Helpex® anticold

INSTRUCTIONS FOR MEDICAL USE OF MEDICINAL PRODUCT HELPEX® ANTICOLD (HELPEX® ANTICOLD)

Composition:

Active substances: paracetamol, caffeine, phenylephrine hydrochloride, chlorpheniramine maleate;

1 tablet contains paracetamol 500 mg, caffeine 30 mg, phenylephrine hydrochloride 10 mg, chlorpheniramine maleate 2 mg;

Excipients: maize starch, microcrystalline cellulose, calcium hydrogen phosphate, povidone, magnesium stearate, talc, sodium starch glycolate (type A), yellow FCF dye (E 110).

Pharmaceutical form. Tablets.

Main physicochemical properties: orange or light orange tablets with speckles, elongated oval shape, with a score line; imprinted with "M" and "H" on the side with the score line, uncoated.

Pharmacotherapeutic group. Analgesics and antipyretics. Anilides. Paracetamol combinations without psychotropic agents.

ATC code N02BE51.

Pharmacological properties.

Pharmacodynamics.

A combined medicinal product for the treatment of influenza and colds. Has antipyretic, analgesic, antihistamine, and mild anti-inflammatory properties. Relieves symptoms of nasal congestion, rhinorrhea, lacrimation, sneezing, headache, and improves general well-being.

Paracetamol acts as an antipyretic, analgesic, and anti-inflammatory agent. The analgesic and antipyretic effects of paracetamol are associated with the drug's influence on the thermoregulatory center and its ability to inhibit prostaglandin synthesis.

Phenylephrine hydrochloride acts as a vasoconstrictor, reducing swelling of the nasal mucosa and paranasal sinuses.

Chlorpheniramine maleate has antihistamine effects, relieving lacrimation and nasal itching.

Caffeine exerts a stimulating effect on the central nervous system, primarily on the cerebral cortex, respiratory and vasomotor centers, enhances mental and physical performance, reduces drowsiness, fatigue, and attenuates the effects of agents that depress the central nervous system.

Clinical characteristics.

Indications.

For the treatment of symptoms associated with acute respiratory viral infections and influenza (to reduce elevated body temperature, relieve rhinitis, reduce nasal mucosa swelling, eliminate body aches, and relieve headache).

Contraindications.

Hypersensitivity to any component of the medicinal product or to other xanthine derivatives (theophylline, theobromine). Decompensated heart failure, ventricular tachycardia, acute myocardial infarction, cardiac conduction disorders, severe form of ischemic heart disease, severe arterial hypertension, marked atherosclerosis, peripheral arterial thrombosis. Pheochromocytoma. Bronchial asthma. Stenosing peptic ulcer of the stomach and duodenum, pyloroduodenal obstruction. Severe impairment of liver and kidney function, acute pancreatitis, hepatitis. Benign prostatic hyperplasia with urinary retention, bladder neck obstruction. Blood disorders (including severe anemia, leukopenia). Glucose-6-phosphate dehydrogenase deficiency, congenital hyperbilirubinemia. Epilepsy, increased excitability, sleep disturbances. Hyperthyroidism, diabetes mellitus, alcoholism. Advanced age (60 years and older). Closed-angle glaucoma. Concomitant use with tricyclic antidepressants, ß-blockers; use concomitantly with monoamine oxidase inhibitors or within 2 weeks after discontinuation of such agents.

Interaction with other medicinal products and other types of interactions.

When used concomitantly with paracetamol, the following interactions may occur:

• may slow the elimination of antibiotics from the body;
• barbiturates reduce the antipyretic effect of paracetamol;
• concomitant use of paracetamol with hepatotoxic agents increases hepatotoxic effects;
• inducers of hepatic microsomal enzymes (anticonvulsants (phenytoin, barbiturates, carbamazepine), rifampicin), alcohol, and isoniazid enhance the hepatotoxicity of paracetamol;
• metoclopramide and domperidone increase, while cholestyramine decreases, the absorption rate of paracetamol;
• tetracycline increases the risk of anemia and methemoglobinemia caused by paracetamol;
• paracetamol reduces the efficacy of diuretics.

