MSD® ENTERIC COATED ASA
Johnson & Johnson Merck
ASA
Nonsteroidal Anti-inflammatory – Analgesic – Platelet Aggregation Inhibitor
Action And Clinical Pharmacology: ASA has analgesic, antipyretic and anti-inflammatory properties.
In rheumatic diseases, although the analgesic and antipyretic effects are useful, the major purpose for which ASA is used is to reduce the intensity of the inflammatory process. Inhibition of prostaglandin synthesis may be involved in the anti-inflammatory action of ASA.
ASA also alters platelet aggregation and release reaction by inhibiting prostaglandin synthesis. Thromboxane A2 is an essential step in platelet aggregation. ASA prevents thromboxane A2 formation by acetylation of platelet cyclooxygenase. This inhibition of prostaglandin synthesis is irreversible and affects platelet function for the life of the platelet.
The enteric coating substantially resists disintegration in aqueous fluids having a pH lower than 3.5 for a period of at least 2 hours and is capable of disintegrating in aqueous fluids having a pH of at least 5.5 in from 10 to 30 minutes. Thus, enteric coating effectively inhibits the release of ASA in the stomach, while allowing the tablet to dissolve in the upper portion of the small intestine for absorption from the duodenal area.
Clinical experience has shown that enteric-coated ASA diminishes or eliminates gastric distress during long-term treatment with high doses of ASA.
Pharmacokinetics: Since this product is enteric-coated, the pharmacological effects are not immediate. Peak serum salicylate concentrations are reached 6 to 8 hours after single oral administration. This means that MSD Enteric Coated ASA tablets are more useful for chronic administration as in arthritis, than for providing prompt relief of pain and fever.
The plasma half-life of salicylate concentrations is dose-dependent being 3 to 6 hours at low doses (325 mg to 1.3 g) and 15 to 30 hours at high doses.
Indications And Clinical Uses: Whenever gastric intolerance to ASA is of concern.
For the relief of signs and symptoms of the following: osteoarthritis, rheumatoid arthritis, spondylitis, bursitis and other forms of rheumatism, musculoskeletal disorders and rheumatic fever, however, penicillin and other appropriate therapy should be administered concomitantly. ASA is generally considered to be the primary therapy for most forms of arthritis.
Also indicated for reducing the risk of recurrent transient ischemic attacks or stroke in men who have had transient ischemia of the brain due to fibrin platelet emboli. At present, there is no evidence that ASA is effective in reducing transient ischemic attacks in women, or is of benefit in the treatment of completed strokes in men or women.
Contra-Indications: Sensitivity to the ingredients; active peptic ulcer; patients who had a bronchospastic reaction to ASA or nonsteroidal anti-inflammatory drugs.
Manufacturers’ Warnings In Clinical States: ASA is one of the most frequent causes of accidental poisoning in toddlers and infants. ASA should, therefore, be kept well out of the reach of all children.
Precautions: Salicylates should be administered with caution to patients with asthma and other allergic conditions, with a history of gastrointestinal ulcerations, with bleeding tendencies, with significant anemia or with hypoprothrombinemia.
Salicylates can produce changes in thyroid function tests.
Acute hepatitis has been reported rarely in patients with systemic lupus erythematosus and juvenile rheumatoid arthritis with plasma salicylate concentrations above 25 mg/100 mL. Patients have recovered upon cessation of therapy.
Pregnancy: ASA does not appear to have any teratogenic effects. ASA has been found to delay parturition in rats. This effect has also been described with nonsteroidal anti-inflammatory agents which inhibit prostaglandin synthesis.
High doses (3 g daily) of ASA during pregnancy may lengthen the gestation and parturition time.
Because of possible adverse effects on the neonate and the potential for increased maternal blood loss, ASA should be avoided during the last three months of pregnancy.
Children: Recent studies have suggested that ASA usage may cause the development of Reye’s syndrome in children and teenagers with acute febrile illnesses, especially influenza and varicella. Although a direct causal relationship has not been established, it is recommended that salicylates be avoided when possible, in children and teenagers with influenza or varicella.
Drug Interactions: Caution is necessary when ASA and anticoagulants are prescribed concurrently, as ASA may potentiate the action of anticoagulants.
Salicylates may potentiate sulfonylurea hypoglycemic agents. Large doses of salicylates may have a hypoglycemic action, and thus, affect the insulin requirements of diabetics.
Although salicylates in large doses are uricosuric agents, smaller amounts may depress uric acid clearance, and thus decrease the uricosuric effects of probenecid, sulfinpyrazone and phenylbutazone.
Sodium excretion produced by spironolactone may be decreased in the presence of salicylates.
Salicylates also retard the renal elimination of methotrexate.
Adverse Reactions: Gastrointestinal: nausea, vomiting, diarrhea, gastrointestinal bleeding and/or ulceration.
Ear: tinnitus, vertigo, hearing loss.
Hematologic: leukopenia, thrombocytopenia, purpura.
Dermatologic and Hypersensitivity: urticaria, angioedema, pruritus, various skin eruptions, asthma and anaphylaxis.
