Citramon-f

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT CITRAMON-F

Composition:

Active substances: acetylsalicylic acid, paracetamol, caffeine;

One tablet contains: acetylsalicylic acid 0.24 g; paracetamol 0.18 g; caffeine, calculated as dry substance, 0.03 g;

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

Pharmaceutical form. Tablets.

Main physico-chemical properties: mottled light-brown tablets with a cocoa odor.

Pharmacotherapeutic group.

Analgesics and antipyretics. Acetylsalicylic acid, combinations without psycholeptics.

ATC code N02B A51.

Pharmacological Properties.

Pharmacodynamics.

Due to the presence of acetylsalicylic acid and paracetamol in the tablet, the drug has anti-inflammatory, antipyretic, and analgesic effects.

The components contained in the medicinal product enhance 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 involves inhibition of prostaglandin synthesis in inflamed tissues; the central effect involves action on hypothalamic centers. Acetylsalicylic acid also reduces platelet aggregation.

Paracetamol exerts analgesic, antipyretic, and very weak anti-inflammatory effects, which are associated with its influence 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 drugs, and potentiates the effects of analgesics and antipyretic agents.

Pharmacokinetics.

Not studied.

Clinical characteristics.

Indications. For the treatment of mild or moderate pain: headache or toothache, primary dysmenorrhea, migraine, arthralgia, neuralgia, and conditions accompanied by hyperthermia of various etiologies (as an antipyretic agent).

Contraindications. Hypersensitivity to components of the drug or to other salicylates; severe impairment of liver and/or kidney function; congenital hyperbilirubinemia; glucose-6-phosphate dehydrogenase deficiency; alcoholism; blood disorders; Gilbert's syndrome; hemophilia; hemorrhagic diathesis; pronounced anemia; leukopenia; thrombosis; thrombophlebitis; hemorrhagic diseases; active peptic ulcer; states of increased excitation; sleep disorders; severe arterial hypertension; organic cardiovascular diseases (including atherosclerosis); 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; closed-angle glaucoma; bronchial asthma induced by salicylates in the past; pediatric age (except for use in Kawasaki disease); pregnancy; breastfeeding; 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 beta-blockers. Combination with methotrexate at doses of 15 mg/week or higher is contraindicated (see "Interaction with other medicinal products and other types of interactions").

Interaction with other medicinal products and other types of interactions.

Paracetamol. The absorption rate of paracetamol may be increased by metoclopramide and domperidone, and decreased by cholestyramine. The anticoagulant effect of warfarin and other coumarins may be enhanced by long-term, regular daily 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. Concurrent use of paracetamol with hepatotoxic agents increases the hepatotoxic effects of both drugs.

Concomitant use of high-dose paracetamol with isoniazid increases the risk of hepatotoxic syndrome. Paracetamol reduces the efficacy of diuretics.

Paracetamol should be used with caution when administered concurrently with flucloxacillin, as co-administration has been associated with metabolic acidosis with a high anion gap due to pyroglutamic acidosis, particularly in patients with risk factors (see section "Special precautions for use").

Do not use concurrently with alcohol.

Caffeine. Concomitant use of caffeine with monoamine oxidase inhibitors (MAOIs) may cause dangerous increases in blood pressure.

Caffeine enhances the effect (improves bioavailability) of analgesic-antipyretic agents, and potentiates the effects of xanthine derivatives, alpha- and beta-adrenergic agonists, psychostimulants.

Cimetidine, hormonal contraceptives, isoniazid enhance the effect 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 adenosine triphosphate (ATP) preparations.

When used concomitantly with ergotamine, caffeine improves the gastrointestinal absorption of ergotamine; when used with thyrotropic agents, it enhances the thyroid effect.

Caffeine reduces blood lithium concentrations.

Acetylsalicylic acid.

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 cautious use.

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 compromise 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 with nonsteroidal anti-inflammatory drugs (NSAIDs) increases the risk of ulcers and gastrointestinal bleeding due to mutual enhancement of effects.

Concomitant use with uricosuric agents such as benzbromarone and 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 agents of the sulfonylurea group or insulin enhances the hypoglycemic effect of the latter due to the hypoglycemic effect of acetylsalicylic acid and displacement of sulfonylurea from plasma protein binding.

Diuretics in combination with high doses of acetylsalicylic acid reduce glomerular filtration due to decreased renal prostaglandin synthesis.

Systemic glucocorticosteroids (excluding hydrocortisone), used as replacement therapy in Addison's disease, reduce blood salicylate levels during corticosteroid treatment 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, cause reduced glomerular filtration due to inhibition of vasodilatory prostaglandins and diminished antihypertensive effect.

Concomitant use with valproic acid: acetylsalicylic acid displaces valproic acid from plasma protein binding, increasing its toxicity.

Concomitant use with selective serotonin reuptake inhibitors (SSRIs) increases the risk of gastrointestinal bleeding due to synergistic effects.