The anticoagulant effect of warfarin and other coumarins, with an increased risk of bleeding, may be enhanced by prolonged regular use of paracetamol. Single doses do not show a significant effect.

When used concomitantly with flucloxacillin, there is a risk of metabolic acidosis with a high anion gap as a result of pyroglutamic acidosis, especially in patients with risk factors (see section "Special precautions").

Use of phenylephrine hydrochloride with monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants, indomethacin, and bromocriptine may cause severe arterial hypertension; may reduce the effectiveness of ß-blockers and other antihypertensive agents (reserpine, methyldopa), increasing the risk of arterial hypertension and adverse cardiovascular reactions; when used with sympathomimetic amines, digoxin, and cardiac glycosides, increases the risk of arrhythmias and myocardial infarction.

Alkaloids of Rauwolfia reduce the therapeutic effect of phenylephrine hydrochloride.

Chlorpheniramine maleate enhances the anticholinergic effects of atropine, spasmolytics, tricyclic antidepressants, and agents that depress the central nervous system (tranquilizers, barbiturates), antiparkinsonian drugs. Do not use concomitantly with alcohol. Chlorpheniramine maleate, when used concomitantly with alcohol, potentiates the effects of each other. Concomitant use with hypnotics, barbiturates, sedatives, neuroleptics, tranquilizers, anesthetics, narcotic analgesics, and alcohol enhances the effects of chlorpheniramine maleate.

Maprotiline (a tetracyclic antidepressant) and other anticholinergic agents: the anticholinergic effect of these agents or antihistamines such as chlorpheniramine may be intensified.

Caffeine enhances the effect (improves bioavailability) of analgesic-antipyretic agents, potentiates the action of xanthine derivatives, α- and ß-adrenomimetics, and psychostimulants.

Caffeine reduces the effect of opioid analgesics, anxiolytics, hypnotics, and sedatives; acts as an antagonist to anesthetic agents and other drugs that depress the central nervous system; acts as a competitive antagonist to adenosine and adenosine triphosphate. When caffeine is used concomitantly with ergotamine, absorption of ergotamine in the gastrointestinal tract improves; when used with thyroid-stimulating agents, the thyroid effect is enhanced. Caffeine reduces blood lithium concentration.

Special precautions for use.

Do not exceed the recommended dose or duration of treatment.

Avoid concomitant use with other medicinal products containing paracetamol, as this may lead to paracetamol overdose, potentially causing liver failure. Prolonged use of high doses may result in liver and kidney damage. Patients with liver disease have an increased risk of hepatotoxic effects of paracetamol. 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 should be sought if these symptoms occur.

Cases of high anion gap metabolic acidosis (HAGMA) due to 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.

Consult a physician regarding the possibility of using the drug in patients with mild to moderate renal or hepatic impairment.

The simultaneous use of multiple medications, alcoholism, alcoholic liver disease, sepsis, or diabetes mellitus increases the risk of hepatotoxicity associated with therapeutic doses of paracetamol (acetaminophen).

Concomitant use with sedatives, hypnotics, or alcohol is not recommended (this may enhance the sedative effect of chlorpheniramine and increase the risk of paracetamol hepatotoxicity). If symptoms persist, consult a physician. If headache becomes persistent, seek medical advice. In case of high fever or prolonged fever lasting more than 3 days despite treatment, or if signs of superinfection appear, consult a physician.

Severe skin reactions have been reported very rarely. If skin redness, rash, blisters, or peeling occur, discontinue paracetamol and seek immediate medical attention.

When using the drug, avoid excessive consumption of coffee, strong tea, other tonic beverages, and medicinal products containing caffeine. This may cause sleep disturbances, tremor, tension, irritability, and palpitations.

