Salsalate

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Tablet, Oral:

Disalcid: 500 mg [DSC], 750 mg [DSC]

Generic: 500 mg, 750 mg

Pharmacology

Mechanism of Action

Salsalate inhibits prostaglandin synthesis providing, anti-inflammatory effects with less inhibition of platelet aggregation than aspirin

Pharmacokinetics/Pharmacodynamics

Absorption

Complete, from small intestine; food slows absorption

Metabolism

Salsalate is partially hydrolyzed in the intestine to two moles of salicylic acid (active) and metabolites; salicylates are further metabolized in the liver

Excretion

Primarily urine

Onset of Action

Therapeutic: 3 to 4 days of continuous dosing

Half-Life Elimination

Salsalate: ~1 hour; Salicylic acid 3.5 to ≥16 hours (due to capacity limited biotransformation)

Use: Labeled Indications

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

Contraindications

Hypersensitivity to salsalate 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.

Documentation of allergenic cross-reactivity for salicylates is limited. However, because of similarities in chemical structure and/or pharmacologic actions, the possibility of cross-sensitivity cannot be ruled out with certainty.

Dosage and Administration

Dosing: Adult

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

Dosing: Geriatric

Refer to adult dosing. May require lower dosage.

Administration

Administer with food to decrease GI distress.

Dietary Considerations

May be taken with food to decrease GI distress.

Storage

Store at 15°C to 30°C (59°F to 86°F).

Drug Interactions

Agents with Antiplatelet Properties (e.g., P2Y12 inhibitors, NSAIDs, SSRIs, etc.): May enhance the adverse/toxic effect of Salicylates. Increased risk of bleeding may result. Monitor therapy

Ajmaline: Salicylates may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. Monitor therapy

Ammonium Chloride: May increase the serum concentration of Salicylates. Monitor therapy

Angiotensin-Converting Enzyme Inhibitors: Salicylates may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Salicylates may diminish the therapeutic effect of Angiotensin-Converting Enzyme Inhibitors. Monitor therapy

Anticoagulants: Salicylates may enhance the anticoagulant effect of Anticoagulants. Monitor therapy

Benzbromarone: Salicylates may diminish the therapeutic effect of Benzbromarone. Monitor therapy

Blood Glucose Lowering Agents: Salicylates may enhance the hypoglycemic effect of Blood Glucose Lowering Agents. Monitor therapy

Carbonic Anhydrase Inhibitors: Salicylates may enhance the adverse/toxic effect of Carbonic Anhydrase Inhibitors. Salicylate toxicity might be enhanced by this same combination. Management: Avoid these combinations when possible.Dichlorphenamide use with high-dose aspirin as contraindicated. If another combination is used, monitor patients closely for adverse effects. Tachypnea, anorexia, lethargy, and coma have been reported. Exceptions: Brinzolamide; Dorzolamide. Consider therapy modification

Corticosteroids (Systemic): Salicylates may enhance the adverse/toxic effect of Corticosteroids (Systemic). These specifically include gastrointestinal ulceration and bleeding. Corticosteroids (Systemic) may decrease the serum concentration of Salicylates. Withdrawal of corticosteroids may result in salicylate toxicity. Monitor therapy

Dexketoprofen: Salicylates may enhance the adverse/toxic effect of Dexketoprofen. Dexketoprofen may diminish the therapeutic effect of Salicylates. Salicylates may decrease the serum concentration of Dexketoprofen. Management: The use of high-dose salicylates (3 g/day or more in adults) together with dexketoprofen is inadvisable. Consider administering dexketoprofen 30-120 min after or at least 8 hrs before cardioprotective doses of aspirin to minimize any possible interaction. Avoid combination

Ginkgo Biloba: May enhance the anticoagulant effect of Salicylates. Management: Consider alternatives to this combination of agents. Monitor for signs and symptoms of bleeding (especially intracranial bleeding) if salicylates are used in combination with ginkgo biloba. Consider therapy modification

Herbs (Anticoagulant/Antiplatelet Properties) (eg, Alfalfa, Anise, Bilberry): May enhance the adverse/toxic effect of Salicylates. Bleeding may occur. Consider therapy modification

Hyaluronidase: Salicylates may diminish the therapeutic effect of Hyaluronidase. Management: Patients receiving salicylates (particularly at larger doses) may not experience the desired clinical response to standard doses of hyaluronidase. Larger doses of hyaluronidase may be required. Consider therapy modification

Influenza Virus Vaccine (Live/Attenuated): May enhance the adverse/toxic effect of Salicylates. Specifically, Reye's syndrome may develop. Avoid combination

Loop Diuretics: Salicylates may diminish the diuretic effect of Loop Diuretics. Loop Diuretics may increase the serum concentration of Salicylates. Monitor therapy

