Analgin

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT ANALGIN (Analgin)

Composition:

Active substance: sodium metamizole;

1 tablet contains sodium metamizole 500 mg (0.5 g);

Excipients: potato starch, calcium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: tablets of white or white with yellowish tint color, with flat surface, scored line and bevelled edge.

Pharmacotherapeutic group. Analgesics and antipyretics. Sodium metamizole.

ATC code N02B B02.

Pharmacological properties.

Pharmacodynamics.

Analgin (sodium metamizole) exerts analgesic, antipyretic, and anti-inflammatory effects. The analgesic effect is due to cyclooxygenase inhibition and blockade of prostaglandin synthesis from arachidonic acid, which are involved in the response to pain stimuli (bradykinins, prostaglandins); slowing of transmission of exteroceptive and proprioceptive pain impulses in the central nervous system; increased excitability threshold of thalamic pain centers; and attenuation of responses in brain structures responsible for pain perception. The antipyretic effect results from reduced formation and release of substances affecting heat production by neutrophil granulocytes. The anti-inflammatory effect is associated with inhibition of prostaglandin synthesis.

Pharmacokinetics.

Sodium metamizole is well absorbed in the gastrointestinal tract. Therapeutic plasma concentration is achieved approximately half an hour after administration. Maximum plasma concentration of sodium metamizole after oral administration at a dose of 6 mg/kg body weight is reached within 1–1.5 hours. It binds minimally to plasma proteins and is extensively metabolized in the liver: a significant portion of the substance undergoes hydrolysis to form 4-methylaminoantipyrine, which is demethylated to yield pharmacologically active 4-aminoantipyrine, 50–60% of which binds to plasma proteins; its acetylated derivative is excreted in urine. The drug also crosses the placenta and is excreted in breast milk.

Clinical characteristics.

Indications.

Pain syndrome of various origins: headache, toothache, neuralgia, radiculitis, myalgia, menstrual pain. As an adjunctive agent to reduce pain following surgical and diagnostic procedures. Hyperthermic syndrome in infectious-inflammatory diseases.

Contraindications.

Known or suspected hypersensitivity to sodium metamizole and other components of the drug, pyrazolone derivatives (phenylbutazone, tribuzon, antipyrine); suspected acute surgical pathology; anemia of any etiology, cytostatic or infectious neutropenia; changes in peripheral blood composition: agranulocytosis, leukopenia; severe impairment of liver and/or kidney function; glucose-6-phosphate dehydrogenase deficiency; bronchial asthma; hereditary hemolytic anemia.

Interaction with other medicinal products and other types of interactions.

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.

Indirect anticoagulants, phenytoin, glucocorticosteroids, indomethacin, ibuprofen – sodium metamizole increases the activity of these drugs by displacing them from protein binding.

Glutethimide reduces the efficacy of sodium metamizole.

Other nonsteroidal anti-inflammatory drugs – their analgesic and antipyretic effects are enhanced, and the risk of additive adverse effects increases.

Thiamazole, drugs that suppress bone marrow activity, including gold compounds – increase the risk of hematotoxicity, including development of leukopenia.

Methotrexate – high doses of sodium metamizole may lead to increased methotrexate plasma concentration and enhanced toxic effects (primarily on the gastrointestinal tract and hematopoietic system).

Diuretics (furosemide) – possible reduction of diuretic effect.

Concomitant use of sodium metamizole with other non-narcotic analgesics may result in mutual enhancement of toxic effects. Sedatives and tranquilizers (sibazone, trioxazine, valocordin, codeine, anaprilin, H2-receptor blockers) enhance the analgesic effect of sodium metamizole. Tricyclic antidepressants (amizole, doxepin), oral contraceptives, allopurinol impair the metabolism of sodium metamizole in the liver and increase its toxicity. Barbiturates (phenobarbital, belaspon), phenylbutazone, and other inducers of hepatic microsomal enzymes reduce the effect of sodium metamizole. Caution is required when using the drug concomitantly with sulfonamides, hypoglycemic agents (potentiates hypoglycemic effect), and diuretics (furosemide). Sarcolysin and mercazole increase the risk of developing leukopenia. Sodium metamizole enhances the sedative effect of alcohol and reduces plasma cyclosporine concentration.

Special precautions for use

Before starting treatment with the medicinal product, consult a physician.

Do not exceed the recommended doses of the medicinal product.

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.

Avoid alcohol consumption during treatment with the medicinal product.

Risk of drug-induced liver injury

Cases of acute hepatitis, predominantly of hepatocellular type, have been observed in patients treated with sodium metamizole. The manifestations 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 rashes, 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 sodium metamizole-induced liver injury is not clearly established, but available data suggest an immune-allergic mechanism.

Patients should be instructed to promptly inform their physician if symptoms suggestive of liver injury occur. If liver injury is suspected, sodium metamizole should be discontinued and liver function tests should be performed.

