Aspargit

General characteristics. Structure:

Active ingredients: 350 mg of L-arginine of a hydrochloride, 50 mg of acetylsalicylic acid.

Excipients: calcium stearate, methyl cellulose, citric acid моно­гидрат.

Structure of the capsule: gelatin, glycerin, the water purified titanium E 171 dioxide, sodium lauryl sulfate.

Pharmacological properties:

Pharmacodynamics. Antiagregantny, angioprotektorny, cardiotyre-tread means. Cardiotyre-tread and anti-ischemic properties of Aspargit are implemented due to improvement of paracrine function of endothelial cells owing to the increased release in them of nitrogen oxide which deficit arises at heart ischemia reperfusion. Essential value also probably has improvement by Aspargit of regulatory influence of an endothelium on a functional condition of sokratitelny elements of a myocardium. Due to presence of acetylsalicylic acid at a low dosage (50 mg) Aspargit possesses also antiagregantny and anti-thrombogenic action.

Atsetilsalitsipovy acid: Acetylsalicylic acid suppresses aggregation of thrombocytes by A2 thromboxane synthesis blocking. The mechanism of its action consists in an irreversible inactivation of enzyme of cyclooxygenase (TsOG-1). The specified inhibiting effect is especially expressed for thrombocytes as they are not capable to resynthesis of the specified enzyme. Recognize also that acetylsalicylic acid renders also other inhibiting effects on thrombocytes. Thanks to the specified effects it is applied at many vascular diseases. Acetylsalicylic acid concerns to group of nonsteroid anti-inflammatory leyokarstvenny drugs (NPVS) with analgetic, febrifugal and protivovospaliyotelny properties. Orally in doses of 0,3 g and 1 g drug is used for pain relief and at the states which are followed by fever of easy degree such as cold and flu, for decrease in temperature and weakening of a joint pain and muscles.

L-arginine: L-arginine has anti-atherogenous properties, can be at the expense of the role in a kacheyostvo of the predecessor of nitrogen oxide (NO). NO is made by all body tissues and plays very important role in cardiovascular system, immune system and a nervous system. NO is formed of L-arginine by means of enzyme NO синтетазы (NOS), and the vliyoyaniye of NO is generally mediated by tsGMF. NO activates enzyme guanylate cyclase, koyotory catalyzes synthesis of tsGMF from GTF. tsGMF turns into guanylic acid by means of tsGMF-phosphodiesterase enzyme. NOS is gemsoderzhashchy enzyme, with some sequence similar to cytochrome R-450-reduktazu. There are several NOS isoforms, two of which are constitutive, and one of which is indutsibelny immunological irritants. Constitutive NOS are in a vascular endothelium (eNOS, are present at a head and spinal cord) and a peripheral nervous system (nNOS). The NOS forms induced by immunologicheyosky or inflammatory incentives are known as iNOS. iNOS can be constitutive in some fabrics, such as a pulmonary epithelium. All NO синтетазы ispolzuyotsya by NADPH (никотинамидадениндинуклеотидфосфат) and oxygen (O2) as kosubstrata, also as FAD cofactors (флавинадениндинуклеотид), FMN (флавинмононуклеотид), tetrahydrobiopterine and gems. It is interesting that ascorbic acid appears for a poveniye of NOS of activity by increase in intracellular tetrahydrobiopterines. eNOS and nNOS synthesize N0 in response to increase in concentration of calcium ions or in certain cases in response to calcium - independent irritants. The researches in vitro show that for formation of NOS, L-arginine is necessary in micromolar znayocheniye. Concentration of L-arginine in endothelial cells, and also in other cells, and in plasma is in the range of millimoly. It means what in physiological usloyoviya of NOS is sated with this amount of L-arginine. In other words, L-arginine does not buyodt the limiting factor reducing the speed of formation of enzyme. Nevertheless, the researches in vivo showed that under certain conditions, for example, the hypercholesterolemia, additional amount of L-arginine can raise an endothelial and dependent vazodilatation and synthesis NO.

Pharmacokinetics. Acetylsalicylic acid: After intake acetylsalicylic acid is quickly and completely soaked up from a zheluyodochno-intestinal path. 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 min., salicylates - 20-120 min. according to. Acetilsalicylic and salicylic acids completely contact proteins of a blood plasma and are quickly distributed in an organism. Salicylic acid gets through a platsenyota, and also gets to breast milk. The kinetics of removal of salicylic acid depends on a dose as metabolism is limited to activity of enzymes of a liver. The period of a poluyovyvedeniye depends on a dose and increases of 2-3 o'clock when using low doses up to 15 chayos at use of high doses. Salicylic acid and its metabolites are removed from an orgayonizm preferential by kidneys.

