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

Active substance:
Metamizol sodium	500 mg
Excipients:
Hydrochloric acid solution of 0.5 M or sodium hydroxide solution of 0.5 M	to pH 6.0-7.5
Water for injections	up to 1 ml

Description:

Transparent colorless or slightly colored liquid.

Pharmacotherapeutic group:Analgesic non-narcotic remedy

ATX: & nbsp

N.02.B.B.02 Metamizol sodium

Pharmacodynamics:

Metamizole sodium is a derivative of pyrazolone. It has analgesic, antipyretic and weak anti-inflammatory action, the mechanism of which is associated with oppression of the synthesis of prostaglandins.By the mechanism of action is practically no different from other non-steroidal anti-inflammatory drugs.

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 administration, it is rapidly absorbed and enters the liver, where it undergoes hydrolysis with the formation of an active metabolite, unchanged metamizol sodium is detected in the blood in small amounts only after intravenous administration. After intravenous administration, the elimination half-life for metamizole is 14 minutes. Approximately 96% is excreted in the urine in the form of metabolites. The association of the active metabolite with the blood plasma proteins is 50-60%. It is mainly excreted by the kidneys.

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.Relationship with plasma proteins 4N-methylaminoantipyrine (MAA) is 58%, 4N-aminoantipyrine (AA) - 48%, FAA - 18% and AAA - 14%.

After a single oral administration 85% dose is found in the urine in the form of 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.

Elderly

In elderly patients, the area under the concentration-time curve (AUC) increases by 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, colic, 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 (hives - angioedema), i.e. patients with bronchospasm or other forms of anaphylactoid reactions (eg urticaria, angioedema) in response to the use of salicylates, paracetamol, non-steroidal anti-inflammatory drugs such as diclofenac, ibuprofen, indomethacin or naproxen.

Disturbance 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).

Breast children aged 3 to 12 months (contraindication only for intravenous administration).

Carefully:

Arterial hypotension (systolic blood pressure below 100 mm Hg), 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 polyposis rhinosinusitis; chronic urticaria and other 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).

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 and lactation:

Pregnancy

Metamizole sodium 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 is no adequate data on human use, 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 can not exclude the possibility of premature (intrauterine) closure of the arterial (Botallova) duct, as well as perinatal complications,the violation of aggregation of platelets 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:

Adults and adolescents 15 years and older

The drug is administered intramuscularly or intravenously (with severe pain) 1-2 ml 500 mg / ml solution 2-3 times a day, but not more than 2 g per day. The maximum single dose is 1 g, the daily dose is 2 g.

Children

Metamizole sodium can not be used until 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 500 mg / ml solution).

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

Before administration, the solution is recommended to be heated to body temperature.

With too rapid administration of the drug, a critical drop in blood pressure and shock can occur. Intravenous administration should be slow (the rate of administration is not more than 1 ml (500 mg of metamizole per minute)) in the supine position, while monitoring blood pressure, pulse and respiration rate.

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 prolonged (more than a week) application of the drug, control of the picture of peripheral blood and the functional state of the liver is necessary.

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, <1/10); infrequently (≥ 1/1000, <1/100); rarely (≥ 1/10000, <1/1000); very rarely (<1/10000); frequency is unknown (can not be estimated from available data).

Heart Disease

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

Immune system disorders

Rarely: anaphylactic / anaphylactoid reactions.

Very rarely: analgesic bronchial asthma.

The frequency is 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) or in the form of 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 arrhythmia, a sharp decrease in blood pressure (which is sometimes preceded by an increase in blood pressure), and with 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

Infrequent: fixed drug dermatitis.

Rarely: skin rash.

The frequency is unknown: Stevens-Johnson syndrome, Lyell syndrome (toxic epidermal necrolysis).

Violations of the blood and lymphatic system

Rarely: leukopenia.

Very rarely: agranulocytosis, including fatal cases and thrombocytopenia.

The frequency is unknown: aplastic anemia, pancytopenia, including fatal cases.

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

Typical symptoms of agranulocytosis are mucosal lesions (oral cavity and pharynx, anorectal area and 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 the lymph nodes or spleen. The sedimentation rate of erythrocytes is significantly increased, the content of granulocytes is sharply reduced or they are 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,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

Infrequent: 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); in rare cases, the reduction in blood pressure can be very pronounced. With fever, a dose-dependent sharp drop in blood pressure is also possible without other signs of a hypersensitivity reaction.

Disorders from the kidneys and urinary tract

Very rarely: renal dysfunction.

Frequency unknown: interstitial nephritis.

In very rare cases in patients with impaired renal function, acute renal impairmentfunction (acute renal failure), in some cases with oliguria, anuria, or proteinuria.