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

Use with caution in patients with compensated heart failure, those at risk of seizures, or those with congenital long QT interval or prolonged use of medications that may prolong the QT interval.

The drug may affect laboratory test results for blood glucose and uric acid levels. Chlorpheniramine may mask symptoms of hypersensitivity and interfere with skin test results; therefore, discontinue the drug several days before such procedures.

The colorant Yellow Sunset FCF (E 110) may cause allergic reactions.

Use during pregnancy or breastfeeding.

Do not use.

Ability to influence reaction rate when driving or operating machinery.

During treatment, avoid driving, operating machinery, or engaging in other hazardous activities.

Method of Administration and Dosage

For adults and children aged 12 years and older, the recommended dose is 1 tablet up to 4 times daily. The interval between doses should be no less than 4 hours. The duration of treatment should not exceed 5 days. The maximum duration of use without medical consultation is 3 days. The medication should be taken orally, 1 hour after eating, with a large amount of water.

Children.

The drug is indicated for treatment of children aged 12 years and older.

Overdose.

In patients with risk factors, therapeutic doses of paracetamol may cause symptoms of overdose when used concomitantly with certain medications or in conditions that increase oxidative stress and deplete hepatic glutathione stores (prolonged fasting, sepsis, diabetes mellitus).

In paracetamol overdose, symptoms develop within the first 24 hours and include pallor, nausea, vomiting, anorexia, and abdominal pain. Psychomotor agitation or central nervous system depression, diaphoresis, dizziness, sleep disturbances, somnolence, cardiac arrhythmias, tachycardia, extrasystoles, tremor, hyperreflexia, seizures, and pancreatitis may occur.

Occasionally, nephrotoxicity involving renal colic, interstitial nephritis, and acute renal failure with acute tubular necrosis has been observed. This may manifest as severe lumbar pain, hematuria, proteinuria, and may develop even in the absence of severe liver damage.

In severe cases, liver injury (hepatocellular necrosis) and impaired liver function may occur, potentially progressing to hepatic encephalopathy, hepatic coma, cerebral edema, and may be fatal. Initial clinical and biochemical signs of liver injury may appear 12–48 hours after overdose. Glucose metabolism disturbances, hypokalemia, metabolic acidosis (including lactic acidosis), elevated liver transaminase activity, increased bilirubin levels, prolonged prothrombin index, and hemorrhages may occur. In children, liver injury may develop after ingestion of more than 150 mg/kg body weight; in adults, after ingestion of 10 g of paracetamol.

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

Arrhythmias (cardiac rhythm disturbances) and pancreatitis have also been reported. In cases of high-dose intake, disturbances in orientation may occur due to central nervous system effects.

With prolonged use of high doses, aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, and thrombocytopenia are possible.

In case of overdose, prompt medical intervention is required. The patient should be immediately hospitalized, 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. Activated charcoal should be considered if the excessive dose of paracetamol was ingested within the past hour. Gastric lavage should be performed within the first hours after suspected overdose. Plasma paracetamol concentration should be measured at least 4 hours after ingestion (earlier measurements 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, intravenous N-acetylcysteine should be administered according to current guidelines. In the absence of vomiting, oral methionine may be used as an appropriate alternative in remote areas outside hospital settings.

In case of caffeine overdose, symptoms of central nervous system stimulation are observed, including dizziness, insomnia, nervous excitation, irritability, emotional lability, anxiety, tremor, and seizures. Increased diuresis, tachypnea, tachycardia or cardiac arrhythmia, extrasystoles, vomiting, and epigastric pain may also occur. Clinically significant symptoms of caffeine overdose may also be associated with liver injury caused by paracetamol. There is no specific antidote, but supportive measures such as beta-adrenergic receptor antagonists may help alleviate cardiotoxic effects. Gastric lavage is required; oxygen therapy is recommended; diazepam is indicated in case of seizures. Symptomatic treatment is necessary.

