Cofalgin

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT COFALGIN

Composition:

Active substances: metamizole sodium salt, sodium caffeine benzoate;

1 tablet contains metamizole sodium salt (calculated as 100 % dry substance) –
300 mg, sodium caffeine benzoate (with 40 % caffeine content) (calculated as 100 % dry substance) – 50 mg;

Excipients: microcrystalline cellulose, povidone, magnesium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: round-shaped tablets, white or yellowish-white, with beveled edges (beveled tablet) and a score line.

Pharmacotherapeutic group. Analgesics and antipyretics. Metamizole sodium, combinations without psychotropic agents. ATC code N02B B52.

Pharmacological properties.

Pharmacodynamics.

Kofalgine is a combined medicinal product whose action is determined by the properties of its constituent components.

Metamizole sodium is an analgesic and antipyretic, a pyrazolone derivative, which has analgesic, antipyretic and weak anti-inflammatory effects; the mechanism of action is associated with inhibition of prostaglandin synthesis, predominantly in the central nervous system.

Caffeine, a methylxanthine derivative, stimulates psychomotor centers in the brain, has analeptic action, enhances the effect of metamizole sodium, relieves drowsiness and fatigue, and increases physical and mental performance.

Pharmacokinetics.

Not studied.

Clinical characteristics.

Indications.

Moderate pain syndrome, headache, neuralgias, arthritis, myositis, rheumatism; as an antipyretic agent in fever of various origins.

Contraindications.

• Hypersensitivity to any component of the drug;
• Hypersensitivity to pyrazolone derivatives, other xanthine derivatives (theophylline, ephedrine, theobromine);
• Arterial hypertension;
• Glaucoma;
• Increased excitability;
• Sleep disorders;
• Severe liver and kidney function impairment;
• Bone marrow dysfunction or hematopoietic system disorders: anemia of any etiology, cytostatic or infectious neutropenia, agranulocytosis (induced by metamizole, other pyrazolones or pyrazolidines in history), leukopenia;
• Bronchial asthma;
• Suspected acute surgical pathology;
• Organic cardiovascular diseases (including acute myocardial infarction, severe atherosclerosis, decompensated heart failure, paroxysmal tachycardia);
• Prostate hypertrophy with urinary retention;
• Glucose-6-phosphate dehydrogenase deficiency;
• Elderly age;
• Pediatric age under 14 years.

Do not use concomitantly with monoamine oxidase inhibitors (MAOIs) or within 2 weeks after discontinuation of MAO inhibitors.

Interaction with other medicinal products and other forms of interactions.

Barbiturates, codeine, paracetamol, H2-histamine receptor blockers, propranolol: enhanced effects.

Sarcolysin, mercazole, thiamazole, drugs suppressing bone marrow activity, including gold compounds: increased risk of hematotoxicity, including development of leukopenia.

Ketoconazole, disulfiram, ciprofloxacin, norfloxacin, enoxacin, pipemidic acid: possible slowing of caffeine elimination and increased plasma caffeine concentration.

Oral antidiabetic agents: increased hypoglycemic activity.

Alcohol: enhanced sedative effect.

Metamizole may induce metabolic enzymes, including CYP2B6 and CYP3A4.

Concomitant use of metamizole with bupropion, efavirenz, methadone, valproate, cyclosporine, tacrolimus, and sertraline may lead to decreased plasma concentrations of these drugs with potential reduction in clinical efficacy. Therefore, caution is recommended when using metamizole concomitantly; monitoring of clinical response and/or drug levels may be required.

Ergotamine: caffeine may potentiate its effect.

Fluvoxamine: increased plasma caffeine concentration.

Mexiletine: 50% reduction in caffeine clearance.

Nicotine: increased rate of caffeine elimination.

Psoralen (methoxsalen): reduced elimination of caffeine from the body, potentially enhancing its effect and causing toxic reactions.

Clozapine: increased plasma clozapine concentration.

Theophylline and other xanthines: reduced clearance of these drugs, increased risk of additive pharmacodynamic and toxic effects.

Lithium: increased urinary lithium excretion.

Other drugs whose effects may be altered by interaction with caffeine: hydroxyzine, phenylpropanolamine, phenytoin, pentobarbital, diazepam.

MAO inhibitors, furazolidone, procarbazine, and selegiline: possible dangerous increase in blood pressure.

Analgesic-antipyretics: caffeine enhances their effect (improves bioavailability).

Psychostimulants, α- and β-adrenomimetics: potentiation of their effects.

Cimetidine, hormonal contraceptives, isoniazid: enhanced caffeine effects.

Opioid analgesics, anxiolytics, hypnotics and sedatives: caffeine reduces their effects.

Caffeine is an antagonist of anesthetic agents and other drugs that suppress the central nervous system (CNS), and a competitive antagonist of adenosine and adenosine triphosphate (ATP).

Thyrotropic agents: enhanced thyroid effect.

Beverages and medicinal products containing caffeine, when used concomitantly with the drug, may lead to excessive stimulation of the central nervous system. High doses of caffeine may cause tremors and palpitations. Patients should avoid excessive consumption of coffee or tea.

Interactions possibly caused by the presence of sodium metamizole

Metamizole may reduce the antiplatelet effect of low-dose acetylsalicylic acid when used concomitantly. Therefore, metamizole should be used with caution in patients taking low-dose acetylsalicylic acid for cardioprotection.

When used concomitantly with drugs that suppress bone marrow function (gold-containing drugs, antineoplastic agents, chloramphenicol, etc.), there is a risk of leukocyte damage.

