(Acetylsalicylic acid suppositories, USP) 150 mg and 650 mg
(Acetylsalicylic acid tablets, USP)
(Acetylsalicylic acid delayed-release tablets, USP) Analgesic, anti-inflammatory, antipyretic and platelet aggregation inhibitor Pharmascience, Inc Date of Preparation: 6111 Royalmount Ave # 100 June 28, 2006 Montreal, Quebec Date of Revision: H4P 2T4 July 5, 2006
(Acetylsalicylic acid suppositories USP)
,
(Acetylsalicylic acid tablets, USP)
(Acetylsalicylic acid delayed release tablets, USP)
Analgesic, anti-inflammatory, anti-pyretic and platelet aggregation inhibitor.
ACTION AND CLINICAL PHARMACOLOGY
ASA interferes with the production of prostaglandins in various organs and tissues through acetylation of the enzyme cyclo-oxygenase. Prostaglandins are themselves powerful irritants and produce headaches and pain on injection in man. Prostaglandins also appear to sensitize pain receptors to other noxious substances such as histamine and bradykinin. By preventing the synthesis and release of prostaglandins in inflammation, ASA may avert the sensitization of pain receptors. The antipyretic activity of ASA is due to its ability to interfere with the production of prostaglandin E 1 in the brain. Prostaglandin E 1 is one of the most powerful pyretic agents known. The inhibition of platelet aggregation by ASA is due to its ability to interfere with the production of thromboxane A 2 within the platelet. Thromboxane A 2 is largely responsible for the aggregating properties of platelets.
INDICATIONS AND CLINICAL USE
Acetylsalicylic acid (ASA) is indicated for the relief of pain, fever and inflammation of a variety of conditions such as influenza, common cold, low back and neck pain, dysmenorrhea, headache, toothache, sprains and strains, fractures, myositis, neuralgia, synovitis, arthritis, bursitis, burns, injuries, following surgical and dental procedures. ASAPHEN 81 mg and ASAPHEN E.C. 81 mg and ASAPHEN E.C. 162 mg are also indicated for the following uses, based on its platelet aggregation inhibitory properties: -For reducing the risk of morbidity and death in patients with unstable angina and in those with previous myocardial infarction. -For reducing the risk of transient ischemic attacks (TIA) and for secondary prevention of atherothrombotic cerebral infarction; -For prophylaxis of venous thromboembolism after total hip replacement; -For reduction of adhesive properties of platelets in patients following carotid endarterectomy to prevent recurrence of TIA and in hemodialysis patients with a silicone rubber arteriovenous cannula. In addition, ASAPHEN E.C. 81 mg and ASAPHEN E.C. 162 mg is also indicated for the following uses, based on its platelet aggregation inhibitory properties: -For reducing the risk of vascular mortality in patients with a suspected acute myocardial infarction. -For reducing the risk of a first non-fatal myocardial infarction in individuals deemed to be at sufficient risk of such an event by their physician. There is no evidence for a reduction in the risk of first fatal myocardial infarction. ASA does not reduce the risk of either cardiovascular mortality or first strokes, fatal or non-fatal . The decrease in the risk of first non-fatal myocardial infarction must be assessed against a much smaller but not insignificant increase in the risk of haemorrhagic stroke as well as gastrointestinal bleeding.
Salicylate sensitivity, active peptic ulcer.
ASA is one of the most frequent causes of accidental poisonings in toddlers and infants. Tablets should be kept well out of the reach of children. A possible association between Reye's syndrome and the use of salicylates has been suggested but not established. Reye's syndrome has also occurred in many patients not exposed to salicylates. However, caution is advised when prescribing salicylate-containing medications for children and teenagers with influenza or chickenpox.
