Analgin - instructions for use, dose, side effects, contraindications

Metamizole sodium is a derivative of pyrazolone, nonselectively blocks cyclooxygenase and reduces the formation of prostaglandins from arachidonic acid.Possesses anesthetizing, antipyretic, and also some spasmolytic (in respect of smooth muscles and bile ducts) action.

The action develops in 20-40 minutes and reaches a maximum after 2 hours.

With intravenous administration, the maximum effect develops after 20-40 minutes.

Pharmacokinetics:

After intravenous administration, the half-life for metamizole sodium is 14 minutes. The main metabolite 4N-methylaminoantipyrine. Othermetabolites 4N-aminoantipyrine, 4N-acetylaminoantipyrine and 4N-formylaminoantipyrine, the last two do not have pharmacological activity.

Metabolites 4N-Acetylaminoantipyrine (AAA) and 4N-formylaminoantipyrine (FAA) have no pharmacological activity.

All metabolites are characterized by non-linear pharmacokinetics. The clinical significance of this phenomenon is not known. In the short term, cumulation of metabolites does not play a big role.

Metamizole sodium penetrates the placenta. Metabolites metamizole penetrate into breast milk.

The connection with plasma proteins MAA is 58%, AA - 48%, FAA - 18% and AAA - 14%.

After a single oral intake, 85% of the dose is found in the urine as metabolites, of which 3 ± 1% - MAA, 6 ± 3% - AA, 26 ± 8% - AAA and 23 ± 4% - FAA.Renal clearance after a single dose of 1 g of metamizole sodium inside for MAA is 5 ± 2 ml / min, AA - 38 ± 13 ml / min, AAA - 61 ± 8 ml / min and FAA - 49 ± 5 ml / min. The corresponding half-lives from plasma for MAA are 2.7 ± 0.5 h, AA - 3.7 ± 1.3 h, AAA - 9.5 ± 1.5 h and FAA - 11.2 ± 1.5 h.

When high doses of sodium metamilose are administered through the kidneys, a metabolite, rubric acid, capable of staining urine in red can be released. Metamizol sodium penetrates the placenta. The association of the active metabolite with the blood plasma proteins is 50-60%. It is mainly excreted by the kidneys. Approximately 96% is excreted by the kidneys in the form of metabolites. In therapeutic doses penetrates into breast milk.

Elderly

In elderly patients AUC increases 2-3 times. In patients with cirrhosis of the liver, the half-lives of MAA and FAA with a single dose of the drug increase approximately 3-fold, while the half-lives of AA and AAA do not follow the same pattern. Such patients should avoid the use of high doses.

Impaired renal function

According to available data, with renal failure, the rate of excretion of some metabolites (AAA and FAA) decreases. Such patients should avoid the use of high doses.

Indications:

Severe acute or chronic pain syndrome with trauma and postoperative pain syndrome, with colic, with oncological diseases and other conditions, where other therapeutic measures are contraindicated.

Fever resistant to other methods of treatment.

Contraindications:

- Hypersensitivity to metamizol sodium and other pyrazolone derivatives, as well as to pyrazolidines, for example, phenylbutazone (including patients who undergone agranulocytosis due to the use of these drugs), or other components of the drug;

- Analgesic bronchial asthma or intolerance to analgesics (type of urticaria-angioneurotic edema), i.e. patients with bronchospasm or other forms of anaphylactoid reactions (eg urticaria, angioedema) in response to the use of salicylates, paracetamol or non-steroidal anti-inflammatory drugs such as diclofenac, ibuprofen, indomethacin or naproxen;

- violation of bone marrow hematopoiesis (for example, after cytostatic therapy) or diseases of the hematopoietic organs;

- hereditary deficiency of glucose-6-phosphate dehydrogenase (hemolysis);

- acute intermittent hepatic porphyria (risk of developing porphyria attack);

- acute renal or hepatic insufficiency;

- pregnancy and the period of breastfeeding;

- Infant age (up to 3 months or with a body weight of less than 5 kg);

- Infants at the age of 3 to 12 months (contraindication only for intravenous administration).

Carefully:

Arterial hypotension (systolic blood pressure below 100 mmHg), a decrease in the volume of circulating blood, instability of hemodynamics (myocardial infarction, multiple trauma, beginning shock), heart failure, high fever (increased risk of a sharp drop in blood pressure).

Diseases in which a significant reduction in blood pressure may have an increased risk (patients with severe coronary heart disease and stenosis of the cerebral arteries).