Chlorpromazine or other phenothiazine derivatives: possible development of pronounced hypothermia.

Contrast agents for radiography, colloidal plasma substitutes, and penicillin: should not be used during treatment with sodium metamizole.

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

Phenylbutazone, other hepatic enzyme inducers: reduced efficacy of sodium metamizole.

Tricyclic antidepressants, hormonal contraceptives, and allopurinol: possible increase in sodium metamizole toxicity.

Sedatives and tranquilizers (diazepam, trioxazine), valocordin: enhanced analgesic effect of sodium metamizole.

Non-narcotic analgesics, other nonsteroidal anti-inflammatory drugs (NSAIDs): enhanced analgesic and antipyretic effects, but increased risk of additive adverse effects.

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

Sulfonylurea oral hypoglycemic agents: possible potentiation of their hypoglycemic effect when used concomitantly with NSAIDs, including sodium metamizole.

Diuretics (furosemide): possible reduction in diuretic effect.

Special precautions for use.

Agranulocytosis

Treatment with metamizole may cause agranulocytosis, which can be fatal (see section "Adverse reactions"). This condition may occur even after previous use of metamizole without complications.

Metamizole-induced agranulocytosis is an idiosyncratic adverse reaction unrelated to dose and may occur at any time during treatment, even shortly after discontinuation of therapy.

Patients should be informed of the necessity to discontinue metamizole and immediately seek medical advice if any symptoms suggestive of agranulocytosis occur (e.g., fever, chills, sore throat, and painful mucosal lesions, particularly in the mouth, nose, and throat, or in the genital or anal areas).

If metamizole is taken during fever, some symptoms of developing agranulocyt游戏副本

Method of Administration and Dosage.

Cofalgine should be administered to adults and children aged 14 years and older at a dose of 1 tablet 2–3 times daily. The tablets must not be chewed and should be taken with a small amount of water. The maximum daily dose is 3 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.

Cofalgine is contraindicated in children under 14 years of age.

Overdose.

Sodium metamizole overdose: hypothermia, palpitations, tremor, marked 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.

Caffeine overdose: gastralgia, anxiety, excitement, nervousness, dizziness, insomnia, irritability, affective disturbances, facial flushing, psychomotor agitation, confusion, delirium, dehydration, tachycardia, arrhythmias, hyperthermia, increased frequency of urination, increased respiratory rate, headache, increased tactile or pain sensitivity, tremor or muscle twitching; nausea and vomiting, sometimes with blood, epigastric pain; tinnitus, seizures (in acute overdose – tonic-clonic seizures).

Treatment: gastric lavage, forced diuresis, administration of enterosorbents, maintenance of pulmonary ventilation and oxygenation; for seizures – intravenous diazepam, phenobarbital, or phenytoin; fluid and electrolyte balance support. In severe cases, hemodialysis, hemoperfusion, or peritoneal dialysis may be indicated. Symptomatic therapy is directed toward supporting vital functions.

Side effects

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").

Immune system, skin and subcutaneous tissue disorders: Hypersensitivity reactions may occur, including skin and mucous membrane rashes, conjunctivitis, pruritus, urticaria, angioneurotic edema (Quincke's edema), bronchospasm, anaphylactic shock, Stevens-Johnson syndrome, Lyell's syndrome (toxic epidermal necrolysis), and drug reaction with eosinophilia and systemic symptoms (DRESS).

Gastrointestinal system: Loss of appetite, nausea, vomiting, epigastric pain, exacerbation of peptic ulcer disease, exacerbation of gastritis.

Cardiovascular system: Chest tightness, palpitations, tachycardia, arrhythmias, increased or decreased arterial pressure.

Nervous system: Dizziness, anxiety, increased excitability, tremor, restlessness, headache, sleep disturbances, muscle twitching, seizures, increased reflexes, tachypnea; upon abrupt discontinuation – increased central nervous system depression with symptoms of increased fatigue, drowsiness, muscle tension, and depression.

Urinary system: Acute kidney injury, transient oliguria, anuria, interstitial nephritis, proteinuria, increased creatinine clearance, increased excretion of sodium and calcium may develop, usually in patients with impaired renal function and/or after excessive doses. Urine may turn red.

Hepatobiliary system: Liver function abnormalities, cholestasis, drug-induced liver injury, including acute hepatitis, jaundice, elevated liver enzymes (see section "Special precautions").

Hematopoietic system: With prolonged use, leukopenia, thrombocytopenia, hemolytic anemia, granulocytopenia/agranulocytosis, and transient purpura may occur.

Laboratory findings: Possible false increase in blood uric acid levels when measured by the Bittner method, hypoglycemia/hyperglycemia, slight increase in urinary levels of 5-hydroxyindoleacetic acid (5-HIAA), vanillylmandelic acid (VMA), and catecholamines.

Other: Nasal congestion; with prolonged use – reduced effect of caffeine due to formation of new adenosine receptors, drug dependence.

Reporting 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 professionals and patients, or their legal representatives, should report all suspected adverse reactions and lack of efficacy via the Automated Pharmacovigilance Information System at: https://аіsf.dec.gov.ua.

Shelf life. 3 years.

Storage conditions.

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

Keep out of reach of children.

Packaging. 10 tablets per blister, 1 blister per carton.

Supply category. Over-the-counter.

Manufacturer.

Public Joint-Stock Company "Scientific and Production Center "Borshchahivskiy Chemical and Pharmaceutical Plant".

LLC "Agrofarm".

Manufacturer's address and place of business.

17 Mиру Street, Kyiv, 03134, Ukraine.

113-A Tsentralna Street, Irpin, 08200, Ukraine.