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 is 4N-methylaminoantipyrine (MAA). Other metabolites: 4N-aminoantipyrine (AA), 4N-acetylaminoantipyrine (AAA) and 4N-formylaminoantipirin (FAA), the last two do not have pharmacological activity.

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

Metamizole sodium penetrates the placenta. Metabolites of metamizole sodium 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 metamizole sodium are administered through the kidneys, metaboliturbuzone acid, capable of staining urine in red, can be released. 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 patients, patients with cirrhosis of the liver

In elderly patients, the AUC (the area under the concentration-time curve) rises 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.

Patients with 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 pyrazolones (phenazone, propifenazone) or to pyrazolidines (phenylbutazone, oxyphenbutazone), including, for example, indications of an anamnesis on the development of agranulocytosis with the administration of one of these drugs.

- Disturbances of bone marrow hematopoiesis (for example, after treatment with cytostatics) or diseases of the hemopoietic system.

- Instructions for anamnesis on bronchospasm or other anaphylactic reactions (eg urticaria, rhinitis, angioedema) with analgesics such as salicylates, paracetamol, diclofenac, ibuprofen, indomethacin, naproxen.

- Hereditary hemolytic anemia associated with deficiency of glucose-6-phosphate dehydrogenase (risk of hemolysis development).

Acute hepatic and / or renal failure.

- Acute intermittent hepatic porphyria (risk of developing porphyria attacks).

- Pregnancy.

- The period of breastfeeding.

- Newborns under the age of 3 months or with a body weight of less than 5 kg.

- Children aged 3 to 12 months (contraindication only for intravenous administration).

- Arterial hypotension, instability of hemodynamics (contraindication only for intravenous administration).

Carefully:

- Arterial hypotension (systolic blood pressure below 100 mm Hg), instability of hemodynamics (myocardial infarction, multiple trauma, beginning shock), decrease in the volume of circulating blood, beginning heart failure, high fever (fever to 39-41 ° C ) (increased risk of a sharp drop in blood pressure).

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

- 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).

- Alcoholism, prolonged alcohol abuse and alcohol intolerance (reactions to alcohol in the form of itching, lacrimation and severe reddening of the face) (increased risk of anaphylactic / anaphylactoid reactions).

- Intolerance to dyes (eg tartrazine) or preservatives (eg benzoates) (increased risk of anaphylactic / anaphylactoid reactions).

- Severe violations 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:

Application during pregnancy and during breastfeeding is contraindicated.

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 are no adequate data on use in humans, metamizol sodium it is contraindicated to apply in the first trimester of pregnancy. In the second trimester of pregnancy metamizol sodium 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.

Breastfeeding period

Metabolites of metamizole sodium penetrate into breast milk. If the drug is used during breastfeeding, breastfeeding should be discontinued for at least 48 hours.

Dosing and Administration:

Parenteral administration of the drug is indicated only if it can not be taken orally.

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

Adults and adolescents 15 years and older

Adults and adolescents 15 years and older receive the drug intramuscularly or intravenously 1-2 ml 0.5 g / ml solution 2-3 times a day, but not more than 2 grams per day. The maximum single dose is 1 g, the daily dose is 2 g.

Children and newborns

The drug should not be administered until the age of 3 months or with a body weight of less than 5 kg.

For children, the drug is administered at the rate of 0.1-0.2 ml of 0.5 g / ml solution for every 10 kg of the child's body weight 2-3 times a day. Children aged 3 to 12 months, the drug is administered only intramuscularly (body weight of the child from 5 to 9 kg), the course is not more than 3 days.

Doses greater than 1 g should be administered intravenously. Intravenous administration should be slow (at a rate of not more than 1 ml / min), in the patient's lying position, under the control of blood pressure, heart rate and respiration, so that at the first signs of anaphylactic / anaphylactoid reaction stop the drug administration, as well as for minimizing the risk of lowering blood pressure. Since a possible hypotensive effect is dose-dependent, the drug in doses greater than 2 ml (1 g) should be administered with extreme caution.

With too rapid administration of the drug, a very sharp drop in blood pressure and shock can be observed. If necessary, carry out anti-shock therapy.

Elderly patients

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

Severe general condition and impaired creatinine clearance

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.

