Lysine Acetylsalicylate

Pharmacological properties

Acelisinum is an injectable form of acetylsalicylic acid and has its characteristic properties, and also increases its bioavailability and analgesic effect. It has an analgesic, anti-inflammatory, antipyretic and antiplatelet effect.

The drug inhibits COX, as a result of which the synthesis of prostaglandins and the formation of thromboxane A2 in platelets are inhibited. The ability of platelets and red blood cells to adhere and adhere (adhesion) to the blood vessel endothelium decreases. Reducing the surface tension of erythrocyte membranes, the drug facilitates their deformation during passage through the capillaries and improves blood flow.

Pharmacokinetics The drug binds to plasma proteins by 80–90%. Penetrates into most body tissues, including synovial, cerebrospinal, peritoneal fluids. It undergoes hydrolysis in the blood, forming acetylsalicylic acid and lysine. In the liver, acetylsalicylic acid is converted to salicylic acid. T_½ acetylsalicylic acid is 15–20 min; salicylic acid and its active metabolites are from 3–6 hours (low doses) to 15–30 hours (high doses). It is excreted mainly by the kidneys in unchanged form (60%) and in the form of metabolites.

Indications

Pain syndrome of various origins (headache and toothache, earache, postoperative pain, myalgia, neuralgia, arthralgia, with rheumatic diseases, colicky pain, with rheumatic diseases); feverish conditions; thrombophlebitis of superficial veins; prevention and treatment of postoperative thrombosis and embolism.

Application

Before starting therapy, it is necessary to exclude the presence of a patient hypersensitivity to the drug Acelisinum by making a skin test.

Use as directed and under the supervision of a physician.

Acelisin is administered in / m (deep) and / in. For i / m administration, the contents of the vial are dissolved immediately before use: 1 g (1 vial) in 5 ml of water for injection, shaking until the powder is completely dissolved.

For the prevention of thrombosis, the drug is administered in / m (deep) in 0.5–3 ml of a solution once a day or every other day. The course of treatment is up to 5 injections, after which, if necessary, you can proceed to the intake of acetylsalicylic acid. A single dose and frequency of repeated injections of the drug are determined by the dynamics of the data of a laboratory examination of hemostasis after the first injection of Acelisin.

With the on / in the introduction of Acelisin for the prevention of thrombosis, a slow infusion of the drug is preferable. Before use, 1 g (1 vial) is dissolved in 5 ml of water for injection, shaking until the powder is completely dissolved, the prepared solution is injected into 150-200 ml of 5% dextrose solution or 0.9% sodium chloride solution at a rate 1 ml / min.

For adult patients with moderate pain, fever, rheumatic diseases, neuritis, a single injection of 1 g of Acelisin is recommended. With severe pain, colic-like pain, a single dose can be increased to 2 g. With repeated use of Acelisin, its daily dose should not exceed 10 g.

For children, the daily dose of Acelisin is 0.01-0.025 g / kg body weight. This dose should be divided into 2-3 injections. Injection solution must be prepared ex tempore.

The course of treatment is 3-10 days.

Contraindications

Hypersensitivity to acetylsalicylic acid, other salicylates or to any component of the drug.

AD caused by taking salicylates or substances with a similar effect, especially a history of NSAIDs.

Acute gastrointestinal ulcers.

Hemorrhagic diathesis.

Severe renal failure.

Severe liver failure.

Severe heart failure.

Combination with methotrexate at a dose of 15 mg / week or higher.

The combination of acetylsalicylic acid in anti-inflammatory / antipyretic / analgesic doses with oral anticoagulants in patients with a history of gastroduodenal ulcer.

