Copacil

INSTRUCTION FOR MEDICAL USE OF THE MEDICINAL PRODUCT COPECIL® (SORASUL)

Composition:

Active substances: acetylsalicylic acid, paracetamol, caffeine;

1 tablet contains acetylsalicylic acid* – 300 mg; paracetamol* – 100 mg; caffeine* – 50 mg;

Excipients: potato starch, sodium croscarmellose, hypromellose, colloidal anhydrous silicon dioxide, talc, calcium stearate, cocoa (powder), vanilla flavor, anhydrous citric acid.

* calculated as 100% substance

Pharmaceutical form. Tablets.

Main physicochemical characteristics: light brown tablets with specks, oval-shaped, biconvex surface, with a score line on one side of the tablet, with a cocoa and vanilla odor.

Pharmacotherapeutic group. Analgesics and antipyretics. ATC code N02BA51.

Pharmacological Properties

Pharmacodynamics

Kopatsyl® is a combination medication that provides analgesic and anti-inflammatory effects by inhibiting prostaglandin synthesis. The components of the drug potentiate each other's actions. Acetylsalicylic acid moderately inhibits platelet aggregation and improves microcirculation at the site of inflammation. Caffeine stimulates the central nervous system (CNS), activates the respiratory and vasomotor centers, and enhances the effects of analgesics and antipyretics.

Pharmacokinetics

The therapeutic effect of the drug begins 30–60 minutes after oral administration, reaches its maximum within 2–2.5 hours, and lasts for 3–4 hours.

Clinical Characteristics

Indications

Mild to moderate pain (headache, arthralgia, migraine, toothache, neuralgias, primary dysmenorrhea). The drug can also be used as an antipyretic in diseases accompanied by fever.

Contraindications

Hypersensitivity to components of the drug, other xanthine derivatives (theophylline, theobromine), other salicylates; bronchial asthma caused by administration of salicylates or other nonsteroidal anti-inflammatory drugs (NSAIDs) in medical history; congenital hyperbilirubinemia, congenital glucose-6-phosphate dehydrogenase deficiency, blood disorders, leukopenia, anemia, thrombosis, thrombophlebitis, acute gastrointestinal ulcers, hemorrhagic diathesis, severe renal insufficiency, severe hepatic insufficiency, severe cardiovascular diseases including arrhythmias, marked atherosclerosis, severe form of ischemic heart disease, severe heart failure, severe arterial hypertension, tendency to vascular spasm; acute pancreatitis, prostate hyperplasia, severe forms of diabetes mellitus; conditions of increased excitation, sleep disorders, epilepsy, hyperthyroidism, glaucoma, alcoholism. The period of administration of MAO inhibitors, as well as within 2 weeks after discontinuation of their use, is contraindicated in patients taking tricyclic antidepressants or beta-blockers. Combination with methotrexate at doses of 15 mg/week or higher.

Interaction with other medicinal products and other forms of interactions

Contraindicated combinations

Methotrexate – when used concomitantly with salicylates at a dose of 15 mg per week or higher, hematological toxicity of methotrexate increases due to reduced renal clearance of methotrexate by anti-inflammatory agents and its displacement from plasma protein binding; therefore, this combination is contraindicated.

Barbiturates reduce the antipyretic effect of paracetamol.

Due to the presence of acetylsalicylic acid, the drug may enhance the hypoglycemic effect of oral antidiabetic agents.

Combinations requiring caution

Paracetamol: antidepressants and other stimulators of microsomal oxidation – these drugs increase the production of hydroxylated active metabolites affecting liver function, potentially leading to severe intoxication even with small overdoses of the drug. The absorption rate of paracetamol may be increased when used concomitantly with metoclopramide and domperidone, and decreased when used with cholestyramine. Paracetamol reduces the effectiveness of diuretics. Long-term use of paracetamol increases the risk of bleeding when used with coumarin derivatives (warfarin). Under the influence of paracetamol, the half-life of chloramphenicol increases fivefold. Concurrent use of high doses of paracetamol with isoniazid increases the risk of developing hepatotoxic syndrome.

Paracetamol should be used with caution when administered simultaneously with flucloxacillin, as such concurrent use has been associated with metabolic acidosis with a high anion gap due to pyroglutamic acidosis, especially in patients with risk factors (see section "Special precautions").

Caffeine: 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 suppress the central nervous system (CNS) (competitive antagonist of CNS depressants), competitive antagonist of adenosine and ATP drugs. When used concomitantly with ergotamine, caffeine improves ergotamine absorption from the gastrointestinal tract; when used with thyrotropic agents, thyroid effect is enhanced. Caffeine reduces lithium concentration in blood. Caffeine enhances the effect (improves bioavailability) of analgesic-antipyretic drugs, potentiates the effects of xanthine derivatives, alpha- and beta-adrenomimetics, psychostimulants. Concurrent use of caffeine with MAO inhibitors may cause dangerous elevation of blood pressure.