Cases of liver injury during treatment with sodium metamizole are very rare, but the exact frequency of this adverse reaction cannot be determined. In some patients, recurrence of liver injury has been observed upon re-exposure to sodium metamizole. If a patient has previously experienced liver injury during treatment with sodium metamizole and no other cause of liver injury has been identified, re-administration of medicinal products containing sodium metamizole is contraindicated.

If symptoms of impaired liver function occur, including gastrointestinal disturbances, jaundice, or elevated liver enzymes, the medicinal product must be discontinued.

Severe skin reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, 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 monitored closely.

If signs or symptoms suggestive of these reactions occur, treatment with metamizole should be discontinued immediately and must not be restarted under any circumstances (see section "Contraindications").

The medicinal product should be used with caution in patients:

• of advanced age – may lead to increased frequency of adverse reactions, particularly gastrointestinal;
• with existing allergic conditions (including hay fever) or history thereof – increased risk of allergic reactions;
• with inflammatory bowel diseases, including ulcerative colitis and Crohn’s disease;
• with impaired renal function or history of kidney disease (pyelonephritis, glomerulonephritis);
• with pronounced arterial hypotension or cardiovascular insufficiency;
• with chronic alcoholism;
• when used concomitantly with cytostatic agents (only under physician supervision).

Patients should be warned before starting treatment that if unexplained chills, fever, sore throat, difficulty swallowing, bleeding gums, pallor of the skin, asthenia, or development of vaginitis or proctitis occur, the medicinal product should be discontinued immediately. The medicinal product should also be discontinued at the first sign of skin or mucosal rashes. In case of these symptoms, patients should seek immediate medical advice.

The medicinal product is contraindicated for relief of acute abdominal pain until the cause is established.

Patients with atopic bronchial asthma and hay fever have an increased risk of hypersensitivity reactions.

Regular long-term use of the medicinal product is not recommended due to the myelotoxicity of sodium metamizole. If prolonged use (more than 7 days) is necessary, peripheral blood picture (leukocyte count and differential), renal and liver function should be monitored.

Use in children should be under constant medical supervision.

During treatment, urine may turn red due to excretion of a metabolite; this is clinically insignificant.

Do not use the medicinal product beyond the recommended duration without consulting a physician.

If symptoms of illness do not improve or worsen, or if adverse effects occur, discontinue use of the medicinal product and consult a physician regarding further treatment.

During treatment with the medicinal product, peripheral blood parameters (leukocyte count and differential) should be monitored.

Use during pregnancy or breastfeeding

The medicinal product is contraindicated during pregnancy or breastfeeding.

Ability to affect reaction rate when driving or operating machinery

No effect.

Dosage and Administration

For adults and adolescents aged 14 years and older, the recommended dose is ½–1 tablet 1–2 times daily. The tablets should be taken after meals with a small amount of water. The maximum single dose is 1 g (2 tablets); the maximum daily dose is 1 g (2 tablets). The duration of treatment should not exceed 3 days.

If symptoms do not resolve within 3 days, consult a physician regarding further use of the medication.

Children

This medication is indicated for children aged 14 years and older.

Overdose

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

Treatment: discontinue the drug immediately, induce vomiting, perform gastric lavage via tube, administer saline laxatives and activated charcoal. Initiate forced diuresis, blood alkalinization, and symptomatic therapy aimed at supporting vital functions. In case of convulsive syndrome, administer diazepam and fast-acting barbiturates intravenously. In severe cases, hemodialysis, hemoperfusion, or peritoneal dialysis may be required.

In the event of early signs of overdose, seek immediate medical assistance.

Side effects.

Urinary system disorders: transient oliguria, anuria, proteinuria, interstitial nephritis, red-colored urine.

Hematopoietic system disorders: granulocytopenia, anemia, agranulocytosis, leukopenia, thrombocytopenia.

Hepatobiliary system disorders: drug-induced liver injury, including acute hepatitis, jaundice, elevated liver enzyme levels (see section "Special precautions for use").

Allergic reactions: hypersensitivity reactions may occur, including skin and mucous membrane rashes, hyperemia, conjunctivitis, pruritus, urticaria, angioneurotic edema, bronchospastic syndrome, anaphylactic shock, and Lyell's syndrome.

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) (see section "Special precautions for use").

Skin and subcutaneous tissue disorders: drug reaction with eosinophilia and systemic symptoms (DRESS) (frequency not known).

Other: decreased blood pressure, weakness, numbness, tremor, loss of consciousness, hepatitis.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after medicine registration is important. It allows ongoing monitoring of the benefit-risk balance of the medicine. Healthcare professionals and patients, as well as their legal representatives, should report any suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life: 5 years.

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

Storage conditions.

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

Keep out of reach and sight of children.

Packaging.

6 or 10 tablets in blisters.

Prescription status.

Over-the-counter.

Manufacturer.

JSC "CHEMICAL PHARMACEUTICAL PLANT "CHERVONA ZIRKA".

Manufacturer's address and location of business activity.

1 Gordienkovskaya Street, Kharkiv, Kharkiv Region, 61010, Ukraine.