Analgin

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ANALGIN

Composition:

Active substance: sodium metamizole;

One tablet contains sodium metamizole (calculated as anhydrous substance) 500 mg;

Excipients: potato starch, calcium stearate, talc.

Pharmaceutical form. Tablets.

Main physicochemical properties: tablets of white or white with a yellowish tint color, with a flat surface, beveled edges, and a score line.

Pharmacotherapeutic group. Analgesics. Pyrazolones. Metamizole sodium. ATC Code N02B B02.

Pharmacological properties.

Analgin exerts analgesic, antipyretic, and anti-inflammatory effects.

Clinical characteristics.

Indications.

• Pain of various origins (headache, toothache, neuralgia, radiculitis, muscle and joint pain, menstrual pain, postoperative and post-diagnostic procedural pain (as an adjunct));
• fever associated with infectious-inflammatory diseases.

Contraindications.

• Known or suspected hypersensitivity to sodium metamizole and/or other pyrazolone derivatives, or to any of the excipients;
• bronchial asthma;
• severe impairment of liver and kidney function (porphyrin metabolism disorders);
• bone marrow dysfunction or hematopoietic system disorders: anemia of any etiology, cytostatic or infectious neutropenia;

peripheral blood abnormalities: metamizole-induced agranulocytosis, agranulocytosis caused by other pyrazolones or pyrazolidines in medical history; leukopenia;

• suspected acute surgical pathology;
• glucose-6-phosphate dehydrogenase deficiency.

Interaction with other medicinal products and other forms of interactions.

If you are taking any other medicinal products, you must inform your physician!

• X-ray contrast agents, colloidal plasma substitutes, penicillin – should not be used during treatment with sodium metamizole.
• Chlorpromazine or other phenothiazine derivatives – may cause pronounced hypothermia.
• Metamizole may induce metabolic enzymes, particularly CYP2B6 and CYP3A4. Concomitant use of metamizole with bupropion, efavirenz, methadone, valproate, cyclosporine, tacrolimus, and sertraline may lead to decreased plasma concentrations of these drugs and thus reduce their therapeutic efficacy. Therefore, caution is recommended when co-administering sodium metamizole with other medicinal products; clinical response and/or drug levels should be monitored as necessary.
• Indirect anticoagulants, phenytoin, glucocorticosteroids, indometacin, ibuprofen – sodium metamizole enhances the activity of these drugs by displacing them from protein binding.
• Phenylbutazone, glutethimide, barbiturates, and other inducers of hepatic microsomal enzymes – reduce the efficacy of sodium metamizole.
• Tricyclic antidepressants, hormonal contraceptives, allopurinol, alcohol – may increase the toxicity of sodium metamizole. Sodium metamizole enhances the sedative effect of alcohol.
• Other nonsteroidal anti-inflammatory drugs (NSAIDs) – their analgesic and antipyretic effects are potentiated, and the risk of additive adverse effects increases.
• Sedatives and tranquilizers (diazepam, trioxazine, valocordin), codeine, H₂-histamine receptor blockers, propranolol – enhance the analgesic effect of sodium metamizole.
• Sarcolysin (mechloretamine), mercaptoimidazole (methimazole), thiamazole, drugs that suppress bone marrow activity, including gold compounds – increased risk of hematotoxicity, including development of leukopenia.
• Methotrexate – high-dose metamizole may increase methotrexate plasma concentration and enhance its toxic effects (particularly on the gastrointestinal tract and hematopoietic system).
• Sulfonamide oral hypoglycemic agents – possible potentiation of their hypoglycemic effect when used concomitantly with nonsteroidal anti-inflammatory drugs (NSAIDs), including sodium metamizole.
• Diuretics (furosemide) – possible reduction of diuretic effect.

Special precautions for use.

Agranulocytosis

Treatment with metamizole may cause agranulocytosis, including fatal cases (see section "Adverse reactions"). This condition may occur even if previous use of metamizole was uncomplicated.

Agranulocytosis caused by metamizole is an idiosyncratic adverse reaction unrelated to dose and may occur at any time during treatment, as well as shortly after discontinuation.

Patients should be informed of the necessity to discontinue metamizole and immediately consult a physician if any symptoms suggestive of agranulocytosis appear (e.g., fever, chills, sore throat, and painful mucosal lesions, particularly in the mouth, nose, and throat, as well as in genital or anal areas).

If metamizole is used during fever, some symptoms of developing agranulocytosis may remain undetected. Similarly, these symptoms may go unnoticed in patients receiving antibiotic therapy.

In the event of signs or symptoms suggestive of agranulocytosis, a complete blood count (including differential leukocyte count) must be performed immediately, and treatment should be discontinued until test results are obtained. If the diagnosis of agranulocytosis is confirmed, treatment must not be resumed (see section "Contraindications").

Prior to initiating treatment with Analgin, consult a physician.

Do not exceed the recommended doses of the drug.

Do not use the drug to relieve acute abdominal pain (before determining the cause).

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.

Alcoholic beverages should be avoided during treatment.

