Analgin
Ukraine
Table of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ANALGIN (ANALGINE)
Composition:
Active substance: metamizole sodium;
1 ml of solution contains 500 mg of sodium metamizole (analgin), calculated as 100% substance;
Excipients: sodium metabisulfite (E223), disodium edetate (Trilon B), sodium formaldehyde sulfoxylate, sodium hydroxide, water for injections.
Dosage form. Injection solution.
Main physicochemical properties: clear, colorless or slightly yellowish liquid.
Pharmacotherapeutic group.
Analgesics and antipyretics. Pyrazolones. ATC code N02B B02.
Pharmacological properties.
Pharmacodynamics.
A non-steroidal anti-inflammatory agent, a derivative of pyrazolone. Non-selectively inhibits cyclooxygenase, thereby reducing the formation of prostaglandins from arachidonic acid. Interferes with transmission of pain-related extra- 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. A distinctive feature is the relatively weak anti-inflammatory effect, which results in minimal impact on water-electrolyte balance (sodium and water retention) and on the gastrointestinal mucosa. Demonstrates analgesic, antipyretic, and some spasmolytic effects (particularly on the smooth musculature of the urinary and biliary tracts).
Pharmacokinetics.
After intramuscular administration, it is rapidly and completely absorbed into the bloodstream. In the liver, it undergoes oxidative deamination to form an active metabolite. Protein binding of the active metabolite is 50–60%. In children, deamination processes proceed somewhat slower than in adults. With frequent administration (more than four times daily), drug accumulation and intoxication are possible in pediatric patients. It distributes rapidly and evenly in tissues. Maximum plasma concentration is reached within 1–1.5 hours after intramuscular injection. The elimination half-life (T1/2) is approximately 7 hours. Excreted in urine.
Clinical characteristics.
Indications.
Mild to moderate pain of various origins and localizations (headache, toothache, burns, postoperative pain, dysmenorrhea, arthralgia, neuralgia, radiculitis, myositis); hyperthermic syndrome and febrile conditions (in influenza, acute respiratory and other infections); renal and hepatic colic (in combination with spasmolytic agents).
Contraindications.
Hypersensitivity to components of the drug. Increased individual sensitivity to other pyrazolone derivatives. History of agranulocytosis induced by metamizole, other pyrazolones or pyrazolidines. Cytostatic or infectious neutropenia. Hepatic and/or renal insufficiency. Hereditary hemolytic anemia associated with glucose-6-phosphate dehydrogenase deficiency. Asthma attacks induced by acetylsalicylic acid. Abdominal pain of unknown origin. Anemia, leukopenia. Kidney diseases: pyelonephritis, glomerulonephritis, including in medical history. Intravenous administration is contraindicated in patients with systolic blood pressure below 100 mm Hg. Polytrauma. Shock. Porphyria. Impaired bone marrow function or hematopoietic system disorders.
Interaction with other medicinal products and other types of interactions.
Due to a high risk of pharmaceutical incompatibility, the drug must not be mixed with other medicinal products in the same syringe.
Ethanol – the effect of ethanol is enhanced.
Chlorpromazine or other phenothiazine derivatives – concomitant use may lead to pronounced hypothermia.
X-ray contrast agents, colloidal plasma substitutes, and penicillin should not be used during treatment with analgin.
Pharmacokinetic induction of metabolic enzymes – metamizole may induce metabolic enzymes, particularly CYP2B6 and CYP3A4. Concomitant use of metamizole with bupropion, efavirenz, methadone, valproate, cyclosporine, tacrolimus, or sertraline may lead to reduced plasma concentrations of these drugs, potentially reducing their clinical efficacy. Therefore, caution is recommended when using metamizole concomitantly; clinical response and/or drug levels should be monitored if necessary.
Oral hypoglycemic agents, indirect anticoagulants, glucocorticosteroids, phenytoin, ibuprofen, and indometacin – analgin increases the activity of these drugs by displacing them from protein binding.
Phenylbutazone, barbiturates, and other hepatostimulators – concomitant use reduces the effectiveness of analgin.
Non-narcotic analgesics, tricyclic antidepressants, hormonal contraceptives, and allopurinol – concomitant use with analgin may increase its toxicity.
