Analgin

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT ANALGIN

Composition:

Active substance: metamizole sodium;

1 tablet contains 500 mg of sodium metamizole;

Excipients: potato starch, calcium stearate, stearic acid.

Pharmaceutical form. Tablets.

Main physico-chemical properties: intact, regular, round cylindrical tablets with flat upper and lower surfaces, beveled edges, a score line for division, white or slightly yellowish in color, bitter in taste.

Pharmacotherapeutic group.

Analgesics and antipyretics. Pyrazolones. ATC code N02BB02.

Pharmacological properties.

Pharmacodynamics.

A pyrazolone derivative, cyclooxygenase inhibitor. Reduces the formation of prostaglandins from arachidonic acid. Differs from other cyclooxygenase inhibitors by having a weak anti-inflammatory effect, while exhibiting pronounced analgesic, antipyretic, and spasmolytic actions. The spasmolytic effect is directed toward the smooth musculature of the urinary and biliary tracts.

Inhibits the conduction of extra- and proprioceptive pain impulses along the posterior funiculi (Goll and Burdach bundles), increases the excitation threshold of thalamic pain sensitivity centers, and enhances heat dissipation.

Pharmacokinetics.

Rapidly absorbed from the gastrointestinal tract. Hydrolyzed in the intestinal wall to form an active metabolite. The unchanged compound is not present in the blood. The active metabolite is 50–60% bound to plasma proteins. Time to reach maximum plasma concentration is 1–2 hours. Elimination half-life is 2.5 hours. Excreted mainly by the kidneys.

Clinical Characteristics

Indications.

Pain syndrome of various origins: headache, toothache, neuralgia, radiculitis, myositis, menstrual pain. As an adjunctive agent, it may be used to reduce pain following surgical and diagnostic procedures. Hyperthermic syndrome in infectious-inflammatory diseases.

Contraindications.

Hypersensitivity to the components of the drug, pyrazolone derivatives. Alterations in peripheral blood composition; blood system disorders: agranulocytosis, leukopenia, anemia of any etiology, cytostatic or infectious neutropenia; severe liver and kidney dysfunction (porphyrin metabolism disorders); congenital glucose-6-phosphate dehydrogenase deficiency; bronchial asthma; suspicion of acute surgical pathology.

Interaction with other medicinal products and other types of interactions.

Ethanol. Enhances the effect of ethanol.

Chlorpromazine or other phenothiazine derivatives. Concurrent use may lead to pronounced hypothermia.

X-ray contrast agents, colloidal plasma substitutes, and penicillin. Should not be used during treatment with analgin.

Cyclosporine. Concurrent use reduces cyclosporine blood concentration.

Oral hypoglycemic agents. Analgin increases the activity of these agents by displacing them from protein binding sites in the blood, enhances the sedative effect of alcohol.

The drug enhances the activity of indirect anticoagulants, glucocorticosteroids, and indomethacin (by displacing them from protein binding), and increases the sedative effect of alcohol.

Phenylbutazone, glutethimide, barbiturates, and other hepatic enzyme inducers. Concurrent use reduces the effectiveness of analgin.

Non-narcotic analgesics, tricyclic antidepressants, hormonal contraceptives, and allopurinol. Concurrent use with analgin may increase its toxicity.

Other nonsteroidal anti-inflammatory drugs. Their analgesic and antipyretic effects are enhanced, and the risk of additive adverse effects increases.

Sedatives and tranquilizers (sibazone, trioxyazine, valocordin). Enhance the analgesic effect of analgin.

Thiamazole and sarcosine. Increase the risk of developing leukopenia.

Codeine, histamine H2-blockers, and propranolol. Enhance the effect of analgin.

Caution is required when using the drug concurrently with sulfonamide hypoglycemic agents (hypoglycemic effect is enhanced) and diuretics (furosemide).

Methotrexate. Metamizole in high doses may increase methotrexate plasma concentration and enhance its toxic effects (on the gastrointestinal tract and hematopoietic system).

Special precautions for use

Before starting treatment with the drug, consult a physician.

Do not exceed the recommended doses of the drug.

Do not use the drug to relieve acute abdominal pain (before the cause is determined). Since sodium metamizole has anti-inflammatory and analgesic properties, it may mask signs of infection, symptoms of non-infectious diseases, and complications associated with pain syndrome, which may complicate their diagnosis.

Avoid consuming alcoholic beverages during treatment with the drug.

The drug should be used with caution in the following patients:

• Elderly patients – may lead to an increased frequency of adverse reactions, especially those affecting the gastrointestinal tract;
• Patients with existing allergic diseases (including pollinosis) or a history of such conditions – increased risk of allergic reactions;
• Patients with impaired renal function or a history of kidney diseases (pyelonephritis, glomerulonephritis);
• Patients with inflammatory bowel diseases, including ulcerative colitis and Crohn's disease;
• Patients with marked arterial hypotension or cardiovascular insufficiency;
• Patients with a history of chronic alcohol dependence;
• Patients receiving concomitant cytostatic drugs (only under physician supervision).

Risk of drug-induced liver injury

Cases of acute hepatitis, predominantly of hepatocellular type, have been observed in patients treated with sodium metamizole. Symptoms typically appeared from several days to several months after initiation of treatment. Manifestations included elevated serum liver enzymes, with or without jaundice, often occurring in the context of hypersensitivity reactions to other drugs (e.g., skin rashes, blood dyscrasias, fever, and eosinophilia) or accompanied by features of autoimmune hepatitis. Most patients recovered after discontinuation of sodium metamizole; however, in isolated cases, progression to liver failure requiring liver transplantation has been reported.

