Analgin solution for IV and IM administration 500 mg/ml

Pharmacokinetics

Metabolized to form the main metabolite 4N-methylaminoantipyrine (MAA) and other metabolites - 4N-aminoantipyrine (AA), 4N-acetylaminoantipyrine (AAA) and 4N-formylaminoantipyrine (FAA).

Metabolites AAA and PAA do not have pharmacological activity. All metabolites have nonlinear pharmacokinetics; with short-term use, the accumulation of metabolites does not play a big role. Plasma protein binding is 58% for MAA, 48% for AA, 18% for FAA, and 14% for AAA.

Metamizole sodium crosses the placenta. Metamizole sodium metabolites pass into breast milk. Approximately 96% is excreted by the kidneys in the form of metabolites. After intravenous administration, the half-life of metamizole sodium is 14 minutes.

When high doses of metamizole sodium are administered, the kidneys may excrete a metabolite, rubazonic acid, which can turn urine red.

Elderly

In elderly patients, the area under the concentration-time curve increases by 2-3 times.

Liver dysfunction

In patients with liver cirrhosis, the half-life of MAA and FAA with a single dose of the drug increases approximately 3 times, the half-life of AA and AAA does not change. In such patients, high doses should be avoided.

Renal dysfunction

In renal failure, the rate of elimination of some metabolites (AAA and FAA) is reduced. In such patients, high doses should be avoided.

Contraindications

- hypersensitivity to pyrazolone derivatives (propyphenazone, phenazone or phenylbutazone);

- bronchial asthma induced by taking acetylsalicylic acid, salicylates or other non-steroidal anti-inflammatory drugs (NSAIDs);

— bronchial obstruction, rhinitis, urticaria, provoked by taking acetylsalicylic acid or other NSAIDs (including a history);

— condition after coronary artery bypass grafting;

- inhibition of hematopoiesis (agranulocytosis, cytostatic or infectious neutropenia);

- acute renal or liver failure;

- acute intermittent hepatic porphyria;

- confirmed hyperkalemia;

- erosive and ulcerative changes in the mucous membrane of the stomach and duodenum, active gastrointestinal bleeding, inflammatory bowel diseases;

- anemia, leukopenia;

- hereditary hemolytic anemia associated with deficiency of glucose-6-phosphate dehydrogenase;

— pregnancy (I and III trimester), breastfeeding period;

— infancy (up to 3 months with body weight less than 5 kg);

- for intravenous administration - children up to 12 months (body weight up to 9 kg).

Carefully

Arterial hypotension (systolic blood pressure (BP) below 100 mm Hg); decrease in circulating blood volume (CBV); hemodynamic instability (myocardial infarction, multiple trauma, incipient shock); incipient heart failure; high fever (increased risk of a sharp decrease in blood pressure).

Diseases in which a significant decrease in blood pressure may be of increased danger (severe coronary heart disease, stenosis of cerebral arteries).

Chronic alcohol abuse.

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

Alcohol intolerance (reaction to even small amounts of certain alcoholic beverages in the form of itching, watery eyes and severe redness of the face) (increased risk of developing anaphylactic/anaphylactoid reactions).

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

Severe impairment of liver and kidney function (the use of low doses is recommended due to the possibility of slowing the rate of excretion of metamizole sodium).

Pregnancy (II trimester).

Use during pregnancy and breastfeeding

Pregnancy

Metamizole sodium penetrates the placental barrier. Data on the use of metamizole sodium during pregnancy are limited. Since there are no adequate data on use in humans, metamizole sodium should not be used in the first trimester of pregnancy; in the second trimester of pregnancy, the drug can be used if the expected benefit to the mother outweighs the potential risk to the fetus. Despite the fact that metamizole sodium weakly inhibits the synthesis of prostaglandins, the possibility of premature (intrauterine) closure of the ductus arteriosus, as well as perinatal complications caused by impaired platelet aggregation in the mother or newborn cannot be excluded. In this regard, metamizole sodium is contraindicated in the third trimester of pregnancy.

Breastfeeding period

Metamizole sodium metabolites pass into breast milk, therefore, when using the drug, as well as within 48 hours after taking the last dose, breastfeeding should be stopped.

special instructions

In patients receiving cytotoxic drugs, as well as in children under 5 years of age, the use of metamizole sodium should only be carried out under medical supervision.

