Analgin
Ukraine
Table of Contents
I N S T R U C T I O N for medical use of the medicinal product A N A L G I N (ANALGIN)
Composition:
active substance: metamizole sodium;
1 tablet contains 500 mg of sodium metamizole;
excipients: potato starch, calcium stearate, talc.
Pharmaceutical form. Tablets.
Main physico-chemical properties: white or slightly yellowish tablets with a flat surface, bevelled edges and a score line.
Pharmacotherapeutic group. Analgesics and antipyretics. Sodium metamizole.
ATC code N02B B02.
Pharmacological properties.
Pharmacodynamics.
An analgesic, antipyretic, and spasmolytic agent (regarding smooth musculature of the urinary and biliary tracts) belonging to the pyrazolone derivatives group. Its anti-inflammatory effect is weak.
The mechanism of action is due to cyclooxygenase inhibition, leading to reduced synthesis of prostaglandins, which in inflammatory foci cause pain, elevated temperature, and increased tissue permeability. It also interferes with transmission of extra- and proprioceptive pain impulses, raises the excitation threshold of thalamic pain sensitivity centers, and enhances heat dissipation.
Pharmacokinetics.
Sodium metamizole is well absorbed in the gastrointestinal tract. It is hydrolyzed in the intestinal wall to form an active metabolite (unchanged metamizole is not present in the blood). Therapeutic concentration of the active metabolite in the blood is reached approximately 0.5 hours after administration; maximum concentration occurs within 1–1.5 hours (after a dose of 6 mg/kg body weight). Plasma protein binding of the active metabolite is 50–60%. It is metabolized in the liver and excreted by the kidneys. It crosses the placental barrier and is excreted into breast milk.
Clinical characteristics.
Indications.
Pain syndrome of various origins: headache, toothache, neuralgia, myalgia, radiculitis, myositis, menstrual pain. As an auxiliary agent, it may be used to reduce pain after surgical and diagnostic procedures. Hyperthermic syndrome in infectious-inflammatory diseases.
Contraindications.
Hypersensitivity to metamizole sodium or to other pyrazolone derivatives. Agranulocytosis caused by metamizole, other pyrazolones or pyrazolidines in medical history. Disorders of bone marrow function or diseases of the hematopoietic and blood system: agranulocytosis, leukopenia, anemia of any etiology, cytostatic or infectious neutropenia. Severe impairment of liver or kidney function (porphyrin metabolism). Congenital glucose-6-phosphate dehydrogenase deficiency. Bronchial asthma. Suspicion of acute surgical pathology.
Interaction with other medicinal products and other types of interactions.
Ethanol – sedative effect of ethanol is enhanced.
Chlorpromazine or other phenothiazine derivatives – simultaneous use may lead to development of pronounced hypothermia.
X-ray contrast agents, colloidal plasma substitutes and penicillin – should not be used during treatment with metamizole sodium.
Cyclosporine – when used concomitantly, cyclosporine blood concentration decreases.
Oral hypoglycemic agents, indirect anticoagulants, glucocorticosteroids, phenytoin, ibuprofen and indometacin – metamizole sodium increases 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 metamizole sodium when used concomitantly.
Non-narcotic analgesics, tricyclic antidepressants (amitriptyline, doxepin), hormonal contraceptives and allopurinol – concomitant use of metamizole sodium with these drugs may increase its toxicity.
Other non-steroidal anti-inflammatory drugs – their analgesic and antipyretic effects are enhanced, and the risk of additive adverse side effects increases.
Sedatives and tranquilizers (diazepam, trioxazane, valocordin) – enhance the analgesic effect of metamizole sodium.
Melphalan, mercaptopurine, thiouracil, drugs that suppress bone marrow activity, including gold compounds – increases the risk of hematotoxicity, including development of leukopenia.
Codeine, histamine H2-blockers and propranolol (anaprilin) – enhance the effect of metamizole sodium.
Caution is required when using the drug concomitantly with sulfonylurea hypoglycemic agents (hypoglycemic effect is enhanced) and diuretics (furosemide).
Methotrexate – high doses of metamizole may lead to increased methotrexate plasma concentration and enhanced toxic effects (on gastrointestinal tract and hematopoietic system).
Metamizole may induce metabolic enzymes, particularly CYP2B6 and CYP3A4.
Concomitant use of metamizole with bupropion, efavirenz, methadone, valproate, tacrolimus or sertraline may result in decreased plasma concentrations of these drugs, with potential reduction in clinical efficacy. Therefore, co-administration of these drugs with metamizole is recommended with caution; monitoring of clinical response and/or drug levels may be necessary.
Special precautions for use.
| Agranulocytosis Metamizole treatment may cause agranulocytosis, which may lead to a fatal outcome (see section "Adverse reactions"). Agranulocytosis may occur even if previous use of metamizole was without adverse effects. Metamizole-induced agranulocytosis is an idiosyncratic adverse reaction. This reaction may occur independently of the drug dose and at any time during treatment or shortly after its discontinuation. Patients should be informed of the necessity to discontinue treatment and seek immediate medical attention if any symptoms indicating agranulocytosis occur (e.g., fever, chills, sore throat, and painful mucosal lesions, particularly in the mouth, nose, and throat, as well as in the 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. If signs or symptoms suggestive of agranulocytosis appear, a complete blood count (particularly a differential blood count) should be performed immediately, and treatment should be discontinued pending the results. If the diagnosis is confirmed, treatment must not be resumed (see section "Contraindications"). |
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 (until 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.