L-arginine: Absorption: It is soaked up from a gleam of a small bowel in enterocytes. Absorption is effective and happens by the active transport mechanism.

Metabolism: Some metabolism of L-arginine happens in enterocytes. Nemetabolizirovanny L-arginine in enterocytes is included into portal circulation from where it is transported in a liver where again some part of amino acids is metabolized.

Indications to use:

Antiagregantny therapy and increase in tolerance to an exercise stress at patients with stable stenocardia, prevention of loss of efficiency of nitroglycerine; a proyofilaktika of an ischemic stroke at persons with the increased risk, for example, at dinamicheyosky disturbance of cerebral circulation; prevention of repeated strokes at bolyyony, already having an ischemic stroke in the anamnesis; prevention of a thromboembolism after surgeries on coronary or peripheral blood vessels and druyogy similar interventions (for example, aortocoronary shunting, a coronary anyogioplastika, arteriovenous shunting at the patients who are on a hemodialysis).

Route of administration and doses:

Aspargit's capsules should be swallowed entirely, without chewing, together with a small amount of water (1/2 glasses), whenever possible after food.

Duration of antiagregantny therapy by Aspargit depends on specific clinical conditions.

Antiagregantny therapy and increase in tolerance to an exercise stress at patients with stable stenocardia: on 1 capsule 1-3 times a day:

Prevention of loss of efficiency of nitroglycerine: on 2 capsules 3-4 times a day;

Prevention of a brain stroke in the presence of prodromal symptoms (passing ischemia), prevention of repeated strokes: on 1 capsule 3 times a day or on 3 kapsuyola of 1 times a day.

Prevention of a thromboembolism after transplantation of the shunt; prevention of a tromboemboyoliya at patients with the arteriovenous shunt for a hemodialysis, prevention of a tromboemboyoliya after angioplasty (transdermal transluminal coronary angioplasty): on 1-3 capsules 1-2 times a day.

Features of use:

Use for children. Safety of use of acetylsalicylic acid: use of drug without existence of special indications, such as a syndrome or a disease of Kawasaki, prevention of a thrombogenesis after kardioyologichesky operations and prevention of a myocardial infarction at children with high risk is contraindicated to children up to 16 years. It is not necessary to use the drugs containing acetylsalicylic acid, to children with the acute respiratory viral infection (ARVI) which is followed or does not soprovozhyodatsya by fervescence.

Safety of use of L-arginine: L-arginine is safe when using orally at premature children in the corresponding doses. At use in high doses L-arginine is potentially dangerous: doses which are too high can cause serious side effects, including death in children.

Use during pregnancy and in the period of a lactation. Safety of use of L-arginine: at the correct short-term use during pregnancy L-arginine is safe. There are no sufficient data about safety of long-term use of L-arginine during pregnancy and during breastfeeding. Pregnant and koryomyashchy women are recommended to apply L-arginine short courses.

Safety of use of acetylsalicylic acid: drug can be used during pregnancy only in that case when other medicines are inefficient.

Use of salicylates in the I trimester of pregnancy in some retrospective epidemiological researches was associated with the increased risk of development of inborn poroyok (палатосхиз ("a wolf mouth"), heart diseases). However at prolonged use of a preparayot in therapeutic doses, prevsh1ayushchikh 150 mg/days, this risk was low: as a result of the research conducted on 32 000 couples "mother - the child", communication between a primeyoneniye of acetylsalicylic acid and increase in amount of inborn defects is not revealed. Salicylates can be applied in I and II trimesters of pregnancy only after sootyonosheniye assessment risk/advantage. According to preliminary estimates, at prolonged use of acetylsalicylic acid it is desirable not to accept it 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) at children. Use of acetylsalicylic acid in high doses shortly before childbirth can priyovest to intracranial bleedings, especially at premature children. Thus, except extremely special cases caused by cardiological or obstetric medical indications with use of special monitoring, use of atseyotilsalitsilovy acid during the last trimester of pregnancy is contraindicated.

Salicylates and their metabolites get into breast milk in a small amount.

