Analginum

General characteristics. Structure:

Active ingredient: 500 mg of metamizole sodium (analginum).

Excipients: calcium stearate, icing sugar, talc, potato starch.

The drug rendering analgeziruyushchy, febrifugal and moderate antiinflammatory action.

Pharmacological properties:

Pharmacodynamics. Activity of cyclooxygenase oppresses, reduces formation of endoperoxides, bradykinins, some prostaglandins, free radicals, inhibits peroxide oxidation of lipids. Interferes with carrying out painful extra-and proprioceptive impulses on Gaulle and Burdakh's bunches, raises an excitation threshold of the thalamic centers of painful sensitivity, increases a thermolysis.

Pharmacokinetics. At intake analginum (metamizol) is quickly and fully absorbed. In a wall of intestines it is hydrolyzed with formation of an active metabolite; not changed metamizol in blood is absent. It is metabolized in a liver.

The active metabolite 4 methyl-aminoantipyrine is in turn metabolized in 4-formyl-aminoantipyrine and other metabolites. Level of linkng of an active metabolite with proteins makes 50-60%. At reception in therapeutic doses gets into maternal milk. Metabolites are removed by kidneys. Action develops in 20-40 min. and reaches a maximum in 2 h after intake.

Indications to use:

- an acute pain after an injury or operation;

- gripes;

- the pain caused by a new growth;

- other acute or chronic megalgias when other medical actions are impossible;

- high temperature which does not react to other measures.

Parenteral administration is shown only at impossibility of enteral use.

Route of administration and doses:

The dosage depends on intensity of pain, fever and individual sensitivity in response to analginum reception.

The smallest effective doses controlling pain and fever have to be chosen.

At children for decrease in temperature the sufficient dose of metamizol makes 10 mg on kilogram of body weight.

The beginning of action fluctuates from 30 to 60 minutes after intake and in 30 minutes after parenteral administration.

For children 10 years and teenagers aged up to 14 years a single dose of metamizol of 8-16 mg/kg are more senior. To adults and teenagers 15 years (> are more senior than 53 kg) it is possible to accept to 1000 mg on one reception. In case of insufficient effect of a single dose, depending on the maximum daily dose, it is possible to accept the maximum single dose to 4 times a day. The table given below contains the recommended dosage and the maximum doses:

Age (body weight)	Single dose	Maximum daily dose
10-14 years (32-53 kg)	On 1 tablet (500 mg metamizole sodium are equivalent)	To 4 tablets (2000 mg metamizole sodium are equivalent)
To adults and teenagers 15 years (> are more senior than 53 kg)	1-2 tablets (500-1000 mg metamizole sodium are equivalent)	To 8 tablets (4000 mg metamizole sodium are equivalent)

Elderly patients. At elderly patients the dose has to be reduced as removal of metabolites can be slowed down at analginum reception.

At depression of function of kidneys and disturbance of clearance of creatinine. At this category of patients, the dose has to be reduced as removal of metabolic products can be slowed down at metamizol reception.

Disturbance of renal or hepatic function. It is necessary to avoid high doses at reduced renal or hepatic function. Perhaps short-term use without dose decline. Prolonged use is inadmissible.

The way of introduction depends on desirable therapeutic effect and a condition of the patient. In many cases of intake it is enough for achievement of satisfactory effect. For bystry approach of effect when peroral or rectal administration is impossible, intravenous or intramuscular administration is recommended. At the choice of a route of administration it is important to remember that parenteral administration of drugs is connected with the increased risk of anaphylactic or anaphylactoid reactions.

Tablets on 500 mg should be swallowed entirely, with enough liquid (for example, a glass of water).

Treatment duration. Duration of treatment depends on a look and disease severity. At long-term treatment regular blood tests, including calculation of the differentiated leukocytes are required.

Features of use:

X-ray contrast agents, colloid blood substitutes and penicillin should not be applied during treatment. At prolonged use it is necessary to control a pattern of peripheral blood. Use for removal of acute abdominal pains before clarification of their reason is inadmissible.

Use during pregnancy and in the period of a lactation. There are no sufficient data about use of analginum during pregnancy at people. In researches on animals of teratogenic effect at metamizol it is not revealed. As there are no sufficient data for people, analginum should not be accepted in the first trimester of pregnancy, in the second trimester it is applied only after careful assessment of medical advantage and risk. In spite of the fact that analginum weak inhibitor of synthesis of prostaglandins, the possibility of premature closing of an arterial channel and perinatal complications is not excluded. Therefore analginum during the last trimester of pregnancy is contraindicated.

Metabolites of analginum are allocated in breast milk because of what its use at a lactation is not recommended. In exceptional cases feeding by a breast perhaps 48 hours later after analginum reception.

Precautionary measures. The anesthetics containing derivative pyrazyl ketone metamizol have rare, but life-threatening risk of development of shock and agranulocytosis.