Chronic abuse of alcohol.

Bronchial asthma, especially in combination with concomitant polypoznym rhinosinusitis; chronic urticaria and other types of atopy (allergic diseases, in the development of which a significant role belongs to the hereditary predisposition to sensitization: pollinosis,allergic rhinitis, etc.) (increased risk of anaphylactic / anaphylactoid reactions).

Alcohol intolerance (reaction even to small amounts of certain alcoholic beverages with symptoms such as itching, lacrimation and severe reddening of the face) (increased risk of anaphylactic / anaphylactoid reactions).

Intolerance or hypersensitivity to dyes (eg, tartrazine) or to preservatives (eg benzoate) (increased risk of anaphylactic / anaphylactoid reactions).

Severe dysfunction of the liver and kidneys (recommended the use of low doses in connection with the possibility of slowing the excretion of metamizole sodium).

Pregnancy (second trimester).

Pregnancy and lactation:

Pregnancy

Metamedesol penetrates the placental barrier. Data on the use of sodium metamizole during pregnancy are limited. According to the results of preclinical studies, the teratogenic effect of metamizole sodium in rats and rabbits was not detected, and fetotoxicity was observed at high doses. Since there are no adequate data on use in humans, metamizol sodium should not be taken in the first trimester of pregnancy, in the second trimester of pregnancy metamizol sodium It can only be used if the expected benefit to the mother exceeds the potential risk to the fetus. Although metamizol sodium weakly inhibits the synthesis of prostaglandins, it is impossible to exclude the possibility of premature (intrauterine) closure of the arterial (Botallova) duct, as well as perinatal complications caused by a violation of platelet aggregation in the mother or newborn. therefore metamizol sodium contraindicated in the third trimester of pregnancy.

Lactation period

Metabolites metamizol sodium penetrate into breast milk, so when using the drug, and also within 48 hours after taking the last dose, it is necessary to stop breastfeeding.

Dosing and Administration:

Parenteral administration is indicated only if it can not be ingested.

Before the introduction it is recommended to heat up to body temperature.

Adults and adolescents 15 years and older: as a single dose, 1-2 ml of 50% (500 mg / ml) or 2-4 ml of 25% solution of metamizole sodium (intramuscular or intravenous) is recommended, the maximum daily dose can be up to 4-8 ml of 50% or 25% of the injection solution (no more than 2 g), divided into 2-3 doses.The maximum single dose may be 1 g (2 ml of a 50% solution or 4 ml of a 25% solution).

Children: metamizol sodium contraindicated under the age of 3 months or with a body weight of less than 5 kg.

Children metamizol sodium is prescribed in a dose of 50-100 mg per 10 kg of body weight (0.1-0.2 ml of a 50% solution or 0.2-0.4 ml of a 25% solution).

A single dose can be prescribed up to 2-3 times a day.

For children aged 3-12 months (body weight of the child 5-9 kg) the introduction is only intramuscular.

Intravenous administration should be slow (injection rate not more than 1 ml (500 mg metamizole sodium per minute)) in the supine position, while monitoring blood pressure, pulse and respiration rate to minimize the risk of lowering blood pressure.

At the first signs of the development of anaphylactic / anaphylactoid reactions, stop the drug.

Since there is a concern that the drop in arterial pressure of non-allergic genesis is dose-dependent, the amount of methamizole sodium solution greater than 2 ml (1 g) should be administered with extreme caution.

With too rapid administration of the drug, a critical drop in blood pressure and shock can occur.

Elderly patients need to use smaller dosages in connection with the possible decrease in excretion of metamizol metabolites from the body.

Patients in serious condition and with violation of creatinine clearance should use lower doses in connection with a decrease in the rate of excretion of metamizole sodium metabolites.

In patients with impaired hepatic or renal function, the rate of excretion of the drug is slowed, so it is necessary to avoid repeated use of the drug, long-term experience is absent.

With short-term therapy, dose adjustment is not required.

Duration of treatment

When used as an analgesic agent, the duration is 1-5 days. When used as an antipyretic agent - 1-3 days.

Side effects:

Undesirable reactions are classified as follows, according to the classification of the WHO (World Health Organization): very often (> 1/10), often (≥1 / 100 to <1/10), infrequently (≥1 / 1000 to <1/100) rarely (≥1 / 10000 to <1/1000), very rarely (up to <1/10000) and the frequency is unknown (it is impossible to estimate based on available data).

