Download INSTRUCTION SHEET on medical application of the preparation

INSTRUCTION SHEET
on medical application of the preparation
ACECARDOL
Registration number
Preparation trade name: Acecardol
International nonproprietary name - Acetylsalicylic acid
Dosage form: enteric coated tablets.
Composition for a tablet:
Active substance: 50, 100 or 300 mg of Acetylsalicylic acid.
Accessory substances: low-molecular povidone (medicinal low-molecular polyvinyl pyrrolidone
12600+2700), corn starch, microcrystalline cellulose, magnsium stearate, talcum powder, lactose
monohydrate (milk sugar).
Accessory substances for obtaining the coat: cellacefate (acetylftali-cellulose), titanium dioxide, castor oil.
Description: round tablets of double convex form coated with white or almost white casing.
Pharmacotherapeutic group: antiplatelet agent.
ATC Code: [В01АС06].
Pharmacological action
The basis of mechanism of antiplatelet action of acetylsalicylic acid is formed of irreversible inhibition of cyclooxygenase (COG-1), as a result of which thromboxane A2 synthesis is blocked and
thrombocyte aggregation is suppressed. Antiplatelet action develops even with low dosages of the
preparation and is retained within 7 days after a single intake.
It is considered that Acetylsalicylic acid has also other mechanisms of thrombocyte aggregation suppression.
In large doses Acetylsalicylic acid (more than 300 mg per day) also has an anti-inflammatory, antipyretic and analgesic effect.
Pharmacokinetics
After ingestion the acetylsalicylic acid is quickly and completely absorbed from the gastrointestinal
tract. The Acetylsalicylic acid is partially metabolized at the time of absorption. At the time of and
after absorption the Acetylsalicylic acid turns into a principal metabolite - salicylic acid, which is
metabolited principally in liver under the influence of ferments with formation of such metabolites as
phenyl salicylate, salicylic acid glucuronid and salicyluric acid, those are appeared to be found in
many tissues and urina. In women the metabolism process runs slower (less ferment strength in
blood plasma).
The maximum concentration in blood plasma is observed after ingestion in 10 - 20 minutes after
administration, the maximum concentration of salicylic acid is got in the space of 0.3 -2 hours.
Due to the fact that the tablets are covered with acid-resistant coat, the acetylsalicylic acid is released
not in the stomach (the coat effectively blocks dissipation of the preparation in stomach), but in alcaline condition of the dodecadactylon. In that way absorption of acetylsalicylic acid in tabloid form
covered with enteric coat is retarded for 3-6 hours as compared to common (without such coating)
tablets.
Acetylsalicylic acid and salicylic acid become bound with plasma proteins (from 66 % to 98 % depending on the dose) and quickly disperse in the organism. Salicylic acid works way through the placenta and also into human milk. Egestion of the salicylic acid depends on the dose, because its metabolism is limited by the abilities of the fermentative system. Half-life period is at least 2-3 hours in case of
application of acetylsalicylic acid in small doses and up to 15 hours in case of application of the preparation
in high doses (common doses of acetylsalicylic acid in the capacity of pain reliever). In contrast to other
salicylates, in multiple intake of the medication non-hydrolyzed Acetylsalicylic acid is not accumulated in
blood serum. Salicylic acid and its metabolites are egested by the kidneys. In patients with normal kidney function 80-100% of a single dose of the preparation is egested by the kidneys within 24-72 hours.
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Indication for application
Prevention of acute myocardial infarction with risk factors (for example diabetes, hyperlipemia, arterial hypertension, obesity, smoking, elderly age) and the secondary myocardial infarction;
Unstable angina; Blood-stroke prevention (including in patients with transient ischemic attack);
Prevention of thrombembolia after vessels surgery and invasive interventions (for example aortocoronary bypass, endarterectomy of carotid arteries, arteriovenous bypass, angioplasty of carotid arteries);
Prevention of deep venous thrombosis and embolism of pulmonary artery and its branches including
in patients with long-term immobilization because of major surgical intervention.
Counter-indications
Hypersensitivity to Acetylsalicylic acid, erosive-ulcerous damage of gastrointestinal tract (in phase
of aggravation), gastrointestinal bleedings, hemorrhagic diathesis, bronchial asthma induced by administration of salicylates, -complete or incomplete combination of bronchial allergy, recrudescent
polyposis of nose and paranasal sinuses and Acetylsalicylic acid intolerance, frank renal insufficiency (creatine clearance is less than 30 ml/minute), frank hepatic insufficiency (B and C grade according to Child –Pugh scale), chronic cardiac failure (III-IV functional grade according to NYHA classification), simultaneous intake of methotrexate in dose 15 mg per week and more, pregnancy (I and
III trimesters) and lactation period, age under 18 years old, lactase deficit, lactose intolerance, glucose-galactose malabsorption syndrome.
If you have one of the mentioned diseases, be sure to consult a doctor before intake of the medication.
