Citramon-darnitsa

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT CITRAMON-DARNITSA (CITRAMON-DARNITSA)

Composition:

Active substances: acetylsalicylic acid, paracetamol, caffeine;

One tablet contains: acetylsalicylic acid 240 mg, paracetamol 180 mg, caffeine 30 mg;

Excipients: citric acid monohydrate, potato starch, povidone, cocoa, calcium stearate.

Pharmaceutical form. Tablets.

Main physicochemical properties: light brown tablets with specks, flat cylindrical in shape, bevelled edge and a score line, with cocoa odour.

Pharmacotherapeutic group. Analgesics and antipyretics. Acetylsalicylic acid, combinations without psychotropic agents. ATC code N02BA51.

Pharmacological properties.

Pharmacodynamics.

The medicinal product exerts analgesic, antipyretic, and anti-inflammatory effects. The components contained in the medicinal product potentiate each other's effects.

The antipyretic effect of acetylsalicylic acid is mediated via the central nervous system by inhibiting the synthesis of PGE2 in the hypothalamus in response to the action of endogenous pyrogens. The analgesic effect has both peripheral and central origins: the peripheral effect results from inhibition of prostaglandin synthesis in inflamed tissues; the central effect is due to its action on hypothalamic centers. Acetylsalicylic acid also reduces platelet aggregation.

Paracetamol exerts analgesic and antipyretic effects, as well as a very weak anti-inflammatory effect, which is associated with its action on the thermoregulatory center in the hypothalamus and its weak ability to inhibit prostaglandin synthesis in peripheral tissues.

Caffeine stimulates the central nervous system. Caffeine enhances positive conditioned reflexes, stimulates motor activity, reduces the effects of sedatives and narcotic substances, and potentiates the action of analgesics and antipyretic agents.

Pharmacokinetics.

Not studied.

Clinical characteristics.

Indications.

Treatment of mild to moderate pain syndromes due to headache or toothache, primary dysmenorrhea, migraine, arthralgia, neuralgia, and conditions associated with hyperthermia of various etiologies (as an antipyretic agent).

Contraindications.

Hypersensitivity to components of the drug or other salicylates; severe impairment of liver and/or kidney function; congenital hyperbilirubinemia, Gilbert’s syndrome, glucose-6-phosphate dehydrogenase deficiency; alcoholism; blood disorders, hemophilia, hemorrhagic diathesis; severe anemia, leukopenia, thrombosis, thrombophlebitis, hemorrhagic diseases; active peptic ulcer; states of increased excitation, sleep disturbances; severe arterial hypertension; organic cardiovascular diseases (including atherosclerosis); angle-closure glaucoma; epilepsy; hyperthyroidism; decompensated heart failure; cardiac conduction disorders; severe atherosclerosis; predisposition to vascular spasm; ischemic heart disease; acute pancreatitis; benign prostatic hyperplasia; severe forms of diabetes mellitus; bronchial asthma induced by salicylates in medical history; elderly age.

Do not use concomitantly with monoamine oxidase inhibitors (MAOIs) or within 2 weeks after discontinuation of MAOIs; contraindicated in patients taking tricyclic antidepressants or β-blockers; contraindicated in combination with methotrexate at doses of 15 mg/week or higher (see "Interaction with other medicinal products and other types of interactions").

Interaction with other medicinal products and other types of interactions.

Paracetamol

Metoclopramide and domperidone may increase the absorption rate of paracetamol, while cholestyramine may reduce it. The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged concomitant use of paracetamol, increasing the risk of bleeding. Barbiturates reduce the antipyretic effect of paracetamol. Anticonvulsant drugs (including phenytoin, barbiturates, carbamazepine), which stimulate hepatic microsomal enzyme activity, may enhance the hepatotoxic effect of paracetamol due to increased conversion of the drug into hepatotoxic metabolites. Concomitant use of paracetamol with hepatotoxic agents increases the hepatotoxic effects of these drugs.

Concomitant use of high doses of paracetamol with isoniazid increases the risk of hepatotoxic syndrome. Paracetamol reduces the efficacy of diuretics. Do not use concomitantly with alcohol.