Methotrexate: Salicylates may increase the serum concentration of Methotrexate. Salicylate doses used for prophylaxis of cardiovascular events are not likely to be of concern. Consider therapy modification

Nonsteroidal Anti-Inflammatory Agents (Nonselective): May enhance the adverse/toxic effect of Salicylates. An increased risk of bleeding may be associated with use of this combination. Nonsteroidal Anti-Inflammatory Agents (Nonselective) may diminish the cardioprotective effect of Salicylates. Salicylates may decrease the serum concentration of Nonsteroidal Anti-Inflammatory Agents (Nonselective). Consider therapy modification

Potassium Phosphate: May increase the serum concentration of Salicylates. Monitor therapy

PRALAtrexate: Salicylates may increase the serum concentration of PRALAtrexate. Salicylate doses used for prophylaxis of cardiovascular events are unlikely to be of concern. Consider therapy modification

Probenecid: Salicylates may diminish the therapeutic effect of Probenecid. Monitor therapy

Salicylates: May enhance the anticoagulant effect of other Salicylates. Monitor therapy

Sulfinpyrazone: Salicylates may decrease the serum concentration of Sulfinpyrazone. Avoid combination

Thrombolytic Agents: Salicylates may enhance the adverse/toxic effect of Thrombolytic Agents. An increased risk of bleeding may occur. Monitor therapy

Valproate Products: Salicylates may increase the serum concentration of Valproate Products. Monitor therapy

Varicella Virus-Containing Vaccines: Salicylates may enhance the adverse/toxic effect of Varicella Virus-Containing Vaccines. Specifically, the risk for Reye's syndrome may increase. Avoid combination

Test Interactions

False results for plasma T₄; salsalate is metabolized to salicylic acid; consider test interactions for salicylic acid.

Adverse Reactions

Frequency not defined.

Cardiovascular: Hypotension

Central nervous system: Vertigo

Dermatologic: Skin rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria

Gastrointestinal: Abdominal pain, diarrhea, gastrointestinal hemorrhage, gastrointestinal perforation, gastrointestinal ulcer, nausea

Hematologic & oncologic: Anemia

Hepatic: Abnormal hepatic function tests, hepatitis

Hypersensitivity: Anaphylactic shock, angioedema

Otic: Auditory impairment, tinnitus

Renal: Decreased creatinine clearance, nephritis

Respiratory: Bronchospasm

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylactoid reactions: Even in patients without prior exposure to salsalate, 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: [U.S. Boxed Warning]: NSAIDs are associated with an increased risk of adverse cardiovascular thrombotic events, including MI and stroke. 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 salsalate, 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: [U.S. Boxed Warning]: NSAIDs may increase risk of gastrointestinal irritation, inflammation, ulceration, bleeding, and perforation. 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: [U.S. Boxed Warning]: Use is contraindicated for treatment of perioperative pain in the setting of coronary artery bypass graft (CABG) 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.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Pediatric: Children and teenagers who have or are recovering from chickenpox or flu-like symptoms should not use this product.

Monitoring Parameters

Signs and symptoms of GI bleeding; BP; renal function; urinary pH; plasma salicylate, CBC, and chemistry profile periodically during long term therapy.

Pregnancy

Pregnancy Risk Factor

C

Pregnancy Considerations

Adverse events have not been observed in animal reproduction studies. Due to the known effects of salicylates (closure of ductus arteriosus), use during late pregnancy should be avoided.

Patient Education

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
• Patient may experience nausea. Have patient report immediately to prescriber signs of abdominal ulcers (severe abdominal or back pain; black, tarry, or bloody stools; vomiting blood or vomit that looks like coffee grounds; or weight gain or abnormal swelling), signs of bleeding (vomiting blood or vomit that looks like coffee grounds; coughing up blood; blood in the urine; black, red, or tarry stools; bleeding from the gums; abnormal vaginal bleeding; bruises without a reason or that get bigger; or any severe or persistent bleeding), signs of kidney problems (unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain), signs of high potassium (abnormal heartbeat, confusion, dizziness, passing out, weakness, shortness of breath, numbness or tingling feeling), signs of severe cerebrovascular disease (change in strength on one side is greater than the other, difficulty speaking or thinking, change in balance, or vision changes), shortness of breath, excessive weight gain, swelling of arms or legs, chest pain, fast heartbeat, severe headache, noise or ringing in the ears, hearing loss, severe abdominal pain, severe loss of strength and energy, severe dizziness, passing out, vision changes, signs of Stevens-Johnson syndrome/toxic epidermal necrolysis (red, swollen, blistered, or peeling skin [with or without fever]; red or irritated eyes; or sores in mouth, throat, nose, or eyes), or signs of liver problems (dark urine, fatigue, lack of appetite, nausea, abdominal pain, light-colored stools, vomiting, or yellow skin) (HCAHPS).
• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.