Anaphylactic/anaphylactoid reactions

When choosing a 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 developing hypersensitivity reactions to metamizole sodium may be due to the following conditions: - analgesic bronchial asthma, especially with concomitant polypous rhinosinusitis; - chronic urticaria; - alcohol intolerance (increased sensitivity to alcohol), against the background of which, even when taking a small amount of certain alcoholic beverages, patients experience sneezing, lacrimation and severe redness of the face.

Alcohol intolerance may indicate previously unidentified aspirin asthma syndrome; - intolerance or hypersensitivity to dyes (for example, tartrazine) or preservatives (for example, benzoate).

Before using metamizole sodium, it is necessary to conduct a thorough survey of the patient in order to determine medical history. If the risk of developing anaphylactic reactions is identified, use is possible only after a thorough assessment of the ratio of the expected benefit to the possible risk of using metamizole sodium.

In the case of using metamizole sodium in such patients, it is necessary to ensure the availability of funds to provide them with emergency assistance in the event of the development of anaphylactic/anaphylactoid reactions and strict medical monitoring of their condition.

Metamizole sodium should be used with caution in patients with asthma or atopy.

Patients who experience anaphylactoid reactions when using metamizole sodium are also at risk of developing them when using other non-narcotic analgesics/NSAIDs.

Patients who experience anaphylactic or other immune-mediated reactions (eg, agranulocytosis) in response to the use of metamizole sodium are also at risk of developing them when using other pyrazolones and pyrazolidines.

Severe skin reactions

Life-threatening skin reactions, such as Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), have been described with the use of metamizole sodium.

If symptoms of SJS and TEN appear, including a progressive skin rash, often with blisters or lesions of the mucous membrane, treatment with metamizole sodium should be stopped immediately and should not be continued in this category of patients. Patients should be aware of the symptoms of these skin reactions.

They should be carefully monitored for skin reactions, especially during the first days of treatment.

Agranulocytosis

With long-term use (more than 7 days), it is necessary to monitor the peripheral blood picture. With the use of metamizole sodium, agranulocytosis may develop. It occurs very rarely, lasts at least a week, is not dose-dependent, can be severe, life-threatening and, in some cases, fatal. Therefore, if you identify symptoms such as an unmotivated rise in temperature, chills, sore throat, difficulty swallowing, stomatitis, erosive and ulcerative lesions of the oral cavity, vaginitis or proctitis, a decrease in the number of neutrophils in the peripheral blood less than 1500/mm3, you must immediately contact See your doctor and stop taking the drug.

Pancytopenia

If pancytopenia develops, use of the drug should be stopped immediately, and complete blood count indicators should also be monitored until they return to normal. All patients should be aware that pathological changes in the blood during the use of metamizole sodium may be accompanied by the appearance of symptoms such as general malaise, infections, persistent fever, hematoma formation, bleeding, pale skin, which requires immediate consultation with a doctor.

Isolated hypotensive reactions

Metamizole sodium may cause isolated hypotensive reactions, which may be dose-dependent. The risk of reactions is increased with previous arterial hypotension, decreased blood volume or dehydration, unstable hemodynamics or acute circulatory disorders (for example, in patients with myocardial infarction or trauma), in patients with fever. Such patients should be assessed in detail and closely monitored.

In order to reduce the risk of developing hypotensive reactions, preventive measures (hemodynamic stabilization) may be required. In patients in whom blood pressure reduction should be avoided at all costs (for example, with severe coronary artery disease or significant cerebral artery stenosis), the drug can be used with careful monitoring of hemodynamic parameters.

Abdominal pain

It is unacceptable to use metamizole sodium to relieve acute abdominal pain (until the cause is determined).

Liver and kidney dysfunction

In patients with impaired liver or kidney function, it is recommended to avoid the use of metamizole sodium in high doses due to a decrease in its elimination rate. The drug contains sodium, which should be taken into account by people on a low sodium diet.

Rules for administering the drug

Intravenous administration should be carried out very slowly (no more than 1 ml per minute) in order to quickly stop the drug at the first signs of anaphylactic/anaphylactoid reactions and/or to minimize the occurrence of isolated hypotensive reactions.

For intramuscular administration, it is necessary to use a long intramuscular needle.

