Analgin-zdorovya
Ukraine
Table of Contents
INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT ANALGIN-ZDOROVYE (ANALGIN-ZDOROVYE)
Composition:
Active substance: metamizole sodium;
1 tablet contains 500 mg of sodium metamizole monohydrate;
Excipients: potato starch, calcium stearate.
Pharmaceutical form. Tablets.
Main physicochemical properties: white or white with a yellowish tint, flat cylindrical tablets with beveled edges and a score line.
Pharmacotherapeutic group. Analgesics and antipyretics. Pyrazolones. Sodium metamizole. ATC code N02BB02.
Pharmacological Properties.
Pharmacodynamics.
Sodium metamizole is a pyrazolone derivative and cyclooxygenase inhibitor. It reduces the formation of prostaglandins from arachidonic acid. Unlike other cyclooxygenase inhibitors, it has a weak anti-inflammatory effect but pronounced analgesic, antipyretic, and spasmolytic actions. The spasmolytic effect affects smooth muscle of the urinary and biliary tracts.
It interferes with the conduction of pain-related exteroceptive and proprioceptive impulses through the posterior columns of the spinal cord (Goll's and Burdach's fasciculi), increases the excitation threshold of thalamic pain centers, and enhances heat dissipation.
Pharmacokinetics.
Rapidly absorbed from the gastrointestinal tract. In the intestinal wall, it undergoes hydrolysis to form an active metabolite. The unchanged drug is not present in the blood. The active metabolite is 50–60% bound to plasma proteins. Peak plasma concentration is reached within 1–2 hours. Elimination half-life is 2.5 hours. It is primarily excreted by the kidneys.
Clinical characteristics.
Indications.
Pain syndrome of various origins: headache, toothache, neuralgia, radiculitis, muscle and joint pain, menstrual pain. As an adjunctive agent to reduce pain following surgical and diagnostic procedures. Hyperthermic syndrome in infectious-inflammatory diseases.
Contraindications.
Hypersensitivity to components of the drug, pyrazolone derivatives. Changes in peripheral blood composition: history of agranulocytosis caused by metamizole, other pyrazolones or pyrazolidines, leukopenia. Blood disorders: anemia of any etiology, cytotoxic or infectious neutropenia. Severe impairment of liver and kidney function (porphyrin metabolism). Bone marrow dysfunction or hematopoietic system 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 sedative effect of ethanol.
Chlorpromazine or other phenothiazine derivatives – simultaneous use may lead to pronounced hypothermia.
X-ray contrast agents, colloidal plasma substitutes, and penicillin – should not be used during treatment with sodium metamizole.
Metamizole may induce metabolic enzymes, including CYP2B6 and CYP3A4. Concurrent use of metamizole with bupropion, efavirenz, methadone, valproate, cyclosporine, tacrolimus, and sertraline may reduce plasma concentrations of these drugs, potentially leading to decreased therapeutic efficacy. Therefore, caution is recommended when co-administering metamizole with other medicinal products; clinical response and/or drug levels should be monitored as necessary.
Oral hypoglycemic agents, indirect anticoagulants, glucocorticoids, phenytoin, ibuprofen, and indomethacin – sodium metamizole increases the activity of these drugs by displacing them from protein binding sites in the blood.
Phenylbutazone, glutethimide, barbiturates, and other inducers of hepatic microsomal enzymes – concurrent use reduces the effectiveness of sodium metamizole.
Non-narcotic analgesics, tricyclic antidepressants, hormonal contraceptives, and allopurinol – simultaneous use of sodium metamizole with these drugs may increase its toxicity.
Other nonsteroidal anti-inflammatory drugs (NSAIDs) – potentiate their analgesic and antipyretic effects and increase the likelihood of additive adverse effects.
Sedatives and tranquilizers (diazepam, trioxazine, valocordin) – enhance the analgesic effect of sodium metamizole.
Sarcolysin, mercazole (thiamazole), drugs that suppress bone marrow activity, including gold compounds – increased risk of hematotoxicity, including development of leukopenia.
Codeine, histamine H2-blockers, and propranolol – enhance the effect of sodium metamizole.
Caution is required when co-administering the drug with sulfonamide hypoglycemic agents (enhanced hypoglycemic effect) and diuretics (furosemide).
Myelotoxic medicinal products lead to increased hematotoxicity.
Methotrexate – high-dose metamizole may increase methotrexate plasma concentration and enhance its toxic effects (on the gastrointestinal tract and hematopoietic system).
Special precautions for use.
| Agranulocytosis. Metamizole treatment may cause agranulocytosis, which can lead to fatal outcomes (see section "Adverse Reactions"). It may occur even after previous use of metamizole without adverse effects. Metamizole-induced agranulocytosis is an idiosyncratic adverse reaction. Agranulocytosis is not dose-dependent and may occur at any time during treatment, even shortly after discontinuation of treatment. Patients must be informed of the necessity to discontinue treatment and seek immediate medical attention if any symptoms indicating agranulocytosis occur (e.g., fever, chills, asthenia, pallor, sore throat, difficulty swallowing, bleeding gums, painful mucosal lesions, particularly in the mouth, nose and throat, as well as in the genital area (vaginitis) or anal region (proctitis)). If metamizole is used for fever, some symptoms of developing agranulocytosis may remain unnoticed. Similarly, symptoms may be masked in patients receiving antibiotic therapy. Upon appearance of signs and symptoms suggestive of agranulocytosis, a complete blood count (including differential blood count) should be performed immediately and treatment should be discontinued pending test results. If the diagnosis is confirmed, treatment must not be resumed (see section "Contraindications"). |
Consult a physician before starting treatment with this medication.