In case of phenylephrine hydrochloride overdose, symptoms include headache, hyperhidrosis, somnolence, insomnia, behavioral changes, arrhythmias, tremor, seizures, hyperreflexia, dizziness, nausea, vomiting, irritability, restlessness, impaired consciousness, tachycardia, extrasystoles, and arterial hypertension.

In case of chlorpheniramine maleate overdose, the clinical picture may range from depression to excitation (restlessness and seizures). Anticholinergic-like symptoms may occur, including mydriasis, photophobia, dryness of the skin and mucous membranes, elevated body temperature, and intestinal atony. Central nervous system depression may be accompanied by respiratory depression and cardiovascular disturbances (decreased pulse rate, decreased arterial pressure, up to circulatory failure).

Side effects.

Immune system side effects: hypersensitivity reactions, including itching, skin and mucous membrane rashes (usually generalized rash (erythematous, urticaria)), anaphylactic shock, angioedema, erythema multiforme (including Stevens-Johnson syndrome), toxic epidermal necrolysis.

Central nervous system side effects: psychomotor agitation and disorientation, restlessness, fear, anxiety, irritability, sleep disturbances, insomnia, drowsiness, dizziness, confusion, hallucinations, depressive states, tremor, tingling and heaviness in limbs, tinnitus, headache; in rare cases – coma, seizures, dyskinesia, behavioral changes, general weakness, increased sweating.

Respiratory system side effects: bronchospasm in patients sensitive to aspirin and other nonsteroidal anti-inflammatory drugs.

Eye disorders: visual disturbances and accommodation disorders, mydriasis, increased intraocular pressure, dry eyes.

Gastrointestinal side effects: nausea, vomiting, heartburn, dry mouth, epigastric discomfort and pain, diarrhea, hypersalivation, decreased appetite, exacerbation of peptic ulcer, flatulence, constipation.

Hepatobiliary system side effects: liver function abnormalities, increased liver enzyme activity (usually without development of jaundice), hepatonecrosis (with high-dose use).

Endocrine system side effects: hypoglycemia, up to hypoglycemic coma.

Blood and lymphatic system side effects: anemia, including hemolytic anemia, bruising or bleeding; sulfhemoglobinemia and methemoglobinemia (cyanosis, dyspnea, chest pain).

With prolonged use at high doses – aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, thrombocytopenia.

Renal and urinary system side effects: with high-dose use – nephrotoxicity (including papillary necrosis), urinary disturbances, urinary retention and difficulty urinating, dysuria, interstitial nephritis, increased creatinine clearance, increased sodium and calcium excretion, aseptic pyuria, renal colic.

Cardiovascular system side effects: arterial hypertension, tachycardia or reflex bradycardia, arrhythmia, dyspnea, chest pain.

Metabolism and nutrition side effects: metabolic acidosis with high anion gap.

Description of specific side effects

Metabolic acidosis with high anion gap, resulting from pyroglutamic acidosis, has been observed in patients with risk factors who used paracetamol (see section "Special precautions"). Pyroglutamic acidosis may occur due to low glutathione levels in these patients.

Concurrent use of the drug at recommended doses with caffeine-containing products may enhance caffeine-related side effects such as dizziness, increased excitability, insomnia, restlessness, anxiety, irritability, headache, gastrointestinal disturbances, and tachycardia.

Reporting suspected side effects

Reporting suspected adverse reactions after drug registration is important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals, pharmacists, patients, or their legal representatives should report all suspected adverse reactions and lack of drug efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life.

4 years.

Storage conditions.

Store in original packaging, out of reach of children, at a temperature not exceeding 25 °C.

Packaging.

4 or 10 tablets per blister, 1 blister per cardboard pack; 10 packs of 4 tablets in a group cardboard box (No. 40), 20 packs of 4 tablets in a group cardboard box (No. 80), 10 packs of 10 tablets in a group cardboard box (No. 100).