Acetylsalicylic acid: concomitant use with uricosuric agents such as benzbromarone, probenecid reduces uric acid excretion effect (due to competition for renal tubular excretion of uric acid). When used concomitantly with digoxin, digoxin concentration in plasma increases due to reduced renal excretion. ACE inhibitors in combination with high doses of acetylsalicylic acid cause reduced glomerular filtration due to inhibition of vasodilatory prostaglandins and reduced antihypertensive effect. Selective serotonin reuptake inhibitors: increased risk of upper gastrointestinal bleeding due to possible synergistic effect. When used concomitantly with valproic acid, acetylsalicylic acid displaces it from plasma protein binding, increasing its toxicity.

Special precautions for use

Do not use this medication together with other products containing paracetamol or acetylsalicylic acid. Do not exceed the recommended dosage.

Pre-existing liver disease increases the risk of liver damage associated with paracetamol.

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

Allergic reactions or exacerbation of underlying disease may occur in patients with bronchial asthma, allergic disorders, or hypersensitivity to NSAIDs. This medication should be used with caution in elderly patients.

During treatment, excessive consumption of caffeine-containing beverages (e.g., coffee, tea) is not recommended, as it may cause sleep disturbances, tremor, or chest discomfort due to palpitations.

Alcoholic beverages should not be consumed during treatment.

Use with caution in the following situations:

• Hypersensitivity to analgesics, anti-inflammatory, or antirheumatic agents, or allergy to other substances;
• Gastrointestinal ulcers, including chronic or recurrent peptic ulcer disease or history of gastrointestinal bleeding;
• Concomitant use of anticoagulants;
• Patients with impaired renal function or conditions associated with cardiovascular compromise (e.g., renal vascular disease, congestive heart failure, hypovolemia, major surgery, sepsis, or severe bleeding), as acetylsalicylic acid may increase the risk of renal impairment and acute renal failure;
• Patients with severe glucose-6-phosphate dehydrogenase (G6PD) deficiency, in whom acetylsalicylic acid may cause hemolysis or hemolytic anemia, especially in the presence of risk factors such as high drug doses, fever, or acute infection;
• Impaired liver function.

Acetylsalicylic acid may provoke bronchospasm, asthma attacks, or other hypersensitivity reactions. Risk factors include a history of asthma, hay fever, nasal polyps, or chronic respiratory disease, as well as prior allergic reactions (e.g., skin reactions, pruritus, urticaria) to other substances.

Due to the inhibitory effect of acetylsalicylic acid on platelet aggregation, which persists for several days after administration, the use of acetylsalicylic acid-containing medications may increase the risk and severity of bleeding during surgical procedures (including minor interventions such as tooth extraction).

When low doses of acetylsalicylic acid are used, urinary excretion of uric acid may be reduced. This may trigger gout attacks in predisposed individuals.

Acetylsalicylic acid-containing medications should not be used in children and adolescents with acute viral respiratory infections (ARVI), regardless of fever, without prior medical consultation. In certain viral illnesses, particularly influenza A, influenza B, and varicella, there is a risk of Reye's syndrome—a very rare but life-threatening condition requiring urgent medical intervention. The risk may be increased if acetylsalicylic acid is used concomitantly, although a causal relationship has not been definitively established. Persistent vomiting in these conditions may be a sign of Reye's syndrome.

If symptoms persist, consult a physician.

If headache becomes persistent, medical advice should be sought.

Use during pregnancy or breastfeeding

Do not use.

Ability to affect the speed of reactions when driving or operating machinery

If dizziness occurs, avoid potentially hazardous activities such as driving a vehicle and/or performing tasks requiring heightened attention and rapid psychomotor reactions.

Dosage and Administration

Take Copacil® orally after meals. For adults, 1 tablet 2-3 times daily, with intervals between doses of at least 4 hours. Maximum daily dose – 6 tablets (in 3 doses).

The duration of treatment depends on the course and severity of the disease and should not exceed 5 days when used as an analgesic, and 3 days when used as an antipyretic.

Children

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

Overdose

Paracetamol overdose symptoms

Hepatic injury may occur in adults who have ingested 10 g or more of paracetamol, and in children who have received doses exceeding 150 mg/kg body weight. Liver damage may become apparent 12–48 hours after ingestion of excessive doses. Within the first 24 hours, the following symptoms may occur: pallor, nausea, vomiting, anorexia, abdominal pain, hepatonecrosis, elevated activity of "liver" transaminases, prolonged prothrombin time. In severe poisoning, hepatic failure may lead to encephalopathy, coma, and death. 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. Pancreatitis has also been reported. Glucose metabolism disturbances and metabolic acidosis may occur. Cardiac arrhythmias have also been observed. With prolonged use of high doses, aplastic anemia, thrombocytopenia, pancytopenia, agranulocytosis, neutropenia, and leukopenia may develop.

In patients with risk factors (long-term treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. John's wort, or other drugs inducing liver enzymes; alcohol abuse; glutathione deficiency, e.g., due to gastrointestinal disorders, cystic fibrosis, HIV infection, malnutrition, cachexia), ingestion of 5 g or more of paracetamol may lead to liver injury.

