Acetylsalicylic acid

General characteristics. Structure:

Active ingredient: 1 tablet contains acetylsalicylic acid in terms of 100% substance of 500 mg;

excipients: cellulose microcrystallic, sodium of a kroskarmeloz, silicon dioxide colloid anhydrous (aerosil), magnesium stearate.

Description. Tablets of white or almost white color, a round form, with a flat surface, with risky and a facet. On a surface of tablets the mramornost is allowed.

Pharmacological properties:

Acetylsalicylic acid concerns to group of nonsteroid antiinflammatory medicines with analgetic, febrifugal and antiinflammatory properties. The mechanism of its action consists in an irreversible inactivation of enzymes of cyclooxygenase which play an important role at synthesis of prostaglandins.

Peroraln in doses from 0,3 g to 1 g drug is used for pain relief and states which are followed by fever of easy degree, such as cold and flu, for decrease in temperature and reduction of expressiveness of a joint pain and muscles.

Acetylsalicylic acid is also applied at acute and chronic inflammatory diseases, such as a pseudorheumatism, an osteoarthritis and an ankylosing spondylitis. At these diseases apply, as a rule, high doses of drug – from 4 g to 8 g of acetylsalicylic acid a day.

Acetylsalicylic acid suppresses aggregation of thrombocytes by blocking of synthesis of A2 thromboxane and is applied at many vascular diseases in doses of 75-300 mg a day.

After intake acetylsalicylic acid is quickly and completely soaked up from digestive tract. In time and after absorption it turns into the main active metabolite – salicylic acid. The maximum concentration of acetylsalicylic acid in a blood plasma is reached in 10-20 minutes, salicylates – 20-120 minutes respectively.

Acetilsalicylic and salicylic acids completely contact proteins of a blood plasma and are quickly distributed in an organism. Salicylic acid gets through a placenta and is excreted in breast milk.

Salicylic acid is exposed to metabolism in a liver. Metabolites of salicylic acid are salitsilmochevy acid, салицилфенол a glucuronide, the glucuronide, gentisic acid and gentizinmochevy acid salitsilatsit.

The kinetics of removal of salicylic acid depends on a dose as metabolism is limited to activity of enzymes of a liver. The elimination half-life depends on a dose and increases of 2-3 o'clock at use of low doses till 15 o'clock at use of high doses. Salicylic acid and its metabolites are removed from an organism preferential by kidneys.

Indications to use:

For a symptomatic treatment of a headache, a dentagra; the pharyngalgia caused by cold; algodismenory; muscle and joints pains; dorsodynias; the moderate pain caused by arthritis.

At cold or acute respiratory diseases for symptomatic pain relief and fever.

Route of administration and doses:

Acetylsalicylic acid is accepted inside after food, washing down with enough liquid. It is impossible to apply longer than 3-5 days without consultation of the doctor.

Adults and children are more senior than 15 years.

0,5-1 g as single dose. Repeated reception is possible in 4-8 hours. The maximum daily dose should not exceed 4 g.

At rheumatism, rhematoid polyarthritis, infectious and allergic myocarditis the adult drug is used it is long on 2-3 g (occasionally 4 g) in days. The maximum daily dose - 4 g.

For patients with the accompanying abnormal liver functions or kidneys it is necessary to reduce a dose of drug or to increase an interval between uses.

Features of use:

Use during pregnancy and feeding by a breast. Acetylsalicylic acid can be applied during pregnancy only in that case when other medicines are not effective. Salicylates can be applied at pregnancy only after ratio assessment risk/advantage.

During I and II trimesters of pregnancy it is not necessary to appoint the drugs containing acetylsalicylic acid, except cases of extreme need. If the drugs containing acetylsalicylic acid are applied by the women planning pregnancy and also during I and II trimesters of pregnancy, their doses have to be so low, and a course of treatment so short-term as far as it is possible. Use of salicylates in the I trimester of pregnancy during some retrospective epidemiological researches was associated with the increased risk of development of inborn defects (палатосхиз ("a wolf mouth"), heart diseases, гастрошизис). However at prolonged use of drug in the therapeutic doses exceeding 150 mg/days, this risk was low: as a result of the research conducted on 32000 couples "mother child" communication between use of drug of acetylsalicylic acid and increase in risk of inborn defects is not revealed.

According to preliminary estimates, at prolonged use drug of acetylsalicylic acid is not recommended to be accepted in the dose exceeding           150 mg/days.

In the III trimester of pregnancy reception of salicylates in high doses (more than 300 mg/days) can lead to a perenashivaniye of pregnancy and weakening of pains at the time of delivery, and also to cardiopulmonary toxicity (premature closing of ductus arteriosus) or a renal failure at a fruit. Use of acetylsalicylic acid in high doses shortly before childbirth can lead to intracranial bleedings, especially at premature children. Thus, in addition to extremely special cases caused by cardiological or obstetric medical indications, use of acetylsalicylic acid during the III trimester of pregnancy is contraindicated.