Salicylates should be administered cautiously to patients with asthma and other allergic conditions, a history of gastrointestinal ulcerations; bleeding tendencies; significant anemia or hypoprothrombinemia. Patients taking ASA daily are at an increased risk of developing gastrointestinal bleeding following the ingestion of alcohol. Caution is necessary when salicylates and anticoagulants are prescribed concurrently, as salicylates can depress the concentration of prothrombin in the plasma. Diabetics receiving concurrent salicylate and hypoglycemic therapy should be monitored closely; reduction of the sulfonylurea hypoglycemic drug dosage may be necessary; insulin requirements may change. High doses (3g daily) of ASA during pregnancy may lengthen the gestation and parturition time. Salicylates can produce changes in thyroid function tests. Sodium excretion produced by spironolactone may be decreased by salicylate administration. Salicylates in large doses are uricosuric agents; smaller amounts may depress uric acid clearance and thus decrease the uricosuric effects of other drugs. Salicylates retard the renal elimination of methotrexate. Salicylates may alter valproic acid (VPA) metabolism and may displace VPA from protein binding sites, possibly intensifying the effects of VPA. Caution is recommended when VPA is administered concomitantly with salicylates. The hyponatremic and hypotensive effects of ACE inhibitors may be diminished by the concomitant administration of ASA due to its indirect effect on the renin-angiotensin conversion pathway. The potential interaction may be related to the dose of ASA.
Gastrointestinal
: (the frequency and severity of these adverse effects are dose-related): nausea, vomiting, diarrhea, gastrointestinal bleeding and/or ulceration, dyspepsia, heartburn.
Ear
: tinnitus, vertigo, hearing loss.
Hematologic
: leukopenia, thrombocytopenia, purpura, anemia.
Dermatologic and hypersensitivity
: urticaria, angioedema, pruritus, skin eruptions, asthma, anaphylaxis.
Miscellaneous:
mental confusion, drowsiness, sweating, thirst.
Symptoms:
in mild overdosage these may include rapid and deep breathing, nausea, vomiting, vertigo, tinnitus, flushing, sweating, thirst, arid tachycardia. In more severe cases, acid-base disturbances including respiratory alkalosis and metabolic acidosis can occur. Severe cases may show fever, hemorrhage, excitement, confusion, convulsions or coma and respiratory failure.
Treatment
consists of prevention and management of acid-base and fluid and electrolyte disturbances. Renal clearance is increased by increasing urine flow and by alkaline diuresis but care must be taken in this approach to not aggravate further the metabolic acidosis that develops and the hypokalemia. Acidemia should be prevented by administration of adequate sodium containing fluids and sodium bicarbonate. Hypoglycemia is an occasional accompaniment of salicylate overdosage and can be managed by glucose solutions. If a hemorrhagic diathesis is evident, give vitamin K. Hemodialysis may be useful in complex acid base disturbances particularly in the presence of abnormal renal funtion.
Analgesic and antipyretic:
Adults:
1-2 tablets (325 mg to 650 mg) orally every 4 hours.
Children under 12:
10 to 15 mg/kg every 6 hours, not to exceed a total daily dose of 2.4 g.
Anti-inflammatory: Adults: 3 tablets (975 mg) 4 to 6 times a day, up to 30 tablets daily, may be required for optimal anti-inflammatory effect. A blood level between 15 and 30 mg per 100 mL is in the desirable therapeutic range.
Children:
60 to 125 mg/kg daily in 4 to 6 divided doses.
Platelet aggregation inhibitor:
For suspected acute myocardial infarction: An initial dose of at least 160 -162.5 mg chewed or crushed to ensure rapid absorption as soon as a myocardial infarction is suspected. The same dose should be given as maintenance over the next 30 days. After 30 days, consider further therapy based on dosage and administration for prevention of recurrent MI (see Prior Myocardial Infarction). ASAPHEN E.C. 81 mg and ASAPHEN E.C. 162 mg (Acetylsalicylic acid delayed release tablets) is specifically indicated for these uses. For the prevention of a first myocardial infarction: 80 - 325 mg daily according to the individual needs of the patient, as determined by the physician. ASAPHEN E.C. 81 mg and ASAPHEN E.C. 162 mg (Acetylsalicylic acid delayed release tablets) is specifically indicated for these uses. For reducing the risk of morbidity and death in patients with unstable angina and in those with previous myocardial infarction: 80 - 325 mg daily according to the individual needs of the patient, as determined by the physician. ASAPHEN 81 mg (Acetylsalicylic acid tablets), ASAPHEN E.C. 81 mg and ASAPHEN E.C. 162 mg (Acetylsalicylic acid delayed release tablets) is specifically indicated for these uses. For reducing the risk of transient ischemic attacks (TIA) and for secondary prevention of atherothrombotic cerebral infarction: 80 - 325 mg daily according to the individual needs of the patient, as determined by the physician. ASAPHEN 81 mg (Acetylsalicylic acid tablets), ASAPHEN E.C. 81 mg and ASAPHEN E.C. 162 mg (Acetylsalicylic acid delayed release tablets) is specifically indicated for these uses. For prophylaxis of venous thromboembolism after total hip replacement: 650 mg twice a day (1,300 mg daily), started 1 day before surgery and continued for 14 days. ASAPHEN 81 mg (Acetylsalicylic acid tablets), ASAPHEN E.C. 81 mg and ASAPHEN E.C. 162 mg (Acetylsalicylic acid delayed release tablets) is specifically indicated for these uses.