Renal or hepatic impairment

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

Duration of treatment for pain syndrome is 1-5 days, with fever syndrome - 1-3 days.

Side effects:

Side effects are classified according to the recommendations of the World Health Organization as follows: very often (≥ 10%); often (≥ 1%, <10%); infrequently (≥ 0.1%, <1%); rarely (≥ 0.01%, <0.1%); very rarely (<0.01%); the frequency is unknown (according to available data it is impossible to estimate the incidence of side effects).

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 or 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 used many times without any complications.

Such drug reactions can develop during the injection of metamizole sodium or a few hours after its administration, but usually they are observed within one hour after the administration of the drug.

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 arrhythmia, 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

Infrequent: fixed drug dermatitis.

Rarely: skin rash.

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

Violations of the blood and lymphatic system

Rarely: leukopenia.

Very rarely: agranulocytosis (including fatal cases), thrombocytopenia. The frequency is unknown: aplastic anemia, pancytopenia (including fatal cases).

These reactions are immunological in nature. They can occur even if the drug was previously used many times without any complications. Typical symptoms are agranulocytosis lesions of the mucous membranes (oral cavity and pharynx, the anorectal area and genitals), 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, fever does not subside, or new or painful ulcers appear on the mucous membranes, especially in the mouth, nose or throat, it is necessary to immediately cancel the drug without waiting for the results of laboratory tests.

With the development of pancytopenia, the drug should be discontinued and the general blood test should be monitored until the indicators return to normal (see section "Special instructions").

Vascular disorders

Infrequent: isolated arterial hypotension.

After the administration of 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: a pronounced decrease in blood pressure.

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, possibly a sharp deterioration in kidney function (acute renal failure), in some cases with oliguria, anuria, proteinuria.

General disorders

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

Overdose:

SymptomsNausea, vomiting, abdominal pain, decreased renal function / acute renal failure with oliguria (e.g., due to the development of interstitial nephritis), more seldom - the symptoms from the central nervous system (dizziness, somnolence, tinnitus, delirium, impaired consciousness, coma, convulsions) and a sharp decrease in blood pressure (sometimes progressing to shock), as well as cardiac arrhythmia (tachycardia), hypothermia, dyspnea, acute agranulocytosis, hemorrhagic syndrome, acute liver failure, paralysis of the respiratory muscle activation.

Upon receiving high doses of excretion through the kidney nontoxic metabolite (rubazonovoy acid) may cause red coloration of urine.

Treatment: symptomatic.

There is no specific antidote for metamizole sodium.

In the conditions of a medical institution - conducting forced diuresis, hemodialysis, hemofiltration, hemoperfusion or plasma filtration.

With the development of convulsive syndrome - intravenous diazepam and high-speed barbiturates.

Interaction:

With cyclosporine

Metamizole sodium can reduce the concentration of cyclosporine in the blood serum, so when combined, the concentrations of cyclosporin should be monitored.

With other jaaricotic 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 enzymes of the liver

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. With the simultaneous use of metamizole sodium and chlorpromazine can develop severe hypothermia.

With drugs that have a high association with plasma proteins

Metamizole sodium, displacing from the connection with plasma proteins, oral hypoglycemic agents, indirect anticoagulants, glucocorticosteroids and indomethacin, enhances their action.

With myelotoxic drugs

Myelotoxic drugs increase the manifestation of hematotoxicity of metamizole sodium.

With methotrexate

The addition of metamizole sodium to methotrexate treatment may increase the hematotoxic effect of methotrexate, especially in elderly patients. Therefore, this combination should be avoided.

With thiamazole and sarcolysin

Thiamazole and sarcolysin increase the risk of developing leukopenia.

With codeine, H blockers₂-gistaminovyh receptors and propranolol

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

With radiocontrast 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

When combined 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 for cardioprotection (prevention of thrombosis).

With bupropion

Metamizole sodium can reduce the concentration of bupropion in the blood, which should be taken into account when concomitantly using metamizole sodium and bupropion.

Special instructions:

Treatment with metamizole sodium patients receiving cytotoxic drugs, and children under 5 years 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 use is associated with a higher risk of anaphylactic / anaphylactoid reactions.