Precautionary measures. The cautions connected with reception of acetylsalicylic acid. Drug is used with care at:

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

- Digestive tract ulcers, including chronic and recurrent ulcer bolezyon or gastrointestinal bleedings in the anamnesis;

- Simultaneous use of anticoagulants;

- Disturbances of functions of kidneys and/or liver.

At prolonged use of acetylsalicylic acid before reception of an ibuprofen the patient has to consult with the doctor.

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 in combination with persistent infections of respiratory tracts and at patients with a giyoperchuvstvitelnost to NPVP against the background of treatment by acetylsalicylic acid perhaps razyovity a bronchospasm or an attack of bronchial asthma.

At surgeries (including dental) use of drugs, soyoderzhashchy acetylsalicylic acid, can increase probability a bleeding emergence / usileyoniya.

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

At some viral diseases, especially flu A, flu B and chicken pox, sushcheyostvut risk of development of a syndrome of Ray which is very rare, but life-threatening, demanding urgent medical intervention. The risk can be increased if atseyotilsalitsilovy acid is applied as the accompanying medicine, however relationship of cause and effect in this case is not proved. If the specified states soproyovozhdatsya by long vomiting, it can be a sign of a syndrome of Ray.

The cautions connected with reception of L-arginine. Herpes: there is fear that L-arginine can weight the course of herpes - there is a number of proofs that L-arginine is necessary for replication of a virus of herpes.

There is fear that L-arginine can increase risk of death after a cordial priyostup, especially at elderly people, with recently postponed cordial pristuyop it is recommended to patients not to accept L-arginine.

Surgery: L-arginine can influence arterial pressure. There is fear that it can interfere with control of arterial pressure in time and after operation. Neobyokhodimo to stop reception of L-arginine, at least, in 2 weeks prior to the planned operation.

Influence on ability to control of motor transport and other potentially opasyony mechanisms. Because of a possibility of development of side reactions from a nervous system drug should be taken with caution.

Side effects:

The side effects caused by reception of acetylsalicylic acid: Digestive tract: dyspepsia, pain in epigastric area and an abdominal pain, in otyodelny cases - a digestive tract inflammation, digestive tract erosive cankers which can cause in some cases gastrointestinal hemorrhages and perforation with the corresponding laboratory indicators and clinical manifestations.

Owing to antiagregantny action on thrombocytes acetylsalicylic acid can increase risk of development of bleedings. Such bleedings as intraoperative hemorrhages, hematomas, bleedings from bodies of urinogenital system, nasal kroyovotecheniye, odontorrhagias were observed, it is rare or very rare - serious bleedings, such as GIT hemorrhages, cerebral hemorrhages (especially at patients with uncontrollable hypertensia and/or at simultaneous use of antigemostatichny means) which in isolated cases could threaten life potentially.

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

At patients with individual povsh1ennoy sensitivity to salicylates of perhaps razyovity skin of allergic reactions, including such symptoms as rash, urticaria, hypostasis, an itch. At patients with bronchial asthma increase in frequency of emergence of a bronchospasm is possible; allergic reactions from insignificant to moderate degree which potentsialyyono affect skin, a respiratory path, digestive tract and cardiovascular system. Heavy reactions, including an acute anaphylaxis were very seldom observed.

Seldom - a tranzitorny liver failure with increase in level of transaminases of a liver. Dizziness and a ring in ears were observed that can demonstrate overdose.

The side effects caused by reception of L-arginine: Allergic reactions: L-arginine can cause allergic reaction or hypostasis of respiratory tracts. At patients with the allergological anamnesis to use L-arginine with care. L-arginine can reduce arterial pressure: it can be dangerous if the patient has a low blood pressure or recently postponed heart attack.

Interaction with other medicines:

Interactions of acetylsalicylic acid:

Contraindications for interaction. Use of a methotrexate in doses of 15 mg/week and raises a hematologic toksichyonost of a methotrexate more (decrease in renal clearance of a methotrexate by antiinflammatory agents and replacement by methotrexate salicylates from communication with proteins of plasma).

Combinations which should be applied with care. At use of a methotrexate in doses less than 15 mg/week increase a hematologic tokyosichnost of a methotrexate (decrease in renal clearance of a methotrexate by protivovospalitelyyony agents and replacement by methotrexate salicylates from communication with proteins of plasma).

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

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

At simultaneous use of high doses of salicylates with NPVP (thanks to mutually exclusive effect) the risk of developing of ulcers and gastrointestinal kroyovotecheniye increases.