Prescription status.

Over-the-counter.

Manufacturer.

Sava Helskea Ltd.

Manufacturer's address and place of business.

India, GIDC Estate, 507-B-512, Vadodhan City - 363 035, Surendranagar.

Marketing authorization holder: LLC "Movi Health"

Address of the marketing authorization holder:

162 A, Shevchenka Street, Shevchenkove village, Kyiv-Sviatoshyn district, Kyiv region, 08140, Ukraine

Date of last review.

INSTRUCTIONS

for medical use of the medicinal product

HELPEX® ANTICOLD

(HELPEX® ANTICOLD)

Composition:

Active ingredients: paracetamol, caffeine, phenylephrine hydrochloride, chlorpheniramine maleate;

1 tablet contains 500 mg of paracetamol, 30 mg of caffeine, 10 mg of phenylephrine hydrochloride, and 2 mg of chlorpheniramine maleate;

Excipients: maize starch, microcrystalline cellulose, calcium hydrogen phosphate, povidone, magnesium stearate, talc, sodium starch glycolate (type A), colouring agent Yellow West FCF (E 110).

Pharmaceutical form. Tablets.

Main physicochemical properties: orange or light-orange tablets with speckles, elongated oval-shaped, with a score line, imprinted with "M" and "H" on the side with the score line, uncoated.

Pharmacotherapeutic group. Analgesics and antipyretics. Anilides. Paracetamol combinations without psychotropic agents.

ATC code N02B E51.

Pharmacological properties.

Pharmacodynamics.

A combined medicinal product for the treatment of influenza and colds. Has antipyretic, analgesic, antiallergic, and mild anti-inflammatory properties. Relieves symptoms of nasal congestion, rhinorrhea, lacrimation, sneezing, headache, and improves general well-being.

Paracetamol acts as an antipyretic, analgesic, and anti-inflammatory agent. The analgesic and antipyretic effects of paracetamol are associated with the drug's influence on the thermoregulatory center and its ability to inhibit prostaglandin synthesis.

Phenylephrine hydrochloride acts as a vasoconstrictor, reducing swelling of the nasal mucosa and paranasal sinuses.

Chlorpheniramine maleate has antiallergic effects and relieves lacrimation and nasal itching.

Caffeine exerts a stimulant effect on the central nervous system, primarily on the cerebral cortex, respiratory, and vasomotor centers, enhances mental and physical performance, reduces drowsiness, fatigue, and counteracts the effects of agents that depress the central nervous system.

Clinical characteristics.

Indications.

For the treatment of symptoms occurring in acute respiratory viral infections and influenza (to reduce elevated body temperature, alleviate rhinitis, relieve nasal mucosa edema, eliminate body aches, and relieve headache).

Contraindications.

Hypersensitivity to any component of the medicinal product or to other xanthine derivatives (theophylline, theobromine). Decompensated heart failure, ventricular tachycardia, acute myocardial infarction, cardiac conduction disorders, severe form of ischemic heart disease, severe arterial hypertension, marked atherosclerosis, peripheral arterial thrombosis. Pheochromocytoma. Bronchial asthma. Stenosing peptic ulcer of the stomach and duodenum, pyloroduodenal obstruction. Severe impairment of liver and kidney function, acute pancreatitis, hepatitis. Prostate adenoma with difficult urination, bladder neck obstruction. Blood disorders (including severe anemia, leukopenia). Glucose-6-phosphate dehydrogenase deficiency, congenital hyperbilirubinemia. Epilepsy, increased excitability, sleep disturbances. Hyperthyroidism, diabetes mellitus, alcoholism. Advanced age (60 years and older). Closed-angle glaucoma. Concomitant use with tricyclic antidepressants, ß-blockers; use concomitantly with monoamine oxidase inhibitors or within 2 weeks after discontinuation of such agents.

Interaction with other medicinal products and other forms of interaction.