Sedatives and tranquilizers (diazepam, trioxazine, valocordin) enhance the analgesic effect of analgin.
Codeine, histamine H2-blockers, and propranolol enhance the effect of analgin.
Caution is required when using the drug concomitantly with sulfonylurea hypoglycemic agents (hypoglycemic effect is enhanced) and diuretics (furosemide).
Concomitant use with other nonsteroidal anti-inflammatory drugs potentiates their analgesic and antipyretic effects but increases the risk of hypersensitivity reactions and other adverse effects.
High doses of metamizole may increase plasma concentrations of methotrexate and enhance its toxic effects (on the gastrointestinal tract and hematopoietic system).
Concomitant use with sarkolysin, mercaptopurine (thiamazole), drugs that suppress bone marrow activity, including gold compounds, increases the risk of hematotoxicity, including the development of leukopenia.
Special precautions for use.
| Agranulocytosis. Treatment with metamizole may cause agranulocytosis, including fatal cases (see section "Side Effects"). This condition may occur even if previous use of metamizole was without adverse effects. Metamizole-induced agranulocytosis is an idiosyncratic adverse reaction, independent of dose, and may occur at any time during treatment as well as shortly after its discontinuation. Patients should be informed of the necessity to discontinue treatment and seek immediate medical attention 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 the genital or anal area). If metamizole is used for fever, some symptoms indicating the development of agranulocytosis may remain unnoticed. Similarly, these symptoms may be masked in patients receiving antibiotic therapy. In the event 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 the results. If the diagnosis is confirmed, treatment must not be resumed (see section "Contraindications"). |
Parenteral administration requires medical supervision (due to a high frequency of allergic reactions, including fatal outcomes) and availability of facilities for shock therapy.
Patients with atopic bronchial asthma and pollenosis have an increased risk of hypersensitivity reactions.
The drug must not be used to relieve acute abdominal pain of unknown origin (until the cause is determined).
Careful monitoring of hemodynamics is required when prescribing to patients with acute cardiovascular disorders. Use with caution in myocardial infarction, during cytostatic therapy, in chronic alcoholism, and in patients with a history of severe allergies.
Regular long-term use of the drug is not recommended due to the myelotoxicity of sodium metamizole; peripheral blood picture (leukocyte formula) must be monitored.
Subcutaneous administration should not be used due to possible tissue irritation.
During treatment, urine may turn red (due to excretion of a metabolite), which has no clinical significance.
The drug should be used with caution in the following patients:
- elderly patients – may lead to increased frequency of adverse reactions, especially those affecting the gastrointestinal tract;
- patients with inflammatory bowel diseases, including ulcerative colitis and Crohn’s disease.
Severe skin reactions, including Stevens-Johnson syndrome, Lyell’s syndrome, and drug-induced eosinophilia with 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 skin reactions and closely monitored.
If signs and symptoms indicating these reactions appear, treatment with metamizole must be discontinued and must never be restarted.
Drug-induced liver injury. Cases of acute hepatitis, predominantly hepatocellular in nature, have been reported in patients treated with metamizole. Signs of liver injury appeared 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 metamizole; however, in isolated cases, progression to acute liver failure requiring liver transplantation has been reported.
The mechanism of metamizole-induced liver injury is not fully understood, but available data suggest an immune-allergic mechanism.
Patients should be instructed to contact their physician if symptoms suggesting liver injury occur. In such cases, metamizole should be discontinued and liver function should be evaluated.
Metamizole must not be re-administered to patients who have experienced liver injury during previous treatment with metamizole, unless another cause of liver injury has been clearly established.
Sodium metabisulfite may rarely cause hypersensitivity reactions and bronchospasm.
The product contains 1.533 mmol (35.235 mg)/dose of sodium. Caution is advised when administering to patients on a sodium-controlled diet.
Use during pregnancy or breastfeeding.
Contraindicated during pregnancy, especially in the first trimester and the last 6 weeks.
Breastfeeding should be discontinued during treatment, as sodium metamizole passes into breast milk.
Ability to affect reaction speed when driving or operating machinery.
During treatment, driving vehicles and engaging in other potentially hazardous activities requiring increased attention and rapid psychomotor reactions are not permitted.
