Ascofen-darnitsa

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

Composition:

Active substances: acetylsalicylic acid, paracetamol, caffeine;

One tablet contains: acetylsalicylic acid 200 mg, paracetamol 200 mg, caffeine 40 mg;

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

Pharmaceutical form. Tablets.

Main physico-chemical properties: white-colored, flat cylindrical tablets with bevel and score line. Marbling on the surface of tablets is permissible.

Pharmacotherapeutic group. Analgesics. Other analgesics and antipyretics. Acetylsalicylic acid, combinations without psychotropic agents. ATC code N02B A51.

Pharmacological properties.

Pharmacodynamics.

The medicinal product exerts analgesic, antipyretic, and anti-inflammatory 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 inhibition of prostaglandin PGE2 synthesis 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 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 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. It also 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: headache, toothache, neuralgia, myalgia, arthralgia, primary dysmenorrhea, as well as antipyretic therapy in diseases accompanied by fever.

Contraindications.

• Hypersensitivity to components of the drug, hypersensitivity to other xanthine derivatives (theophylline, theobromine), or other salicylates;
• Bronchial asthma, urticaria, or rhinitis induced by salicylates or other NSAIDs in medical history;
• Congenital hyperbilirubinemia, severe renal or hepatic insufficiency, Gilbert's syndrome, congenital glucose-6-phosphate dehydrogenase deficiency;
• Blood disorders, hemophilia, hemorrhagic diathesis, hypoprothrombinemia, anemia, leukopenia, increased tendency to bleeding, thrombosis, thrombophlebitis, hemorrhagic diseases;
• Acute gastrointestinal ulcers, gastrointestinal bleeding, surgical interventions associated with significant bleeding;
• Severe cardiovascular diseases, including arrhythmias, paroxysmal tachycardia, marked atherosclerosis, severe form of ischemic heart disease, severe heart failure, acute myocardial infarction, severe arterial hypertension, portal hypertension, predisposition to vascular spasm;
• Conditions of increased excitation, sleep disorders, elderly age, alcoholism, glaucoma, hyperthyroidism, acute pancreatitis, benign prostatic hyperplasia, severe forms of diabetes mellitus.

Concomitant use with MAO inhibitors, as well as within 2 weeks after discontinuation of such therapy. Combination with methotrexate at doses of 15 mg/week or higher.

Contraindicated in patients receiving tricyclic antidepressants or β-blockers.

Interaction with other medicinal products and other forms of interaction.

Contraindicated combinations.

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

MAO inhibitors – concomitant use with caffeine may lead to dangerous elevation of blood pressure; therefore, this combination is contraindicated.

Combinations requiring caution.

Paracetamol: Anticonvulsant drugs (including phenytoin, barbiturates, carbamazepine), antidepressants, and other microsomal oxidation stimulants – these drugs increase the production of hydroxylated active metabolites affecting liver function, increasing the risk of severe intoxication even with minor overdoses of the drug.

Concomitant use with hepatotoxic agents increases the hepatotoxic effects of drugs. Simultaneous use of high-dose paracetamol with isoniazid increases the risk of hepatotoxic syndrome.

The absorption rate of paracetamol may increase when used concomitantly with metoclopramide and domperidone, and decrease with cholestyramine. Paracetamol reduces the efficacy of diuretics. Long-term use of paracetamol increases the risk of bleeding with coumarin derivatives (warfarin). Do not use simultaneously with alcohol.

Under the influence of paracetamol, the elimination half-life of chloramphenicol increases fivefold.

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 depress the central nervous system (CNS), and as a competitive antagonist of adenosine and ATP drugs. Concomitant use of caffeine with ergotamine improves absorption of ergotamine from the gastrointestinal tract; with thyrotropic agents – thyroid effect is enhanced. Caffeine reduces lithium blood concentration. Caffeine enhances the effect (improves bioavailability) of analgesic-antipyretic drugs, potentiates the effects of xanthine derivatives, α- and β-adrenomimetics, psychostimulants.

Caution is required when using paracetamol concomitantly with flucloxacillin, as simultaneous administration is associated with metabolic acidosis with a high anion gap, particularly in patients with risk factors (see section "Special precautions").

