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

Metamizole sodium is a derivative of pyrazolone, which has analgesic, antipyretic and antispasmodic effect. The mechanism of action is not fully understood.According to the results of the studies metamizole and its active metabolite (4N- methylaminoantipyrine) have a central and peripheral mechanism of action. Nonselectively inhibits cyclooxygenase and reduces the formation of prostaglandins from arachidonic acid.

Pharmacokinetics:

After oral administration metamizol sodium is hydrolyzed to pharmacologically active 4N-methylaminoantipyrine (MAA). Bioavailability of MAA after oral administration is 90%, which is somewhat higher than with parenteral administration. Simultaneous food intake does not have a significant effect on the pharmacokinetics of metamizole sodium. Clinical efficacy is determined predominantly by MAA, and to a lesser extent by 4N-aminoantipyrine (AA) metabolites. The area under the "concentration-time" curve (AUC) AA is 25% of this value for the IAA. Metabolites 4N-acetylaminoantipyrine (AAA) and 4N-formylaminoantipyrine (FAA) do not have 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.

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:

Pain syndrome of moderate and severe degree: incl. neuralgia, myalgia, arthralgia, colic of various genesis, trauma, burns,postoperative pain syndrome, headache, toothache, algodismenorea, pain in cancer.

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, rhinitis, angioedema) in response to the use of salicylates, paracetamol or non-steroidal anti-inflammatory drugs such as diclofenac, ibuprofen, indomethacin or naproxen;

- Disturbance of bone marrow hematopoiesis (eg, 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 attacks);

- Pregnancy and the period of breastfeeding;

- Children up to 15 years.

Pregnancy and lactation:

Application during pregnancy and during breastfeeding is contraindicated.

Pregnancy

Data on the use of sodium metamizole during pregnancy are limited. Metamizol sodium penetrates the placenta. According to the results of preclinical studies, the teratogenic effect of metamizole sodium was not detected. Although metamizol sodium weakly inhibits the synthesis of prostaglandins, premature (intrauterine) closure of the arterial duct, as well as perinatal complications caused by a violation of platelet aggregation in the mother or newborn can not be ruled out.

Breast-feeding

Metabolites of metamizole sodium penetrate into breast milk, so when using the drug, and also within 48 hours after taking / administering the last dose, it is necessary to refuse breastfeeding (see the section "Contraindications"),

Dosing and Administration:

The dose depends on the severity of the pain or fever, as well as the individual susceptibility to the action of analgesics.

Tablets should be swallowed whole, with a sufficient amount of liquid (for example, a glass of water).

Initially, the lowest effective dose should be used.

The maximum effect of the drug develops, usually after 30-60 minutes after ingestion.

A single dose for adults and adolescents older than 15 years (with a body weight> 53 kg) is 250-1000 mg (0.5-2 tablets). In case of insufficient effect, a single dose can be taken up to 4 times a day. The maximum daily dose is 4000 mg (8 tablets).

Duration of reception no more than 5 days as an anesthetic and no more than 3 days as an antipyretic.

Elderly

Elderly patients need to reduce the dose, because they can be reduced excretion of metamizole sodium metabolites.

Severe general condition and impaired creatinine clearance

Patients with a severe general condition and a violation of creatinine clearance should reduce the dose, because they can be reduced excretion of metamizole sodium metabolites.

Renal or hepatic impairment

Since in patients with impaired renal or hepatic function the rate of elimination of the drug is reduced, the repeated use of high doses should be avoided. In the short term, dose reduction is not required.Experience with prolonged use is absent.

Side effects:

The frequency of potential adverse reactions is classified as follows: very often (≥1 / 10), often (≥1 / 100 to <1/10), infrequently (≥1 / 1000 to <1/100), rarely (≥1 / 10,000 up to <1/1000), very rarely (up to <1/10 000) and the frequency is unknown (it is impossible to estimate based on available data).

On the part of the blood and lymphatic system

Rarely: leukopenia

Very rarely: agranulocytosis, including fatal cases, thrombocytopenia

The frequency is unknown: aplastic anemia, pancytopenia, including cases with lethal outcome

These reactions can occur even if earlier metamizol sodium did not cause complications. There are a number of signs of increased risk of agranulocytosis, if metamizol sodium apply more than one week.