Side effects

When using the drug Acelisinum are possible:

from the digestive system: erosive and ulcerative lesions of the gastrointestinal tract, which may result in bleeding, perforation, dyspepsia, heartburn, abdominal pain, nausea, vomiting, diarrhea, esophagitis, transient liver failure;

on the part of blood and blood formation: very rarely thrombocytopenia, posthemorrhagic iron deficiency anemia can occur;

from the immune system: allergic reactions, including skin rashes, itching, urticaria, bronchospasm, exacerbation of AD, angioedema, anaphylaxis, including anaphylactic shock;

from the respiratory system: nasal congestion, rhinitis, pulmonary edema;

on the part of the hearing organ: reversible disorders - tinnitus, hearing loss;

from the central and peripheral nervous system: headache, dizziness;

others: rarely - acute renal failure, reversible impaired renal and hepatic function, possibly - the occurrence of hepatotoxicity, Raynauds syndrome, reactions at the injection site, including pain.

Due to the antiplatelet effect on platelets, acetylsalicylic acid can be associated with a risk of bleeding, an increase in bleeding time. Hemorrhages such as perioperative hemorrhages, hematomas, urogenital bleeding, nosebleeds, bleeding from the gums, purpura, heavy bleeding such as cerebral hemorrhages (especially in patients with uncontrolled hypertension and / or with the simultaneous use of antihemostatic agents) were observed, which were observed in some cases, they can potentially be life threatening.

Hemorrhages can lead to acute and chronic posthemorrhagic anemia / iron deficiency anemia (due to the so-called latent microbleeding) with corresponding laboratory manifestations and clinical symptoms, such as asthenia, pale skin, hypoperfusion.

In patients with severe forms of glucose-6-phosphate dehydrogenase deficiency, hemolysis or hemolytic anemia was observed.

special instructions

Acetylsalicylic acid is used with caution in the following situations:

• hypersensitivity to analgesic, anti-inflammatory, anti-rheumatic drugs, as well as in the presence of allergies to other substances;
• gastrointestinal ulcers, including a chronic and recurrent gastric and duodenal ulcer or a history of gastrointestinal bleeding;
• simultaneous use of anticoagulants;
• impaired renal function or impaired cardiovascular circulation (for example, vascular pathology of the kidneys, congestive heart failure, hypovolemia, extensive surgery, sepsis, or severe bleeding), since acetylsalicylic acid can also increase the risk of impaired renal function and the development of acute renal failure;
• severe glucose-6-phosphate dehydrogenase deficiency, since acetylsalicylic acid can cause hemolysis or hemolytic anemia, especially if there are factors that may increase the risk of hemolysis, such as high doses of the drug, fever, or an acute infection process;
• impaired liver function.

In the case of the use of Acelisin, the patient should consult a doctor before taking ibuprofen as an anesthetic.

Acetylsalicylic acid can cause the development of bronchospasm or an attack of AD, or other hypersensitivity reactions. Risk factors include a history of AD, hay fever, nasal polyps or chronic respiratory infections, allergic reactions (eg, skin reactions, itching, hives) to other substances.

Due to the ability of acetylsalicylic acid to suppress platelet aggregation, which persists for several days after administration, the use of drugs containing acetylsalicylic acid can increase the likelihood / increase of bleeding during surgery (including minor surgeries such as tooth extraction).

When acetylsalicylic acid is used in low doses, uric acid excretion may be reduced. This can lead to an attack of gout in susceptible patients.

Regular use of analgesics can lead to persistent kidney damage (with a risk of renal failure).

Use with caution in patients with a history of gastritis, with metrorrhagia and / or menorrhagia.

During treatment, gastrointestinal bleeding, ulcers / perforations can occur at any time, without the presence of any condition in the patients history. The relative risk is increased in the elderly, in patients with low body weight, in patients receiving anticoagulants or platelet aggregation inhibitors. In case of gastrointestinal bleeding, treatment should be stopped immediately.

When using high anti-inflammatory doses in rheumatology, it is necessary to control the possible signs of an overdose. In case of hearing loss, tinnitus or dizziness, treatment should be reviewed.