Impact on the ability to drive vehicles and machinery

Considering the profile of adverse reactions when using metamizole sodium, caution should be exercised when driving vehicles, machinery, as well as when performing work that requires increased concentration and speed of psychomotor reactions.

Analgin solution for intravenous and intramuscular injection. 500 mg/ml in amp. 2 ml in pack No. 10

Name

Analgin solution for IV and IM injection. 500 mgml in amp. 2 ml in pack No. 10

Compound

One ampoule (2 ml) contains: active ingredient - metamizole sodium - 1000 mg; excipient - water for injection.

Description

Transparent yellowish liquid.

Pharmacotherapeutic group

Other analgesics and antipyretics. Pyrazolones. ATX code: N02BB02.

Pharmacological properties

Pharmacodynamics Analgin is a pyrazolone derivative and has analgesic, antipyretic and mild antispasmodic effects. The mechanism of action is not fully understood. Some research results indicate that analgin and its main metabolite (4-N-methylaminoantipyrine) probably have both a central and peripheral mechanism of action. Pharmacokinetics After intramuscular administration, it is quickly absorbed into the blood. In the liver, it undergoes hydrolysis with the formation of the active metabolite 4-methylaminoantipyrine (4-MAA) and is demethylated to the second active metabolite - 4-aminoantipyrine (4-AA), and is also biotransformed to inactive metabolites - 4-formylaminoantipyrine (4-FAA) and 4- acetylaminoantipyrine (4-AcAA). Unchanged analgin is found in the blood in small quantities only after intravenous administration. In the blood, it reversibly binds to plasma proteins (4-MAA by 58%, 4-AA by 48%). The effective concentration of the sum of analgin metabolites is 10 mcg/ml. The toxic effect occurs when the concentration of metabolites exceeds 20 mcg/ml. With repeated administration of the drug, its pharmacokinetics do not change. There is no accumulation of the drug. The total systemic clearance of the active metabolites 4-MAA and 4-AA is (182.9 ± 15.1) ml/min and (55.2 ± 6.4) ml/min, respectively. Their half-life (T?) is 2.5-3.0 hours and 6-8 hours, respectively. Excreted in the form of metabolites in the urine. In patients with impaired liver and kidney function, if the recommended dosage regimen is followed, accumulation of the unchanged active substance is not observed. Changes in pharmacokinetics in children over 3 years of age, elderly people over 70 years of age, as well as during pregnancy have not been established.

Indications for use

• acute pain after injury or surgery;
• renal and hepatic colic (in combination with antispasmodics);
• pain caused by a tumor;
• other acute and chronic intense pain, when other therapeutic measures are impossible;
• fever, if other measures are ineffective.

Parenteral administration of the drug is used only in cases where enteral administration is not possible.

Contraindications

• hypersensitivity to the active substance or other pyrazolone or pyrazolidine derivatives (including patients who developed agranulocytosis after using these drugs);
• in patients with a history of aspirin asthma or analgesic intolerance syndrome (urticaria, angioedema), that is, in patients with bronchospasm or other forms of anaphylactoid reactions to salicylates, paracetamol or other non-narcotic analgesics such as diclofenac, ibuprofen, indomethacin or naproxen;
• suppression of bone marrow function (for example, after treatment with cytostatics) or diseases of the hematopoietic system;
• genetic deficiency of glucose-6-phosphate dehydrogenase (hemolysis);
• acute intermittent hepatic porphyria (risk of developing an attack of porphyria);
• arterial hypotension and/or unstable hemodynamics;
• last trimester of pregnancy;
• breastfeeding period;
• newborns and children under 3 months of age or weighing less than 5 kg (no information on use);
• children aged 3 months to 11 months for intravenous administration.

With caution Long-term alcohol abuse. Intravenous administration to patients with systolic blood pressure below 100 mm Hg. or in case of instability of blood circulation (for example, against the background of myocardial infarction, multiple trauma, incipient shock).