This reaction is dose-independent and may occur at any time during treatment. It is manifested by high fever, chills, sore throat, pain when swallowing, inflammation of the mucous membranes of the mouth, nose, throat, genital and anal area. However, with the use of antibiotics, these phenomena may be mild. There is a slight increase in lymph nodes and spleen, or it is completely absent.The sedimentation rate of erythrocytes is significantly increased, the granulocyte content is sharply reduced or they are not determined. As a rule, but not always, maintain normal parameters of hemoglobin, erythrocytes and platelets (see section "Special instructions").

Tactics of treatment implies immediate withdrawal of the drug, i.e. the drug should be discontinued immediately, without waiting for the results of laboratory tests, if there is an unexpected deterioration in the general condition, fever does not subside or new or painful ulceration on the mucous membranes, especially in the mouth, nose or throat.

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

From the immune system

Rarely: anaphylactoid or anaphylactic reactions *

Very rarely: analgesic bronchial asthma.

In patients with analgesic bronchial asthma Intolerance, as a rule, is manifested by attacks of bronchial asthma.

Frequency unknown: anaphylactic shock *

* These reactions are especially characteristic for parenteral administration,can be severe and endanger life, in some cases, lead to death. These reactions can occur even if earlier metamizol sodium did not cause complications.

These reactions can occur during administration or immediately after swallowing or develop, after several hours. However, they predominantly occur within the first hour after application. In more mild cases, they are manifested by rashes on the skin and mucous membranes shells (eg, itching, burning, redness, blisters and swelling), shortness of breath and, rarely, gastrointestinal disorders. In severe cases, these mild reactions turn into generalized urticaria, severe angioedema (including the larynx), severe bronchospasm, cardiac arrhythmias, arterial hypotension (in some cases it is preceded by an increase in blood pressure), shock.

In this regard, at the first signs of skin reactions the drug should be discarded.

From the side of the vessels

Infrequent: an isolated decrease in blood pressure (possibly pharmacologically conditioned and not accompanied by other manifestations of anaphylactic / anaphylactoid reactions). Reduction of blood pressure can be pronounced

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

From the skin and subcutaneous tissues

Infrequent: persistent drug rash

Rarely: a rash (eg, maculopapular)

Very rarely: Stevens-Johnson syndrome, toxic epidermal necrolysis (treatment should be discontinued, see section "Special instructions")

From the side of the kidneys and urinary tract

Very rarely: acute renal dysfunction, which is very rare cases can lead to proteinuria, oligo- or anuria and acute renal failure, acute interstitial nephritis

General disorders and disorders at the site of administration

The frequency is unknown: it has been reported that the urine stains red, which can be due to the presence of rubric acid in a low concentration (metamizol sodium metabolite)

Overdose:

Symptoms

Acute overdose is manifested by nausea, vomiting, abdominal pain, impaired renal function / acute renal failure (eg, as a manifestation of interstitial nephritis) and, rarely, by symptoms from the central nervous system (dizziness, drowsiness, coma, seizures) and a decrease in blood pressure, leading to tachycardia and shock.

With a high overdose, the excretion of rubric acid can stain the urine red.

Treatment

The specific antidote is not known. In case of a recent overdose, in order to limit the intake of the drug, primary detoxification (for example, gastric lavage) or sorption therapy (for example, Activated carbon). The main metabolite (4N-methylaminoantipyrine) is removed during hemodialysis, haemofiltration, hemoperfusion and plasmafiltration.

Treatment of an overdose, as well as the prevention of serious complications, may require general and special intensive medical supervision and treatment.

Interaction:

With cyclosporine

Metamizole sodium can cause a decrease in plasma concentrations of cyclosporine, so when they are used simultaneously, monitor the concentration of cyclosporine.

FROM chlorpromazine

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

FROM methotrexate

Simultaneous application metamizole sodium and methotrexate or other myelotoxic agents may increase the hematotoxicity of the latter, especially in elderly patients. Therefore, this combination should be avoided.

FROM other non-narcotic analgesics

Simultaneous use of metamizole sodium with other non-narcotic Analgesic agents can lead to a mutual enhancement of toxic effects.

FROM 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.

With sedatives and tranquilizers

Sedatives and tranquilizers increase the analgesic effect of metamizole sodium.

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

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

With timazole

Timazol increases the risk of developing leukopenia.

FROM codeine, blockers H₂-gistaminovyh receptors and propranolol

Codeine, blockers H₂-gistaminovyh receptors and propranolol strengthen effects metamizole sodium.

FROM acetylsalicylic acid (ASA)

With simultaneous application 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.