Caution is advised when using paracetamol concomitantly with flucloxacillin, as this combination has been associated with metabolic acidosis with a high anion gap, particularly in patients with risk factors (see section "Special precautions").

Caffeine

Concomitant use of caffeine with MAO inhibitors may cause dangerous elevation of blood pressure. Caffeine enhances the effect (improves bioavailability) of analgesic-antipyretic agents, potentiates the effects of xanthine derivatives, α- and β-adrenergic agonists, and psychostimulants. Cimetidine, hormonal contraceptives, and isoniazid enhance the action of caffeine. Caffeine reduces the effect of opioid analgesics, anxiolytics, hypnotics, and sedatives; it acts as an antagonist of anesthetic agents and other drugs that depress the central nervous system, and as a competitive antagonist of adenosine and ATP preparations. Concomitant use of caffeine with ergotamine improves absorption of ergotamine from the gastrointestinal tract; with thyrotropic agents, it increases their effect. Caffeine reduces lithium concentration in blood.

Acetylsalicylic acid

Contraindicated combinations.

Use of methotrexate at doses of 15 mg/week or higher increases the hematological toxicity of methotrexate (due to reduced renal clearance of methotrexate by anti-inflammatory agents and displacement of methotrexate from plasma protein binding by salicylates).

Combinations requiring caution.

Concomitant use of ibuprofen interferes with the irreversible inhibition of platelets by acetylsalicylic acid. Treatment with ibuprofen in patients at risk of cardiovascular disease may reduce the cardioprotective effect of acetylsalicylic acid. Concomitant use of acetylsalicylic acid and anticoagulants increases the risk of bleeding. Concomitant use of high doses of salicylates and NSAIDs increases the risk of ulceration and gastrointestinal bleeding due to mutual enhancement of effects. Concomitant use with uricosuric agents such as benzbromarone or probenecid reduces uric acid excretion (due to competition for renal tubular excretion of uric acid). Concomitant use with digoxin increases digoxin plasma concentration due to reduced renal excretion. Concomitant use of high doses of acetylsalicylic acid with oral antidiabetic sulfonylurea agents or insulin enhances the hypoglycemic effect of the latter due to the hypoglycemic effect of acetylsalicylic acid and displacement of sulfonylureas from plasma protein binding. Diuretics in combination with high doses of acetylsalicylic acid reduce glomerular filtration due to decreased renal prostaglandin synthesis. Systemic glucocorticosteroids (except hydrocortisone) used for replacement therapy in Addison’s disease reduce salicylate levels in blood during corticosteroid therapy and increase the risk of overdose after discontinuation of therapy. Concomitant use with corticosteroids increases the risk of gastrointestinal bleeding. Acetylsalicylic acid enhances the effect of phenytoin. Angiotensin-converting enzyme (ACE) inhibitors in combination with high doses of acetylsalicylic acid reduce glomerular filtration due to inhibition of vasodilatory prostaglandins and diminished antihypertensive effect. Concomitant use with valproic acid results in displacement of valproic acid from plasma protein binding by acetylsalicylic acid, increasing its toxicity. Concomitant use with selective serotonin reuptake inhibitors (SSRIs) increases the risk of gastrointestinal bleeding due to possible synergistic effects. Ethanol promotes damage to the gastrointestinal mucosa and prolongs bleeding time due to synergism between acetylsalicylic acid and alcohol.

Special precautions for use.

In patients with allergic complications, including bronchial asthma, allergic rhinitis, urticaria, skin itching, mucosal edema, and nasal pollinosis, as well as in combination with chronic respiratory tract infections, and in patients with hypersensitivity to NSAIDs, treatment with the medicinal product may lead to the development of bronchospasm or an attack of bronchial asthma.

During surgical procedures (including dental procedures), the use of medicinal products containing acetylsalicylic acid may increase the risk of occurrence or intensification of bleeding.

Use with caution in patients with liver or kidney disease, with a history of gastrointestinal erosive or ulcerative lesions and gastrointestinal bleeding, in patients with increased bleeding tendency, or when undergoing concurrent anti-inflammatory therapy.