Side effect

The frequency of possible side effects listed below is determined as follows: very often (? 1/10), often (? 1/100 to

Precautionary measures

The painkiller contains a pyrazolone derivative, analgin, which can cause rare but life-threatening side effects such as shock and agranulocytosis. If a patient has an anaphylactoid reaction to analgin, it is impossible to exclude allergic reactions to other non-narcotic analgesics. Patients with a history of anaphylactic or other immunologically mediated reactions (eg, agranulocytosis) to analgin are likely to develop cross-allergy to other pyrazolones and pyrazolidines. Agranulocytosis If signs of agranulocytosis or thrombocytopenia appear, you must immediately stop taking the drug and conduct a blood test (including the leukocyte formula). Treatment should be discontinued pending laboratory results. Pancytopenia If pancytopenia develops, treatment should be stopped immediately, followed by monitoring the blood test until it returns to normal. The patient should be informed to seek medical attention if signs and symptoms suggestive of blood abnormalities occur during treatment (eg, malaise, infection, persistent fever, bruising, bleeding, pallor). Anaphylactic/anaphylactoid reactions When choosing a route of administration, it is important to remember that parenteral administration of analgesics is associated with a higher risk of anaphylactic or anaphylactoid reactions. The risk of potentially severe anaphylactoid reactions to analgin increases significantly in patients with:

• asthma syndrome on analgesics or angioedema on non-narcotic analgesics;
• bronchial asthma, especially with concomitant rhinosinusitis and nasal polyps;
• chronic urticaria;
• intolerance to dyes (for example, tartrazine) and preservatives (for example, benzoates);
• alcohol intolerance. Such patients may react to alcoholic beverages, even in small quantities, with symptoms such as sneezing, watery eyes, and severe facial flushing. Such alcohol intolerance may be a sign of previously undiagnosed asthma on analgesics.

Anaphylactic shock usually develops in predisposed patients. Therefore, special attention should be paid to patients with asthma or atopy. Severe skin reactions Life-threatening skin reactions, such as Stevens-Johnson syndrome and toxic epidermal necrolysis, have been reported with the use of analgin. If symptoms or signs of Stevens-Johnson syndrome or toxic epidermal necrolysis (for example, progressive skin rash, often with blisters, or mucosal lesions) appear, treatment with analgin should be discontinued immediately. Patients should be aware of the signs and symptoms and closely monitor skin changes, especially during the first weeks of treatment. Isolated hypotensive reactions Analgin can lead to hypotensive reactions. These reactions may be dose dependent. These reactions usually occur with parenteral rather than enteral administration. The risk of such reactions is also increased:

• with rapid intravenous injection;
• in patients with previous hypotension, dehydration or dehydration, unstable blood pressure, or incipient circulatory failure (for example, in patients with multiple traumas or a heart attack);
• in patients with high fever.

These patients require careful evaluation and close monitoring. Preventive measures (such as circulatory stabilization) may be necessary to reduce the risk of hypotensive reactions. In exceptional cases, analgin can be used in patients in whom lowering blood pressure should be avoided at all costs, for example, with severe ischemic heart disease or corresponding stenosis of the cerebral arteries, only after careful monitoring of hemodynamic parameters. In patients with renal or hepatic insufficiency, the use of analgin is possible only after a careful assessment of the benefit-risk ratio and the use of appropriate precautions (see section "Method of administration and dosage"). It is necessary to collect anamnesis from the patient before administering analgin. In patients at increased risk of developing anaphylactic reactions, analgin should be used only after a careful assessment of benefits and risks. It is necessary to use analgin in this situation under close medical supervision and the possibility of providing emergency assistance. Long-term use of analgin (more than 7 days). If it is necessary to regularly use analgin for more than 5 days, the peripheral blood picture should be monitored weekly. Acute pain in the abdomen. The use of analgin to relieve acute abdominal pain is not recommended until its cause is determined. Use in persons with pathology of the cardiovascular system. Careful monitoring of hemodynamics is necessary, especially in patients with a systolic pressure level below 100 mm Hg, a history of kidney disease (pyelonephritis and glomerulonephritis), as well as in persons with alcohol dependence.

Pregnancy

There are no adequate data on the use of analgesics during pregnancy. Metamizole penetrates the placental barrier. In animal studies, analgin did not cause the development of teratogenic effects. Due to the lack of adequate human studies, analgin in the second and first trimester of pregnancy should be used only after a strict assessment of benefits and risks. Despite the fact that analgin is a weak inhibitor of prostaglandin synthesis, there is a possibility of premature closure of the ductus arteriosus and the development of perinatal complications due to a decrease in platelet aggregation in the child and mother. In this regard, analgin is contraindicated during the last trimester of pregnancy.

Lactation period

Analgin metabolites are excreted in breast milk, so it is necessary to avoid breastfeeding for 48 hours after taking analgin.