Simultaneous use with uricosuric means, such as бензобромарон, пробенецид, removal of uric acid decreases (thanks to the competition of 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 from group of derivatives of sulphonylurea or an inyosulin the hypoglycemic effect of the last due to hypoglycemic effect of acetylsalicylic acid and replacement of the sulphonylurea connected with blood plasma belyoka amplifies.

Diuretics in a combination with high doses of acetylsalicylic acid reduce filtering of balls, thanks to decrease in synthesis of prostaglandins in kidneys. System glucocorticosteroids (excepting a hydrocortisone) which are applied to replacement therapy at Addison's disease, during treatment by corticosteroids reduce the level of salicylates in blood and increase risk of overdose after the end of treatment.

At use with GKS the risk of development of gastrointestinal bleeding increases. Inhibitors of an angiotensin-converting enzyme (APF) in a combination with high doyoza of acetylsalicylic acid cause decrease in filtering in balls vsledyostvy inhibition of vazodilatatorny effect of prostaglandins and decrease in anti-hypertensive effect.

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

Alcohol promotes injury of a mucous membrane of a GIT and prolongs a bleeding time owing to a synergism of acetylsalicylic acid and alcohol.

Interactions of L-arginine. Contraindications for interaction. Anti-hypertensive means. L-arginine reduces the ABP. Reception of L-arginine together with anti-hypertensive means increases risk of development of an orthostatic collapse.

Combinations which should be applied with care. Drugs which increase inflow of blood to heart (nitrates). L-arginine uvelichivayot blood inflow. Reception of L-arginine with drugs which increase inflow of blood to heart can increase risk of developing of dizziness.

Moderate interaction. Sildenafil (Viagra). Sildenafil (Viagra) can lower blood pressure. L-arginine can also lower blood pressure. Sildenafit reception (Viagra) and can sovyomestno lead L-arginine to a severe lowering of arterial pressure. Low arterial pressure can become the reason of dizziness and other side effects.

Contraindications:

- Hypersensitivity to acetylsalicylic acid, other salicylates or to a lyuboyom to a drug component;

- The chronic asthma caused by use of salicylates or NPVP in the anamnesis;

- Acute round 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. "Interaction with other medicines and other types of interactions");

- The postponed myocardial infarction;

- Children's and teenage age up to 16 years.

Overdose:

Overdose of acetylsalicylic acid: the overdose of salicylates is possible owing to the chronic intoxication which arose because of long therapy (use can result more than 2 days more than 100 mg/kg/days in toxic effects), and also owing to acute intoxication which poses threat for life (overdose) and which reasons can be, for example, an accidental priyomeneniye children or unexpected overdose.

Chronic poisoning with salicylates can have the hidden character as signs and symptoms its nonspecific. The moderate chronic intoxication caused by salitsilayota or a salitsilizm meets, as a rule, only after repeated receptions of high doses.

Symptoms: dizziness, a ring in ears, deafness, the strengthened sweating, nausea and vomiting, a headache, confusion of consciousness. The specified symptoms can be controlled a dose decline. The ring in ears can meet at concentration of salicylates in a blood plasma more than 150-300 mkg/ml. Serious side reactions meet at concentration of salicylates in a blood plasma above 300mkg/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 sostoyoyaniye cannot be estimated 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 or in case of a priyeyom of drug in the form of the tablets covered with a kishechnorastvorimy cover.

Treatment: treatment of intoxication caused by overdose of acetylsalicylic acid is defined by severity, clinical symptoms and is provided with standartyony methods which apply at poisoning. All applied measures have to be directed to acceleration of removal of drug and recovery of electrolytic and acid-base balance. Use reception of absorbent carbon, the forced alkaline diuresis. Depending on a condition of acid-base equilibrium and elekyotrolitny balance carry out infusional administration of solutions of electrolytes. At seryezyony poisonings the hemodialysis is shown.

Overdose of L-arginine: oral administration of L-arginine in a dose to 15 g, as a rule, is well transferred to day. The most frequent side reactions of higher doses from 15 to 30 grams a day are nausea, an abdominal pain and diarrhea. Some of patients can test these symptoms in lower doses.

Storage conditions:

In the place protected from moisture and light at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity 2 years. Not to use after the termination of a period of validity.

Issue conditions:

According to the recipe

Packaging:

On 10 capsules in a blister strip packaging. On three blister strip packagings together with the application instruction place in a pack from a cardboard bandbox.