Analgin

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT ANALGIN (ANALGIN)

Composition:

Active substance: metamizole sodium;

1 ml of solution contains 500 mg of sodium metamizole;

Excipients: sodium metabisulfite (E 223), disodium edetate, sodium hydroxide, water for injections.

Pharmaceutical form. Injection solution.

Main physicochemical properties: clear, colorless or slightly yellowish or greenish-yellow liquid.

Pharmacotherapeutic group. Analgesics and antipyretics. Pyrazolones.

ATC code N02B B02.

Pharmacological properties.

Pharmacodynamics.

An analgesic, antipyretic, and spasmolytic agent (affects smooth muscle of the urinary and biliary tracts) belonging to the pyrazolone derivatives group. Its anti-inflammatory effect is weak.

The mechanism of action is based on inhibition of cyclooxygenase, leading to reduced synthesis of prostaglandins, which mediate pain, fever, and increased tissue permeability at the site of inflammation. It also interferes with transmission of nociceptive and proprioceptive impulses, raises the excitation threshold of thalamic pain sensitivity centers, and enhances heat dissipation.

Pharmacokinetics.

After administration, metamizole is hydrolyzed to its active metabolite (following intravenous administration, unchanged metamizole is found in plasma only in negligible amounts). The active metabolite is 50–60% protein-bound. Metamizole is metabolized in the liver and excreted by the kidneys. It crosses the placental barrier and is excreted into breast milk.

Clinical characteristics.

Indications.

Mild to moderate pain of various origins and localizations (headache, toothache, burns, postoperative pain, dysmenorrhea, arthralgia, neuralgia, radiculitis, myositis); hyperthermic syndrome, febrile conditions (influenza, acute respiratory and other infections); renal and hepatic colic (in combination with spasmolytic agents).

Contraindications.

Hypersensitivity to metamizole sodium and other pyrazolone derivatives. History of bronchial asthma attacks, rhinitis, or conjunctivitis induced by acetylsalicylic acid or other nonsteroidal anti-inflammatory drugs. Disorders of hematopoiesis (agranulocytosis, cytostatic or infectious neutropenia). Hepatic and/or renal insufficiency. Hereditary hemolytic anemia associated with glucose-6-phosphate dehydrogenase deficiency. Abdominal pain of unknown origin. Anemia, leukopenia. Kidney diseases: pyelonephritis, glomerulonephritis, including in history. Intravenous administration is contraindicated in patients with systolic blood pressure below 100 mm Hg. Polytrauma. Shock. Porphyria.

Interaction with other medicinal products and other types of interactions.

The toxic effect of the drug is enhanced when used concomitantly with other non-narcotic analgesics, tricyclic antidepressants (amitriptyline, doxepin), hormonal contraceptives, and allopurinol. Sarcolysin and mercazole (thiamazole) increase the risk of developing leukopenia. The drug's effect is enhanced by histamine H2-blockers and propranolol (anaprilin), and reduced by phenylbutazone, barbiturates, and other inducers of hepatic microsomal enzymes. Analgesic action of the drug is enhanced by sedatives and tranquilizers (diazepam, trioxazine, valocordin, codeine, etc.). The drug increases the activity of oral hypoglycemic agents, indirect anticoagulants, phenytoin, ibuprofen, glucocorticosteroids, and indomethacin (by displacing them from plasma protein binding), enhances the sedative effect of alcohol, and reduces plasma concentration of cyclosporine. Concurrent use with phenothiazine derivatives (chlorpromazine, etc.) may lead to the development of pronounced hyperthermia.

Concomitant use with other nonsteroidal anti-inflammatory drugs potentiates their analgesic and antipyretic effects and increases the risk of additive adverse effects.

High doses of metamizole may increase plasma concentration of methotrexate and enhance its toxic effects (on the gastrointestinal tract and hematopoietic system).

Concomitant use with sarcolysin, mercazole (thiamazole), and drugs that suppress bone marrow activity, including gold compounds, increases the risk of hematotoxicity, including development of leukopenia.

Caution is required when using the drug concomitantly with diuretics (furosemide).

The drug must not be used simultaneously with X-ray contrast agents, colloidal plasma substitutes, and penicillin.

Metamizole may induce metabolic enzymes, including CYP2B6 and CYP3A4.

Concomitant use of metamizole with bupropion, efavirenz, methadone, valproate, tacrolimus, or citalopram may reduce plasma concentrations of these drugs, potentially decreasing their 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.

Metamizole may reduce serum levels of cyclosporine; therefore, cyclosporine levels should be monitored when used concomitantly with metamizole.

The effect of ethanol is enhanced when used concomitantly with metamizole.

Special precautions for use

Parenteral administration requires medical supervision (due to a high incidence of allergic reactions, including fatal outcomes) and availability of facilities for emergency anti-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).

The medicinal product should be used with caution in the following patients:

• Elderly patients – may lead to an increased frequency of adverse reactions, particularly those affecting the gastrointestinal system;
• Patients with inflammatory bowel diseases, including ulcerative colitis and Crohn’s disease.

Careful hemodynamic monitoring is required when prescribing to patients with acute cardiovascular disorders. Use with caution in patients with myocardial infarction, during cytostatic therapy, chronic alcoholism, a history of severe allergies, and blood disorders.