The drug should be used with caution in patients:

• of advanced age – may lead to increased frequency of adverse reactions, especially those affecting the gastrointestinal tract;
• with allergic diseases (including hay fever), either currently or in medical history – risk of allergic reactions is increased;
• with impaired renal function or history of kidney disease (pyelonephritis, glomerulonephritis);
• with inflammatory bowel diseases, including ulcerative colitis and Crohn's disease;
• with marked arterial hypotension or cardiovascular insufficiency;
• with chronic alcoholism;
• when used concomitantly with cytostatic drugs (only under physician supervision).

When used in children, continuous medical supervision is required. Qualitative and quantitative composition of peripheral blood should be monitored.

During prolonged use of the drug (more than 7 days), peripheral blood composition (due to myelotoxicity of metamizole), as well as renal and hepatic function, should be monitored.

Severe skin reactions

Severe skin reactions, including Stevens–Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), which may be life-threatening or fatal, have been reported during treatment with metamizole.

Patients should be informed about the signs and symptoms of severe skin reactions and closely monitored.

If symptoms suggestive of such reactions occur, treatment with metamizole must be discontinued and must never be restarted (see section "Contraindications").

Drug-induced liver injury

Cases of drug-induced liver injury have been reported following the use of metamizole. Liver damage was predominantly hepatocellular in nature and developed from several days to one month after initiation of treatment.

Signs and symptoms included elevated serum liver enzymes with or without jaundice, often in the context of hypersensitivity reactions to other drugs (e.g., skin rash, hematological disorders, fever, eosinophilia) or manifestations of autoimmune hepatitis. In some patients, liver injury recurred upon re-exposure to metamizole.

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

Most patients recovered after discontinuation of metamizole; however, in isolated cases, progression to acute liver failure requiring liver transplantation has been reported.

Patients should be informed of the need to consult a physician if symptoms suggestive of liver injury occur. In such cases, metamizole should be discontinued and liver function assessed. Metamizole must not be re-administered to patients who experienced liver injury during previous treatment with metamizole unless other causes of liver injury have been ruled out.

Patients should be warned before starting treatment that the drug must be discontinued immediately in case of unexplained chills, fever, sore throat, painful swallowing, gum bleeding, pallor of the skin, asthenia, or development of vaginitis or proctitis. The drug should also be discontinued at the first sign of skin or mucosal rash. In case any of these symptoms occur, immediate medical consultation is required.

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

Do not use the drug for longer than the recommended duration without consulting a physician!

If symptoms of illness do not begin to subside, or if the patient's condition worsens, or if adverse effects occur, treatment should be discontinued and medical advice sought regarding further use.

Use during pregnancy or breastfeeding.

Use during pregnancy is contraindicated.

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

Ability to affect reaction speed when driving or operating machinery.

No effect.

Dosage and Administration.

For adults and children aged 14 years and older, administer orally 250–500 mg (1/2–1 tablet) 1–2 times daily. Tablets should be taken after meals, without chewing or crushing, and swallowed with sufficient amount of water.

Maximum daily dose − 1 g.

For children aged 12 to 14 years − 250 mg 1–2 times daily.

Analgin is intended for symptomatic short-term use only. Treatment duration should not exceed 3 days.

If symptoms persist for more than 3 days, consult a physician regarding further use of the medication.

Children.

The drug must not be administered to children under 12 years of age.

Overdose.

Symptoms: hypothermia, palpitations, pronounced decrease in arterial blood pressure, tachycardia, dysphagia, dyspnea, tinnitus, nausea, vomiting, gastralgia/gastritis, weakness, drowsiness, delirium, impaired consciousness, convulsive syndrome; possible development of acute agranulocytosis, hemorrhagic syndrome, oliguria, anuria, acute renal and hepatic failure, respiratory muscle paralysis.

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

In case of first signs of overdose, seek immediate medical attention!

Side effects.

Skin and subcutaneous tissue: severe skin reactions have been reported with metamizole use, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) (see section "Special precautions") – frequency unknown.

Allergic reactions: hypersensitivity reactions may occur, including skin and mucous membrane rashes, conjunctivitis, pruritus, urticaria, angioneurotic edema, bronchospastic syndrome, anaphylactic shock; very rarely – Stevens-Johnson syndrome, Lyell’s syndrome.

Blood and lymphatic system: with prolonged use agranulocytosis, leukopenia, thrombocytopenia, anemia, granulocytopenia may occur.

Urinary system: usually in patients with impaired renal function and/or with overdose – transient oliguria, anuria, proteinuria, interstitial nephritis.

Hepatobiliary system: hepatitis; drug-induced liver injury, including acute hepatitis, jaundice, increased liver enzyme levels (see section "Special precautions").

Other: decreased blood pressure.

If any adverse reactions occur, discontinue the drug immediately and consult a physician without delay.

Reporting suspected adverse reactions

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

Shelf life. 4 years.

Do not use after the expiry date stated on the packaging.

Storage conditions.

Store in a dry, light-protected place at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging.

10 tablets in a blister pack, 1 blister pack per carton; 10 tablets in a blister pack.

Supply category. Over-the-counter (without prescription).

Manufacturer.

Agrofarm, Limited Liability Company.

Manufacturer’s address.

113-A Centralna St., Irpin, Kyiv region, 08200, Ukraine.