Analgin

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

Composition:

Active substance: 1 tablet contains 0.5 g of sodium metamizole;

Excipients: potato starch, talc, calcium stearate.

Pharmaceutical form. Tablets.

Main physicochemical characteristics: tablets are white or white with a yellowish tint, with a flat surface, a score line and beveled edges.

Pharmacotherapeutic group.

Analgesics and antipyretics. ATC code N02B B02.

Pharmacological properties.

Pharmacodynamics. Metamizole (sodium metamizole) exhibits analgesic, antipyretic, and anti-inflammatory effects. The analgesic effect is due to inhibition of cyclooxygenase (COX) and blockade of prostaglandin synthesis from arachidonic acid, which are involved in the development of pain reactions (bradykinins, prostaglandins, etc.); slowing of transmission of exteroceptive and proprioceptive pain impulses in the central nervous system; increased excitability threshold of thalamic pain centers; and reduced response of brain structures responsible for pain perception to external stimuli. The antipyretic effect is attributed to decreased formation and release from neutrophil granulocytes of substances affecting heat production. 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 30 minutes after administration. Maximum plasma concentration of sodium metamizole after an oral dose of 6 mg/kg body weight is reached within 1–1.5 hours. It binds to plasma proteins to a negligible extent 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 into breast milk.

Clinical characteristics.

Indications.

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

Contraindications.

Known or suspected hypersensitivity to metamizole sodium and/or other pyrazolone derivatives, or to any of the excipients; bronchial asthma; severe impairment of liver and kidney function (porphyrin metabolism disorders); blood disorders: anemia of any etiology, cytostatic or infectious neutropenia; changes in peripheral blood composition: agranulocytosis in history induced by metamizole, other pyrazolones or pyrazolidines, impaired bone marrow function or diseases of the hematopoietic system, leukopenia; suspected acute surgical pathology; glucose-6-phosphate dehydrogenase deficiency.

Special precautions.

Prior to initiating treatment with Analgin, consult a physician.

Do not exceed the recommended dosage.

Do not use the drug 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, which could complicate their diagnosis.

Avoid alcohol consumption during treatment.

Treatment in children should be conducted under constant medical supervision.

Use with caution in the following patients:

• Elderly patients – may lead to increased frequency of adverse reactions, especially gastrointestinal;
• Patients with existing allergic conditions (including pollinosis) or history thereof – increased risk of allergic reactions;
• Patients with impaired renal function or history of kidney disease (pyelonephritis, glomerulonephritis);
• Patients with inflammatory bowel diseases, including ulcerative colitis and Crohn’s disease;
• Patients with severe arterial hypotension or cardiovascular insufficiency;
• Patients with chronic alcoholism;
• When used concomitantly with cytostatic drugs (only under physician supervision).

During treatment in children, continuous medical monitoring is required. Qualitative and quantitative composition of peripheral blood must be monitored.

With prolonged use of the drug (more than 7 days), peripheral blood count (due to myelotoxicity of metamizole), as well as renal and hepatic function, should be monitored.

Drug-induced liver injury

Cases of acute hepatitis, predominantly hepatocellular type, have been reported in patients receiving metamizole. Symptoms appeared from several days to several months after initiation of treatment. Manifestations 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. In such cases, metamizole should be discontinued and liver function evaluated.

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.

Patients should be warned prior to treatment initiation that if chills of unknown origin, fever, sore throat, difficulty swallowing, gingival bleeding, pallor of the skin, asthenia, or development of vaginitis or proctitis occur, the drug should be discontinued immediately. The drug should also be discontinued at the first sign of skin or mucosal rashes. In case of such symptoms, immediate medical consultation is required.

Red discoloration of urine may occur during treatment due to excretion of a metabolite of sodium metamizole.

Do not use the drug longer than the recommended duration without consulting a physician!

If symptoms of illness do not begin to resolve, or if health status worsens, or if adverse effects occur, discontinue use of the drug and consult a physician regarding further treatment.

Interaction with other medicinal products and other forms of interaction.

If you are taking any other medicinal products, inform your physician immediately!