Use in pediatrics

The use of analgin in children in the first 3 months of life is not recommended, due to the increased risk of developing renal dysfunction.

Impact on the ability to drive vehicles and operate machinery

The recommended dosage range does not affect the concentration or rate of reaction. As a precaution, avoid driving cars, vehicles, or other hazardous activities while taking high doses. This applies, in particular, to combination with alcohol. Excretion of analgin biotransformation products in urine can cause red coloration of urine, which has no clinical significance and disappears after discontinuation of the drug.

Interaction with other drugs

Analgin may cause a decrease in the concentration of cyclosporine in the blood serum. It is necessary to monitor the concentration of cyclosporine when prescribing analgesics simultaneously. With the simultaneous administration of analgesics and aminazine, severe hypothermia may develop. Prescribing metamizole while taking methotrexate may lead to increased hematological toxicity of methotrexate, especially in elderly patients. It is recommended to avoid prescribing this combination. The possibility of interaction of pyrazolone derivatives with oral anticoagulants, captopril, lithium and triamterene, as well as the effect on the effectiveness of antihypertensive drugs and diuretics, has been established. The extent of the described interactions for analgin is not known. Due to potential incompatibility, it is not recommended to mix analgin injection solution with other drugs for injection or infusion (see also section “Method of administration and dosage”).

Overdose

Symptoms: hypothermia, marked decrease in blood pressure, palpitations, shortness of breath, tinnitus, nausea, vomiting, gastralgia, weakness, oliguria, anuria, drowsiness, delirium, impaired consciousness, tachycardia, convulsive syndrome, possible development of acute agranulocytosis, hemorrhagic syndrome, acute renal and liver failure, paralysis of the respiratory muscles. Treatment: forced diuresis, hemodialysis, blood alkalization, symptomatic therapy aimed at maintaining vital functions. If a convulsive syndrome develops, intravenous administration of diazelam and fast-acting barbiturates is carried out.

Package

2 ml in glass ampoules. 10 ampoules, together with an insert for medical use, are placed in a cardboard box (No. 10). 10 ampoules, along with a knife for opening ampoules and a leaflet for medical use, are placed in a cardboard pack (No. 10).

Storage conditions

In a place protected from light, at a temperature not exceeding 25 ° C. Keep out of the reach of children.

Best before date

3 years. Do not use the medicine after the expiration date.

Conditions for dispensing from pharmacies

On prescription.

Buy Analgin solution for IV and IM injection. 500 mg/ml in amp. 2 ml in pack No. 10 in the pharmacy

Price for Analgin solution for intravenous and intramuscular injection. 500 mg/ml in amp. 2 ml in pack No. 10

Instructions for use for Analgin solution for intravenous and intramuscular injection. 500 mg/ml in amp. 2 ml in pack No. 10

Directions for use and doses

Intravenously, intramuscularly deep into the muscle.

Parenteral administration of the drug is indicated only if it is impossible to take it orally. Before administration, it is recommended to warm the drug to body temperature.

Adults and adolescents over 15 years of age: 1.0-2.0 ml (500 mg/ml) of metamizole solution (intramuscular or intravenous) is recommended as a single dose. The maximum daily dose is 2000 mg, divided into 2-3 administrations per day. The maximum daily dose is 1000 mg.

For children aged 3-11 months (body weight more than 5 kg to 9 kg), the drug is administered only intramuscularly at a dose of 50-100 mg per 10 kg of body weight (0.1-0.2 ml of a 500 mg/ml solution). A single dose can be divided into 2-3 injections.

The following table contains recommended doses of the drug.

Intravenous administration should be carried out very slowly (infusion rate no more than 1 ml/min) with the patient lying down, under blood pressure control. At the first signs of the development of anaphylactic/anaphylactoid reactions, it is necessary to stop administering the drug.

Since the hypotensive reactions are dose-dependent, parenteral administration of a dose of 1000 mg of metamizole should be carried out with extreme caution. If the drug is administered too quickly, a critical drop in blood pressure and shock may occur.

Elderly patients need to use lower dosages due to a possible decrease in the excretion of metamizole metabolites from the body. Patients in serious condition and with impaired creatinine clearance should use smaller doses due to a possible decrease in the excretion of metamizole metabolites from the body.

