Description
Latin name
Analgin-ExtraCap
Release form
Hard gelatin capsules No. 00, white, the contents of the capsule are white or white powder with a yellowish tint. A capsule mass seal is allowed, which when crushed with a glass rod easily disintegrates.
Pharmacological action
Analgesic non-narcotic drug.
It has analgesic, antipyretic and mild anti-inflammatory effects, is a derivative of pyrazolone.
Pharmacodynamics
The mechanism of action is not fully understood. According to the results of studies, metamizole and its active metabolite (4Y-methylaminoantipyrine) have a central and peripheral mechanism of action. It non-selectively inhibits cyclooxygenase and reduces the formation of prostaglandins from arachidonic acid.
Pharmacokinetics: After oral administration, metamizole sodium is hydrolyzed to pharmacologically active 4N-methylaminoantipyrine (MAA). The bioavailability of MAA after oral administration is 90%, which is slightly higher than with parenteral administration. Simultaneous eating does not significantly affect the pharmacokinetics of metamizole sodium. Clinical efficacy is determined primarily by MAA, as well as to a lesser extent by metabolites of 4N-aminoantipyrine (AA). The area under the concentration-time curve (AUC) AA is 25% of this value for MAA. The metabolites 4N-acetylaminoantipyrine (AAA) and 4N-formylaminoantipyrine (FAA) do not have pharmacological activity. All metabolites are characterized by nonlinear pharmacokinetics. The clinical significance of this phenomenon is not known. With short-term use, the accumulation of metabolites does not play a big role. Metamizole sodium crosses the placenta. Metamizole metabolites pass into breast milk. Communication with plasma proteins MAA is 58%, AA – 48%, FAA – 18% and AAA – 14%. After a single oral administration, 85% of the dose is found in the urine in the form of metabolites, of which 3 ± 1% -MAA, 6 ± 3 % – AA, 26 ± 8% – AAA and 23 ± 4% – FAA. Renal clearance after a single dose of 1 g of metamizole sodium inside for MAA is 5 ± 2 ml / min, AA – 38 ± 13 ml / min, AAA – 61 ± 8 ml / min and FAA – 49 ± 5 ml / min. The corresponding plasma elimination half-lives for MAA are 2.7 ± 0.5 hours, AA is 3.7 ± 1.3 hours, AAA is 9.5 ± 1.5 hours, and FAA is 11.2 ± 1.5 hours.
Elderly patients
In elderly patients, AUC rises 2 3 times. In patients with liver cirrhosis, the half-lives of MAA and FAA with a single dose of the drug increase by about 3 times, while the half-lives of AA and AAA do not follow the same pattern. In such patients, the use of high doses should be avoided.
Impaired renal function
According to available data, in renal failure, the rate of elimination of certain metabolites (AAA and FAA) is reduced. In such patients, the use of high doses should be avoided.
Indications
Severe acute or chronic pain syndrome with injuries and postoperative pain, with colic, with oncological diseases and other conditions where other therapeutic measures are contraindicated.
Fever resistant to other treatments.
Contraindications
– Hypersensitivity to metamizole sodium and other pyrazolone derivatives, as well as to pyrazolidines, such as phenylbutazone (including patients undergoing agranulocytosis due to the use of these drugs), or other components of the drug
– Analgesic bronchial asthma or intolerance to analgesics (such as urticaria-angioedema), i.e. patients with bronchospasm or other forms of anaphylactoid reactions (for example, urticaria, rhinitis, angioedema) in response to the use of salicylates, paracetamol or non-steroidal anti-inflammatory drugs, such as diclofenac, ibuprofen, indomethacin or naproxen sorelkorosis – e.g. ) or diseases of the blood-forming organs
– Hereditary deficiency of glucose-6-phosphate dehydrogenase (hemolysis)
– Acute intermittent hepatic porphyria (risk developed I attacks of porphyria)
– Pregnancy and lactation
– Children up to age 15 years.
Caution:
– Arterial hypotension (systolic blood pressure below 100 mmHg), decreased circulating blood volume, hemodynamic instability (myocardial infarction, multiple trauma, onset of shock), beginning heart failure, high fever (increased risk of a sharp decrease in blood pressure) .
– Diseases in which a significant decrease in blood pressure may be at increased risk (patients with severe coronary heart disease and stenosis of the arteries of the brain).