Acetylsalicylic acid contained in the medicinal product, even in small doses, reduces the excretion of uric acid from the body, which may trigger an acute attack of gout in sensitive patients.

It is not recommended to use the medicinal product for more than 5 days as an analgesic or for more than 3 days as an antipyretic without consulting a physician.

In patients with impaired kidney or liver function, the interval between doses should be at least 8 hours.

Alcohol consumption should be avoided during treatment. With prolonged use, monitoring of the blood coagulation system and hemoglobin levels is required.

During treatment, excessive consumption of beverages containing caffeine (such as coffee, tea) is not recommended. This may cause sleep disturbances, tremor, and discomfort behind the sternum due to palpitations.

Paracetamol

Consult a physician before using the medicinal product if the patient is taking warfarin or similar drugs with anticoagulant effects. The risk of overdose is highest in patients with non-cirrhotic alcoholic liver disease. The medicinal product may affect laboratory test results for blood glucose and uric acid levels.

Patients who take analgesics daily for mild forms of arthritis should consult a physician. In patients with severe infections such as sepsis, associated with reduced glutathione levels, the use of paracetamol increases the risk of developing metabolic acidosis. Symptoms of metabolic acidosis include deep, rapid, or labored breathing, nausea, vomiting, and loss of appetite. Immediate medical attention is required if these symptoms occur.

Caution is required when using paracetamol concurrently with floxacillin due to an increased risk of high anion gap metabolic acidosis, especially in patients with severe renal impairment, sepsis, malnutrition, or other causes of glutathione deficiency (e.g., chronic alcoholism), as well as when maximum daily doses of paracetamol are used. Careful monitoring, including measurement of urinary 5-oxoproline levels, is recommended.

Do not exceed the recommended doses. Do not take the medicinal product with other products containing paracetamol.

If symptoms persist, consult a physician.

If headache becomes persistent, consult a physician.

Keep the medicinal product out of sight and reach of children.

Acetylsalicylic acid

Use with caution in patients with hypersensitivity to analgesic, anti-inflammatory, or antirheumatic agents, when used concomitantly with anticoagulants, and in patients with circulatory disorders (e.g., renal vascular pathology, congestive heart failure, hypovolemia, extensive surgery, sepsis, or severe bleeding), as acetylsalicylic acid may increase the risk of impaired kidney function and acute renal failure. Ibuprofen may reduce the inhibitory effect of acetylsalicylic acid on platelet aggregation. If the medicinal product is used prior to starting ibuprofen as an analgesic, the patient should consult a physician.

Use during pregnancy or breastfeeding.

The medicinal product is not used during pregnancy or breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

When high doses of the medicinal product are used, patients should refrain from driving or operating machinery due to possible adverse reactions affecting the nervous system (dizziness, increased excitability, impaired orientation, and attention).

Dosage and Administration

The medicinal product is prescribed to adults at 1 tablet 2–3 times daily after meals. The maximum daily dose of the medicinal product is 6 tablets (in 3 divided doses). Citramon-Darnytsia tablets should not be taken for more than 5 days as an analgesic and for more than 3 days as an antipyretic.

Do not exceed the recommended dose.

Do not take together with other medicinal products containing paracetamol.

Children

Medicinal products containing acetylsalicylic acid should not be used in children with acute respiratory viral infection (ARVI), whether accompanied by fever or not. In certain viral diseases, particularly influenza A, influenza B, and varicella, there is a risk of Reye's syndrome, which requires urgent medical intervention. The risk may be increased if acetylsalicylic acid is used concomitantly; however, a causal relationship has not been established. If these conditions are accompanied by persistent vomiting, this may be a sign of Reye's syndrome. Considering the above reasons, the use of this medicinal product in children is contraindicated unless there are specific indications (e.g., Kawasaki disease).

Overdose

Symptoms of overdose may occur with prolonged use of the medicinal product or when used in doses many times higher than recommended.

Symptoms of overdose caused by acetylsalicylic acid.