At patients with atonic bronchial asthma and a pollinosis the risk of development of reactions of hypersensitivity is increased.

Patients with anaphylactoid reactions or others immunological the mediated reactions (for example, an agranulocytosis) can react in the same way to other pyrazyl ketones and Pyrazolidinums.

At use of medicine development of an agranulocytosis is possible. In this connection at identification of unmotivated temperature increase, a fever, pharyngalgias, the complicated swallowing of stomatitis, and also an inflammation of external genitals and an anus immediate cancellation of medicine is necessary.

At the choice of a route of administration it is important to remember that parenteral administration of analginum is connected with the increased risk of anaphylactic or anaphylactoid reactions.

The risk of potentially heavy anaphylactoid reactions to analginum considerably increases at patients with:

- asthma syndrome on analgetics or a Quincke's disease on non-narcotic analgesics;

- bronchial asthma, especially with accompanying rinosinusity and polyps in a nose;

- chronic small tortoiseshell;

- intolerance of dyes (for example, tartrazine) and preservatives (for example, benzoates);

- intolerance of alcohol. These patients can react to alcoholic beverages even in small amounts such symptoms as sneezing, the watering eyes and strong face reddening. Such intolerance of alcohol can be a symptom of earlier diagnosed asthma on analgetics.

At appointment as the patient with acute cardiovascular pathology careful control of a hemodynamics is necessary. With care apply at patients with the ABP level lower than 100 mm of mercury., at a myocardial infarction, a multiple injury, with anamnestic instructions on diseases of a liver and kidneys (pyelonephritis, a glomerulonephritis), at treatment by cytostatics, at an alcoholism, the burdened allergological anamnesis, blood diseases.

Analginum can lead to hypotensive reactions. These reactions can be dependent on a dose. Usually these reactions arise at parenteral administration, but not enteral.

The risk of development of such reactions increases:

- at bystry intravenous administration;

- at patients with the previous hypotension, dehydration or dehydration, unstable arterial pressure or with the beginning circulatory unefficiency (for example, at patients with multiple injuries or heart attack);

- at patients with high temperature.

Careful survey and careful control is required from similar patients. Preventive measures (such as blood circulation stabilization) can be necessary for decrease in risk of hypotensive reactions.

In exceptional cases analginum can be used at patients at whom the lowering of arterial pressure is inadmissible, for example, at heavy coronary heart disease or the corresponding stenosis of brain arteries. Use is possible only after careful control of indicators of a hemodynamics.

Patients with a renal or liver failure should accept analginum only after careful assessment of advantage, risks and necessary precautionary measures. It is necessary to hold consultations with the patient before administration of analginum. At patients with the increased risk of anaphylactic reactions analginum can be used only after the careful analysis of possible risks concerning the expected advantage. At reception of analginum in such cases, the patient has to be controlled carefully for ensuring medical care and readiness for emergency situations.

Influence on ability to control of motor transport and other potentially dangerous mechanisms. The recommended range of doses does not influence concentration and speed of response. As precautionary measures it is necessary to avoid driving of cars, vehicles or other dangerous types of activity at reception of high doses.

Side effects:

Frequency of the possible side effects which are listed below is defined as follows: very often (> 1/10), the general (> 1/100 to <1/10), sometimes (> 1/1000 to <1/100), rare (> 1/10000 to <1/1000), it is very rare (<1/10000), it is not known (it cannot be estimated on the basis of the available data).

Skin allergic reactions. Sometimes: rash. Seldom: makulopapulezny dieback. Anaphylactic or anaphylactoid reactions, especially after parenteral use. Such reactions can develop later, during an injection or right after introduction, and also after 10-12 hours. But meet preferential within the first hour after reception. Reactions are usually shown in a mucous membrane of a GIT and in the form of skin reactions (such as itch, burning, reddening, rash, hypostasis), seldom an asthma. These reactions can proceed with more severe forms such as: a small tortoiseshell, a Quincke's edema of heavy degree (including throats), a heavy bronchospasm, disturbances of a cordial rhythm, arterial hypotension (increase in arterial pressure sometimes precedes).

Reception of analginum at emergence of skin reactions has to be immediately stopped.

At patients with aspirinovy asthma of reaction are usually shown in the form of asthma attacks. Very seldom: an analgetic - the induced bronchial asthma, Stephens-Johnson's syndrome or a Lyell's disease, shock.

Blood and lymphatic system. Seldom: leukopenia. Very seldom: agranulocytosis or thrombocytopenia. These reactions probably are immunological. They can arise even if metamizol was given in the previous cases without complications. The risk of development of an agranulocytosis can be increased if analginum is accepted more than 1 week. The agranulocytosis is shown by high temperature, the fever, pharyngalgias complicated by swallowing, stomatitis, an inflammation of a mucous nose, throat and generative organs or a proctal itch. The patients receiving antibiotics, can have minimum these symptoms.