Use with care
In patients with podagra, hyperuricemia because the Acetylsalicylic acid in low dosages reduces
egestion of uric acid; it is well to bear in mind that the Acetylsalicylic acid in low dosages can provoke development of uratic arthritis by liable patient (having low egestion of uric acid); peptic ulcer
of the stomach and dodecadactylon or gastrointestinal hemorrhage (in anamnesis); compromised
liver function (A grade according to Child-Pugh scale); parafunction kidney (creatine clearance is
more than 30 ml/minute); bronchial asthma, chronical diseases of respiratory organs, pollen fever,
nasal polyposis, medicamentous allergy; in combination with methotrexate in a dose of less than 15
mg a week, associated therapy by anticoagulating agents, pregnancy (II trimrster); in supposed surgical intervention (including insignificant, for example tooth extraction), because the Acetylsalicylic
acid can cause a tendency to development of hemorrhage within several days after intake of the medication.
If you have one of the mentioned diseases, be sure to consult a doctor before intake of the medication.
Administration during pregnancy and in the breast feeding period
Use of big doses of salicylates in the first 3 months of pregnancy is associated with overfrequency of
fetal development defects (cleft palate, cardiac anomaly). Prescription of salicylates in I trimester of
pregnancy is contraindicative. In the second trimester of pregnancy salicylates can be indicated only
with the strict assessment of risk for the fetus and benefit for the mother, preferably in doses not exceeding 150 mg/day and of short duration.
In the last trimester of the pregnancy, salicylates in a big dose (more than 300 mg/day) may cause
inhibition of birth activities, untimely closing of fetus arterial canal, increased hemorrhage in mother
and fetus; administration immediately before birth may cause intracerebral bleedings, especially in
immature infants.
Indication of salicylates in the last trimester of pregnancy is contraindicative.
Salicylates and their metabolites in small amounts penetrate in human milk, therefore in the lactation period breast feeding should be discontinued.
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Method of application and dosage
The tablets of the preparation of Acecardol should be ingested before meals with a big quantity of
water once a day. Acecardol is intended for long administration. The therapy duration is determined
by a physician in charge.
Prophylaxis in case of acute myocardial infarction suspicion. 100 mg a day or 300 mg every other day (the first tablet should be chewed for quicker absorption).
Prophylaxis of new onset of acute myocardial infarction with risk factors 100 mg per day or 300 mg
every other day
Prophylaxis of repeated myocardial infarction and unstable angina: 100 - 300 mg per day.
Prophylaxis ischemic blood-stroke and transient ischemic attack: 100 - 300 mg per day.
Prophylaxis of thromboembolic disorders after surgeries and intrusive interference on the vessels:
100 - 300 mg per day.
Prophylaxis of deep venous thrombosis and embolism of pulmonary artery and its branches: 100 mg
per day or 300 mg every other day.
Adverse events
Gastrointestinal tract: nausea, epigastric burning, vomit, pains in the abdominal region; ulcers of
mucous coat of stomach and dodecadactylon; ruptured ulcers of stomach and dodecadactylon, gastrointestinal hemorrhage, transient compromised liver function with increment in activity of hepatic
transaminases.
Hematopoietic system: administration of Acetylsalicylic acid is accompanied with increased risk of
hemorrhage in consequence of depressant action of the Acetylsalicylic acid on thrombocyte aggregation, anemia.
Allergic reactions: exanthema, skin itch, urticaria fever, Quincke's disease, rhinitis, rhinedema, cardiorespiratory distress-syndrome as well as severe reactions including anaphylactic shock.
Respiratory system: bronchismus.
Central nervous system: faintness, decrease of hearing, headache, entotic sound.
If any one of the mentioned adverse events worsen or if you notice any other adverse events not
specified in the instruction, please inform thereof to the doctor.
Overdosage
Overdose is unlikely to occur in consequence of low content of Acetylsalicylic acid in the medication.
Excess of Acetylsalicylic acid dose is linked with risk of gastrointestinal hemorrhage.
Overdosage is especially dangerous in patients of elderly age.
Symptom of overdosage from light to medium rate of severity: faintness, entotic sound, impairment of
hearing, excessive sweating (including profuse), nausea, vomiting, headache, confused mental state,
polypnea, hyperventilation, respiratory alkalosis.
Medical treatment: gastrodialysis, multiple dose of activated carbon, forced alcaline diuresis, reactivation
of water-electrolytic balance and acid-base balance.
Symptoms of overdosage from medium to severe:
- respiratory alkalosis with compensatory metabolic acidosis;
- hyperpyrexia (extremely high body temperature);
- respiration disturbance: hyperventilation, cardiogenic pulmonary edema, respiratory depression,
asphyxia;
- disorders on the part of cardiovascular system: heart rhythm disturbance, decrease of arterial tension, suppression of cardio activity;
- water and electrolyte imbalance: anhydration, parafunction of kidney from oligohydruria down to development of renal insufficiency characterized by
- hypokalemia, hypernatremia, hyponatremia;
- error of glucose metabolism: hyperglycemia, hypoglycaemia (especially in children), ketoacidosis;
- entotic sound, deafness;
- gastrointestinal hemorrhages;
- hematologic disorders: from inhibition of thrombocyte aggregation to coagulopathy, lengthening of
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prothrombin time, hypoprothrombinemia;
- neurological disorders: toxic encephalopathy and suppression of central nervous function (drowsiness, confused mental state, coma, convulsions).