In patients with impaired liver and kidney function, the rate of elimination of the drug is slowed down, so repeated use of the drug should be avoided. There is no experience with long-term use. For short-term therapy, no dose adjustment is required.

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

Application

Prescribe intramuscularly, intravenously and orally. The route of administration and dose depend on the severity of the disease and are determined individually. the analgesic effect with i.v. administration is higher than with i.m.

The solution administered must be at body temperature. To prevent a sharp decrease in blood pressure, intravenous administration should be carried out slowly (at a rate of no more than 1 ml/min), the patient should be in a supine position, and monitoring of blood pressure, heart rate and respiration is necessary. The procedure requires the availability of conditions for anti-shock therapy. When administered intravenously, it is necessary to use a long needle.

For adults, prescribe 0.5–1 ml (250–500 mg) 2–3 times a day. The maximum single dose for both routes of administration is 1 ml (500 mg), daily dose is 2 ml (1 g).

For children under 1 year of age, administer at a dose of 0.01 ml/kg body weight. For children under 1 year of age, administer the drug only intramuscularly.

Duration of use - up to 3 days.

For children over 1 year of age, administer 0.1 ml per 1 year of age 1–2 times a day. Duration of use - up to 3 days.

In tablet form, use 250–500 mg (½–1 tablet) 1–2 times a day in adults and children over 14 years of age. Take the tablets after meals, without chewing or dissolving, with a sufficient amount of water.

The maximum daily dose is 1 g.

Children aged 12–14 years: 250 mg 1–2 times a day.

Analgin-Darnitsa is intended for symptomatic short-term use. The course of treatment is no more than 3 days.

If the symptoms of the disease do not disappear within 3 days, you should consult a doctor regarding further use of the drug.

Side effect

Adverse reactions are classified as follows according to the World Health Organization (WHO) classification: very common (>1/10), common (>1/100 to <1/10), uncommon (>1/1000 to <1/100), rare (>1/10000 to <1/1000), very rare (up to <1/10000) and frequency unknown (cannot be estimated from available data).

Immune system disorders

Rarely: anaphylactic or anaphylactoid reactions.

Very rare: analgesic bronchial asthma.

Frequency unknown: anaphylactic shock.

Metamizole sodium may cause anaphylactic or anaphylactoid reactions, which in very rare cases can be severe and life-threatening. They can occur even if metamizole sodium has been previously used many times without any complications. Such drug reactions may develop immediately or some time after using metamizole sodium, usually within one hour. In milder cases, reactions manifest themselves in the form of skin and mucous membrane symptoms (itching, burning, flushing, urticaria, swelling); shortness of breath or patient complaints of gastrointestinal symptoms. In severe cases, they develop into generalized urticaria, severe angioedema (especially involving the larynx), severe bronchospasm, cardiac arrhythmias, 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 and intolerance to analgesic drugs, these reactions usually manifest themselves in the form of attacks of bronchial asthma.

From the blood and lymphatic system

Rarely: leukopenia.

Very rare: agranulocytosis (including fatal cases), thrombocytopenia.

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

These reactions are immunological and can occur even if metamizole sodium has been previously used many times without any complications. Typical symptoms of agranulocytosis are lesions of the mucous membranes (oral cavity and pharynx, anorectal area, genital organs), sore throat, fever. However, when antibiotics are used, these phenomena may be mild. Sometimes, but not always, there is a slight enlargement of the lymph nodes or spleen. The erythrocyte sedimentation rate increases significantly, the content of granulocytes is sharply reduced or not determined. As a rule, hemoglobin, red blood cells and platelets remain normal, but deviations may occur. Typical symptoms of thrombocytopenia are an 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 go away or ulcerations appear on the mucous membranes, especially the oral cavity, nose, and larynx, treatment tactics involve immediate discontinuation of the drug without waiting for the results of laboratory tests.

If pancytopenia develops, metamizole sodium should be discontinued and a complete blood count should be monitored until its values ​​return to normal (see section “Special Instructions”).

Heart disorders

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

Vascular disorders

Uncommon: isolated decrease in blood pressure.

An isolated transient decrease in blood pressure is possible (possibly pharmacologically caused, and not accompanied by other manifestations of anaphylactic/anaphylactoid reactions).

Rarely: a sharp pronounced decrease in blood pressure.

