SALSALATE- salsalate tablet, film coated
Preferred Pharmaceuticals Inc.
Disclaimer: This drug has not been found by FDA to be safe and effective, and this labeling has not been approved by FDA. For further information about unapproved drugs, click here.
SALSALATE - Salsalate Tablet, Film Coated
Westminster Pharmaceuticals, LLC
Disclaimer: This drug has not been found by FDA to be safe and effective, and this labeling has not been approved by FDA. For further information about unapproved drugs, visit http://www.fda.gov/.
Salsalate, is a nonsteroidal anti-inﬂammatory agent for oral administration. Chemically, salsalate (salicylsalicylic acid or 2-hydroxybenzoic acid, 2-carboxyphenyl ester) is a dimer of salicylic acid; its structural formula is shown below.
Inactive Ingredients: D&C Yellow No. 10 Aluminum Lake, Hypromellose, Magnesium Stearate, Microcrystalline Cellulose, Pregelatinized Starch, Polyethylene Glycol, Polysorbate 80, Polyvinyl Alcohol, Silicon Dioxide, Talc.
Salsalate 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. A 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 a 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 a salicylic acid molar equivalent basis (3.6 g salsalate/5 g 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 a day will satisfactory 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 a weak inhibitor of prostaglandin synthesis in vitro, salsalate appears to selectively inhibit prostaglandin synthesis in vivo1, providing anti-inﬂammatory activity equivalent to aspirin2 and indomethacin3. Unlike aspirin, salsalate does not inhibit platelet aggregation4.
The usefulness of salicylic acid, the active in vivo product of salsalate, in the treatment of arthritic disorders has been established5,6. In contrast to aspirin, salsalate causes no greater fecal gastrointestinal blood loss than placebo7.
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 WARNINGS).
Salsalate is indicated for relief of the signs and symptoms of rheumatoid arthritis, and related rheumatic disorder.
Salsalate Tablets, USP is contraindicated in patients with known hypersensitivity to salsalate.
Salsalate Tablets, USP is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see 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.
Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown on 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 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 10-14 days following CABG surgery found an increased incidence of myocardial infarction and stroke (see CONTRAINDICATIONS).
NSAIDs, including Salsalate Tablets, USP, 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, USP, 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.
NSAIDs, including Salsalate Tablets, 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 1 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.
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.
No information is available from controlled clinical studies regarding the use of Salsalate Tablets, USP in patients with advanced renal disease. Therefore, treatment with Salsalate Tablets, USP is not recommended in these patients with advanced renal disease. If Salsalate Tablets, USP therapy must be initiated, close monitoring of the patient's renal function is advisable.
As with other NSAIDs, anaphylactoid reactions may occur in patients without known prior exposure to Salsalate Tablets, USP. Salsalate Tablets, USP should not be given to patients with the aspirin trial. This symptom complex typically occurs in asthmatic patients who experience rhinitis with or without nasal polyps, or who exhibit severe, potentially fatal bronchospasm after taking aspirin or other NSAIDs (see CONTRAINDICATIONS and PRECAUTIONS - Preexisting Asthma). Emergency help should be sought in cases where an anaphylactoid reaction occurs.
NSAIDs, including Salsalate Tablets, USP, can cause serious skin adverse events such as exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be fatal. These serious events may occur without warning. Patients should be informed about the signs and symptoms of serious skin manifestations and use of the drug should be discontinued at the ﬁrst appearance of skin rash or any other sign of hypersensitivity.
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 broncho spasm, 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 patients10.
Salsalate Tablets, USP cannot be expected to substitute for corticosteroids or to treat corticosteroid insufﬁciency. Abrupt discontinuation of corticosteroid 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, USP in reducing [fever and] inﬂammation may diminish the utility of these diagnosis 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 Tablets, 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 Tablets, USP. If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur (e.g., eosinophilia, rash, etc.) Salsalate Tablets, USP should be discontinued.
Anemia is sometimes seen in patients receiving NSAIDs including Salsalate Tablets, 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 Tablets, 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 Tablets, 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 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, USP should not be administered to patients with this form of aspirin sensitivity and should be used with caution in patients with preexisting asthma.
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/ 100mL. Toxic manifestations are not usually seen until plasma concentrations exceed 30 mg/100mL (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 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 Tablets, USP should be discontinued.
Reports 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.
Salicylates 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 a number of drugs for protein binding site, notably penicillin thiopental, thyroxine, triiodothyronine, phenytoin, sulﬁnpyrazone, naproxen, warfarin, methotrexate, and possibly corticosteroids. [When Salsalate Tablets, USP is administered with aspirin, its protein binding is reduced, although the clearance of free Salsalate Tablets, USP 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.
Clinical studies, as well as post marketing observations, have shown that Salsalate Tablets, USP 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.
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.
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.
Salicylate competes with thyroid hormone for binding to plasma proteins, which may be reﬂected in a depressed plasma T4 value in some patients; thyroid function and basal metabolism are unaffected.
No long-term animal studies have been performed with salsalate to evaluate its carcinogenic potential.
Reproductive 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.
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 Tablets, USP on labor and delivery in pregnant women are unknown.
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 levels. 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.
Safety and effectiveness of salsalate use in children have not been established (see WARNINGS section).
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, ie., 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.
Death has followed ingestion of 10 to 30 g of salicylates in adults, but much larger amounts have been ingested without fatal outcome.
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.
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 Error! Hyperlink reference not valid.).
After observing the response to initial therapy with Salsalate Tablets, 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.
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 a 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 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.
Appearance, 750 mg: Yellow colored, capsule-shaped, ﬁlm-coated tablets debossed '810' on one side and bisect on the other.
Dispense contents with a child-resistant closure (as required) and in a tight container as deﬁned in the USP.
Westminster Pharmaceuticals, LLC
Nashville, TN 37217
Repackaged By: Preferred Pharmaceuticals Inc.
salsalate tablet, film coated
|Labeler - Preferred Pharmaceuticals Inc. (791119022)|
|Registrant - Preferred Pharmaceuticals Inc. (791119022)|
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