With large doses, central nervous system (CNS) effects may include dizziness, psychomotor agitation, and disorientation; urinary system effects may include nephrotoxicity (renal colic, interstitial nephritis, papillary necrosis).

Treatment with N-acetylcysteine can be administered within 24 hours after paracetamol ingestion, but maximum protective effect is achieved when administered within 8 hours after overdose. The efficacy of the antidote decreases sharply after this time.

Acetylsalicylic acid overdose symptoms

Salicylate overdose may occur due to chronic intoxication resulting from prolonged therapy (use of more than 100 mg/kg/day for over 2 days may cause toxic effects), or due to acute, life-threatening intoxication (overdose), which may result from accidental ingestion by children or unintentional overdose.

Chronic salicylate intoxication may have an insidious presentation, as its signs are nonspecific. Moderate chronic intoxication caused by salicylates, or salicylism, typically occurs only after repeated intake of large doses. Main symptoms include: impaired balance, dizziness, tinnitus, hearing loss, excessive sweating, nausea and vomiting, headache, confusion. These symptoms can be managed by reducing the dose. Tinnitus may occur at plasma salicylate concentrations above 150–300 μg/mL. More serious adverse reactions occur at plasma salicylate concentrations above 300 μg/mL. Acute intoxication is characterized by marked disturbances in acid-base balance, which may vary depending on patient age and severity of intoxication. The severity of condition cannot be determined solely by plasma salicylate concentration.

Due to the complex pathophysiological effects of salicylate poisoning, clinical manifestations and laboratory findings may include:

Mild to moderate intoxication may be accompanied by: tachypnea, hyperventilation, respiratory alkalosis (alkalemia, alkaluria); increased sweating; nausea, vomiting.

Moderate to severe intoxication may be accompanied by: respiratory alkalosis with compensatory metabolic acidosis (acidemia, aciduria); hyperpyrexia; respiratory disorders: hyperventilation, non-cardiogenic pulmonary edema, respiratory failure, asphyxia; cardiovascular disorders: arrhythmia, arterial hypotension, cardiovascular collapse; fluid and electrolyte loss: dehydration, oliguria, renal failure; glucose metabolism disturbances, ketoacidosis; tinnitus, hearing loss; gastrointestinal hemorrhage; hematological disorders: platelet inhibition, coagulopathy; neurological disorders: toxic encephalopathy and CNS depression, manifesting as lethargy, confusion, coma, and seizures.

Caffeine overdose symptoms

Large doses of caffeine may cause epigastric pain, vomiting, diuresis, rapid breathing, extrasystoles, tachycardia or cardiac arrhythmia, and effects on the central nervous system (dizziness, insomnia, nervous excitation, irritability, restlessness, anxiety, tremor, seizures).

Treatment

Treatment is determined by the severity and clinical symptoms and is provided using standard methods. In case of overdose, prompt medical assistance is required, even if symptoms of overdose are not present. Oral administration of methionine or intravenous administration of acetylcysteine may be effective within 48 hours after overdose. General supportive measures and symptomatic therapy should also be implemented, including the use of beta-adrenergic receptor antagonists, which may counteract cardiotoxic effects.

Side effects

Allergic reactions: skin rashes (usually erythematous, urticaria), itching, angioedema, erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis, non-cardiogenic pulmonary edema, asthma.

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

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

Metabolism and nutrition: metabolic acidosis with high anion gap (frequency unknown).

Endocrine system: hypoglycemia, up to hypoglycemic coma.

Blood and lymphatic system disorders: sulfhemoglobinemia and methemoglobinemia (cyanosis, dyspnea, chest pain), hemolytic anemia, thrombocytopenia, agranulocytosis, perioperative hemorrhages, hematomas, genitourinary system hemorrhages, epistaxis, gingival hemorrhages, cerebral hemorrhages.

Hemorrhages 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.

Immune system disorders: angioedema, anaphylactic shock, which may be accompanied by cardiorespiratory failure, hypersensitivity reactions, rhinitis, nasal congestion, bronchospasm.

Cardiovascular system: transient arterial hypertension, tachycardia, arrhythmia.

Central nervous system: dizziness, insomnia, restlessness, tinnitus.

Renal and urinary system: renal function impairment and development of acute renal failure have been reported.

Concomitant use of the medicinal product at recommended doses with caffeine-containing products may enhance caffeine-related side effects such as increased excitability, anxiety, irritability, headache, gastrointestinal disturbances, and rapid heartbeat.

Description of selected side effects

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 suspected adverse reactions after medicinal product authorization is important. It allows ongoing monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical 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 the following link: https://aisf.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. Tablets: 6 or 10 tablets in a blister pack; 10 tablets in a blister; 1 or 2 blisters per carton.

Release classification. Over-the-counter.

Manufacturer. JSC "Kyivmedpreparat".

Manufacturer's address and place of business

139 Saksahanskoho Street, Kyiv, 01032, Ukraine.