Indications and Usage
Carefully 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.
Dosage and Administration
Carefully 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 patient's 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 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.
Children: Dosage recommendations and indications for salsalate use in children have not been established.
Contraindications
Salsalate tablets are 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 are contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS ).
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.
Drug Abuse and Dependence
Drug abuse and dependence have not been reported with salsalate.
Overdosage
Death has followed ingestion of 10 to 30 g 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.
Treatment: 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.
Description
Salsalate USP, is a nonsteroidal anti-inflammatory agent for oral administration. Chemically, salsalate, USP (salicylsalicylic acid or 2-hydroxy-benzoic acid, 2-carboxyphenyl ester) is a dimer of salicylic acid; its structural formula is shown below.
Chemical Structure:
Tablets:
Inactive Ingredients: Carnauba wax, Colloidal Silicon Dioxide, Croscarmellose
Sodium, D&C Yellow #10, Hypromellose, Microcrystalline Cellulose, Polyethylene Glycol, Stearic Acid, Titanium Dioxide,
401aea08-figure-01Clinical Pharmacology
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 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 a weak inhibitor of prostaglandin synthesis in vitro , salsalate appears to selectively inhibit prostaglandin synthesis in vivo 1, 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.
How Supplied / Storage and Handling
Salsalate tablets, USP 500 mg are available as yellow colored, round, film-coated tablets debossed “AN” over “512” on one side and plain on the other.
They are supplied as follows:
Bottles of 100 NDC 65162-512-10
Bottles of 500 NDC 65162-512-50
Bottles of 1,000ct NDC 65162-512-11
Salsalate tablets, USP 750 mg are available as yellow colored, capsule-shaped, scored, film-coated tablets debossed “AN 513” on one side and plain on the other.
They are supplied as follows:
Bottles of100 NDC 65162-513-10
Bottles of 500 NDC 65162-513-50
Bottles of 1,000 NDC 65162-513-11
Dispense contents with a child-resistant closure (as required) and in a tight container as defined in the USP.
Store at 20°C to 25°C (68°F to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].
Rx only