An increased risk of hypersensitivity reactions metamizol sodium stipulate the following states:

- complete or incomplete combination of bronchial asthma, recurrent nasal polyposis and paranasal sinuses and intolerance to acetylsalicylic acid or other non-steroidal anti-inflammatory drugs (including history);

- chronic urticaria;

- Alcohol intolerance (hypersensitivity to alcohol), against which even with the intake of a small amount of some alcoholic drinks, 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 (for example, to tartrazine) or to preservatives (for example, benzoates).

Before using metamizole sodium it is necessary to conduct a thorough questioning of the patient.If the risk of developing an anaphylactoid reaction is detected, admission may be possible only after determining the risk / benefit ratio.

In the case of metamizole sodium in patients with an increased risk of hypersensitivity reactions, strict medical control of their condition and the availability of funds to provide them with emergency care in case of anaphylactic / anaphylactoid reactions develop.

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

With prolonged use, it is necessary to monitor the picture of peripheral blood. At any time against the background of metamizole sodium treatment may develop agranulocytosis. It occurs very rarely, lasts at least a week, does not depend on the dose, can be severe, threaten life and even lead to death.

In this regard, if symptoms appear that may be related to neutropenia (fever, chills, sore throat, difficulty swallowing, stomatitis, erosive ulceration of the oral cavity, vaginitis or proctitis, a decrease in the number of neutrophils in the peripheral blood is less than 1500 / mm³), it is necessary to stop treatment with the drug and consult a doctor.

Pancytopenia

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

All patients should be aware that when symptoms of abnormal blood changes (eg, general malaise, infections, persistent fever, formation of hematomas, bleeding, pallor) appear against the background of metamizole sodium intake, seek medical help immediately.

Hypotensive reactions

The administration of metamizole sodium can induce individual hypotensive reactions. These reactions may depend on the dose of the drug and are more likely to occur after parenteral administration. To avoid the development of severe hypotensive reactions, the following recommendations should be adhered to:

- intravenous administration of the drug should be slow;

- patients with existing hypotension, a decrease in the volume of circulating blood, dehydration, instability of hemodynamics or with an initial stage of circulatory insufficiency require normalization of hemodynamics;

Care should be taken when treating patients with high body temperature.

In these patients, the possibility of using the drug should be carefully evaluated. When you enter the drug, you need close medical supervision. To reduce the risk of hypotensive reactions, it may be necessary to carry out preventive measures (stabilization of hemodynamics).

Metamizole sodium should be used only with close monitoring of the hemodynamics of patients who should avoid reducing blood pressure, for example, patients with severe coronary heart disease or stenosis of blood vessels that supply blood to the brain.

Acute 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 to avoid the use of metamizole sodium in high doses because of a decrease in the rate of excretion of the drug.

Rules of drug administration

Intravenous administration of metamizole sodium should be performed very slowly (not more than 1 ml per minute), so that at the first signs of anaphylactic / anaphylactoid reactions the injection could be stopped, and also to minimize the 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:Care should be taken during the treatment of drivers of vehicles and persons engaged in potentially hazardous activities requiring quick physical and mental reactions.

Form release / dosage:Solution for intravenous and intramuscular injection 0.5 g / ml.

Packaging:

In ampoules of 2 ml.

10 ampoules with instructions for use, ampoule scapegrator in a pack or carton box.

When packaging ampoules that have a break ring or a point for dissection, the ampoule scapegrator is not inserted.

5 ampoules in a cassette outline package. 2 cassette contour packs with instructions for use in a pack of cardboard.

Storage conditions:

In the dark place at a temperature of 15 to 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years. Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:P N001942 / 01

Date of registration:09.12.2011 / 27.07.2017

Expiration Date:Unlimited

The owner of the registration certificate:MICROGEN FGUP Scientific and Production Association MICROGEN FGUP Scientific and Production Association Russia

Manufacturer: & nbsp

MICROGEN FGUP NGO Russia

Representation: & nbspMICROGEN FGUP Scientific and Production Association MICROGEN FGUP Scientific and Production Association Russia

Information update date: & nbsp26.08.2017

Illustrated instructions

Instructions

Analgin (Analgin)