate tablets, like oth… [Excerpted — this section continues on DailyMed.]

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