The mechanism of sodium metamizole-induced liver injury is not fully understood, but available data suggest an immune-allergic mechanism.

Patients should be instructed to promptly inform their physician if symptoms suggestive of liver injury occur. In case of suspected liver injury, sodium metamizole should be discontinued immediately, and liver function tests should be performed.

Cases of liver injury during treatment with sodium metamizole are very rare, but the exact frequency of this adverse reaction cannot be determined. Some patients have experienced recurrence of liver injury upon re-exposure to sodium metamizole. Therefore, if a patient previously developed liver injury during treatment with sodium metamizole and no other cause of liver injury was identified, drugs containing sodium metamizole should not be re-administered.

Discontinue the drug immediately and seek urgent medical advice if symptoms such as asthenia, unexplained chills, fever, sore throat, difficulty swallowing, gingival bleeding, pallor of the skin, skin rashes or mucosal eruptions, or development of vaginitis or proctitis occur. Discontinue the drug if symptoms of liver dysfunction develop, including gastrointestinal disturbances, jaundice, or elevated liver enzymes. Inform the physician if any of the following symptoms occur: hot flushes, excessive sweating, headache, increased fatigue, jaundice, nausea, epigastric discomfort, or constipation.

Severe skin adverse reactions

Severe skin adverse reactions have been reported during treatment with sodium metamizole, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), which may be fatal (see section "Adverse reactions"). Before initiating therapy with Analgin, patients should be informed about the signs and symptoms of severe skin reactions. Close monitoring for such symptoms is required during treatment. If symptoms suggestive of severe skin adverse reactions occur, the drug should be discontinued immediately and must not be used again under any circumstances (see section "Contraindications").

When used in children, continuous medical supervision is required.

During treatment with the drug, peripheral blood composition (leukocyte count and differential) should be monitored.

Prolonged regular use of the drug is not recommended due to the myelotoxicity of sodium metamizole.

With prolonged use of the drug (more than 7 days), monitoring of peripheral blood composition (due to the myelotoxicity of metamizole), as well as renal and liver function, is necessary.

Patients should be warned before starting treatment that if unexplained chills, fever, sore throat, difficulty swallowing, gingival bleeding, pallor of the skin, asthenia, or development of vaginitis or proctitis occur, the drug should be discontinued immediately.

During treatment, urine may turn red due to excretion of a metabolite of sodium metamizole.

Do not use the drug beyond the recommended duration without consulting a physician.

If symptoms of illness do not begin to resolve, if the condition worsens, or if adverse effects occur, discontinue the drug and consult a physician regarding further management.

Use during pregnancy or breastfeeding

The drug is contraindicated during pregnancy.

If use of the drug is necessary during lactation, breastfeeding should be discontinued.

Effect on the ability to drive or operate machinery

No effect.

Dosage and Administration.

Tablets should be taken after meals, with a small amount of water.

For adults and children aged 14 years and older, the usual dose is ½–1 tablet 1–2 times daily.

Maximum daily dose – 1000 mg.

For children aged 12 to 14 years – ½ tablet 1–2 times daily.

The duration of treatment should not exceed 3 days.

Children.

The drug is contraindicated in children under 12 years of age.

Overdose.

Symptoms: nausea, vomiting, stomach pain, gastralgia/gastritis, oliguria, anuria, hypothermia, pronounced decrease in arterial pressure, tachycardia, palpitations, dyspnea, dysphagia, tinnitus, drowsiness, weakness, delirium, impaired consciousness, acute agranulocytosis, acute renal or hepatic failure, hemorrhagic syndrome, seizures, respiratory muscle paralysis.

Treatment: discontinue the drug, induce vomiting, gastric lavage, administration of saline laxatives and enterosorbents, forced diuresis, symptomatic therapy aimed at supporting vital functions. In severe cases, hemodialysis, hemoperfusion, or peritoneal dialysis may be required.

In case of the first signs of overdose, seek immediate medical attention.

Side effects.

Immune system disorders: angioedema, anaphylactic shock.

Skin and subcutaneous tissue disorders: hypersensitivity reactions, including skin and mucosal rashes (e.g. urticaria), pruritus, skin hyperemia, severe skin reactions such as polymorphic exudative erythema, Stevens–Johnson syndrome, toxic epidermal necrolysis (Lyell’s syndrome), drug reaction with eosinophilia and systemic symptoms (DRESS syndrome); increased skin photosensitivity (photosensitization), exfoliative dermatitis.

Blood and lymphatic system disorders: with prolonged use, thrombocytopenia, granulocytopenia, leukopenia, anemia, agranulocytosis are possible.

Renal and urinary disorders: usually in patients with impaired renal function and/or when excessive doses are used – transient oliguria, anuria, proteinuria, interstitial nephritis, red discoloration of urine.

Hepatobiliary disorders: increased activity of liver transaminases, impaired liver function, hepatitis, jaundice, drug-induced liver injury, including acute hepatitis (see section "Special precautions").

Respiratory system disorders: in patients predisposed to bronchospasm, an attack may be provoked, bronchospastic syndrome.

Other: conjunctivitis, hypotension.

If any adverse reactions occur, the drug must be discontinued and medical advice should be sought immediately.

Reporting suspected adverse reactions.

Reporting of suspected adverse reactions after registration of the medicinal product is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, as well as patients or their legal representatives, are encouraged to report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 5 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

10 tablets in blisters.

10 tablets per blister, 1 or 10 blisters per carton.

Supply classification.

Over-the-counter – No. 10.

By prescription – No. 100.

Manufacturer.

JSC "Lubnifarm".

Manufacturer's address and location of business activity.

16, Barvinkova St., Lubny, Poltava region, 37500, Ukraine.