Heart Disease

Frequency unknown: the syndrome of Kounis (allergic coronary syndrome, manifested clinical and laboratory signs of angina caused by mediators of inflammation).

Immune system disorders

Rarely: anaphylactic or anaphylactoid reactions.

Rarely: analgesic bronchial asthma.

Frequency unknown: anaphylactic shock.

Metamizole sodium can cause anaphylactic or anaphylactoid reactions, which in very rare cases can be severe and life threatening. They can occur even if the drug was previously taken many times without any complications.

Such drug reactions can develop immediately or a few hours after taking metamizole sodium, usually within one hour.

In more mild cases, they manifest themselves as skin symptoms and symptoms from the mucous membranes (itching, burning, flushing, urticaria, edema), dyspnea or complaints from the gastrointestinal tract. In severe cases, these reactions go to generalized urticaria, severe angioedema, especially with involvement of the larynx, severe bronchospasm, cardiac rhythm disturbance,a sharp decrease in blood pressure (which is sometimes preceded by an increase in blood pressure) and the development of circulatory shock.

In persons with analgesic bronchial asthma syndrome with analgesic drugs intolerance, these reactions usually manifest as asthma attacks.

Disturbances from the skin and subcutaneous tissues:

Infrequently: fixed drug dermatitis.

Rarely: skin rash.

Frequency unknown: Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome).

On the part of the blood and lymphatic system:

Rarely: leukopenia

Rarely: agranulocytosis (including fatal cases), thrombocytopenia.

Frequency unknown: aplastic anemia, pancytopenia (including cases with fatal).

These reactions are inherently immunological. They can occur even if the drug was previously used many times without any complications.

Typical symptoms of agranulocytosis are lesions of the mucous membranes (oral and pharyngeal cavities, anorectal area, genital organs), sore throat, fever.However, with the use of antibiotics, these phenomena may be mild. Sometimes, but not always, there is a slight increase in lymph nodes or spleen. The rate of erythrocyte sedimentation is significantly increased, the granulocyte content is sharply reduced or not determined. As a rule, the parameters of hemoglobin, erythrocytes and platelets remain normal, but deviations may occur. Typical symptoms of thrombocytopenia are increased tendency to bleeding and the appearance of petechiae on the skin and mucous membranes.

If there is an unexpected deterioration in the general condition, the fever does not subside, or new or painful ulcers appear on the mucous membranes, especially in the mouth, nose or throat, the treatment tactics presuppose the immediate abolition of the drug without waiting for the results of laboratory tests.

With the development of pancytopenia, the drug should be discarded and the general blood test should be monitored before returning to normal (see "Special instructions").

Vascular disorders

Infrequently: isolated arterial hypotension.

After taking the drug, an isolated transient decrease in blood pressure is possible (possibly pharmacologically conditioned,and not accompanied by other manifestations of anaphylactic / anaphylactoid reactions).

Rarely: decrease in blood pressure is pronounced.

With fever, a dose-dependent sharp drop in blood pressure is also possible without other signs of a hypersensitivity reaction.

From the side of the kidneys and urinary tract:

Rarely: impaired renal function.

Frequency unknown: interstitial nephritis.

In very rare cases, patients with impaired renal function may have an acute impairment of renal function (acute renal failure), in some cases with oliguria, anuria, proteinuria.

General disorders

Infrequently: it is possible to stain the urine red due to the presence in the urine of the metabolite - rubanzonic acid.

Overdose:

Symptoms

In case of overdose, the following symptoms may appear: nausea, vomiting, abdominal pain, decreased kidney function / acute renal failure with oliguria (for example, due to the development of interstitial nephritis), rarer symptoms from the central nervous system (dizziness, drowsiness, tinnitus, delirium, impaired consciousness, coma,convulsions) and a sharp decrease in blood pressure (sometimes progressing to shock), as well as heart rhythm disturbances (tachycardia), hypothermia, dyspnea, acute agranulocytosis, hemorrhagic syndrome, respiratory muscle paralysis. After taking high doses, the excretion through the kidneys of a non-toxic metabolite (rubanzone acid) can cause red staining of urine.

Treatment: There is no specific antidote for metamizole sodium. If after taking the drug did not take more than 1-2 hours, you can induce vomiting, conduct a gastric lavage through the probe; appoint salt laxatives, Activated carbon. Overdose shows forced diuresis. The main metabolite (4-N-methylaminoantipyrine) can be excreted by hemodialysis, haemofiltration, hemoperfusion or filtration of blood plasma. With the development of convulsive syndrome - intravenous diazepam and high-speed barbiturates.