– Chronic alcohol abuse.
– Bronchial asthma, especially in combination with concomitant polyposis of rhinosinusitis, chronic urticaria and other types of atopy (allergic diseases, in the development of which a significant role belongs to a hereditary predisposition to sensitization: hay fever, allergic rhinitis, etc.) (increased risk of anaphylactic / anaphylactoid reactions).
– Alcohol intolerance (reaction to even small amounts of certain alcoholic beverages with symptoms such as itching, lacrimation and severe redness of the face) (increased risk of anaphylactic / anaphylactoid reactions).
– Intolerance to dyes (e.g. tartrazine) or preservatives (e.g. benzoates) (increased risk of anaphylactic / anaphylactoid reactions).
– Severe impairment of liver and kidney function (low doses are recommended due to the possibility of slowing the elimination of metamizole sodium).
If you have one of the listed diseases / conditions, be sure to consult your doctor before taking the drug.
Special instructions
The drug contains a pyrazolone derivative – metamizole sodium, which can occasionally cause life-threatening shock and agranulocytosis (see section Side effects). Patients who experience anaphylactoid reactions in response to the use of metamizole sodium are also at risk of developing them in response to the use of other non-narcotic analgesics / NSAIDs.
Patients who experience anaphylactic or other immuno-mediated reactions (such as agranulocytosis) in response to metamizole sodium are also at risk of developing them in response to other pyrazolones and pyrazolidines.
Agranulocytosis
If there are signs of agranulocytosis or thrombocytopenia (see section Side effects), the drug must be immediately canceled and a general blood test performed (with the definition of the leukocyte formula). Discontinuation of therapy should not be delayed until laboratory results are obtained.
Pancytopenia
With the development of pancytopenia, the drug must be immediately canceled and the blood count checked until its parameters return to normal (see section Side effects). All patients should be advised to seek immediate medical attention if signs and symptoms appear during treatment that resemble blood disorders (e.g., general weakness, infections, persistent fever, hematomas, bleeding, pallor).
Anaphylactic / anaphylactoid reactions
Before using metamizole sodium, a thorough patient survey is necessary. If a risk of anaphylactoid reactions is identified, the use of the drug is allowed only after a thorough assessment of the possible risks and expected benefits. If a decision is made to use metamizole sodium, it is necessary to establish strict medical supervision of the patient and ensure that emergency measures are prepared. The following conditions are associated with an increased risk of hypersensitivity reactions to metamizole sodium: analgesic bronchial asthma or intolerance to analgesics (urticaria-angioedema type) (see Contraindications) bronchial asthma, especially accompanied by rhinosinusitis and nasal polyposis, eg, urticaria, urticaria tartrazine) or preservatives (for example, benzoates) intolerance to alcohol, against which even when taking a small amount of alcoholic beverages, patients experience sneezing, lacrimation and severe redness of the face. Alcohol intolerance may indicate previously unidentified analgesic bronchial asthma (see section Contraindications))).
Susceptible patients may experience anaphylactic shock, so patients with bronchial asthma or atopy should be especially careful.
Severe skin reactions
Life-threatening skin reactions have been described with the use of metamizole sodium: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). When signs of SJS or TEN (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 be resumed. Patients should be made aware of 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 may cause hypotensive reactions (see also section Adverse effects). These reactions may be dose dependent. The risk of such reactions is also increased with: previous arterial hypotension, decreased circulating blood volume or dehydration, unstable hemodynamics or acute circulatory disturbance (for example, in patients with myocardial infarction or trauma), in patients with high fever. In this regard, in such patients, detailed diagnostics should be carried out and careful monitoring should be established for them. In order to reduce the risk of antihypertensive reactions, preventive measures (e.g., cardiovascular resuscitation) may be required. In patients in whom a decrease in blood pressure should be avoided at all costs (for example, with severe coronary heart disease or significant stenosis of the cerebral arteries), metamizole sodium is allowed to be used only with careful monitoring of hemodynamic parameters.
Abdominal pain
The use of the drug to relieve acute abdominal pain is unacceptable (until their cause is clarified).
Impaired renal or hepatic function
In patients with impaired renal or hepatic function, metamizole sodium is allowed only after a rigorous assessment of the benefits and risks, observing all necessary precautions.