Salicylate toxicity may occur following prolonged use of therapeutic doses or acute intoxication from doses exceeding 100 mg/kg/day for more than 2 days (accidental ingestion by children or accidental overdose), potentially life-threatening. Chronic salicylate poisoning may be asymptomatic, as it lacks specific symptoms. Moderate salicylate intoxication (salicylism) usually develops only after repeated high-dose administration.

Symptoms: dizziness, tinnitus, hearing loss, increased sweating, nausea, vomiting, headache, and impaired consciousness—these can be managed by dose reduction. Tinnitus may occur at plasma concentrations of 150–300 mcg/mL. More severe adverse effects occur at concentrations exceeding 300 mcg/mL. The hallmark of acute poisoning is severe acid-base imbalance, which may vary depending on patient age and severity of intoxication. Metabolic acidosis is a common feature in children. Severity of poisoning cannot be assessed solely by plasma concentration. Absorption of acetylsalicylic acid may be delayed due to delayed gastric emptying, formation of gastric concretions, or use of enteric-coated formulations.

Emergency management of acetylsalicylic acid poisoning depends on the severity, stage, and clinical symptoms and follows standard protocols for poisoning. Initial measures should focus on accelerating drug elimination and restoring electrolyte and acid-base balance. Due to the complex pathophysiological effects of salicylate poisoning, various symptoms and laboratory abnormalities may occur.

Mild to moderate poisoning: tachypnea, hyperventilation, respiratory alkalosis, increased sweating, nausea, vomiting. Laboratory findings: alkalosis, alkaline urine reaction.

Severe poisoning: respiratory alkalosis with compensatory metabolic acidosis, hyperpyrexia, tinnitus, hearing loss. Respiratory system: from hyperventilation and non-cardiogenic pulmonary edema to respiratory arrest and asphyxia; laboratory findings: alkalosis, alkaline urine reaction. Cardiovascular system: from cardiac arrhythmias and arterial hypotension to cardiac arrest. Fluid and electrolyte loss: dehydration, oliguria, renal failure. Laboratory findings: hypokalemia, hypernatremia, hyponatremia, impaired renal function. Glucose metabolism disturbances, ketosis—laboratory findings include hyperglycemia, hypoglycemia (especially in children), elevated ketone bodies. Gastrointestinal tract: gastrointestinal bleeding. Hematological: from platelet function inhibition to coagulopathy. Laboratory findings: prolonged prothrombin time, hypoprothrombinemia. Neurological: toxic encephalopathy and CNS depression ranging from lethargy and impaired consciousness to coma and seizures.

Symptoms of overdose within the first 24 hours caused by paracetamol: pallor, loss of appetite, anorexia, nausea, vomiting, abdominal pain, hepatonecrosis, elevated liver transaminase activity, increased prothrombin index. Liver injury symptoms typically appear 12–48 hours after overdose. Glucose metabolism disturbances and metabolic acidosis may also occur. In severe poisoning, liver failure may progress, leading to toxic encephalopathy with impaired consciousness, hemorrhages, hypoglycemia, coma, and, in some cases, fatal outcome. Acute renal failure with acute tubular necrosis may present with severe lumbar pain, hematuria, proteinuria, and may develop even in the absence of severe kidney damage. Cardiac arrhythmias and pancreatitis have also been reported.

With prolonged high-dose use of the medicinal product, hematological disorders such as aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, and thrombocytopenia may develop. High doses may cause CNS effects such as dizziness, psychomotor agitation, and disorientation; urinary system effects—nephrotoxicity (renal colic, interstitial nephritis, cortical necrosis).

Liver injury is possible in adults who ingest 10 g or more of paracetamol and in children who ingest more than 150 mg/kg body weight. In patients with risk factors (chronic use of carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. John’s wort, or other hepatic enzyme-inducing drugs; alcohol abuse; glutathione system deficiency, e.g., gastrointestinal disorders, HIV infection, fasting, cystic fibrosis, cachexia), ingestion of 5 g or more of paracetamol may lead to liver injury.

In case of overdose, prompt medical assistance is required. The patient should be immediately hospitalized, even if early symptoms of overdose are absent.