Acetylsalicylic acid: concomitant use with uricosuric agents such as benzbromarone, probenecid reduces uric acid excretion effect (due to competitive renal tubular excretion of uric acid). When used concomitantly with digoxin, its plasma concentration 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: increase the risk of upper gastrointestinal bleeding due to possible synergistic effect. Concomitant use with valproic acid results in acetylsalicylic acid displacing valproic acid from plasma protein binding, increasing its toxicity.

The drug enhances the effect of agents reducing blood coagulation and platelet aggregation, the adverse effects of corticosteroids, sulfonylureas, and methotrexate.

Combinations with barbiturates, anticonvulsants, salicylates, rifampicin, and alcohol should be avoided.

Special precautions for use

Before using the medicinal product, consult a physician.

Do not exceed the recommended dosage. For short-term use only.

Do not use this medicinal product together with other products containing paracetamol or acetylsalicylic acid.

In patients with hepatic or renal impairment, the dose should be reduced or the dosing interval increased. In case of impaired kidney or liver function, the interval between doses should be at least 8 hours.

Since acetylsalicylic acid, like all non-selective nonsteroidal anti-inflammatory drugs (NSAIDs), may irritate the gastrointestinal mucosa, the medicinal product should be taken only after food, with water, alkaline mineral water, sodium bicarbonate solution, or preferably milk.

During prolonged use of the medicinal product, fecal occult blood testing is recommended to detect potential ulcerogenic effects, and blood tests should be performed (to monitor effects on platelet aggregation and possible anticoagulant activity).

In cases of hyperthermia, the medicinal product should be prescribed only if other analgesic-antipyretic agents are ineffective, due to the risk of Reye's syndrome. If vomiting occurs after taking the medicinal product, Reye's syndrome should be suspected.

It should be noted that in patients with alcoholic liver disease, the risk of hepatotoxic effects of paracetamol is increased. Liver diseases increase the risk of liver damage caused by paracetamol. The risk of overdose is higher in patients with non-cirrhotic alcoholic liver disease.

In patients with severe infections such as sepsis, which are 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.

The use of medicinal products containing acetylsalicylic acid during surgical procedures (including dental procedures) increases the risk of bleeding or increased bleeding due to inhibition of platelet aggregation, which persists for some time after administration. The medicinal product should be discontinued 5–7 days prior to surgery to reduce the risk of excessive bleeding.

The patient should inform the physician in advance about taking the medicinal product Ascofen-Darnytsia.

In patients with allergic complications, including bronchial asthma, allergic rhinitis, urticaria, skin pruritus, mucosal edema, nasal polyposis, or their combination with chronic respiratory tract infections, and in patients with hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs), bronchospasm or an asthma attack may occur; therefore, NSAIDs are contraindicated in these patients.

Acetylsalicylic acid, a component of the medicinal product, even in small doses, may reduce the excretion of uric acid from the body, potentially triggering an acute attack of gout in susceptible individuals.

During treatment with the medicinal product, excessive consumption of caffeine-containing beverages (e.g., coffee, tea) is not recommended, as it may cause sleep disturbances, tremor, tension, irritability, and discomfort behind the sternum due to palpitations.

Patients who take analgesics daily for mild forms of arthritis, those taking warfarin or similar anticoagulant agents, or those planning to start using ibuprofen as an analgesic should consult a physician before using this product.

Do not use in patients with hypersensitivity to analgesic, anti-inflammatory, or antirheumatic agents. Use with caution when used concomitantly with anticoagulants or 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 renal function and acute renal failure. Ibuprofen may reduce the inhibitory effect of acetylsalicylic acid on platelet aggregation.

Caution is recommended when using paracetamol concomitantly with flucloxacillin due to an increased risk of high anion gap metabolic acidosis, particularly in patients with severe renal insufficiency, sepsis, malnutrition, or other causes of glutathione deficiency (e.g., chronic alcoholism), and especially when using maximum daily doses of paracetamol. Close monitoring of the patient's condition is recommended, including measurement of 5-oxoproline in urine.

The medicinal product may affect laboratory test results for blood glucose and uric acid levels.

The medicinal product should not be used without medical advice for more than 5 days as an analgesic or more than 3 days as an antipyretic.

Alcoholic beverages should be avoided during treatment (increased risk of gastrointestinal bleeding).

If symptoms persist, consult a physician.