When used concomitantly with paracetamol, the following interactions may occur:

• excretion of antibiotics from the body may be slowed;
• barbiturates reduce the antipyretic effect of paracetamol;
• concomitant use of paracetamol with hepatotoxic agents increases hepatotoxic effects;
• inducers of hepatic microsomal enzymes (anticonvulsants (phenytoin, barbiturates, carbamazepine), rifampicin), alcohol, and isoniazid enhance the hepatotoxicity of paracetamol;
• metoclopramide and domperidone increase, while cholestyramine decreases, the rate of paracetamol absorption;
• tetracycline increases the risk of anemia and methemoglobinemia caused by paracetamol;
• paracetamol reduces the effectiveness of diuretics.

The anticoagulant effect of warfarin and other coumarins, with an increased risk of bleeding, may be enhanced by prolonged regular use of paracetamol. Single doses do not show a significant effect.

Concomitant use with flucloxacillin may result in metabolic acidosis with a large anion gap as a consequence of pyroglutamic acidosis, especially in patients with risk factors (see section "Special precautions for use").

Use of phenylephrine hydrochloride with monoamine oxidase inhibitors, tricyclic antidepressants, indomethacin, and bromocriptine may cause severe arterial hypertension; may reduce the effectiveness of ß-blockers and other antihypertensive agents (reserpine, methyldopa), increasing the risk of arterial hypertension and adverse cardiovascular reactions; when used with sympathomimetic amines, digoxin, and cardiac glycosides, increases the risk of arrhythmias and myocardial infarction.

Alkaloids of Rauwolfia reduce the therapeutic effect of phenylephrine hydrochloride.

Chlorpheniramine maleate enhances the anticholinergic effect of atropine, spasmolytics, tricyclic antidepressants, and agents that suppress the central nervous system (tranquilizers, barbiturates), antiparkinsonian drugs. Do not use concomitantly with alcohol. Chlorpheniramine maleate, when used concomitantly with alcohol, potentiates the effects of each other. Concomitant use with hypnotics, barbiturates, sedatives, neuroleptics, tranquilizers, anesthetics, narcotic analgesics, and alcohol enhances the effect of chlorpheniramine maleate.

Maprotiline (a tetracyclic antidepressant) and other anticholinergic agents: the anticholinergic effect of these agents or antihistamines such as chlorpheniramine may be intensified.

Caffeine enhances the effect (improves bioavailability) of analgesic-antipyretic agents, potentiates the action of xanthine derivatives, ɑ- and ß-adrenomimetics, and psychostimulants.

Caffeine reduces the effect of opioid analgesics, anxiolytics, hypnotics, and sedatives; acts as an antagonist of anesthetic agents and other drugs that depress the central nervous system; acts as a competitive antagonist of adenosine and adenosine triphosphate. When caffeine is used concomitantly with ergotamine, absorption of ergotamine in the gastrointestinal tract improves; with thyrotropic agents, the thyroid effect is enhanced. Caffeine reduces blood lithium concentration.

Special precautions for use.

Do not exceed the indicated dose or duration of treatment.

Avoid concomitant use with other medicinal products containing paracetamol, as overdose of paracetamol may occur, potentially leading to liver failure. Long-term use of high doses may cause liver and kidney damage. The risk of hepatotoxic effects of paracetamol is increased in patients with liver disease. In patients with severe infections such as sepsis, which are associated with reduced glutathione levels, administration 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 should be sought if these symptoms occur.

Cases of high anion gap metabolic acidosis (HAGMA) due to 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 over a prolonged period 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.

Consult a physician regarding the possibility of using the drug in patients with mild to moderate impairment of kidney or liver function.

Concomitant use of multiple medications, alcoholism, alcoholic liver disease, sepsis, or diabetes mellitus increases the risk of hepatotoxicity with therapeutic doses of paracetamol (acetaminophen).

