Salsalate Information
Salsalate () Description
Salsalate () , is a nonsteroidal anti-inflammatory agent for oral administration. Chemically, Salsalate () (salicylsalicylic acid or 2-hydroxy-benzoic acid, 2- carboxyphenyl ester) is a dimer of salicylic acid; its structural formula is shown below.
Each tablet, for oral administration contains 500 mg or 750 mg of Salsalate () , USP. In addition each tablet contains the following inactive ingredients: Microcrystalline Cellulose, Sodium Starch Glycolate, Povidone, and Stearic Acid. Also contains: Hydroxypropyl Methylcellulose, Polydextrose, Titanium Dioxide, Triacetin, FD&C Blue No. 1 Aluminum Lake, FD&C Blue No. 2 Aluminum Lake and Polyethylene Glycol.
Salsalate () Clinical Pharmacology
Salsalate () is insoluble in acid gastric fluids (
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 , Salsalate () appears to selectively inhibit prostaglandin synthesis , providing anti-inflammatory activity equivalent to aspirin and indomethacin. Unlike aspirin, Salsalate () does not inhibit platelet aggregation.
The usefulness of salicylic acid, the active product of Salsalate () , in the treatment of arthritic disorders has been established . In contrast to aspirin, Salsalate () causes no greater fecal gastrointestinal blood loss than placebo.
Salsalate () Indications And Usage
Carefully consider the potential benefits and risks of Salsalate () tablets, USP and other treatment options before deciding to use Salsalate () tablets, USP. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see ).
Salsalate () is indicated for relief of the signs and symptoms of rheumatoid arthritis, osteoarthritis and related rheumatic disorder.
Salsalate () Contraindications
Salsalate () tablet, USP is contraindicated in patients with known hypersensitivity to Salsalate () .
Salsalate () tablet, USP 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 , and ).
Salsalate () tablet, USP is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see ).
Salsalate () 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.
Salsalate () Cardiovascular Effects
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 ).
Two large, controlled, clinical trials of a COX-2 selective NSAID for the treatment of pain in the first 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke (see ).
NSAIDs, including Salsalate () tablet, USP, 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 3-6 months, and in about 2-4% 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.
Salsalate () Precautions
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 Salsalate () is less likely than aspirin to induce asthma in such patients.
Salsalate () tablet, USP 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 () tablet, USP in reducing [fever and] inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions.
Borderline elevations of one or more liver tests may occur in up to 15% of patients taking NSAIDs including Salsalate () tablet, USP. 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 () tablet, USP. If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.), Salsalate () tablet, USP should be discontinued.
Anemia is sometimes seen in patients receiving NSAIDs, including Salsalate () tablet, USP. 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 () tablet, USP, 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 () tablet, USP, who may be adversely affected by alterations in platelet function, such as those with coagulation disorders or patients receiving anticoagulants, should be carefully monitored.
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.
Plasma 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 ). 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 a 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 () tablet, USP should be discontinued.
There 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 () tablet, USP on labor and delivery in pregnant women are unknown.
Salsalate () 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.
Salsalate () Drug Abuse And Dependence
Drug abuse and dependence have not been reported with Salsalate () .
Salsalate () Overdosages
Death has followed ingestion of 10 to 30 g of salicylates in adults, but much larger amounts have been ingested without fatal outcome.
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.
Salsalate () Dosage And Administration
Carefully consider the potential benefits and risks of Salsalate () tablet, USP and other treatment options before deciding to use Salsalate () tablet, USP. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see ).
After observing the response to initial therapy with Salsalate () tablet, USP, the dose and frequency should be adjusted to suit an individual patient's needs. Salsalate () is indicated for relief of the signs and symptoms of rheumatoid arthritis, osteoarthritis and related rheumatic disorder.
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.
Salsalate () How Supplied
Salsalate () Tablets, USP, 750 mg are capsule shaped, blue colored film coated tablet, debossed "105" on one side, and "C/C" scored on other side.
Bottles of 60 NDC 21695-392-60
Store at controlled room temperature 15-30°C (59-86°F).
Salsalate () References
Distributed by: C.S. No. 5015T33 Caraco Pharmaceutical Laboratories, Ltd. Iss 03/08 1150 Elijah McCoy Drive, Detroit, MI 48202
Repackaged by:
Rebel Distributors Corp
Thousand Oaks, CA 91320
Salsalate () Package Label.principal Display Panel Tablets