If headache becomes persistent, consult a physician.

Contraindicated in patients with bronchial asthma, increased bleeding tendency, and with particular caution during concomitant therapy with anticoagulants (coumarins and heparin), impaired liver function, kidney diseases, or concurrent anti-inflammatory therapy.

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

Use during pregnancy or breastfeeding

The medicinal product should not be used during pregnancy or breastfeeding.

Acetylsalicylic acid has teratogenic effects: when used during the first trimester of pregnancy, it may cause congenital malformations such as cleft palate; during the third trimester, it may inhibit labor activity (by inhibiting prostaglandin synthesis), cause premature closure of the fetal arterial duct, leading to pulmonary vascular hyperplasia and pulmonary hypertension in the fetal circulation, impair kidney function with possible subsequent development of renal failure and oligohydramnios, prolong bleeding time, and exert an anti-aggregatory effect, which may occur even after very low doses.

Caffeine increases the risk of spontaneous abortion.

The medicinal product passes into breast milk, increasing the risk of bleeding in infants due to impaired platelet function.

Ability to influence reaction speed when driving or operating machinery

Due to possible adverse effects on the nervous system (dizziness, increased excitability, impaired orientation and attention), driving vehicles or operating machinery requiring high attention and rapid psychomotor reactions should be avoided during treatment with this medicinal product.

Dosage and Administration

The medicinal product is prescribed to adults at a dose of 1 tablet 2–3 times daily after meals. The maximum daily dose is 6 tablets (taken 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, or 3 days when used as an antipyretic.

Do not exceed the recommended dose.

Do not take together with other medicinal products containing paracetamol.

Children

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

Overdose

Paracetamol overdose symptoms

Hepatic injury 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 treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. John's wort, or other drugs inducing liver enzymes; chronic excessive ethanol consumption; glutathione depletion due to malnutrition, cystic fibrosis, HIV infection, fasting, or cachexia), ingestion of 5 g or more of paracetamol may lead to liver damage.

Symptoms within the first 24 hours include pallor, nausea, vomiting, anorexia, and abdominal pain. Hepatic injury may become evident 12–48 hours after overdose. Glucose metabolism disturbances and metabolic acidosis may occur. In severe poisoning, liver failure may progress to encephalopathy, hemorrhage, hypoglycemia, coma, and may be fatal. 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 injury. Cardiac arrhythmias and pancreatitis have also been reported.

With prolonged use of the drug in high doses, hematological disorders such as aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, and thrombocytopenia may develop. High doses may also cause central nervous system (CNS) effects such as dizziness, psychomotor agitation, and disorientation; and urinary system effects such as nephrotoxicity (renal colic, interstitial nephritis, papillary necrosis).

Treatment: In case of overdose, prompt medical attention is required. The patient should be immediately transported to a hospital, even if early symptoms are absent. Symptoms such as nausea and vomiting may be mild and do not necessarily reflect the severity of overdose or risk of organ damage. Administration of activated charcoal should be considered if the excessive dose was taken 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. 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, especially in remote areas outside hospital settings. General supportive measures should also be implemented.

Acetylsalicylic acid overdose symptoms

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

Chronic salicylate intoxication may be insidious in nature, as its signs are nonspecific. Moderate chronic intoxication, or salicylism, typically occurs only after repeated ingestion of high doses. Main symptoms include loss of balance, dizziness, tinnitus, hearing loss, diaphoresis, nausea and vomiting, headache, and confusion. These symptoms may be controlled by dose reduction. Tinnitus may occur at plasma salicylate concentrations above 150–300 μg/mL. More serious adverse reactions occur at plasma concentrations exceeding 300 μg/mL. Acute intoxication is characterized by marked disturbances in acid-base balance, which may vary depending on age and severity of intoxication. The severity of the condition cannot be determined solely by plasma salicylate concentration.

Absorption of acetylsalicylic acid may be delayed due to delayed gastric emptying or formation of gastric concretions.