In overdose, symptoms such as nausea, vomiting, increased sweating, psychomotor agitation or CNS depression, somnolence, impaired consciousness, cardiac arrhythmias, tachycardia, extrasystoles, tremor, hyperreflexia, seizures may occur, or the severity of overdose or risk of organ damage may not be apparent. Plasma paracetamol concentration should be measured 4 hours or later after ingestion (earlier measurements are unreliable).

Treatment: gastric lavage followed by activated charcoal (if excessive paracetamol dose was taken within 1 hour), symptomatic therapy. The specific antidote for paracetamol overdose is N-acetylcysteine. In the absence of vomiting, oral methionine or intravenous N-acetylcysteine may be used. It is effective within 24 hours, but maximum protective effect is achieved when administered within 8 hours after overdose. The efficacy of the antidote sharply decreases after this period. General supportive measures should also be implemented. If necessary, α-adrenoblockers may be used.

Symptoms of overdose caused by caffeine: excitation, dizziness, rapid breathing, vomiting, tremor, seizures, extrasystoles.

Treatment: gastric lavage, repeated administration of activated charcoal, forced alkaline diuresis, oxygen therapy, hemodialysis in severe cases, fluid and electrolyte infusion. Symptomatic therapy. In case of seizures, diazepam should be administered.

Adverse reactions.

Respiratory system, thoracic and mediastinal organs: rhinitis, nasal congestion, bronchospasm in patients sensitive to acetylsalicylic acid and other NSAIDs.

Gastrointestinal tract: dyspeptic disorders including nausea, vomiting, discomfort and pain in the epigastrium, heartburn, abdominal pain; gastrointestinal inflammation, erosive-ulcerative lesions of the gastrointestinal tract, which in individual cases may lead to gastrointestinal bleeding and perforation, with corresponding laboratory and clinical manifestations.

Hepatic and biliary system: liver function abnormalities, increased activity of liver enzymes, usually without development of jaundice, hepatonecrosis (dose-dependent effect).

Metabolism and nutritional disorders: hypoglycemia, up to hypoglycemic coma.

Nervous system: headache, dizziness, tremor, paresthesia, excitement, sleep disturbances, insomnia, general weakness, tinnitus.

Psychiatric disorders: fear, restlessness, anxiety, irritability.

Cardiovascular system: tachycardia, arrhythmia, palpitations, arterial hypertension.

Blood and lymphatic system: thrombocytopenia, agranulocytosis, bruising and hemorrhages, anemia, sulfhemoglobinemia and methemoglobinemia (cyanosis, dyspnea, chest pain); hemolytic anemia. Due to the anti-aggregant effect of acetylsalicylic acid on platelets, the risk of bleeding may increase. Bleeding events observed include intraoperative hemorrhages, hematomas, urogenital tract bleeding, epistaxis, gingival bleeding, gastrointestinal bleeding, and cerebral hemorrhage.

Immune system: hypersensitivity reactions, including anaphylaxis, anaphylactic shock.

Skin and subcutaneous tissue: pruritus, skin and mucous membrane rashes, including generalized and erythematous eruptions; urticaria, angioneurotic edema, multiform exudative erythema, Stevens-Johnson syndrome, toxic epidermal necrolysis (Lyell's syndrome).

General disorders: bleeding may lead to acute and chronic post-hemorrhagic anemia/iron-deficiency anemia (due to so-called occult microbleeding), with corresponding laboratory findings and clinical symptoms such as asthenia, pallor of the skin, hypoperfusion; non-cardiogenic pulmonary edema.

Shelf life. 3 years.

Do not use the medicinal product 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 of children.

Packaging.

6 or 10 tablets in blister packs; 6 or 10 tablets in a blister pack, 1 blister pack in a carton; 10 tablets in a blister pack, 6 or 12 blister packs in a carton.

Availability category. Over-the-counter.

Manufacturer. JSC "Pharmaceutical company "Darnytsia".

Manufacturer's address and place of business.

13, Borispilska Street, Kyiv, 02093, Ukraine.