Alcohol consumption should be avoided during the use of the drug.
The drug should be used with caution in patients:
- elderly – may lead to an increased frequency of adverse reactions, especially those affecting the gastrointestinal system;
- with allergic diseases (including pollinosis), atopic bronchial asthma, including in medical history – risk of allergic reactions is increased;
- with impaired kidney function, or history of kidney diseases (pyelonephritis, glomerulonephritis);
- with inflammatory bowel diseases, including ulcerative colitis and Crohn's disease;
- with marked arterial hypotension, cardiovascular insufficiency;
- with a history of alcoholism;
- when used concomitantly with cytostatic drugs (only under physician supervision).
Continuous medical supervision is required when administering the drug to children.
Regular long-term use of the drug is not recommended due to the myelotoxicity of sodium metamizole.
During prolonged use of the drug (more than 7 days), kidney and liver function should be monitored.
Severe skin reactions
Severe skin reactions have been reported during treatment with metamizole, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), which may be fatal.
Patients should be informed about the signs and symptoms of skin reactions and closely monitored.
If signs or symptoms indicating these reactions occur, treatment with metamizole should be discontinued and must never be restarted (see section "Contraindications").
Risk of drug-induced liver injury
Cases of acute hepatitis, predominantly of hepatocellular type, have been observed in patients taking sodium metamizole, with manifestations appearing from several days to several months after initiation of treatment. Symptoms included elevated serum liver enzymes, with or without jaundice, often in the context of hypersensitivity reactions to other drugs (e.g., skin rash, 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 liver injury induced by sodium metamizole is not clearly established, but available data suggest an immune-allergic mechanism.
Patients should be instructed to inform their physician if symptoms indicating liver injury occur. If liver injury is suspected, patients should discontinue sodium metamizole, and liver function parameters should be evaluated.
Cases of liver injury during treatment with sodium metamizole are very rare, but the exact frequency of this adverse reaction cannot be determined. Liver injury recurrence has been observed in some patients upon re-administration of sodium metamizole. If a patient previously experienced liver injury during treatment with sodium metamizole and no other cause of liver injury was identified, drugs containing sodium metamizole should not be used again.
Red discoloration of urine may occur during treatment due to excretion of a metabolite of sodium metamizole.
Do not use the drug beyond the established period without consulting a physician.
If symptoms of illness do not begin to subside, or conversely, if health deteriorates or adverse effects occur, treatment with the drug should be discontinued and a physician should be consulted regarding further management.
Use during pregnancy or breastfeeding.
The drug is contraindicated during pregnancy. Breastfeeding should be discontinued during treatment, as sodium metamizole passes into breast milk.
Ability to affect reaction speed when driving or operating machinery.
Does not affect.
Dosage and Administration
Take orally after meals, swallowing with a small amount of water.
For adults and children aged 14 years and older, the usual dose is 250–500 mg 1–2 times daily.
Maximum daily dose – 1 g.
For children aged 12–14 years, the recommended dose is 250 mg 1–2 times daily.
Duration of treatment should not exceed 3 days.
Children.
The drug is indicated for children aged 12 years and older.
Overdose.
Symptoms: hypothermia, palpitations, pronounced decrease in arterial pressure, tachycardia, dysphagia, dyspnea, tinnitus, nausea, vomiting, stomach pain, gastralgia/gastritis, weakness, drowsiness, delirium, impaired consciousness, convulsive syndrome; hemorrhagic syndrome, oliguria, anuria, acute renal and hepatic failure, 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, blood alkalinization, hemoperfusion, or peritoneal dialysis may be required. In the event of convulsive syndrome, intravenous administration of diazepam and fast-acting barbiturates is indicated.
In case of the first signs of overdose, seek immediate medical help!
Adverse Reactions
Skin and subcutaneous tissue disorders: 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 for use"). Frequency is unknown.
Allergic reactions: Hypersensitivity reactions may occur, including skin and mucosal rashes, conjunctivitis, skin hyperemia, pruritus, urticaria, angioneurotic edema (Quincke's edema), bronchospastic syndrome, anaphylactic shock; very rarely – Stevens-Johnson syndrome, Lyell's syndrome.
Blood and lymphatic system disorders: agranulocytosis, leukopenia, thrombocytopenia, anemia, granulocytopenia.
Renal and urinary system disorders: usually in patients with impaired renal function and/or following overdose – transient oliguria, anuria, proteinuria, interstitial nephritis, red discoloration of urine.
Hepatobiliary disorders: increased hepatic transaminase activity, impaired liver function, hepatitis, jaundice, drug-induced liver injury, including acute hepatitis (see section "Special precautions for use").
Other: decreased arterial 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 ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmacy professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy via the automated pharmacovigilance information system at: 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 and sight of children.
Packaging.
10 tablets per blister.
10 tablets in a blister; 2, 3, or 10 blisters per carton.
Release category.
Over-the-counter – № 10.
By prescription – № 20, № 30, № 100.
Manufacturer: JSC "Monfarm".
Manufacturer's address and location of business activity:
8, Zavodska Street, Avramivka village, Uman district, Cherkasy region, Ukraine, 19161.