Drug Substance
Proper Name
: Acetylsalicylic acid
Chemical Names
: 2-(Acetyloxy) benzoic acid;
Salicylic acid acetate.
Structure:
O
OH
O O
CH 3 Molecular Formula: C9H8O4
Molecular Weight
: 180.16
Description
: White granules, commonly tabular or needle-like, or white crystalline powder. Odorless or having a faint odor.
Solubility
: Slightly soluble in water; freely soluble in alcohol; soluble in chloroform and ether; sparingly soluble in absolute ether.
pK value (25/C)
: 3.49
Melting Point
: 135/C (rapid heating)
ASA Suppositories
: Each suppository contains 150 mg or 650 mg acetylsalicylic acid as active ingredient. Non-medicinal ingredients: Novata 299.
pms-ASA Tablets
: Each tablet contains 325 mg acetylsalicylic acid as active ingredient.
Non-medicinal ingredients: Croscarmellose sodium, microcrystalline cellulose.
Asaphen
: Each chewable tablet contains 80 mg or 81 mg acetylsalicylic acid as active ingredient.
Non-medicinal ingredients: DC Yellow #10, FDC Red #40, mannitol, orange flavor, pregelatinized starch, sodium saccharin, stearic acid.
Asaphen E.C.
: Each tablet contains 80 mg acetylsalicylic acid as active
(80 mg) ingredient. Non-medicinal ingredients: Hydrogenated soya bean oil, hydroxypropyl methylcellulose, lactose, polyethylene glycol, pregelatinized starch, stearic acid.
Asaphen E.C.
: Each tablet contains 81 mg acetylsalicylic acid as
(81 mg) active ingredient. Non-medicinal ingredients: Colloidal Anhydrous Silica, lactose anhydrous, methacrylic acid polymer, pregelatinized starch, sodium bicarbonate, sodium lauryl sulphate, stearic acid, talc and triethyl citrate.
Asaphen E.C.
: Each caplet contains 162 mg acetylsalicylic acid as active ingredient.
(162 mg) Non-medicinal ingredients: carnauba Wax, colloidal silicon dioxide, hydroxypropyl methylcellulose, lactose, methylated silica, methylcellulose, polydextrose, polydimethylsiloxane, polyethylene glycol, polyethylene glycol sorbitan tristearate, polyvinyl acetate phthalate, pregelatinized starch, sodium alginate, sodium bicarbonate, stearic acid, Talc, titanium dioxide, triethyl citrate.
ASA Suppositories
: White, cone-shaped suppositories. Available in strengths of 150 mg and 650 mg. In package of 10.
pms-ASA Tablets
: Each round, biconvex, compressed white tablet contains 325 mg acetylsalicylic acid. In packages of 100, 500 and 1000 tablets.
Asaphen 80mg
: Each chewable, orange, round, biconvex, scored tablet, embossed "ASAPHEN 80" contains 80 mg acetylsalicylic acid. In packages of 24, 30,
100 and 500 tablets.
Asaphen 81 mg
: Each chewable, salmon coloured, round, biconvex tablet, embossed "ASAPHEN 81" contains 81 mg acetylsalicylic acid. In packages of 30 and 120 tablets.
Asaphen E.C. 80mg
: Each round, white enteric-coated tablet contains 80 mg acetylsalicylic acid.
In packages of 24, 30, 120 and 500 tablets and in blister packs of 7 tablets.
Asaphen E.C. 81mg
: Each round, white enteric-coated tablet contains 81 mg acetylsalicylic acid.
In packages of 24, 30, 100,120, 180, 200, 225, 250 and 255 tablets and in blister packs of 7 tablets.
Asaphen E.C. 162mg
: Each caplet shaped, white enteric-coated tablet contains 162 mg acetylsalicylic acid. In packages of 30, 60, 90 and 120 tablets and in blister packs of 12 tablets.
Store at room temperature (15/-30/C).