Impact on the ability to drive transp. Wed and fur .:
In the recommended dose range, the effect on the concentration of attention and the speed of psychomotor reactions has not been established. When taking high doses, caution is advised when driving vehicles, working with machinery, and engaging in other potentially hazardous activities that require increased concentration and speed of psychomotor reactions.
Composition
1 caps. – metamizole sodium 500 mg.
Excipients: potato starch – 15.32 mg, calcium stearate – 4.68 mg.
Composition of capsule shell (body and cap): titanium dioxide (E 171) – 2%, gelatin up to 100%
Dosage and administration
Dose depends on the severity of pain or fever, as well as individual susceptibility to the action of analgesics.
Capsules should be swallowed whole with plenty of fluids (such as a glass of water).
Initially, the lowest effective dose should be used.
The maximum effect of the drug develops, usually 30-60 minutes after ingestion.
A single dose for adults and adolescents over 15 years of age (body weight> 53 kg) is 500-1000 mg (1-2 capsules). With insufficient effect, a single dose can be taken up to 4 times a day. The maximum daily dose is 4000 mg (8 capsules). Duration of admission is not more than 5 days as an anesthetic and not more than 3 days as an antipyretic.
Elderly patients
Elderly patients need to reduce the dose because they may have reduced excretion of metamizole sodium metabolites.
Severe general condition and impaired creatinine clearance
Patients with severe general condition and impaired creatinine clearance need to reduce the dose, since their excretion of metamizole sodium metabolites may be reduced.
Renal or hepatic insufficiency
Since in patients with impaired renal or hepatic function, the excretion rate of the drug is reduced, multiple doses of high doses should be avoided. With short-term use, dose reduction is not required. There is no experience of prolonged use.
Side effects
Adverse reactions are classified as follows according to the WHO (World Health Organization) classification: very often (? 1/10), often (? 1/100 to <1/10), infrequently (? 1/1000 to < 1/100), rarely (? 1/10000 to <1/1000), very rarely (up to <1/10000) and the frequency is unknown (it is impossible to estimate based on available data). Cardiac abnormalities Frequency unknown: Kounis syndrome (allergic coronary syndrome, manifested by clinical and laboratory signs of angina pectoris caused by inflammatory mediators). Immune system disorders Rarely: anaphylactic / anaphylactoid reactions. Very rare: analgesic bronchial asthma. Frequency 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 previously the drug was taken many times without any complications. Such drug reactions can develop immediately or within a few hours after taking metamizole sodium, usually within one hour. In milder cases, they manifest as skin symptoms and symptoms from the mucous membranes (itching, burning, hyperemia, urticaria, edema) or as shortness of breath, or complaints from the gastrointestinal tract. In severe cases, these reactions pass 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 with the development of circulatory shock. In patients with the syndrome of analgesic bronchial asthma with intolerance to analgesic drugs, these reactions manifest themselves in the form of attacks of bronchial asthma. Disorders of the skin and subcutaneous tissue Infrequently: fixed drug dermatitis. Rarely: skin rash. Frequency unknown: Stevens-Johnson syndrome, Lyell syndrome (toxic epidermal necrolysis). Disorders from the croca and lymphatic system Rarely: leukopenia. Very rare: agranulocytosis, including fatal cases and thrombocytopenia. Frequency unknown: aplastic anemia, pancytopenia, including fatal cases. These reactions are immunological reactions in nature. They can occur even if previously the drug was taken many times without any complications. Typical symptoms of agranulocytosis are lesions of the mucous membranes (cornea and pharynx, anorectal region and genitals), sore throat, and fever. However, when using antibiotics, these phenomena can be mild. Sometimes, but not always, a slight increase in the lymph nodes or spleen is noted. The erythrocyte sedimentation rate increases significantly, the content of granulocytes is sharply reduced or they are not determined. As a rule, hemoglobin indicators, red blood cells and platelets remain normal, but deviations can also occur. Typical symptoms of thrombocytopenia are an increased tendency to bleed 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 subside, or new or painful ulcerations appear on the mucous membranes, especially in the mouth, nose, or throat, the tactics of treatment involve immediate drug withdrawal, 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 its parameters return to normal (see Special instructions). Vascular disorders