With other medicinal products

It is well known that pyrazolone derivatives can interact with indirect anticoagulants, captopril, lithium and triamterene, and also affect the effectiveness of antihypertensive agents and diuretics.The drug interaction of metamizole sodium with these drugs has not yet been studied.

In view of the increased risk of anaphylactic / anaphylactoid reactions during treatment with metamizole sodium, radiocontrast agents, colloidal blood substitutes and penicillin should not be used.

Special instructions:

The preparation contains a pyrazolone derivative - metamizol sodium, which occasionally can cause life-threatening shock and agranulocytosis (see section "Side effect").

Patients who, in response to the use of metamizole sodium, anaphylactoid reactions, are also at risk of developing them in response to other non-narcotic analgesics / NSAIDs.

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

Agranulocytosis

When signs of agranulocytosis or thrombocytopenia appear (see the section "Side effect"), the drug should be immediately canceled and a general blood test performed (with the definition of the leukocyte formula).Termination of therapy should not be postponed until laboratory results are obtained.

Pancytopenia

With the development of pancytopenia, the drug should be immediately discontinued and the general blood test should be monitored until the indicators return to normal (see "Side effect" section). All patients should be advised to seek medical help immediately if there are signs and symptoms reminiscent of blood disorders (for example, general weakness, infections, persistent fever, the appearance of bruising, bleeding, pallor) during treatment.

Anaphylactic / anaphylactoid reactions

Before using metamizole sodium it is necessary to conduct a thorough questioning of the patient. If the risk of developing anaphylactoid reactions is detected, the drug should be used only after a thorough assessment of possible risks and the expected benefit. If a decision is made about the use of metamizole sodium, the patient must establish strict medical supervision and ensure the readiness of urgent measures.

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

analgesic bronchial asthma or intolerance to analgesics (type of urticaria-angioneurotic edema) (see section "Contraindications");

bronchial asthma, especially accompanied by rhinosinusitis and polyposis of the nose; chronic urticaria; intolerance to dyes (eg tartrazine) or preservatives (eg benzoates); intolerance of alcohol, against which even with the intake of a small amount of alcoholic drinks, patients experience sneezing, lacrimation, and severe reddening of the face. Alcohol intolerance may indicate an earlier unidentified analgesic bronchial asthma (see "Contraindications"), Sensitive patients may experience an anaphylactic shock, therefore, patients with bronchial asthma or atopy should be extra careful.

Severe skin reactions

Against the background of the use of metamizole sodium described life-threatening skin reactions: Stevens-Johnson syndrome (SSD) and toxic epidermal necrolysis (TEN). When there are signs of SS or TENS (such as a progressive skin rash, often accompanied by blisters or ulceration of the mucous membrane), treatment with metamizole should be stopped immediately and never restarted.

Patients should be informed about the signs and symptoms of these diseases. They should carefully monitor skin reactions, especially during the first weeks of treatment.

Isolated hypotensive reactions

Metamizole sodium can cause hypotensive reactions (see also the "Side effect" section). These reactions can be dose-dependent. They are more typical for parenteral than oral administration. The risk of such reactions is also increased when:

previous arterial hypotension, decreased circulating blood volume or dehydration, unstable hemodynamics, or acute circulatory disturbances (eg, in patients with myocardial infarction or trauma), in patients with high 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 (for example, cardiovascular resuscitation) 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 can only be used with careful observation 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 renal or hepatic function

In patients with impaired renal or hepatic function metamizol sodium It is allowed only with a rigorous assessment of the benefits and risks, observing all necessary precautions.

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

In the recommended range of doses, the influence on the concentration of attention and the speed of psychomotor reactions is not established. When taking high doses, it is advisable to use caution when driving vehicles, working with mechanisms and practicing other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.

Form release / dosage:

Tablets, 500 mg.

Packaging:

By 3, 4, 10 tablets in a contour mesh box made of polyvinylchloride film and aluminum foil printed lacquered.

For 10, 20, 30, 40, 50, 60, 70, 80, 90 or 100 tablets in cans of polyethylene terephthalate. One bank or 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 20, 30, 40, 50, 60, 70, 80, 90, 100 of the contour mesh packages together with the instruction for use are placed in cardboard packaging (bundle).

Storage conditions:

In the dark place at a temperature of no higher than 25 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date.

Terms of leave from pharmacies:Without recipe

Registration number:LP-002679

Date of registration:24.10.2014

Expiration Date:24.10.2019

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

Manufacturer: & nbsp

OZONE, LLC Russia

Information update date: & nbsp25.08.2017

Illustrated instructions

Instructions

Analgin (Analgin)