Miscellaneous: acute reversible hepatotoxicity, mental confusion, drowsiness, sweating and thirst.
Symptoms And Treatment Of Overdose: Symptoms: In mild overdosage, these may include rapid and deep breathing, nausea, vomiting (leading to alkalosis), hyperpnea, vertigo, tinnitus, flushing, sweating, thirst and tachycardia. (High blood levels of ASA lead to acidosis.) Severe cases may show fever, hemorrhage, excitement, confusion, convulsions or coma and respiratory failure.
Treatment: Treatment is essentially symptomatic and supportive. Administer water, universal antidote and remove by gastric lavage or emesis. Force fluids (e.g., salty broth) to replace sodium loss. If the patient is unable to retain fluids orally, the alkalosis can be treated by hypertonic saline i.v. If salicylism acidosis is present, sodium bicarbonate i.v. is preferred because it increases the renal excretion of salicylates. Vitamin K is indicated if there is evidence of hemorrhage. Hemodialysis has been used with success.
Respiratory depression may require artificial ventilation with oxygen. Convulsions may best be treated by the administration of succinylcholine and artificial ventilation with oxygen. CNS depressant agents should not be used.
Hyperthermia and dehydration are immediate threats to life and initial therapy must be directed to their correction and to the maintenance of adequate renal function. External cooling with cool water or alcohol should be provided quickly to any child who has a rectal temperature over 40°C.
Dosage And Administration: Analgesic/Antipyretic: Patients should be advised not to exceed 4 g daily. Single doses should not be administered more frequently than every 4 hours.
Adults: Single dose should not exceed 650 mg, to be repeated every 4 to 6 hours; the total daily dosage should not exceed 4 000 mg ASA unless otherwise advised by a physician, i.e., 12 tablets 325 mg, or 6 tablets 650 mg. If the underlying condition requires continued use of ASA for more than 5 days, a physician should be consulted.
Children: Only as directed by a physician.
Anti-inflammatory: Because the suppression of inflammation increases with the dose of salicylate even beyond the point of toxicity, the therapeutic objective is to employ as large a dose as possible short of toxicity. Most patients will tolerate blood salicylate levels in the range of 20 to 25 mg %. The most common reason for failing to obtain a therapeutic response to ASA is the administration of inadequate doses.
The generally accepted way to achieve effective “anti-inflammatory” salicylate blood levels of 20 to 25 mg% is to titrate the dosage by starting with 2.6 to 3.9 g daily, according to the size, age and sex of the patient. If necessary, the dosage is then gradually adjusted by daily increments of 0.65 g. Optimally, salicylate therapy should be monitored by periodic blood salicylate level determinations. If this is not practical, the appearance of auditory symptoms in the form of tinnitus or deafness are acceptable as an indication of the maximum tolerated salicylate dose.
In adults, the median dose at which tinnitus develops is 4.5 g/day, but the range extends from 2.6 to 6 g/day.
Intermittent administration is ineffective. Patients should be advised not to vary the dose from day to day depending on the level of pain because that often fluctuates independently of the intensity of the inflammation. A continuous regimen of 0.65 g 4 times daily is considered to be minimum therapy for adults. ASA should be administered 4 times daily. For night-time and early morning benefits, the last dose should be given at bedtime.
There is an inverse relation between blood salicylate levels at which auditory symptoms appear and the age of the patient. In the young adult, this is usually in the range of 20 to 30 mg%. In children, however, the level may be much higher, or the effect apparently absent. Because salicylate toxicity may appear without such warning in children, the usual practice is to give ASA in a daily dose of 50 to 80 mg/kg of body weight and to follow blood levels aiming for a concentration of about 30 mg%.
Rheumatic Fever: A total daily dosage of 80 mg/kg of body weight administered in divided doses to allay the pain, swelling and fever.
Cerebral Ischemic Attacks (Men): The recommended dosage is 1 300 mg/day (650 mg twice a day or 325 mg 4 times a day).
Availability And Storage: 325 mg: Each round, brown, film-coated, unprinted, enteric-coated tablet contains: ASA 325 mg. Nonmedicinal ingredients: cellulose acetate phthalate, cornstarch, dietyl phthalate, guar gum, hydrogenated vegetable oil, hydroxypropyl methylcellulose, microcrystalline cellulose, polyvinyl acetate phthalate, red ferric oxide, sodium lauryl sulfate and sucrose. Bottles of 1 000 (for dispensing use only).
650 mg: Each oval, orange, film-coated, unprinted, enteric-coated tablet contains: ASA 650 mg. Nonmedicinal ingredients: cellulose acetate phthalate, cornstarch, dietyl phthalate, guar gum, hydrogenated vegetable oil, hydroxypropyl cellulose, hydroxypropyl methylcellulose, microcrystalline cellulose, sodium lauryl sulfate, sunset yellow aluminum lake and titanium dioxide. Bottles of 1 000 (for dispensing use only).
Store at 15 to 30°C. Protect from moisture.
MSD® ENTERIC COATED ASA Johnson & Johnson Merck ASA Nonsteroidal Anti-inflammatory – Analgesic – Platelet Aggregation Inhibitor
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