Salasalate

Salasalate  is a Analgesic and Antipyretic belonging to Non-Steroidal anti-inflammatory Drug

Salasalate is used in the treatment of rheumatoid disorder.

Salasalate 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. The amount of salicylic acid available from salasalate is about 15% less than from aspirin, when the two drugs are administered on a salicylic acid molar equivalent basis (3.6 g salasalate/5 g aspirin). Food slows the absorption of all salicylates including salasalate and is 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 and get Primarily excreted in urine

Salasalate shows common side effects like vomiting, indigestion, flatulence, nausea, abdominal pain, constipation, epigastric pain, diarrhoea, large intestine carcinoma

Salasalate is available in tablets.

Salasalate is available in India, Germany, Canada, France, USA.

The mode of anti-inflammatory action of salasalate and other nonsteroidal anti-inflammatory drugs is not fully defined, but appears to be primarily associated with inhibition of prostaglandin synthesis. This inhibition of prostaglandin synthesis is done through the inactivation of cyclooxygenase-1 (COX-1) and COX-2, which are reponsible for catalyzing the formation of prostaglandins in the arachidonic acid pathway. Although salicylic acid (the primary metabolite of salasalate) is a weak inhibitor of prostaglandin synthesis in vitro, salasalate appears to selectively inhibit prostaglandin synthesis in vivo, providing anti-inflammatory activity equivalent to aspirin and indomethacin.

Salasalate is available in the form of tablets.

Salasalate is used in the treatment of Rheumatic disorders.

Salasalate is approved for use in the following clinical indications

Rheumatic disorders: Treatment of signs and symptoms of osteoarthritis, rheumatoid arthritis, and related rheumatic disorders.

Rheumatic disorders:

Oral: Note: Use the lowest effective dose for the shortest duration; after observing the response to initial therapy, adjust dose as needed. Usual dose: 3 g per day in 2 to 3 divided doses.

Salasalate is available in the dosage strength of 500 mg and 750 mg.

Salasalate is available in the form of tablets.

Take after eating and with a full glass of water to decrease gastric upset.

Salasalate is contraindicated in patients with:

Hypersensitivity to salasalate or any component of the formulation; asthma, urticaria, or allergic reaction to aspirin or NSAIDs; perioperative pain in the setting of coronary artery bypass graft (CABG) surgery.

Concerns related to adverse effects:

• Anaphylactoid reactions: Even in patients without prior exposure to salasalate, anaphylactoid reactions may occur; patients with "aspirin triad" (bronchial asthma, aspirin intolerance, rhinitis) may be at increased risk. Do not use in patients who experience bronchospasm, asthma, rhinitis, or urticaria with NSAID or aspirin therapy.

• Cardiovascular events: Risk may be increased with duration of use or pre-existing cardiovascular risk factors or disease. Carefully evaluate individual cardiovascular risk profiles prior to prescribing. Use caution with fluid retention or heart failure. Concurrent administration of salasalate, and potentially other nonselective NSAIDs, may interfere with aspirin’s cardioprotective effect. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of cardiovascular events; alternate therapies should be considered for patients at high risk.

• Gastrointestinal events: These events may occur at any time during therapy and without warning. Use caution with a history of GI disease (bleeding and/or ulcers), concurrent therapy with aspirin, anticoagulants and/or corticosteroids, smoking, use of alcohol, the elderly or debilitated patients. Use the lowest effective dose for the shortest duration of time, consistent with individual patient goals, to reduce risk of GI adverse events; alternate therapies should be considered for patients at high risk. When used concomitantly with ≤325 mg of aspirin, a substantial increase in the risk of gastrointestinal complications (eg, ulcer) occurs; concomitant gastroprotective therapy (eg, proton pump inhibitors) is recommended (Bhatt, 2008).

• Hematologic effects: Platelet adhesion and aggregation may be decreased; may prolong bleeding time; patients with coagulation disorders or who are receiving anticoagulants should be monitored closely. Anemia may occur; patients on long-term NSAID therapy should be monitored for anemia.