Infrequently: isolated arterial hypotension. After taking the drug, an isolated transient decrease in blood pressure is possible (possibly pharmacologically determined and not accompanied by other manifestations of anaphylactic / anaphylactoid reactions) in rare cases, a decrease in blood pressure can be very pronounced. With fever, a dose-dependent sharp decrease in blood pressure is also possible without other signs of a hypersensitivity reaction. Disorders of the night and urinary tract Very rare: impaired renal function. Frequency unknown: interstitial nephritis. In very rare cases, patients with impaired renal function may have an acute deterioration in renal function (acute renal failure), in some cases with oliguria, anuria, or proteinuria. Common disorders Infrequently: it is possible to stain urine in red due to the presence of a metabolite in the urine – rubazonic acid. Drug interaction With cyclosporine Metamizole sodium can cause a decrease in the plasma concentration of cyclosporine, therefore, when used simultaneously, the concentration of cyclosporin should be monitored. With chlorpromazine With the simultaneous use of metamizole sodium and chlorpromazine, severe hypothermia may develop. With methotrexate The simultaneous use of metamizole sodium and methotrexate or other myelotoxic agents can enhance the hematotoxicity of the latter, especially in elderly patients. Therefore, such a combination should be avoided. With other non-narcotic analgesics The simultaneous use of metamizole sodium with other non-narcotic analgesics can lead to a mutually reinforcing toxic effect. With tricyclic antidepressants, oral contraceptives, allopurinol Tricyclic antidepressants, oral contraceptives, allopurinol disrupt the metabolism of sodium metamizole in the liver and increase its toxicity. With barbiturates, phenylbutazone and other inducers of microsomal liver enzymes Barbiturates, phenylbutazone and other inducers of microsomal liver enzymes weaken the effect of sodium metamizole. With sedatives and tranquilizers Sedatives and tranquilizers enhance the analgesic effect of metamizole sodium. With drugs that are highly bound to plasma proteins (oral hypoglycemic agents, indirect anticoagulants, glucocorticosteroids and indomethacin) Metamizole sodium, displacing oral hypoglycemic agents from the plasma protein, indirect anticoagulants, glucose activity. With thymazole timazole increases the risk of developing leukopenia. With codeine, H2-histamine receptor blockers and propranolol Codeine, H2-histamine receptor blockers and propranolol enhance the effects of metamizole sodium. With acetylsalicylic acid (ASA) With simultaneous use, metamizole 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. With bupropion Metamizole sodium can decrease the concentration of bupropion in the blood, which should be taken into account while using them. With other medicines, Khorony knows that pyrazolone derivatives can interact with indirect anticoagulants, captopril, lithium, and triamteren, as well as affect the effectiveness of antihypertensives and diuretics. The drug interaction of metamizole sodium with these drugs has not yet been studied. Due to the increased risk of anaphylactic / anaphylactoid reactions during treatment with sodium metamizole, radiopaque substances, colloidal blood substitutes, and penicillin should not be used. Overdose Do not exceed the recommended dose and duration of administration! symptoms Acute overdose is manifested by nausea, vomiting, abdominal pain, impaired renal function / acute renal failure (such as manifestation of interstitial nephritis) and, rarely, symptoms from the central nervous system (dizziness, drowsiness, drowsiness). blood pressure leading to tachycardia and shock, cardiac arrhythmia (tachycardia), hypothermia, shortness of breath, acute agranulocytosis, hemorrhagic syndrome, respiratory paralysis. With a high overdose, excretion of rubazonic acid can turn the urine red. Treatment The specific antidote is unknown. With a recent overdose, primary detoxification (eg gastric lavage) or sorption therapy (eg activated charcoal) is performed to limit the flow of the drug into the body. The major metabolite (4N-methylaminoantipyrine) is removed by hemodialysis, hemofiltration, hemoperfusion, and plasmafiltration. Overdose treatment, as well as the prevention of serious complications, may require general and special intensive medical monitoring and treatment. Storage Conditions Do not store above 25 ° C. Keep out of the reach and sight of children. Shelf life 2 years. Do not use after the expiration date indicated on the package. Conditions of release from drugstores d9 without prescription recipe dosage form tablets Prescribing Prescribing Pregnant only II trimester as prescribed by the doctor, Children as prescribed by the doctor, For adults, Children over 15 years old