Use during pregnancy and lactation. Suppression of prostaglandin synthesis may adversely affect pregnancy and / or fetal / intrauterine development. There is evidence of a risk of miscarriage and fetal malformations after the use of prostaglandin synthesis inhibitors in early pregnancy. The risk increases depending on the dose increase and the duration of therapy. According to available data, the relationship between the intake of acetylsalicylic acid and an increased risk of miscarriage has not been confirmed.

Data on the occurrence of malformations are not consistent, but the increased risk of gastroschisis cannot be excluded with the use of acetylsalicylic acid.

In the I and II trimester of pregnancy, preparations containing acetylsalicylic acid should not be prescribed without obvious clinical need. For women who are likely to become pregnant, or in the I and II trimester of pregnancy, the dose of drugs containing acetylsalicylic acid should be as low as possible, and the duration of treatment should be shorter.

During the third trimester of pregnancy, all prostaglandin synthesis inhibitors can affect the fetus as follows:

• cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension);
• impaired renal function with possible subsequent development of renal failure with oligohydramnios.

On a woman and a fetus at the end of pregnancy, as follows:

• possibly an increase in bleeding time, an antiplatelet effect that can occur even after very low doses;
• inhibition of uterine contractions, which can lead to a delay or increase in the duration of labor.

With this in mind, acetylsalicylic acid is contraindicated in the III trimester of pregnancy.

Acetylsalicylic acid passes into breast milk, so the use of the drug during lactation is not recommended.

Children. The injection form of acetylsalicylic acid is not used in children.

The ability to influence the reaction rate when driving vehicles or working with other mechanisms. There was no effect on the ability to drive and operate machinery.

Interactions

Contraindications for simultaneous use

The use of acetylsalicylic acid and methotrexate in doses of 15 mg / week and above increases the hematological toxicity of methotrexate (decrease in renal clearance of methotrexate with anti-inflammatory agents and displacement of methotrexate with salicylates due to plasma proteins).

The use of acetylsalicylic acid with oral anticoagulants in anti-inflammatory / antipyretic / analgesic doses in patients with a history of gastroduodenal ulcers: increased risk of bleeding.

Not recommended combinations

The use of acetylsalicylic acid with oral anticoagulants in anti-inflammatory / antipyretic / analgesic doses to patients in the absence of a history of gastroduodenal ulcers: increased risk of bleeding.

The use of acetylsalicylic acid with oral anticoagulants in antiplatelet doses in patients with a history of gastroduodenal ulcers: increased risk of bleeding.

Simultaneous use with low molecular weight heparin, unfractionated heparin in elderly patients (over 65 years old), regardless of the dose of heparin and anti-inflammatory / antipyretic / analgesic doses of acetylsalicylic acid.

Use with clopidogrel (if there are no approved indications for the use of this combination in patients with acute coronary syndrome).

Use with ticlopidine, with uricosuric drugs.

Use with corticosteroids (except replacement therapy) for anti-inflammatory doses of acetylsalicylic acid.

The use of pemetrexed in patients with mild to moderate renal failure (creatinine clearance 45–80 ml / min) increases the risk of pemetrexed toxicity.

Combinations to be used with caution

With the use of acetylsalicylic acid and methotrexate at doses of 15 mg / week, the hematological toxicity of methotrexate increases (a decrease in the renal clearance of methotrexate with anti-inflammatory agents and the displacement of methotrexate with salicylates due to plasma proteins).

The use of acetylsalicylic acid with ibuprofen prevents the irreversible inhibition of platelets by acetylsalicylic acid. Ibuprofen treatment of patients at risk for cardiovascular disease may limit the cardioprotective effect of acetylsalicylic acid.

The use of acetylsalicylic acid and anticoagulants, thrombolytics / other platelet aggregation / hemostasis inhibitors increases the risk of bleeding.

The use of salicylates in high doses with NSAIDs (due to complementary effects) increases the risk of gastrointestinal ulcers and gastrointestinal bleeding.