Salicylates and their metabolites get into breast milk in a small amount. As side reactions at babies after accidental use of drug were not observed, it is not required to interrupt breastfeeding, as a rule. At prolonged use of drug or use of acetylsalicylic acid in high doses it is necessary to resolve an issue of the breastfeeding termination.

Ability to influence speed of response at control of motor transport or work with other mechanisms. Information on influence of drug on ability to manage vehicles and to work with difficult mechanisms is absent.

Individual reaction of the patient to drug will not be found out yet, it is necessary to abstain from control of motor transport or work with other mechanisms as during treatment by acetylsalicylic acid such side reactions from a nervous system are possible as dizziness and a ring in ears, decrease in hearing.

Children. Drug is used to children 15 years are more senior. It is not necessary to use the drugs containing acetylsalicylic acid, to children with the acute respiratory viral infection (ARVI) which is followed or is not followed by fervescence. At some viral diseases, especially flu A, flu B and chicken pox, there is a risk of development of a syndrome of Ray which is very rare, but life-threatening disease demanding urgent medical intervention. The risk can be raised if acetylsalicylic acid is applied as the accompanying medicine, however relationship of cause and effect in this case is not proved. If the specified states are followed by long vomiting, it can be a sign of a syndrome of Ray.

Side effects:

Gastrointestinal frustration. Dyspepsia, pain in epigastric area and abdominal pain; in some cases – a digestive tract inflammation, digestive tract erosive cankers which can cause in isolated cases gastrointestinal bleedings and perforation with the corresponding laboratory and clinical manifestations.

Seldom – a tranzitorny liver failure with increase in level of transaminases of a liver.

System of blood. Owing to antiagregantny action on thrombocytes acetylsalicylic acid can increase risk of development of bleedings. Such bleedings as were observed: intraoperative hemorrhages, hematomas, bleedings from bodies of urinogenital system, nasal bleedings, odontorrhagias; seldom or very seldom - serious bleedings, such as gastrointestinal bleedings and brain hemorrhages (especially at patients with uncontrollable arterial hypertension and/or at simultaneous use of anti-hemostatics) which in isolated cases could threaten life potentially.

Bleedings can lead to acute and chronic posthemorrhagic anemia / an iron deficiency anemia (owing to so-called hidden microbleedings) with the corresponding laboratory manifestations and clinical symptoms, such as an adynamy, pallor of an integument, hypoperfusion.

Allergic reactions. At patients with individual hypersensitivity to salicylates development of allergic reactions, including such symptoms as rash, urticaria, hypostasis, an itch, rhinitis, a nose congestion is possible.

At patients with bronchial asthma increase in frequency of emergence of a bronchospasm, allergic reactions from insignificant to moderate degree which potentially affect skin, respiratory system, digestive tract and cardiovascular system is possible. Heavy reactions, including an acute anaphylaxis and not cardiogenic fluid lungs were very seldom observed.

Nervous system. Dizziness and a ring in ears were observed that can demonstrate overdose.

Interaction with other medicines:

Use of a methotrexate in doses of 15 mg/week and more increases hematologic toxicity of a methotrexate (decrease in renal clearance of a methotrexate by antiinflammatory agents and replacement by methotrexate salicylates from communication with proteins of a blood plasma).

Combinations which should be applied with care.

At use of a methotrexate in doses less than 15 mg/week increase hematologic toxicity of a methotrexate (decrease in renal clearance of a methotrexate by antiinflammatory agents and replacement by methotrexate salicylates from communication with proteins of a blood plasma).

Simultaneous use of an ibuprofen interferes with irreversible inhibition of thrombocytes acetylsalicylic acid. Treatment by an ibuprofen of the patients having risk of cardiovascular diseases can limit cardiotyre-tread effect of acetylsalicylic acid.

At simultaneous use of drugs of acetylsalicylic acid and anticoagulants the risk of development of bleeding increases.

At simultaneous use of high doses of salicylates with NPVS (thanks to the mutually strengthening effect) the risk of developing of ulcers and gastrointestinal bleedings increases.

Simultaneous use with uricosuric means, such as бензобромарон, пробенецид, reduces effect of removal of uric acid (thanks to the competition removal of uric acid renal tubules).

At simultaneous use with digoxin concentration of the last in a blood plasma increases owing to decrease in renal excretion.

At simultaneous use of high doses of acetylsalicylic acid and peroral antidiabetic drugs of group of derivatives of sulfanylurea or insulin the hypoglycemic effect of the last due to hypoglycemic effect of acetylsalicylic acid and replacement of the sulfanylurea connected with proteins of a blood plasma amplifies.