General disorders

Infrequent: it is possible to stain urine red due to the presence of the metabolite rubazonic acid in the urine.

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), more rarely 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 sin rum, paralysis of respiratory muscles. After taking high doses, excretion through the kidneys A nontoxic metabolite (rubric acid) can cause red staining of urine.

Treatment: a specific antidote is not known. When overdose is shown forced diuresis. The main metabolite (4N-methylaminoantipyrine) can be excreted by hemodialysis, haemofiltration, hemoperfusion or filtration of blood plasma.With the development of convulsive syndrome - intravenous diazepam and high-speed barbirurates.

Interaction:

With cyclosporine

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.

FROM barbiturates, phenylbutazone and other inducers of microsomal liver enzymes

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

FROM 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 have a high bond with the protein (oral hypoglycemic agents, indirect anticoagulants, glucocorticosteroids and indomethacin)

Metamizole sodium, displacing from the connection with plasma proteins, hypoglycemic agents for oral administration, indirect anticoagulants, glucocorticosteroid agents 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.

With thiamazole and sarcolysin

Thiamazole and sarcolysin increase the risk of developing leukopenia.

FROM codeine, H blockers₂-gistaminovyh receptors and propranolol

Codeine, blockers H₂-gistaminovyh receptors and propranolol enhance the effects of metamizole sodium.

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 acetylsalicylic acid (ASA)

When combined metamizol sodium can reduce the effect of ASA on platelet aggregation. Therefore, this combination should be used with caution in the treatment of patients taking ASA as an antiplatelet agent.

FROM bupropion

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

Special instructions:

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

Anaphylactic / anaphylactoid reactions

An increased risk of hypersensitivity reactions metamizol sodium causes the following conditions: analgesic bronchial asthma or intolerance to analgesics; bronchial asthma,especially with concomitant polyposis rhinosinusitis; chronic urticaria; alcohol intolerance (hypersensitivity to alcohol) against which even with a small amount of 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 reveal anamnestic information.

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.

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. When symptoms of SSD or TENS (such as a progressive skin rash, often with blisters or mucosal lesions) appear, treatment with methamizole should be stopped immediately, and should not be re-started. Patients should be aware of the symptoms of these diseases. They should carefully monitor skin reactions, especially during the first weeks of treatment.

Agranulocytosis / pancytopenia

With prolonged use, it is necessary 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 even lead to the death of the patient. In this regard, if symptoms of fever, chills, sore throat, swallowing, stomatitis, erosive-ulcerative lesions of the oral cavity, vaginitis or proctitis are detected, the amount of neutrophils in the peripheral blood is reduced to less than 1500 in mm³ it is necessary to stop taking the drug and consult a doctor.

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 when symptoms of abnormal blood changes (eg, general malaise, infections, persistent fever, formation of hematomas, bleeding, pallor) occur with metamizole sodium, medical attention should be sought immediately.

Isolated hypotensive reactions

Metamizole sodium can cause hypotensive reactions (see also the "Side effect" section). 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 and kidney function, it is recommended to avoid metamizol sodium in high doses.

Excipients

Since the drug contains sodium, this should be taken into account for people on a diet low in sodium.

If there is no effect within 3 days, stop taking the drug and consult a doctor.

Rules of drug administration

Intravenous administration of metamizole sodium should be carried out very slowly (no more than 1 ml per minute), so that at the first signs of anaphylactic / anaphylactoid reactions the injection could be stopped, and also in order to minimize risk of individual hypotensive reactions.

For intramuscular injection, a needle should be used for intramuscular injection.

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

Given the profile of the side effects of the drug, be careful when driving and mechanisms, as well as when performing tasks that require increased attention and psychomotor speed reactions.

Form release / dosage:

Solution for intravenous and intramuscular injection 500 mg / ml.

Packaging:

In 2 ml ampoules of a colorless or colored glass.

5 or 10 vials in blisters of PVC or polietilenterefgalatnoy film with the plastic film or lacquered aluminum foil or a polymer film without an aluminum foil and lacquer or in the form of cardboard with cells for stacking ampoules.

1 the contour cellular packaging made of cardboard or form with 10 ampoules or blisters 2 or shapes from a cardboard of 5 ampoules together with instructions for use and a lancet ampulnam or without a pack of cardboard.

Storage conditions:

Store at a temperature not exceeding 30 ° C.

Keep out of the reach of children.

Shelf life:

3 of the year.

Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LP-003777

Date of registration:10.08.2016 / 03.07.2017

Expiration Date:10.08.2021

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

Manufacturer: & nbsp

GROTEKS, LLC Russia

Representation: & nbspGROTEKS, LLCGROTEKS, LLC

Information update date: & nbsp27.08.2017

Illustrated instructions

Instructions

Analgin (Analgin)