Use with selective serotonin reuptake inhibitors (including citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) increases the risk of gastrointestinal bleeding due to a possible synergistic effect.

Use with digoxin: the concentration of the latter in blood plasma increases as a result of a decrease in renal excretion.

The use of high doses of acetylsalicylic acid and antidiabetic drugs from the group of sulfonylurea derivatives enhances the hypoglycemic effect of the latter due to the displacement of sulfonylurea associated with blood plasma proteins, acetylsalicylic acid.

Diuretics in combination with high doses of acetylsalicylic acid reduce glomerular filtration due to a decrease in the synthesis of prostaglandins in the kidneys.

Systemic corticosteroids (with the exception of hydrocortisone, which is used for replacement therapy for Addisons disease) reduce the level of salicylates in the blood. Use with corticosteroids increases the risk of gastrointestinal bleeding.

ACE inhibitors in combination with high doses of acetylsalicylic acid cause a decrease in glomerular filtration due to inhibition of the vasodilator effect of prostaglandins and also a decrease in the antihypertensive effect.

Application with valproic acid: acetylsalicylic acid displaces it from its connection with blood plasma proteins, increasing the toxicity of the latter.

Alcohol contributes to damage to the mucous membrane of the gastrointestinal tract and prolongs bleeding time due to the synergism of acetylsalicylic acid and alcohol.

Use of diuretics, ACE inhibitors, angiotensin II receptor antagonists with anti-inflammatory / antipyretic / analgesic doses of acetylsalicylic acid: risk of acute renal failure. At the beginning of treatment, you need to make sure that the patient does not have dehydration and constantly monitor kidney function.

Use with clopidogrel (in accordance with the approved indications for the use of this combination in patients with acute coronary syndrome). If necessary, simultaneous use requires clinical monitoring of the patient.

Use with pemetrexed in patients with normal renal function.

Use with low molecular weight heparin, unfractionated heparin in patients under 65 years of age.

Use with thrombolytics.

Use with oral anticoagulants in antiplatelet doses.

Use with other NSAIDs in antiplatelet doses.

Use with corticosteroids (except replacement therapy) and analgesic / antipyretic doses.

Overdose

An overdose of salicylates is possible due to chronic intoxication resulting from prolonged therapy (the use of 100 mg / kg / day for more than 2 days can cause toxic effects), as well as acute intoxication, which poses a threat to life (overdose), which may be caused by e.g. accidental use by children or unforeseen overdose.

Chronic salicylate poisoning can be hidden, since its signs are nonspecific. Moderate chronic intoxication caused by salicylates, or salicylism, occurs, as a rule, only after repeated doses of high doses.

Symptoms Imbalance, dizziness, ringing in the ears, deafness, excessive sweating, nausea and vomiting, headache, confusion. These symptoms are dose dependent. Tinnitus can occur when the concentration of salicylates in the blood plasma is 150-300 μg / ml. Serious adverse reactions develop when the concentration of salicylates in blood plasma is 300 μg / ml. In severe poisoning: fever, ketosis, respiratory alkalosis, metabolic acidosis, coma, cardiovascular collapse, respiratory failure, severe hypoglycemia, severe hypokalemia.

Acute intoxication is evidenced by a pronounced change in the acid-base balance, which may differ depending on the age and severity of intoxication. The severity of the condition cannot be determined only on the basis of the concentration of salicylates in blood plasma.

Treatment. Treatment of intoxication caused by an overdose of acetylsalicylic acid is determined by the severity, clinical symptoms and is provided by standard methods that are used in case of poisoning. All measures taken should be aimed at accelerating the removal of the drug and the restoration of electrolyte and acid-base balance. Apply activated carbon, forced alkaline diuresis. Depending on the state of acid-base balance and electrolyte balance, infusion administration of electrolyte solutions is carried out. In severe poisoning, hemodialysis is indicated.

Storage conditions

In the original packaging at a temperature of 2-8 ° C. storage of the finished solution is allowed for no more than 30 minutes.