Citramon b

I N S T R U C T I O N for medical use of the medicinal product CYTROMON V (CITRAMONUM V)

Composition:

active substances: acetylsalicylic acid, paracetamol, caffeine;

1 tablet contains 240 mg of acetylsalicylic acid, 180 mg of paracetamol, 30 mg of caffeine;
excipients: potato starch; povidone; ascorbic acid; citric acid monohydrate; talc; calcium stearate; cocoa.

Medicinal form. Tablets.

Basic physicochemical properties: light brown tablets with speckles, flat surface, with a score line and beveled edges.

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

Pharmacological properties.

Pharmacodynamics.

A combination drug that exerts analgesic, antipyretic, and moderate anti-inflammatory effects. Caffeine contained in the drug enhances and accelerates the therapeutic effect of paracetamol.

Pharmacokinetics.

Acetylsalicylic acid is rapidly absorbed; therapeutic concentration in the blood is reached within 30 minutes, maximum concentration — within 2 hours. Part of the drug is absorbed in the stomach, the majority — in the small intestine. Paracetamol is well absorbed in the upper gastrointestinal tract. Maximum therapeutic effect develops within 30–60 minutes after administration, maximum drug concentration in blood — within 2–2.5 hours, elimination half-life — approximately 2 hours. The drug is excreted from the body via urine.

Clinical characteristics.

Indications.

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

Contraindications.

Hypersensitivity to the components of the drug, other xanthine derivatives (theophylline, theobromine), 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 cardiac arrhythmias (e.g., atherosclerosis); closed-angle glaucoma; epilepsy; hyperthyroidism; decompensated heart failure; conduction disorders; severe atherosclerosis; predisposition to vascular spasm; ischemic heart disease; acute pancreatitis; prostatic hypertrophy; severe forms of diabetes mellitus; bronchial asthma, allergic rhinitis, urticaria 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. Combination with methotrexate at doses of 15 mg/week or higher is contraindicated (see "Interaction with other medicinal products and other forms of interaction").

Interaction with other medicinal products and other forms of interaction.

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 during 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 into hepatotoxic metabolites. Concomitant use of paracetamol with hepatotoxic agents increases the risk of liver toxicity. Simultaneous use of high-dose paracetamol with isoniazid increases the risk of hepatotoxic syndrome. Paracetamol reduces the efficacy of diuretics. Do not use simultaneously with alcohol. Paracetamol increases the elimination half-life of chloramphenicol fivefold.

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 and 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 anesthetics and other central nervous system depressants, and as a competitive antagonist of adenosine and adenosine triphosphate (ATP). Concomitant use of caffeine with ergotamine improves absorption of ergotamine from the gastrointestinal tract; with thyrotropic agents, it enhances their effect. Caffeine reduces blood lithium concentration.

Acetylsalicylic acid.

Contraindicated combinations.

Use of methotrexate at doses of 15 mg/week or higher increases hematological toxicity of methotrexate (due to reduced renal clearance of methotrexate caused 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 diminish the cardioprotective effect of acetylsalicylic acid. Concomitant use of acetylsalicylic acid and anticoagulants increases the risk of bleeding. Simultaneous use of high-dose 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 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-dose 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 sulfonylurea from plasma protein binding. Diuretics in combination with high-dose acetylsalicylic acid reduce glomerular filtration due to decreased renal prostaglandin synthesis. Systemic glucocorticoids (except hydrocortisone) used in replacement therapy for Addison’s disease reduce blood salicylate levels during corticosteroid treatment and increase the risk of overdose after discontinuation. 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-dose 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 effect. Ethanol promotes damage to the gastrointestinal mucosa and prolongs bleeding time due to synergism between acetylsalicylic acid and alcohol.

Caution is advised when using paracetamol concomitantly with flucloxacillin, as this combination 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").

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, treatment with this medicinal product may lead to the development of bronchospasm or an attack of bronchial asthma; therefore, the use of NSAIDs is contraindicated in these patients.

During surgical procedures (including dental surgery), the use of medicinal products containing acetylsalicylic acid 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 or ulcerative gastrointestinal lesions and gastrointestinal bleeding, in patients with increased bleeding tendency, or when anti-inflammatory therapy is administered concomitantly.

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 Citramon V 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 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, retrosternal discomfort 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 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.