Ethyl alcohol 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 pruritus, mucosal edema, and nasal polyposis, as well as in combination with chronic respiratory tract infections and in patients with hypersensitivity to NSAIDs, administration of the drug may lead to the development of bronchospasm or an attack of bronchial asthma.

The use of drugs containing acetylsalicylic acid during surgical procedures (including dental procedures) increases the risk of occurrence or intensification of bleeding.

Use with caution in patients with liver or kidney disease, in those with a history of erosive-ulcerative gastrointestinal lesions or gastrointestinal bleeding, in patients with increased bleeding tendency, or when concomitant anti-inflammatory therapy is administered. Acetylsalicylic acid, one of the components of the drug, 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 Citramon-P without consulting a physician for more than 5 days as an analgesic or for more than 3 days as an antipyretic. In patients with impaired kidney or liver function, the interval between doses should be no less than 8 hours. Alcohol consumption should be avoided during treatment with this drug. With prolonged use, monitoring of blood coagulation system and hemoglobin levels is required.

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

Do not exceed the recommended doses.

Regarding paracetamol: in patients with liver or kidney disease, consult a physician before using the drug.

Consult a physician before using the drug if the patient is taking warfarin or similar agents with anticoagulant effects.

The risk of overdose is highest in patients with non-cirrhotic alcoholic liver disease. The drug 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 metabolic acidosis. Symptoms of metabolic acidosis include deep, rapid, or labored breathing, nausea, vomiting, and loss of appetite. If these symptoms occur, seek immediate medical attention.

Cases of high anion gap metabolic acidosis (HAGMA) due to 5-oxoproline (pyroglutamic) acidosis have been reported in patients with severe underlying conditions such as severe renal failure and sepsis, or in patients with malnutrition or other sources of glutathione deficiency (e.g., chronic alcoholism), who were treated with paracetamol at therapeutic doses for prolonged periods or in combination with flucloxacillin. If HAGMA due to pyroglutamic acidosis is suspected, immediate discontinuation of paracetamol is recommended, along with careful monitoring. Measurement of urinary 5-oxoproline levels may be useful in identifying pyroglutamic acidosis as the underlying cause of HAGMA in patients with multiple risk factors.

Do not take this drug with other products containing paracetamol.

If symptoms persist, consult a physician.

If headache becomes persistent, consult a physician.

Regarding acetylsalicylic acid: use with caution in patients with hypersensitivity to analgesics, anti-inflammatory, or antirheumatic agents; when anticoagulants are used concomitantly; or in patients with cardiovascular disorders (e.g., renal vascular disease, congestive heart failure, hypovolemia, major surgery, sepsis, or severe bleeding), since acetylsalicylic acid may also 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 drug is to be used before starting ibuprofen as an analgesic, the patient should consult a physician.

Use during pregnancy or breastfeeding.

The drug should not be used during pregnancy. Breastfeeding must be discontinued during treatment with this drug.

Ability to affect reaction speed when driving or operating machinery.

When high doses of the drug are used, driving vehicles or operating machinery should be avoided due to possible adverse reactions affecting the central nervous system (dizziness, psychomotor agitation, and disturbances in orientation and attention).

Dosage and Administration

The medicinal product should be administered to adults at a dose of 1 tablet 2–3 times daily after meals.

The maximum daily dose of the drug is 6 tablets (in 3 doses). Citramon-F tablets should not be taken for more than 5 days as an analgesic and for more than 3 days as an antipyretic.

The interval between doses should be at least 4 hours.

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), with or without fever. In certain viral diseases, particularly influenza A, influenza B, and varicella (chickenpox), there is a risk of developing Reye's syndrome, which requires urgent medical intervention. The risk is 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.

Due to the above reasons, the use of the medicinal product is contraindicated in children under 16 years of age unless there are specific indications (e.g. Kawasaki disease).

Overdose.

Symptoms of overdose may occur with prolonged use or with doses significantly exceeding the recommended dose.

Symptoms of overdose caused by acetylsalicylic acid.

Salicylate toxicity may result from chronic intoxication due to prolonged use of therapeutic doses or from acute intoxication (with doses > 100 mg/kg/day for more than 2 days), which is potentially life-threatening, ranging from accidental ingestion by children to accidental poisoning.

Chronic salicylate poisoning may be asymptomatic, as it lacks specific symptoms. Moderate intoxication, or salicylism, usually develops only after repeated administration of high doses.

Symptoms: dizziness, tinnitus, hearing loss, increased sweating, nausea, vomiting, headache, and impaired consciousness may be controlled by reducing the dose. 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 disturbance of acid-base balance, which may vary depending on age and severity of intoxication. The most common sign in children is metabolic acidosis. Severity of poisoning cannot be assessed based solely on plasma concentration. Absorption of acetylsalicylic acid may be delayed due to slowed 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 procedures for managing intoxications. 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.