Interaction:

FROM cyclosporin

When used simultaneously with cyclosporine, there may be a decrease in its concentration in the blood, so when combined, monitoring of the concentration of cyclosporin in the blood is required.

With other non-narcotic analgesics

The simultaneous use of metamizole sodium with other non-narcotic analgesics can lead to a mutual enhancement of toxic effects.

With tricyclic antidepressants, oral contraceptives, allopurinol

Tricyclic antidepressants, oral contraceptives, allopurinol - disrupt the metabolism of metamizole sodium in the liver and increase its toxicity.

With barbiturates, phenylbutazone and other inducers of microsomal liver enzymes

Barbiturates, phenylbutazone and other inducers of microsomal liver enzymes weaken the action of metamizole sodium.

With sedatives and tranquilizers

Sedatives and tranquilizers increase the analgesic effect of metamizole sodium. Simultaneous use with chlorpromazine or other phenothiazine derivatives can lead to the development of severe hypothermia.

With drugs that are highly associated with plasma proteins (oral hypoglycemic agents, indirect anticoagulants, glucocorticosteroids and indomethacin)

Metamizole sodium, displacing from the connection with blood plasma proteins, oral hypoglycemic drugs, indirect anticoagulants, glucocorticosteroids and indomethacin, increases their activity.

With myelotoxic drugs

Myelotoxic drugs increase the manifestation of hematotoxicity of metamizole sodium.

With methotrexate

The simultaneous use of metamizole sodium with methotrexate may increase the hematotoxic effect of methotrexate, especially in elderly patients. Therefore, it is advisable to avoid their simultaneous application.

FROM thiamazole and sarcolysin

Thiamazole and sarcolysin increase the risk of developing leukopenia.

FROM radiopaque substances, colloidal blood substitutes and penicillin

Radiocontrast agents, colloidal blood substitutes and penicillin should not be used during treatment with metamizole sodium (an increased risk of anaphylactic / anaphylactoid reactions).

With codeine, propranolol, H blockers₂-gistaminovyh receptors

The effect of sodium metamizole increases codeine, propranolol, blockers H₂-gistaminovyh receptors.

FROM acetylsalicylic acid

With the simultaneous use of metamizole sodium and acetylsalicylic acid metamizol sodium can reduce the effect of acetylsalicylic acid on platelet aggregation. Therefore, this combination should be used with caution in the treatment of patients taking low doses of acetylsalicylic acid as an antiplatelet agent from buproprion.

Metamizole sodium can reduce the concentration of bupropion in the blood, which should be taken into account when they are used simultaneously.

Because of the high likelihood of pharmaceutical incompatibility, metamizole sodium should not be mixed with other drugs in the same syringe.

Special instructions:

In the treatment of patients receiving cytotoxic drugs, as well as children under 5 years of treatment with metamizole sodium should only be carried out under the supervision of a doctor.

Anaphylactic / anaphylactoid reactions

When choosing the method of drug administration, it should be taken into account that parenteral administration is associated with a higher risk of anaphylactic / anaphylactoid reactions. An increased risk of hypersensitivity reactions metamizol sodium can be caused by the following states:

- analgesic bronchial asthma, especially with concomitant polyposis rhinosinusitis;

- chronic urticaria;

- alcohol intolerance (hypersensitivity to alcohol) against which even with the intake of a small amount of some alcoholic beverages, patients experience sneezing, lacrimation, and severe reddening of the face. Alcohol intolerance may indicate a previously unidentified syndrome of aspirin asthma;

- intolerance or hypersensitivity to dyes (eg, tartrazine) or to preservatives (eg benzoate).

Before using metamizole sodium it is necessary to conduct a thorough questioning of the patient in order to find out anamnestic information.

If there is a risk of developing anaphylactic reactions, reception is only possible after a careful assessment of the relationship between the expected benefit and the possible risk of using the drug. In the case of sodium metamizole, these patients need strict medical supervision of their condition and need to have the means to provide them with emergency care in case of anaphylactic / anaphylactoid reactions.

In predisposed patients, anaphylactic shock can occur, so patients with asthma or atopy metamizol sodium should be administered with caution. Patients who have anaphylactoid reactions in response to metamizole sodium use are also at risk of developing them in response to other non-narcotic analgesics / NSAIDs.

Patients who have anaphylactic or other immuno-mediated reactions (eg agranulocytosis) in response to metamizole sodium use are also at risk of developing them for the use of other pyrazolones and pyrazolidines.

