Pronunciation:
(SAL sa late)(SAL sa late)

U.S. Brand Names: Amigesic�(r); Disalcid�(r) [DSC]; Mono-Gesic�(r); Salflex�(r)

Synonyms: Disalicylic Acid; Salicylsalicylic Acid

Generic Available: Yes

Canadian Brand Names: Amigesic�(r); Salflex�(r)

Use: Treatment of minor pain or fever; arthritis

Pregnancy Risk Factor: C/D (3rd trimester)

Lactation: Enters breast milk/contraindicated

Contraindications: Hypersensitivity to salsalate or any component of the formulation; GI ulcer or bleeding; pregnancy (3rd trimester)

Warnings/Precautions: Use with caution in patients with platelet and bleeding disorders, renal dysfunction, erosive gastritis, or peptic ulcer disease, dehydration, previous nonreaction does not guarantee future safe taking of medication; do not use aspirin in children <16 years of age for chickenpox or flu symptoms due to the association with Reye's syndrome

Adverse Reactions:

>10%: Gastrointestinal: Nausea, heartburn, stomach pain, dyspepsia

1% to 10%:

Central nervous system: Fatigue

Dermatologic: Rash

Gastrointestinal: Gastrointestinal ulceration

Hematologic: Hemolytic anemia

Neuromuscular & skeletal: Weakness

Respiratory: Dyspnea

Miscellaneous: Anaphylactic shock

<1%: Insomnia, nervousness, jitters, leukopenia, thrombocytopenia, iron-deficiency anemia, does not appear to inhibit platelet aggregation, occult bleeding, hepatotoxicity, impaired renal function, bronchospasm

Overdosage/Toxicology: Symptoms of overdose include respiratory alkalosis, hyperpnea, tachypnea, tinnitus, headache, hyperpyrexia, metabolic acidosis, hypoglycemia, and coma. Nomograms, such as the "Done" nomogram, can be very helpful for estimating the severity of aspirin poisoning and for directing treatment using serum salicylate levels. Treatment can also be based upon symptomatology.

Drug Interactions:

Decreased effect with urinary alkalinizers, antacids, corticosteroids; decreased effect of uricosurics, spironolactone; ACE inhibitor effects may be decreased by concurrent therapy with NSAIDs

Increased effect/toxicity of oral anticoagulants, hypoglycemics, methotrexate

Ethanol/Nutrition/Herb Interactions:

Ethanol: Avoid ethanol (may enhance gastric mucosal irritation).

Food: Salsalate peak serum levels may be delayed if taken with food.

Herb/Nutraceutical: Avoid cat's claw, dong quai, evening primrose, feverfew, garlic, ginger, ginkgo, red clover, horse chestnut, green tea, ginseng (all have additional antiplatelet activity).

Mechanism of Action: Inhibits prostaglandin synthesis, acts on the hypothalamus heat-regulating center to reduce fever, blocks prostaglandin synthetase action which prevents formation of the platelet-aggregating substance thromboxane A2

Pharmacodynamics/Kinetics:

Onset of action: Therapeutic: 3-4 days of continuous dosing

Absorption: Complete from small intestine

Metabolism: Hepatically hydrolyzed to two moles of salicylic acid (active)

Half-life elimination: 7-8 hours

Excretion: Primarily urine

Dosage: Adults: Oral: 3 g/day in 2-3 divided doses

Dosing comments in renal impairment: In patients with end-stage renal disease undergoing hemodialysis: 750 mg twice daily with an additional 500 mg after dialysis

Test Interactions: False-negative results for glucose oxidase urinary glucose tests (Clinistix�(r)); false-positives using the cupric sulfate method (Clinitest�(r)); also, interferes with Gerhardt test, VMA determination; 5-HIAA, xylose tolerance test and T3 and T4

Dietary Considerations: May be taken with food to decrease GI distress.