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

Skin and subcutaneous tissue disorders

Uncommon: fixed drug dermatitis.

Rarely: skin rash.

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

From the kidneys and urinary tract

Very rare: renal dysfunction.

Frequency unknown: interstitial nephritis.

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

General disorders

Uncommon: urine may turn red due to the presence of a metabolite in the urine - rubazonic acid.

Overdose

Symptoms: nausea, vomiting, abdominal pain, decreased renal function/acute renal failure with oliguria (for example, due to the development of interstitial nephritis), less common central nervous system symptoms (dizziness, drowsiness, tinnitus, delirium, impaired consciousness, convulsions, coma) and a sharp decrease in blood pressure (sometimes progressing to shock), as well as heart rhythm disturbances (tachycardia), hypothermia, shortness of breath, acute agranulocytosis, hemorrhagic syndrome, paralysis of the respiratory muscles. After high doses, renal excretion of a non-toxic metabolite (rubazonic acid) may cause urine to turn red.

Treatment: There is no specific antidote. In case of overdose, forced diuresis is indicated. The main metabolite (4N-methylaminoantipyrine) can be eliminated by hemodialysis, hemofiltration, hemoperfusion or plasma filtration. With the development of convulsive syndrome, intravenous administration of diazepam and fast-acting barbiturates is indicated.

Side effects

From the liver and biliary tract: hepatitis.

From the kidneys and urinary tract: oliguria, anuria, proteinuria, interstitial nephritis, red staining of urine.

From the cardiovascular system: decreased blood pressure, tachycardia.

From the blood and lymphatic system: agranulocytosis, leukopenia, thrombocytopenia, anemia, granulocytopenia.

From the immune system: hypersensitivity reactions, including rashes on the skin and mucous membranes, skin hyperemia, itching, urticaria, conjunctivitis, Quincke's edema; rarely - Stevens-Johnson syndrome, Lyell's syndrome, bronchospastic syndrome, anaphylactoid reactions, anaphylactic shock.

General disorders and reactions at the injection site: infiltrates at the injection site (with intramuscular injection), hyperemia, swelling, local rashes and itching of the skin at the injection site.

Interaction with other drugs

With cyclosporine: with simultaneous use, a decrease in the concentration of cyclosporine in the blood may be observed, therefore, when they are used together, monitoring of its concentration in the blood is required.

With other non-narcotic analgesics: simultaneous use of metamizole sodium can lead to mutual enhancement of toxic effects.

With tricyclic antidepressants, oral contraceptives, allopurinol: the drugs disrupt the metabolism of metamizole sodium in the liver and increase its toxicity.

With barbiturates, phenylbutazone and other inducers of microsomal liver enzymes: drugs weaken the effect of metamizole sodium.

With sedatives and tranquilizers: drugs enhance the analgesic effect of metamizole sodium. Concomitant use with chlorpromazine or other phenothiazine derivatives can lead to the development of severe hypothermia.

With drugs that are highly bound to plasma proteins (oral hypoglycemic drugs, indirect anticoagulants, glucocorticosteroids (GCS) and indomethacin): metamizole sodium, displacing oral hypoglycemic drugs, indirect anticoagulants, GCS and indomethacin from its connection with plasma proteins, increases their activity .

With myelotoxic drugs: drugs increase the manifestations of hematotoxicity of metamizole sodium.

With methotrexate: simultaneous use of metamizole sodium with methotrexate may enhance the hematotoxic effect of methotrexate, especially in elderly patients. It is recommended to avoid simultaneous use.

With thiamazole and sarcolysine: the risk of developing leukopenia increases.

With radiocontrast agents, colloidal blood substitutes and penicillin: due to the increased risk of anaphylactic/anaphylactoid reactions, they should not be used in conjunction with metamizole sodium.

With codeine, propranolol, H2-histamine receptor blockers: drugs enhance the effect of metamizole sodium.

With acetylsalicylic acid: with simultaneous use, metamizole sodium can reduce the effect of acetylsalicylic acid on platelet aggregation. This combination should be used with caution in patients taking low doses of acetylsalicylic acid as an antiplatelet agent.

With bupropion: Metamizole sodium may reduce the concentration of bupropion in the blood, which should be taken into account when using them simultaneously.

Due to the high probability of pharmaceutical incompatibility, metamizole sodium should not be mixed with other drugs in the same syringe.