Concomitant use with sedatives, hypnotics, or alcohol is not recommended (this enhances the sedative effect of chlorpheniramine and increases the risk of paracetamol hepatotoxicity). If symptoms persist, consult a physician. If headache becomes persistent, consult a physician. In case of high body temperature or prolonged fever lasting more than 3 days during treatment, or if signs of superinfection appear, consult a physician.

Very rare cases of severe skin reactions have been reported. In case of skin redness, rash, blisters, or peeling, discontinue paracetamol and seek immediate medical assistance.

When using the drug, avoid excessive consumption of coffee, strong tea, other stimulant beverages, and medicinal products containing caffeine. This may cause sleep disturbances, tremor, tension, irritability, and palpitations.

Consult a physician before using the drug if you are taking warfarin or similar anticoagulant agents.

Use with caution in patients with compensated heart failure, patients at risk of seizures, patients with congenital long QT syndrome, or in cases of prolonged use of drugs that may prolong the QT interval.

The drug may affect laboratory test results for blood glucose and uric acid levels; chlorpheniramine may mask hypersensitivity symptoms and interfere with skin test results; therefore, the drug should be discontinued several days before such procedures.

The colorant Yellow Sunset FCF (E 110) may cause allergic reactions.

Use during pregnancy or breastfeeding.

Do not use.

Ability to affect reaction speed when driving or operating machinery.

During treatment, avoid driving, operating machinery, and other potentially hazardous activities.

Method of Administration and Dosage.

For adults and children aged 12 years and older, the recommended dose is 1 tablet up to 4 times daily. The interval between doses should be at least 4 hours. The treatment duration should not exceed 5 days. The maximum duration of use without medical consultation is 3 days. The medication should be taken orally, 1 hour after meals, with a large amount of water.

Children.

The drug is indicated for treatment of children aged 12 years and older.

Overdose.

In patients with risk factors, therapeutic doses of paracetamol may cause symptoms of overdose when used concomitantly with certain medications or in conditions that increase oxidative stress and deplete hepatic glutathione reserves (prolonged fasting, sepsis, diabetes mellitus).

In paracetamol overdose, symptoms develop within the first 24 hours and include pallor, nausea, vomiting, anorexia, and abdominal pain. Psychomotor excitation or central nervous system depression, increased sweating, dizziness, sleep disturbances, somnolence, cardiac arrhythmias, tachycardia, extrasystoles, tremor, hyperreflexia, seizures, and pancreatitis may occur.

Occasionally, nephrotoxicity involving renal colic, interstitial nephritis, and acute renal failure with acute tubular necrosis has been observed. These may manifest as severe lumbar pain, hematuria, proteinuria, and may develop even in the absence of severe liver damage.

In severe cases, liver injury (hepatocellular necrosis) and impaired liver function may occur, potentially progressing to hepatic encephalopathy, hepatic coma, cerebral edema, and may be fatal. The first clinical and biochemical signs of liver damage may appear 12–48 hours after overdose. Disorders of glucose metabolism, hypokalemia, metabolic acidosis (including lactic acidosis), elevated liver transaminase activity, increased bilirubin levels, prolonged prothrombin index, and hemorrhages may occur. In children, liver injury may develop after ingestion of more than 150 mg/kg body weight; in adults, after ingestion of 10 g of paracetamol.

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

Arrhythmias (disturbances of cardiac rhythm) and pancreatitis have also been reported. With large doses, disturbances in orientation may occur due to central nervous system effects.

With prolonged use of high doses, aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, and thrombocytopenia are possible.

In case of overdose, immediate medical assistance is required. 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. Administration of activated charcoal should be considered if the excessive dose of paracetamol was taken within the last hour. Gastric lavage should be performed within the first hours after suspected overdose. Plasma paracetamol concentration should be measured at least 4 hours after ingestion (earlier measurements are unreliable). Treatment with N-acetylcysteine may be administered within 24 hours after paracetamol ingestion, but the maximum protective effect is achieved when administered within 8 hours after ingestion. The efficacy of the antidote decreases sharply after this time. If necessary, intravenous N-acetylcysteine should be administered according to current guidelines. In the absence of vomiting, oral methionine may be used as an alternative in remote areas outside the hospital setting.