Treatment: Intoxication due to acetylsalicylic acid overdose is managed according to severity and clinical symptoms using standard poisoning treatment protocols. All measures should aim to accelerate drug elimination and restore electrolyte and acid-base balance. Activated charcoal and forced alkaline diuresis are used. Intravenous electrolyte solutions are administered depending on acid-base and electrolyte status. Hemodialysis is indicated in severe cases. With prolonged use of high doses, aplastic anemia, thrombocytopenia, pancytopenia, agranulocytosis, neutropenia, and leukopenia may occur. High doses may also cause central nervous system disturbances (dizziness, psychomotor agitation, disorientation, insomnia, tremor, nervousness, anxiety) and urinary system effects such as nephrotoxicity (renal colic, interstitial nephritis, papillary necrosis). In overdose, symptoms may include excessive sweating, psychomotor agitation or CNS depression, somnolence, impaired consciousness, cardiac arrhythmias, tachycardia, extrasystoles, tremor, hyperreflexia, and seizures.

Caffeine overdose symptoms

High doses of caffeine may cause epigastric pain, vomiting, diuresis, tachypnea, extrasystoles, tachycardia, or cardiac arrhythmia, and effects on the central nervous system such as dizziness, insomnia, nervousness, nervous excitation, increased neuromuscular excitability, headache, irritability, emotional lability, anxiety, restlessness, tremor, and seizures. Clinically significant caffeine overdose symptoms may also be associated with liver injury caused by paracetamol.

Treatment: Prompt medical attention is required in case of overdose, even if symptoms are absent. Oral methionine or intravenous acetylcysteine may be beneficial within 48 hours after overdose. General supportive measures and symptomatic therapy should also be applied, including use of β-adrenoreceptor antagonists to counteract cardiotoxic effects. No specific antidote is available.

Adverse reactions.

When using the medicinal product, adverse reactions characteristic of medicinal products containing acetylsalicylic acid, paracetamol, or caffeine may occur in individual patients.

Eye disorders: visual disturbances.

Ear and labyrinthine disorders: tinnitus, disorientation.

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

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

Hepatobiliary disorders: increased liver enzyme activity, usually without development of jaundice; hepatonecrosis (dose-dependent effect); transient hepatic insufficiency with elevated liver transaminase levels.

Renal and urinary disorders: nephrotoxicity (renal colic, interstitial nephritis, papillary necrosis).

Endocrine disorders: hypoglycemia, up to hypoglycemic coma.

Nervous system disorders: headache, nervousness, restlessness, dizziness, tremor, paresthesia, tinnitus, visual disturbances, which may indicate overdose: insomnia, sleep disturbances, increased excitability, disorientation, anxiety, irritability.

Psychiatric disorders: fear, restlessness, anxiety.

Cardiac disorders: tachycardia, palpitations, arterial hypertension, arrhythmia.

Blood and lymphatic system disorders: anemia, sulfhemoglobinemia and methemoglobinemia (cyanosis, dyspnea, chest pain), hemolytic anemia, bruising or bleeding; with prolonged use in high doses – aplastic anemia, pancytopenia, neutropenia, thrombocytopenia, agranulocytosis. Due to the antiplatelet effect of acetylsalicylic acid, the risk of bleeding is increased. Bleeding events observed include intraoperative hemorrhages, hematomas, genitourinary tract bleeding, epistaxis, gingival bleeding, gastrointestinal bleeding, and cerebral hemorrhages (especially in patients with uncontrolled arterial hypertension and/or concomitant use of antihemostatic agents), which in rare cases were life-threatening.

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

In patients with individual hypersensitivity to salicylates, allergic skin reactions may occur, including symptoms such as skin hyperemia, sensation of warmth, rash, urticaria, swelling, itching, angioedema, rhinitis, nasal congestion. In patients with bronchial asthma, increased frequency of bronchospasm may occur; allergic reactions ranging from mild to moderate severity affecting the skin, respiratory tract, gastrointestinal tract, cardiovascular system, manifesting as rashes, urticaria, swelling, pruritus.

Skin and subcutaneous tissue disorders: pruritus, skin and mucosal rash (usually generalized, erythematous rash, urticaria), angioedema, erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell’s syndrome).

General disorders: general weakness.

Other: bleeding may lead to acute and chronic post-hemorrhagic / 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, out of reach of children, at a temperature not exceeding 25 °C.

Packaging.

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

Supply category. Over-the-counter.

Manufacturer. JSC "Pharmaceutical company "Darnytsia".

Manufacturer's address and place of business.

13, Boryspilska Street, Kyiv, 02093, Ukraine.