Patient Education: Take this medication exactly as directed; do not increase dose without consulting prescriber. Do not crush tablets. Take with food or milk to reduce GI distress. Maintain adequate hydration (2-3 L/day of fluids) unless instructed to restrict fluid intake. Do not use alcohol, aspirin or aspirin-containing medication, or any other anti-inflammatory medications without consulting prescriber. You may experience drowsiness (use caution when driving or engaging in tasks requiring alertness until response to drug is known); or nausea or heartburn (small, frequent meals, frequent mouth care, sucking lozenges, or chewing gum may help). GI bleeding, ulceration, or perforation can occur with or without pain; discontinue medication and contact prescriber if persistent abdominal pain or cramping, or blood in stool occurs. Report breathlessness or respiratory difficulty; unusual bruising or bleeding; blood in urine, stool, mouth, or vomitus; unusual fatigue; skin rash or itching; change in urinary pattern; or change in hearing or ringing in ears. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to become pregnant. This drug should not be used in the 3rd trimester of pregnancy. Do not breast-feed.

Additional Information: Does not appear to inhibit platelet aggregation

Anesthesia and Critical Care Concerns/Other Considerations: Salsalate does not appear to inhibit platelet aggregation.

Dental Health: Effects on Dental Treatment: NSAID formulations are known to reversibly decrease platelet aggregation via mechanisms different than observed with aspirin. The dentist should be aware of the potential of abnormal coagulation. Caution should also be exercised in the use of NSAIDs in patients already on anticoagulant therapy with drugs such as warfarin (Coumadin�(r)).

Dental Health: Vasoconstrictor/Local Anesthetic Precautions: No information available to require special precautions

Mental Health: Effects on Mental Status: May cause drowsiness; may rarely cause nervousness or insomnia

Mental Health: Effects on Psychiatric Treatment: May rarely cause leukopenia; use caution with clozapine and carbamazepine

Dosage Forms: [DSC] = Discontinued product

Tablet: 500 mg, 750 mg

Amigesic�(r), Disalcid�(r) [DSC]: 500 mg, 750 mg

Mono-Gesic�(r), Salflex�(r): 750 mg

References:

Chapman BJ and Proudfoot AT, "Adult Salicylate Poisoning: Deaths and Outcome in Patients With High Plasma Salicylate Concentrations,"Q J Med, 1989, 72(268):699-707.

Dugandric RM, Tierney MG, and Dickinson GE, "Evaluation of the Done Nomogram in the Management of Acute Salicylate Intoxication,"Ann Emerg Med, 1989, 18(11):1186-90.

Gurwitz JH, Avorn J, Ross-Degnan D, et al, "Nonsteroidal Anti-Inflammatory Drug-Associated Azotemia in the Very Old,"JAMA, 1990, 264(4):471-5.

Hawkey CJ, Karrasch JA, Szczepa&ntilde;ski L, et al, "Omeprazole Compared With Misoprostrol for Ulcers Associated With Nonsteroidal Anti-inflammatory Drugs,"N Engl J Med, 1998, 338(11):727-34.

Spontak SF, Hassan FM, and Spadafora MP, "Salsalate Intoxication and Ramifications of Utilizing Nonspecific Analytical Methods in Estimating Quantitative Blood Concentrations,"J Anal Toxicol, 1994, 18(4):229-31.

Vandenberg SA, Smolinske SC, Spoerke DG, et al, "Nonaspirin Salicylates: Conversion Factors for Estimating Aspirin Equivalency,"Vet Hum Toxicol, 1989, 31(1):49-50.

Verbeeck RK, "Pharmacokinetic Drug Interactions With Nonsteroidal Anti-inflammatory Drugs,"Clin Pharmacokinet, 1990, 19(1):44-66.

Vertrees JE, McWilliams BC, and Kelly HW, "Repeated Oral Administration for Treating Aspirin Overdose in Young Children,"Pediatrics, 1990, 85(4):594-8.

Weissmann G, "Aspirin,"Sci Am, 1991, 264(1):84-90.

Yeomans ND, Tulassay Z, Juhasz L, et al, "A Comparison of Omeprazole With Ranitidine for Ulcers Associated With Nonsteroidal Anti-inflammatory Drugs,"N Engl J Med, 1998, 338(11):719-26.

International Brand Names: Amigesic�(r) (CA); Arthrosal�(r) (LU); Disalcid�(r) (LU, ZA); Salflex�(r) (CA)