• Hepatic effects: Severe hepatic reactions (eg, fulminant hepatitis, liver failure) have occurred with NSAID use, rarely (may be fatal); elevations of ALT or AST may occur; discontinue if signs or symptoms of liver disease develop, or if systemic manifestations occur.

• Salicylate sensitivity: Patients with sensitivity to tartrazine dyes, nasal polyps, and asthma may have an increased risk of salicylate sensitivity. Previous nonreaction does not guarantee future safe taking of medication.

• Skin reactions: NSAIDs may cause serious skin adverse events including exfoliative dermatitis, Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN); may be fatal; discontinue use at first sign of skin rash or hypersensitivity.

Disease-related concerns:

• Asthma: Do not administer to patients with aspirin-sensitive asthma; severe bronchospasm may occur. Use caution in patients with other forms of asthma.

• Coronary artery bypass graft surgery: Risk of MI and stroke may be increased with use following CABG surgery.

• Hepatic impairment: Use with caution in patients with decreased hepatic function. Closely monitor patients with any abnormal LFT.

• Hypertension: Use with caution; may cause new-onset hypertension or worsening of existing hypertension. Response to ACE inhibitors, thiazides, or loop diuretics may be impaired with concurrent use of NSAIDs.

• Renal impairment: NSAID use may compromise existing renal function; dose-dependent decreases in prostaglandin synthesis may result from NSAID use, reducing renal blood flow which may cause renal decompensation. Patients with impaired renal function, dehydration, heart failure, liver dysfunction, those taking diuretics, and ACE inhibitors, and the elderly are at greater risk of renal toxicity. Rehydrate patient before starting therapy; monitor renal function closely. Not recommended for use in patients with advanced renal disease. Long-term NSAID use may result in renal papillary necrosis.

Salasalate may cause liver problems, and using it with substantial quantities of ethanol may increase that risk.

Salasalate is metabolized to salicylic acid which is excreted in breast milk in concentrations equivalent to maternal blood concentrations. An infant may ingest up to 80% per kg body weight as the mother is taking. The manufacturer recommends that caution be exercised when administering salasalate to nursing women.

Food may decrease the rate but not the extent of absorption. Salasalate peak serum levels may be delayed if taken with food. Management: Administer with food or milk to minimize GI upset.

• Common Adverse effects: Tachycardia, hypotension, myocarditis, atrial fibrillation, atrial flutter, angina, CHF, myocardial depression, pericardial effusion/pericarditis, dizziness.

• Less Common Adverse effects: toxic epidermal necrolysis, cutaneous vasculitis, parotitis, GI disorders, anemia, thrombocytopenia, coagulopathy, leukopenia, neutropenia, agranulocytosis, granulocytopenia, red blood cell aplasia, hepatitis, primary biliary cirrhosis.

• Rare Adverse Effects: myoglobinuria, glomerulonephritis, renal vasculitis, pulmonary oedema, pulmonary vasculitis, SLE, lymphadenopathy.

May reduce phenytoin or warfarin metabolism and methotrexate excretion.

The common side effects of Salasalate include the following :

Vomiting, Indigestion, Flatulence, Nausea, Abdominal Pain, Constipation, Epigastric Pain, Diarrhea, Large Intestine Carcinoma.

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 salasalate 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.

• Pharmacodynamics

Salasalate is a nonsteroidal anti-inflammatory agent for oral administration. Salasalate's mode of action as an anti-inflammatory and antirheumatic agent may be due to inhibition of synthesis and release of prostaglandins. The usefulness of salicylic acid, the active in vivo product of salasalate, in the treatment of arthritic disorders has been established. In contrast to aspirin, salasalate causes no greater fecal gastrointestinal blood loss than placebo.

• Pharmacokinetics

Elimination: Primarily urine

1. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1364710/
2. https://reference.medscape.com/drug/colestid-Salasalate -342452
3. https://go.drugbank.com/drugs/DB00375
4. https://www.sciencedirect.com/topics/medicine-and-dentistry/Salasalate
5. https://europepmc.org/article/med/6988203