Administration and Dosage
Administer intramuscularly or intravenously as a bolus injection. The route of administration and dosage depend on the severity of the disease and are determined individually. Analgesic effect is higher with intravenous administration compared to intramuscular.
The solution to be administered must be at body temperature. To prevent a sudden drop in arterial blood pressure, intravenous injection should be performed slowly (at a rate not exceeding 1 ml/min). The patient must be in a lying position, and monitoring of arterial blood pressure, heart rate, and respiration is required. Conditions for anti-shock therapy must be available. A long needle must be used for intravenous administration.
Adults: 0.5–1 ml (250–500 mg) 2–3 times daily. Maximum single dose for both routes of administration is 1 ml (500 mg); maximum daily dose is 2 ml (1 g).
Children under 1 year of age: dose of 0.01 ml/kg body weight. For children under 1 year of age, the drug should be administered only intramuscularly.
Duration of use – up to 3 days.
Children aged 1 year and older: administer 0.1 ml per year of life 1–2 times daily. Duration of use – up to 3 days.
Children
The drug should be administered only intramuscularly in children under 1 year of age. Use in children only under medical supervision and for serious or life-threatening indications.
Overdose
Symptoms: hypothermia, pronounced decrease in arterial blood pressure, palpitations, dyspnea, tinnitus, nausea, vomiting, gastralgia, weakness, oliguria, anuria, drowsiness, delirium, disturbances of consciousness, tachycardia, convulsive syndrome; acute agranulocytosis, hemorrhagic syndrome, acute renal and hepatic failure, and respiratory muscle paralysis may develop.
Treatment: induce vomiting, perform gastric lavage via a tube, administer saline laxatives and activated charcoal. Implement forced diuresis, hemodialysis, blood alkalinization, and symptomatic therapy aimed at supporting vital functions. In case of convulsive syndrome, administer diazepam and fast-acting barbiturates intravenously.
Adverse Reactions.
Urinary system disorders: oliguria, anuria, proteinuria, interstitial nephritis, red discoloration of urine.
Hepatobiliary system disorders: hepatitis; drug-induced liver injury, including acute hepatitis, jaundice, elevated liver enzymes (see section "Special precautions").
Hematopoietic system disorders: agranulocytosis, leukopenia, thrombocytopenia, anemia, granulocytopenia.
Allergic reactions: hypersensitivity reactions, skin and mucous membrane rashes, pruritus, urticaria, conjunctivitis, Quincke's edema; rarely – Stevens-Johnson syndrome, Lyell's syndrome, bronchospastic syndrome, anaphylactoid reactions, anaphylactic shock, skin hyperemia, angioneurotic edema, drug reaction with eosinophilia and systemic symptoms (DRESS).
Cardiovascular system disorders: decreased blood pressure, tachycardia.
Local reactions at the injection site: infiltrates at the injection site (with intramuscular administration), hyperemia, swelling, local rashes, and pruritus at the injection site.
If any adverse reactions occur, discontinue use of the medicinal product immediately and consult a physician without delay.
Shelf life. 3 years.
Storage conditions.
Store in the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.
Incompatibility.
Due to a high risk of pharmaceutical incompatibility, the drug must not be mixed with other medicinal products in the same syringe.
Packaging.
1 ml or 2 ml in an ampoule; 10 ampoules per box.
2 ml in an ampoule; 5 ampoules per blister; 2 blisters per box.
2 ml in an ampoule; 10 ampoules per blister; 1 blister per box.
Prescription category. Prescription only.
Manufacturer.
Limited Liability Company "Kharkiv Pharmaceutical Enterprise "Zdorovya Narodu".
LIMITED LIABILITY COMPANY "CORPORATION ZDOROVYE".
Manufacturer's address and place of business.
Ukraine, 61002, Kharkiv region, city of Kharkiv, Kulikovska Street, building 41.
(Limited Liability Company "Kharkiv Pharmaceutical Enterprise "Zdorovya Narodu")
Ukraine, 61013, Kharkiv region, city of Kharkiv, Shevchenka Street, building 22.
(LIMITED LIABILITY COMPANY "CORPORATION ZDOROVYE")