Severe skin reactions

With the use of metamizole sodium, life-threatening skin reactions, such as Stevens-Johnson syndrome (SSD) and toxic epidermal necrolysis (TEN), have been described. If there are symptoms of SS and TENS, including progressive skin rash, often with blisters or mucosal lesions, treatment with metamizole sodium should be discontinued immediately, and then not be performed in this category of patients. Patients should be aware of the symptoms of these diseases.They should carefully monitor skin reactions, especially during the first days of treatment.

Agranulocytosis

With prolonged use (more than 7 days), you need to monitor the picture of peripheral blood. Against the background of taking metamizole sodium, the development of agranulocytosis is possible. It occurs very rarely, lasts at least a week, does not depend on the dose, can be severe, threaten life and, in some cases, lead to death. In connection with this, in the detection of symptoms such as unmotivated rise in temperature, chills, sore throat, difficulty swallowing, stomatitis, erosive-ulcerative oral lesions, vaginitis or proctitis, a decrease in the number of neutrophils in the peripheral blood is less than 1500 / mm³ it is necessary to immediately consult a doctor and cancel the drug.

Pancytopenia

In case of development of pancytopenia, treatment should be stopped immediately, it is necessary to monitor the indicators of the developed blood test up to their normalization.

All patients should be aware that pathological changes in the blood may be accompanied by the appearance of symptoms such as general malaise, infection, persistent fever, hematoma formation,bleeding, pallor, against the background of metamizole sodium, which requires immediate treatment to the doctor.

Isolated hypotensive reactions

Metamizole sodium can cause isolated hypotensive reactions. These reactions can be dose-dependent. The risk of such reactions is also increased with: previous arterial hypotension, decreased circulating blood volume or dehydration, unstable hemodynamics or acute circulatory disturbance (eg, in patients with myocardial infarction or trauma), in patients with fever.

In this regard, these patients should be carried out detailed diagnostics and establish close monitoring. In order to reduce the risk of hypotensive reactions, preventive measures (stabilization of hemodynamics) may be required.

In patients in whom a reduction in blood pressure should be avoided at all costs (eg, in severe coronary heart disease or significant stenosis of the cerebral arteries), metamizol sodium It can only be used with careful monitoring of hemodynamic parameters.

Abdominal pain

It is inadmissible to use the drug to relieve acute pain in the abdomen (until finding out their cause).

Impaired liver and kidney function

In patients with impaired liver or kidney function, it is recommended that metamizole sodium should not be taken at high doses due to a decrease in the elimination rate of the drug. The drug contains sodium, which must be taken into account by individuals on a diet low in sodium.

Rules of drug administration

Intravenous administration should be carried out very slowly (no more than 1 ml per minute), so that at the first signs of anaphylactic / anaphylactoid reactions it would be possible to stop the administration, as well as to minimize the occurrence of individual hypotensive reactions. With intramuscular injection, a long needle should be used for intramuscular injection.

Effect on the ability to drive transp. cf. and fur:

Given the profile of adverse drug reactions, care should be taken when managing vehicles, mechanisms, and when carrying out work that requires a high concentration of attention and speed of psychomotor reactions.

Form release / dosage:

The solution for intravenous and intramuscular administration is 250 mg / ml and 500 mg / ml.

Packaging:

1 ml or 2 ml in ampoules of colorless neutral glass type I with a colored break ring or with a colored dot and a notch or without a kink ring, a colored dot and a notch. One, two or three color rings and / or a two-dimensional bar code, and / or alphanumeric coding or without additional color rings, a two-dimensional bar code, and alphanumeric coding can additionally be applied to the ampoules.

By 5 or 10 ampoules per contour cell packaging made of polyvinylchloride film and aluminum foil lacquer or film polymer or without foil and without film. Or 5 or 10 ampoules are placed in a pre-made form (tray) made of cardboard with cells for laying ampoules.

1 or 2 contour squares or cardboard trays along with the instruction for use and a scarifier or a knife with an ampoule, or without a scarifier and an ampoule knife are placed in a cardboard package.

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C. Do not freeze.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003966

Date of registration:16.11.2016

Expiration Date:16.11.2021

The owner of the registration certificate:ATOLL, LLC ATOLL, LLC Russia

Manufacturer: & nbsp

OZONE, LLC Russia

Representation: & nbspOZONE LLC OZONE LLC Russia

Information update date: & nbsp27.08.2017

Illustrated instructions

Instructions

Analgin (Analgin)