Regular long-term use of the drug is not recommended due to the myelotoxic potential of sodium metamizole; peripheral blood picture (leukocyte formula) must be monitored.

Agranulocytosis may occur during treatment. Therefore, if unexplained fever, chills, sore throat, difficulty swallowing, stomatitis, or inflammation of the external genitalia and anus occur, the drug must be discontinued immediately.

Subcutaneous administration is not recommended due to possible tissue irritation.

During treatment, urine may turn red (due to excretion of a metabolite), which has no clinical significance.

Sodium metabisulfite may rarely cause hypersensitivity reactions and bronchospasm.

The use of the drug must be discontinued if skin or mucosal rashes appear.

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 skin reactions and closely monitored.

If symptoms suggesting these reactions occur, metamizole therapy must be discontinued and must not be restarted under any circumstances (see section "Contraindications").

Liver injury due to medication

Hepatitis, mainly of hepatocellular type, has been observed in patients treated with metamizole, occurring from several days to several months after initiation of treatment. Signs and symptoms include 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. In most patients, condition resolved after discontinuation of metamizole; however, isolated cases of progression to acute liver failure requiring liver transplantation have been reported.

The mechanism of liver injury caused by metamizole is not fully understood, although available data suggest an immune-allergic mechanism.

Patients should be informed about the need to consult a physician if symptoms suggestive of liver injury occur. In such cases, metamizole should be discontinued and liver function should be evaluated.

If symptoms such as nausea (nausea and vomiting), fever, fatigue, loss of appetite, dark-colored urine, pale-colored stools, jaundice (yellowing of the skin or sclera), pruritus, rash, or upper abdominal pain occur, use of Analgin should be discontinued and medical advice must be sought immediately.

Analgin is not recommended in patients who previously experienced liver problems while taking any medicinal product containing metamizole.

The product contains 3.36 mmol/dose of sodium. Caution is advised when administering to patients on a sodium-restricted diet.

Use during pregnancy or breastfeeding

The drug is contraindicated during pregnancy (particularly in the first trimester and the last 6 weeks). Breastfeeding should be discontinued during treatment, as sodium metamizole passes into breast milk.

Ability to influence reaction rate when driving or operating machinery

No effect.

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 than with intramuscular administration.

The solution to be administered should be at body temperature. To prevent a sudden drop in arterial blood pressure, intravenous administration must 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. The procedure requires availability of facilities for shock therapy. A long needle must be used for intravenous administration.

Adults are prescribed 0.5–1 mL (250–500 mg) 2–3 times daily. The maximum single dose for both routes of administration is 1 mL (500 mg); the maximum daily dose is 2 mL (1 g).

Children under 1 year of age are prescribed at a dose of 0.01 mL/kg body weight.

The drug should be administered intramuscularly only in children under 1 year of age.

Duration of treatment—up to 3 days.

Children aged 1 year and older are administered 0.1 mL per year of life, 1–2 times daily. Duration of treatment—up to 3 days.

Children.

The drug is administered intramuscularly only in children under 1 year of age. The drug should be used in children under medical supervision and only for serious and life-threatening indications.

Overdose.

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

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.

Hepatic and biliary disorders: drug-induced liver injury, including hepatitis, jaundice, elevated liver enzymes. Symptoms of liver injury include nausea (nausea and vomiting), fever, fatigue, loss of appetite, dark-colored urine, pale-colored stools, yellowing of the skin or whites of the eyes, itching, rash, or upper abdominal pain.

Cardiovascular system disorders: tachycardia.

Renal and urinary disorders: oliguria, anuria, proteinuria, interstitial nephritis, red discoloration of urine.

Blood and lymphatic system disorders: agranulocytosis, leukopenia, thrombocytopenia, anemia, granulocytopenia.

Allergic reactions: hypersensitivity reactions, skin rashes, pruritus, urticaria, conjunctivitis, Quincke's edema; rarely – Stevens-Johnson syndrome, Lyell's syndrome, bronchospastic syndrome, anaphylactoid reactions, anaphylactic shock, skin hyperemia, angioneurotic edema.

Serious skin reactions have been reported, including toxic epidermal necrolysis and drug reaction with eosinophilia and systemic symptoms (DRESS), associated with metamizole use (see section "Special precautions").

Skin and subcutaneous tissue disorders: drug reaction with eosinophilia and systemic symptoms (DRESS).

Other: decreased blood pressure, infiltration at injection site (with intramuscular administration), hyperemia, swelling, local skin rashes, and pruritus at the injection site.

Reporting of suspected adverse reactions.

Reporting suspected adverse reactions after drug registration is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmaceutical 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/.

Incompatibility. Due to a high risk of pharmaceutical incompatibility, the drug must not be mixed with other medicinal products in the same syringe.

Shelf life. 2 years.

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

Keep out of reach and sight of children.

Packaging. 2 ml in ampoules. 10 ampoules per partitioned carton; or 5 ampoules in a single-sided blister, 2 blisters per carton.

Prescription status. Prescription only.

Manufacturer. Private Joint-Stock Company "Lekhym-Kharkiv".

Manufacturer’s address and place of business.

36 Severina Pototskoho Street, Kharkiv, Kharkiv Oblast, Ukraine, 61115.