Do not exceed the recommended doses of the drug.
Do not use the medicinal product to relieve acute abdominal pain (prior to 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 could complicate their diagnosis.
Alcoholic beverages should be avoided during use of the medicinal product.
The medicinal product should be used with caution in patients:
- of advanced age – may lead to an increased frequency of adverse reactions, particularly affecting the gastrointestinal system;
- with allergic diseases (including pollinosis) or such conditions in medical history – increased risk of allergic reactions;
- 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 or cardiovascular insufficiency;
- with a history of prolonged alcohol dependence;
- when used concomitantly with cytostatic medicinal products (only under physician supervision).
Continuous medical supervision is required when administering the drug to children.
Regular long-term use of the medicinal product is not recommended due to the myelotoxicity of sodium metamizole.
During prolonged use of the drug (more than 7 days), monitoring of peripheral blood count (due to the myelotoxicity of metamizole), as well as kidney and liver function, is necessary.
Drug-induced liver injury.
Cases of acute hepatitis, predominantly of hepatocellular type, have been reported in patients receiving metamizole, manifesting from several days to several months after initiation of treatment. Symptoms included elevated 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 features of autoimmune hepatitis. Most patients recovered after discontinuation of metamizole; however, in isolated cases, progression to liver failure requiring liver transplantation has been reported.
The mechanism of metamizole-induced liver injury is not fully understood, but evidence suggests an immune-allergic mechanism.
Patients should be instructed to promptly inform their physician if symptoms suggestive of liver injury occur. Such patients should discontinue metamizole and undergo liver function assessment.
Metamizole should 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.
During treatment with metamizole, serious skin reactions have been reported, including Stevens−Johnson syndrome, Lyell’s syndrome (toxic epidermal necrolysis), and drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), which may be life-threatening or fatal.
Patients should be informed about the signs and symptoms of skin reactions and closely monitored.
If symptoms indicative of these reactions occur, treatment with metamizole must be discontinued and must not be restarted under any circumstances.
Use of the drug may result in red discoloration of urine due to excretion of metabolites of sodium metamizole.
Do not use the drug beyond the recommended duration without consulting a physician.
If symptoms of illness do not begin to improve, or if the patient's condition worsens, or if adverse effects occur, discontinue use of the drug and consult a physician regarding further management.
Use during pregnancy or breastfeeding.
The medicinal product is contraindicated during pregnancy.
Breastfeeding should be discontinued during treatment.
Ability to affect reaction speed while driving or operating machinery.
No effect.
Method of Administration and Dosage
Administer to adults and children aged 14 years and older orally, 250–500 mg (½–1 tablet) 1–2 times daily. Take tablets after meals; do not chew or crush; swallow with sufficient amount of water.
Maximum daily dose − 1 g.
Children aged 12 to 14 years − 250 mg 1–2 times daily.
This medicinal product is intended for symptomatic short-term use only. Treatment duration − no more than 3 days.
If symptoms do not resolve within 3 days, consult a physician regarding further use of the medicinal product.
Children. Do not administer this drug 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; acute agranulocytosis, hemorrhagic syndrome, oliguria, anuria, acute renal and hepatic failure, and respiratory muscle paralysis may develop.
Treatment: discontinue the drug, induce emesis, gastric lavage, administer saline laxatives and enterosorbents, forced diuresis, and symptomatic therapy aimed at supporting vital functions. In severe cases, hemodialysis, hemoperfusion, or peritoneal dialysis may be performed. In case of convulsive syndrome, diazepam and fast-acting barbiturates should be administered intravenously.
In case of first signs of overdose, seek immediate medical help.
Adverse Reactions.
Respiratory system, thoracic organs and mediastinum: in patients predisposed to bronchospasm, an attack may be provoked; bronchospastic syndrome, dyspnea.
Hepatobiliary system and bile ducts: hepatitis; drug-induced liver injury, including acute hepatitis, jaundice, increased levels of liver enzymes (see section "Special Precautions").
Immune system: possible manifestations of hypersensitivity reactions, including skin and mucous membrane rashes, conjunctivitis, skin hyperemia, pruritus, urticaria, angioneurotic edema, bronchospastic syndrome, anaphylactic shock; very rarely – Stevens-Johnson syndrome, Lyell's syndrome, drug reaction with eosinophilia and systemic symptoms (DRESS).
Cardiovascular system: decreased blood pressure.
Blood and lymphatic system: agranulocytosis; with prolonged use, leukopenia, thrombocytopenia, anemia, granulocytopenia may occur.
Renal and urinary system: usually in patients with impaired renal function and/or when excessive doses are used – transient oliguria, anuria, proteinuria, interstitial nephritis, red discoloration of urine.
If any adverse reactions occur, discontinue use of the medicinal product immediately and consult a physician without delay.
Reporting of suspected adverse reactions.
Reporting suspected adverse reactions after marketing authorization is an important procedure. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are required to report any suspected adverse reactions through the national pharmacovigilance system.
Shelf life. 5 years.
Storage conditions. Store in original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Packaging. Tablets, 10 in a blister pack in a box; 10 in blisters.
Availability. Over-the-counter (without prescription).
Manufacturer. LIMITED LIABILITY COMPANY "CORPORATION "ZDOROV'YA".
Manufacturer's address and place of business.
22, Shevchenka Street, Kharkiv, Kharkiv Oblast, 61013, Ukraine.