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

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

Use during pregnancy or breastfeeding.

The medicinal product should not be 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).

Method of Administration and Dosage.

For adults, take 1 tablet orally 2–3 times daily after meals. The maximum daily dose is 6 tablets administered in 3 divided doses. Citramon V tablets should not be used for more than 5 days as an analgesic or for more than 3 days as an antipyretic.

Children.

The drug is contraindicated in children due to the risk of Reye's syndrome associated with hyperthermia during viral infections (hyperpyrexia, metabolic acidosis, neurological and psychiatric disturbances, vomiting, liver dysfunction).

Overdose.

Symptoms of overdose may occur with prolonged use of the drug or when administered 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 after doses exceeding 100 mg/kg/day for more than 2 days (accidental ingestion by children or accidental overdose), which may be potentially life-threatening.

Chronic salicylate poisoning may be asymptomatic, as it lacks specific symptoms. Moderate salicylate 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—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 sign in children. The severity of poisoning cannot be assessed solely by 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 poisoning emergencies. 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—manifested in laboratory tests as hyperglycemia, hypoglycemia (especially in children), elevated ketone bodies. Gastrointestinal tract: gastrointestinal bleeding. Hematological effects: from platelet function suppression to coagulopathies. Laboratory findings: prolonged prothrombin time, hypoprothrombinemia. Neurological: toxic encephalopathy and central nervous system (CNS) depression—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, prolonged prothrombin index. Liver damage symptoms 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, death. Acute renal failure with acute tubular necrosis may present as severe lumbar pain, hematuria, proteinuria, and may develop even without severe kidney damage.

Cardiac arrhythmias and pancreatitis have also been reported.

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

In case of overdose, prompt medical attention 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, and seizures may occur, or the severity of overdose or organ damage risk 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, which is effective within 24 hours, but maximum protective effect is achieved when administered within 8 hours of overdose. Antidote efficacy sharply decreases after this time. General supportive measures should also be implemented. If necessary, α-adrenoblockers should 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 organs and mediastinum:
Rhinitis, nasal congestion, bronchospasm in patients sensitive to acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs (NSAIDs).

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

Liver and biliary system:
Liver function abnormalities, increased liver enzyme activity (usually without jaundice), hepatonecrosis (dose-dependent effect).

Metabolism and nutrition disorders:
Hypoglycemia, up to hypoglycemic coma.

Metabolic disorders and nutrition: Metabolic acidosis with high anion gap (frequency unknown).

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

Psychiatric disorders:
Feelings of fear, nervousness, 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 antiplatelet effect, acetylsalicylic acid increases the risk of bleeding. Bleeding events observed include intraoperative hemorrhages, hematomas, bleeding from genitourinary organs, epistaxis, gingival bleeding, gastrointestinal bleeding, and intracranial hemorrhage.

Immune system:
Hypersensitivity reactions, including anaphylaxis and anaphylactic shock.

Skin and subcutaneous tissue:
Skin pruritus, skin and mucous membrane rashes, including generalized and erythematous rashes; 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.

Description of selected adverse reactions.

Metabolic acidosis with high anion gap. Cases of metabolic acidosis with high anion gap due to pyroglutamic acidosis have been observed in patients with risk factors taking paracetamol (see section "Special precautions for use"). Pyroglutamic acidosis may occur due to low glutathione levels in these patients.

Reporting suspected adverse reactions.

Reporting of suspected adverse reactions after drug registration is of great importance. It enables ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare and pharmacy professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of efficacy through the automated pharmacovigilance information system at: https://aisf.dec.gov.ua.

Shelf life.
2 years.

Storage conditions.
In the original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.

Packaging.
6 or 10 tablets in strips;
6 or 10 tablets in blisters;
6 tablets per strip; 2 or 10 strips per cardboard pack;
10 tablets per strip; 2 or 10 strips per cardboard pack;
6 tablets per blister; 2 or 5 or 10 blisters per cardboard pack;
10 tablets per blister; 2 or 10 blisters per cardboard pack.

Supply classification.
Over-the-counter (without prescription).

Manufacturer.
JSC "Monfarm".

Manufacturer's address and location of operations.
8 Zavodska Street, Avramivka village, Uman district, Cherkasy region, 19161, Ukraine.