Overdose of mild to moderate severity: 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 changes: from impaired platelet function to coagulopathies.

Laboratory findings: prolonged prothrombin time, hypoprothrombinemia. Nervous system: toxic encephalopathy and central nervous system depression, ranging from lethargy and impaired consciousness to coma and seizures.

Symptoms of overdose caused by paracetamol.

Symptoms of overdose within the first 24 hours include pallor, loss of appetite, nausea, vomiting, abdominal pain, hepatonecrosis, elevated liver transaminase activity, and increased prothrombin index.

Signs of liver damage appear 12–48 hours after overdose. Disturbances in glucose metabolism and metabolic acidosis may occur. In severe poisoning, liver failure may progress and lead to toxic encephalopathy with impaired consciousness, hemorrhages, hypoglycemia, coma, and, in some cases, death. Acute renal failure with acute tubular necrosis may present with severe lumbar pain, hematuria, proteinuria, and may develop even without severe kidney damage. Cardiac arrhythmias and pancreatitis have also been reported.

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

With prolonged use of the drug in high doses, hematological disorders such as aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, and thrombocytopenia may develop. With high-dose intake, central nervous system effects may include dizziness, psychomotor agitation or central nervous system depression, impaired consciousness and orientation. Urinary system: nephrotoxicity (renal colic, interstitial nephritis, capillary necrosis). In cases of overdose, symptoms may include excessive sweating, drowsiness, cardiac arrhythmias, tachycardia, extrasystoles, tremor, hyperreflexia, and seizures.

Treatment: immediate medical assistance is required in case of overdose. The patient should be taken to hospital immediately, even if early symptoms of overdose are absent. Symptoms may be limited to nausea and vomiting or may not reflect the severity of overdose or risk of organ damage. Treatment with activated charcoal should be considered if excess paracetamol was ingested within 1 hour. Plasma paracetamol concentration should be measured 4 hours or later after ingestion (earlier concentrations are unreliable). Treatment with N-acetylcysteine may be administered within 24 hours after paracetamol ingestion, but maximum protective effect is achieved when administered within 8 hours after ingestion. The efficacy of the antidote decreases sharply after this time. If necessary, N-acetylcysteine should be administered intravenously according to current guidelines. In the absence of vomiting, oral methionine may be used as an alternative in remote areas outside hospital settings.

Symptoms of overdose caused by caffeine.

Caffeine overdose manifests as excitation, dizziness, rapid breathing, vomiting, tremor, seizures, and extrasystoles.

Treatment: gastric lavage, repeated administration of activated charcoal, forced alkaline diuresis, oxygen therapy, hemodialysis in severe cases, fluid and electrolyte infusion. Symptomatic therapy. Diazepam is used in case of seizures. The specific antidote for paracetamol overdose is acetylcysteine.

Side effects.

Immune system disorders: hypersensitivity reactions, including skin itching, rashes on the skin and mucous membranes (usually generalized, erythematous, urticarial rash), angioneurotic edema, erythema multiforme (including Stevens–Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome); including anaphylaxis, anaphylactic shock, rhinitis, nasal congestion, bronchospasm in patients sensitive to acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs.

Skin and subcutaneous tissue disorders: itching, skin and mucous membrane rashes.

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

Hepatobiliary disorders: liver function abnormalities, increased liver enzyme activity, usually without development of jaundice, hepatonecrosis (dose-dependent effect).

Endocrine system disorders: hypoglycemia, up to hypoglycemic coma.

Central nervous system disorders: headache, dizziness, tremor, paresthesia, fear, anxiety, excitement, irritability, sleep disturbances, insomnia, anxiety, general weakness, tinnitus.

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

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

Respiratory system disorders: bronchospasm in patients sensitive to acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs.

Metabolism and nutrition disorders:

Metabolic acidosis with high anion gap, frequency "unknown" (cannot be estimated from available data).

Description of individual adverse reactions:

Metabolic acidosis with high anion gap.

Cases of metabolic acidosis with high anion gap as a result of pyroglutamic acidosis have been observed in patients with risk factors who used paracetamol (see section "Special precautions"). Pyroglutamic acidosis may occur as a consequence of low glutathione levels in these patients.

Other: 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.

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 a blister pack made of polyvinyl chloride film and aluminum foil; 6 tablets in a blister pack made of polyvinyl chloride film and aluminum foil, 20 blisters per carton.

Dispensing category.

Over-the-counter.

Manufacturer.

PJSC "PHYTOPHARM".

Manufacturer's address and location of operations.

2 Sybitsyeva Street, Bakhmut, Donetsk region, 84500, Ukraine.

Marketing Authorization Holder.

LLC "PHARMIS LTD".

Address of the Marketing Authorization Holder.

3 Lebedynska Street, Office 2, Kharkiv, 61001, Ukraine.