• X-ray contrast agents, colloidal plasma substitutes, penicillin – should not be used during treatment with sodium metamizole.
• Chlorpromazine or other phenothiazine derivatives – may lead to pronounced hypothermia.
• Oral anticoagulants, phenytoin, glucocorticosteroids, indomethacin, ibuprofen – sodium metamizole increases the activity of these drugs by displacing them from protein binding sites.
• Sodium metamizole may induce metabolic pathway enzymes, including CYP2B6 and CYP3A4. Concomitant use of sodium 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 advised when co-administering sodium metamizole with other medicinal products; clinical response and/or drug levels should be monitored as necessary.
• Phenylbutazone, glutethimide, barbiturates, and other hepatic microsomal enzyme inducers – reduce the efficacy of sodium metamizole.
• Tricyclic antidepressants, hormonal contraceptives, allopurinol, alcohol – may increase sodium metamizole toxicity. Sodium metamizole enhances the sedative effect of alcohol.
• Other nonsteroidal anti-inflammatory drugs (NSAIDs) – potentiate their analgesic and antipyretic effects, but also increase the risk of additive adverse effects.
• Sedatives and tranquilizers (sibazone, trioxazine, valocordin), codeine, H2-histamine receptor blockers, propranolol – enhance the analgesic effect of sodium metamizole.
• Sarcolysin, mercaptopurine, thiimazole, drugs that suppress bone marrow activity, including gold compounds – increase the risk of hematotoxicity, including leukopenia.
• Methotrexate – high doses of metamizole may increase methotrexate plasma concentration and enhance its toxic effects (particularly on the gastrointestinal tract and hematopoietic system).
• Cyclosporine – reduces cyclosporine plasma concentration.
• Sulfonylurea oral hypoglycemic agents – possible potentiation of hypoglycemic effect when used concomitantly with NSAIDs and sodium metamizole.
• Diuretics (furosemide) – possible reduction in diuretic effect.

Special precautions for use.

When using the medicinal product, it is necessary to monitor peripheral blood composition (leukocyte formula). Use with caution in patients with a history of kidney diseases (pyelonephritis, glomerulonephritis), allergic disorders, or chronic alcohol abuse.

When using Analgin, discoloration of urine to red may occur due to excretion of a metabolite.

Regular long-term use of the drug is not recommended due to the myelotoxicity of sodium metamizole.

Severe skin reactions

Severe skin reactions, including Stevens–Johnson syndrome, toxic epidermal necrolysis, and drug reaction with eosinophilia and systemic symptoms (DRESS syndrome), have been reported during treatment with metamizole, which may result in a fatal outcome.

Patients should be informed about the signs and symptoms of skin reactions and closely monitored.

If symptoms indicating such reactions occur, treatment with metamizole should be discontinued immediately and must never be restarted (see section "Contraindications").

Use during pregnancy or breastfeeding.

Contraindicated during pregnancy and breastfeeding (breastfeeding must be discontinued for the duration of treatment).

Ability to affect reaction speed when driving vehicles or operating machinery.

The drug does not affect the ability to drive vehicles or operate other machinery.

Dosage and Administration

Tablets should be taken after meals, swallowed with a small amount of water.

For adults and children aged 14 years and older, the usual dose is ½–1 tablet (250–500 mg) 1–2 times daily.

Maximum daily dose – 1 g.

For children aged 12 to 14 years – ½ tablet (250 mg) 1–2 times daily.

The duration of treatment should not exceed 3 days.

Children

The medicinal product is contraindicated in children under 12 years of age.

Overdose

Symptoms: hypothermia, palpitations, pronounced decrease in arterial blood pressure, tachycardia, dysphagia, dyspnea, tinnitus, nausea, vomiting, gastritis/gastralgia, 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 vomiting, gastric lavage, administration of saline laxatives and enterosorbents, forced diuresis, and symptomatic therapy aimed at supporting vital functions. In severe cases, hemodialysis, hemoperfusion, or peritoneal dialysis may be used.

In case of first signs of overdose, seek immediate medical help!

Side effects.

Allergic reactions: hypersensitivity reactions may occur, including skin and mucous membrane rashes, conjunctivitis, itching, urticaria, angioneurotic edema, bronchospastic syndrome, anaphylactic shock.

Skin and subcutaneous tissue disorders: very rare — Stevens-Johnson syndrome, Lyell's syndrome; drug reaction with eosinophilia and systemic symptoms (DRESS syndrome) — frequency unknown.

Blood and lymphatic system disorders: with prolonged use agranulocytosis, leukopenia, thrombocytopenia, anemia, granulocytopenia may occur.

Renal and urinary disorders: usually in patients with impaired renal function and/or when excessive doses are used — transient oliguria, anuria, proteinuria, interstitial nephritis. Red discoloration of urine.

Hepatobiliary disorders: hepatitis; drug-induced liver injury, including acute hepatitis, jaundice, increased levels of liver enzymes (see section "Special precautions").

Other: decreased blood pressure.

If any adverse reactions occur, discontinue the drug immediately and consult a physician without delay.

Shelf life. 5 years.

Storage conditions.

Store at temperatures not exceeding 25 °C.

Keep out of reach of children.

Packaging.

10 tablets in blisters.

Prescription status. Over-the-counter.

Manufacturer/Applicant.

LLC "Ternopharm".

Manufacturer's address and place of business / Applicant's address.

46010, Ternopil, Fabrychna St., 4, Ukraine.

Tel./fax: (0352) 521-444, www.ternopharm.com.ua