Diuretic means in a combination with high doses of acetylsalicylic acid reduce filtering of balls thanks to decrease in synthesis of prostaglandins in kidneys.

The system glucocorticosteroids (except for a hydrocortisone) applied to replacement therapy at Addison's disease during treatment reduce the level of salicylates in blood. At use with corticosteroids the risk of development of gastrointestinal bleedings increases.

APF inhibitors in a combination with high doses of acetylsalicylic acid lead to decrease in filtering in balls owing to inhibition of vazodilatatorny prostaglandins and to decrease in hypotensive effect.

Selective serotonin reuptake inhibitors: the risk of bleeding from upper parts of digestive tract because of a possibility of synergetic effect increases.

At simultaneous use with valproic acid acetylsalicylic acid forces out it from communication with proteins of a blood plasma, increasing toxicity of the last.

Alcohol can lead to injury of a mucous membrane of digestive tract and prolongs a bleeding time owing to a synergism of acetylsalicylic acid and alcohol.

Contraindications:

Hypersensitivity to acetylsalicylic acid, other salicylates or to any component of drug; the bronchial asthma in the anamnesis caused by reception of salicylates or other NPVS, deficit glyukozo-6-fosfatdegidrogenazy, acute gastrointestinal ulcers; hemorrhagic diathesis; the expressed renal failure; the expressed liver failure; the expressed heart failure; the combination with a methotrexate in a dosage of 15 mg/week or is more (see the section "Interaction with Other Medicines and Other Types of Interactions").

 

Appropriate security measures at use.

Acetylsalicylic acid is applied with care at:

- hypersensitivity to analgetichesky, anti-inflammatory, antirheumatic drugs, and also in the presence of an allergy to other substances;

- gastrointestinal ulcers in the anamnesis, including at a chronic or recurrent peptic ulcer or gastrointestinal bleedings in the anamnesis;

- simultaneous use of anticoagulants;

- disturbances of functions of kidneys and/or liver.

At patients with allergic complications, including with bronchial asthma, allergic rhinitis, a small tortoiseshell, a skin itch, hypostasis of a mucous membrane and polipozy a nose, and also at their combination to persistent infections of respiratory tracts and at patients with hypersensitivity to NPVP against the background of treatment with drugs of acetylsalicylic acid development of a bronchospasm or attack of bronchial asthma is possible.

At surgeries (including dental) use of the drugs containing acetylsalicylic acid can increase probability of emergence/strengthening of bleeding, caused by oppression of aggregation of thrombocytes for some time after use of acetylsalicylic acid.

At use of small doses of acetylsalicylic acid removal of uric acid can decrease. It can lead to developing of gout at patients with reduced removal of uric acid.

At prolonged use for identification of ulcerogenic action it is necessary to investigate periodically kcal on availability of blood, and also to do blood tests (1 time in 2 weeks). In 5-7 days prior to surgical intervention drug should be cancelled.

Overdose:

The overdose of salicylates is possible because of the chronic intoxication which resulted from long therapy (use more than 100 mg/kg/days longer can cause than 2 days toxic effects), and also because of acute intoxication which poses threat for life (overdose) and which reasons can be, for example, an accidental use by children or unexpected overdose.
 
Chronic poisoning with salicylates can have the hidden character as its signs are not specific. The moderate chronic intoxication caused by salicylates or a salitsilizm, meets, as a rule, only after repeated receptions of high doses.
 
Symptoms. Balance disturbance, dizziness, a ring in ears, deafness, the strengthened sweating, nausea and vomiting, a headache, confusion of consciousness. The specified symptoms can be controlled by a dose decline. The ring in ears can be noted at concentration of salicylates in a blood plasma higher than 150-300 mkg/ml. More serious side reactions meet at concentration of salicylates in a blood plasma  over 300 mkg/ml.
 
The expressed change of acid-base balance which can differ, depending on age and weight of intoxication testifies to acute intoxication. The most general indicator for children is the metabolic acidosis. Weight of a state cannot be defined only on the basis of concentration of salicylates in a blood plasma. Absorption of acetylsalicylic acid can be slowed down in connection with a delay of gastric release, formation of concrements in a stomach.
 
Treatment. Symptomatic. All applied measures have to be directed to acceleration of removal of drug and recovery of electrolytic and acid-base balance. Apply absorbent carbon, the forced alkaline diuresis. Depending on a condition of acid-base equilibrium and electrolytic balance carry out infusional administration of solutions of electrolytes. At serious poisonings the hemodialysis is shown.

Storage conditions:

Period of validity 4 years. Not to apply after the period of validity specified on packaging. To store in original packaging at a temperature up to 25 °C. To store in the place, unavailable to children.

Issue conditions:

Without recipe

Packaging:

On 10 tablets in the blister; on 10 tablets in a strip. On 10 tablets in the blister, on 2 blisters in a pack.