SOE considerably accelerates, granulocytes considerably decrease or completely are absent. As a rule, but not always, laboratory values of hemoglobin, erythrocytes and thrombocytes remain within norm.

Reception analginum has to be immediately stopped at the unexpected deterioration in the general state which is not connected with decrease in temperature and display of catarrhal or inflammatory diseases.

Cardiovascular system. Infrequently: hypotensive reactions in time or after use which can be dependent pharmacological, but do not accompany анафилактоидньм to reactions. Such reactions can lead to serious falling of blood pressure. Bystry intravenous administration increases risk of development of hypotensive reactions. Even at a hyperthermia there can be in critical dependence on a dose a lowering of arterial pressure without any signs of reaction of hypersensitivity.

Diseases of kidneys and urinary tract. Very seldom: acute deteriorations in renal function - deteriorations after which can develop very seldom a proteinuria, oligo-or an anury and an acute renal failure, acute intersticial nephrite. Coloring of urine in red color.

Interaction with other medicines:

Ethanol - amplifies effect of ethanol;

Chlorpromazinum or other derivatives of a fenotiazin - simultaneous use can lead to development of the expressed hypothermia;

Radiopaque substances, colloid blood substitutes and penicillin should not be applied at treatment by analginum;

Cyclosporine - at simultaneous use decreases concentration of cyclosporine in blood;

Peroral hypoglycemic medicines, indirect anticoagulants, GKS and indometacin - analginum increases activity of these medicines by replacement them from communication with protein;

Phenylbutazone, barbiturates and other gepatoinduktor at simultaneous use reduce efficiency of analginum;

Non-narcotic analgesics, tricyclic antidepressants, hormonal contraceptives and Allopyrinolum - simultaneous use of Analginum with these medicines can lead to strengthening of its toxicity;

Sedatives and tranquilizers (Sibazonum, Trioxazinum, valocordin) strengthen the anesthetizing effect of Analginum;

Thiamazolum and Sarkolshin increase risk of development of a leukopenia;

Codeine, histamine H2 blockers and propranolol strengthen effect of analginum.

Care at simultaneous use with sulfanamide antihyperglycemic medicines (hypoglycemic action amplifies) and diuretics is necessary (furosemide).

Myelotoxic medicines lead to strengthening of a gematotoksichnost.

Contraindications:

Analginum should not be used:

- at hypersensitivity to metamizol and other derivatives of pyrazyl ketone or Pyrazolidinums (including patients at whom the agranulocytosis after use of these substances was revealed) or to any other ingredients of analginum;

- at patients with aspirinovy asthma in the anamnesis or a syndrome of intolerance of analgetics (a small tortoiseshell, a Quincke's disease), at patients with a bronchospasm or with other forms of anaphylactoid reactions to salicylates, paracetamol or other non-narcotic analgesics, such as diclofenac, an ibuprofen, indometacin or Naproxenum;

- at dysfunction of marrow (for example, after treatment by cytostatics) or diseases of the hemopoietic system;

- the hereditary hemolitic anemia connected with deficit glyukozo-6-fosfatdegidrogenazy;

- patients with systolic arterial pressure below 100 mm of mercury;

- at the acute alternating porphyria (risk of emergence of an attack of a porphyria);

- in the last trimester of pregnancy.

Tablets on 500 mg are contraindicated to use for children aged up to 10 years.

Overdose:

Symptoms: a hypothermia, the expressed lowering of arterial pressure, heartbeat, an asthma, a sonitus, nausea, vomiting, a gastralgia, weakness, an oliguria, an anury, drowsiness, nonsense, consciousness disturbance, tachycardia, a convulsive syndrome; development of an acute agranulocytosis, hemorrhagic syndrome, an acute renal and liver failure, paralysis of respiratory muscles is possible.

Treatment: induction of vomiting, probe gastric lavage, purpose of salt laxatives, absorbent carbon. Carrying out an artificial diuresis, hemodialysis, blood alkalization, the symptomatic therapy directed to maintenance of the vital functions. At development of a convulsive syndrome carry out intravenous administration of diazepam and high-speed barbiturates.

Storage conditions:

In the place protected from moisture and light at a temperature not above 25 °C. To store in the place, unavailable to children. Period of validity of 5 years. Not to use after the period of validity specified on packaging.

Issue conditions:

Without recipe

Packaging:

On 10 tablets in a blister strip packaging or in planimetric bezjyacheykovy packaging. On one or two planimetric packagings together with the application instruction place in a pack from a cardboard. Packaging for hospitals: on 120 planimetric bezjyacheykovy packagings or 150 blister strip packagings with application instructions place in a box from a cardboard.