Medical treatment: immediate hospitalization to special-purpose departments for performance of
maintenance emergency management - gastrodialysis, multiple dose of activated carbon, forced alcaline diuresis, haemodialysis, reactivation of water-electrolytic balance and acid-base balance, symptom management. In carrying out alcaline diuresis it is necessary to reach pH value between 7.5 and 8.
Forced alcaline diuresis should be conducted when concentration of salicylates in blood plasm compose more than 500 mg/l (3.6 mmol/l) in adults and 300 mg/l (2.2 mmol/l) in children.
Interaction with other medicinal agents
During conjoined administration Acetylsalicylic acid increases action of the following medical
agents:
- methotrexate due to blood clearance rate lowering and its displacement from the link with proteins;
also the combination of acetylsalicylic acid with methotrexate is accompanied by overfrequency of
development of adverse events on the part of blood-forming organs;
- heparin and indirect anticoagulants due to thrombocyte dysfunction and displacement of indirect
anticoagulants from the link with blood serum proteins;
- thrombolytic agents and antiaggregants;
- digoxin due to decline of its renal excretion;
- hypoglycemic agents (insulin and Sulfonylurea derivatives) by means of hypoglycemic properties
of acetylsalicylic acid itself in high doses and displacement of Sulfonylurea derivatives from links
with plasma proteins;
- valproic acid by means of its displacement from links with plasma proteins.
Combination of acetylsalicylic acid with anticoagulating agents, thrombolytics and antiaggregants is
accompanied by increased risk of hemorrhage development.
In simultaneous intake of acetylsalicylic acid with alcohol strengthening of toxic effect of alcohol on
central nervous system is observed, risk of damage of gastrointestinal tract mucous membrane and
bleeding lengthening rises.
Acetylsalicylic acid weakens effect of uricosuric preparations - benzbromarone (weakening of uricosuric action owing to competitive suppression of renal canalicular excretion of uric acid), inhibitirs
of angiotensine transforming enzymes (dose-dependent action decrease in speed of glomerular filtration in consequence of inhibition of prostaglandins possessing vasorelaxant action, correspondingly weakening of hypotensive action are registered), diuretics (in case of simultaneous application
with acetylsalicylic acid in high doses decrease in speed of glomerular filtration in consequence of
decrease of prostaglandin synthesis in kidneys is registered). Strengthen elimination of salicylates the
system glucocorticosteroids weaken their effect.
Special instructions
Acetylsalicylic acid can encourage bronchismus, as well as promote assault of spasmodic asthma and
other hypersensitivity reactions. The main risk factors are bronchial asthma in anamnesis, pollen fever, nasal polyposis, chronical diseases of the respiratory system and allergic reactions for other
preparations (for example, skin reactions, itch, generalized rash).
Inhibitory action of acetylsalicylic acid on thrombocyte aggregation is preserved during several days
after intake, in connection with that raise of risk of hemorrhage in the course of surgical interference
or in postsurgical period is possible. If absolute exception of angiostaxis in the course of operative
measure is required then it is necessary as far as possible to completely refuse the use of acetylsalicylic acid in pre-surgical period.
Acetylsalicylic acid in small doses can provoke development of podagra in liable persons (those having lower excretion of uric acid).
In case of combined administration of acetylsalicylic acid and salicylates, it should be remembered
that salicylates concentration in blood is reduced during treatment, and after Acetylsalicylic acid
withdrawal, overdosage of salicylates is possible.
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Overdosage of acetylsalicylic acid may cause gastroenteric bleedings.
Effect on car driving and mechanism operating
At the time of intake of Acecardol medication one should exercise caution in driving transportation vehicles, machinery and when performing other potentially dangerous kinds of activity, requiring elevated
concentration of attention and quickness of psychomotor actions.
Form of manufacturing
Tablets with enteric coat, 50, 100 and 300 mg.
There are10 tablets in a contour cellular pack. 1, 2, 3 or 5 contour cellular packs with usage instruction are placed into a cardboard container.
Storage conditions
It should be kept in temperature of not more than 25°C. Keep out of reach of children.
Expiration date
3 years. Do not use after expiration date specified on the package.
Manufacturer/organization that accepts claims:
Open Joint Stock “Kurgan Joint Stock Company of Medical Preparations and Articles “Sintez” (Sintez Joint Stock Company);
#7, Prospect Konstitutsii, city of Kurgan, Russian Federation, 640008;
Tel. /fax: (3522)481689
Internet-site: http://www.kurgansintez.ru
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