In case of caffeine overdose, symptoms of central nervous system stimulation occur, including dizziness, insomnia, nervous excitation, irritability, emotional lability, anxiety, tremor, and seizures. Increased diuresis, rapid breathing, tachycardia or cardiac arrhythmia, extrasystoles, vomiting, and epigastric pain may also occur. Clinically significant symptoms of caffeine overdose may also be associated with liver injury caused by paracetamol. There is no specific antidote, but supportive measures such as beta-adrenergic receptor antagonists may help alleviate cardiotoxic effects. Gastric lavage is required; oxygen therapy is recommended, and diazepam may be administered in case of seizures. Symptomatic therapy is indicated.

In case of phenylephrine hydrochloride overdose, symptoms include headache, hyperhidrosis, somnolence, insomnia, behavioral changes, arrhythmias, tremor, seizures, hyperreflexia, dizziness, nausea, vomiting, irritability, restlessness, impaired consciousness, tachycardia, extrasystoles, and arterial hypertension.

In case of chlorpheniramine maleate overdose, the condition may range from depression to excitation (restlessness and seizures). Anticholinergic-like symptoms may occur, including mydriasis, photophobia, dryness of skin and mucous membranes, elevated body temperature, and intestinal atony. Central nervous system depression may be accompanied by respiratory disorders and cardiovascular disturbances (decreased pulse rate, decreased arterial pressure, up to circulatory failure).

Adverse Reactions

Immune system disorders: hypersensitivity reactions including pruritus, skin and mucous membrane rashes (usually generalized rash (erythematous, urticaria)), anaphylactic shock, angioneurotic edema, erythema multiforme (including Stevens–Johnson syndrome), toxic epidermal necrolysis.

Central nervous system disorders: psychomotor agitation and disorientation, restlessness, fear, anxiety, irritability, sleep disturbances, insomnia, somnolence, dizziness, confusion, hallucinations, depressive states, tremor, sensations of tingling and heaviness in the extremities, tinnitus, headache; in individual cases – coma, seizures, dyskinesia, behavioral changes, general weakness, increased sweating.

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

Eye disorders: visual disturbances and accommodation disorders, mydriasis, increased intraocular pressure, dry eyes.

Gastrointestinal disorders: nausea, vomiting, heartburn, dry mouth, epigastric discomfort and pain, diarrhea, hypersalivation, decreased appetite, exacerbation of peptic ulcer, flatulence, constipation.

Hepatobiliary system disorders: liver function abnormalities, elevated liver enzyme activity, usually without development of jaundice, hepatonecrosis (with high-dose use).

Endocrine system disorders: hypoglycemia, up to hypoglycemic coma.

Blood and lymphatic system disorders: anemia, including hemolytic anemia, bruising or bleeding; sulfhemoglobinemia and methemoglobinemia (cyanosis, dyspnea, chest pain).

With prolonged use at high doses – aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, thrombocytopenia.

Renal and urinary system disorders: with high-dose use – nephrotoxicity (including papillary necrosis), urinary disturbances, urinary retention and difficulty in urination, dysuria, interstitial nephritis, increased creatinine clearance, increased excretion of sodium and calcium, aseptic pyuria, renal colic.

Cardiovascular system disorders: arterial hypertension, tachycardia or reflex bradycardia, arrhythmia, dyspnea, chest pain.

Metabolism and nutrition disorders: metabolic acidosis with a high anion gap.

Description of selected adverse reactions

Metabolic acidosis with a high anion gap as a result of pyroglutamic acidosis has been observed in patients with risk factors who used paracetamol (see section "Special precautions for use"). Pyroglutamic acidosis may occur due to low glutathione levels in these patients.

Concomitant use of the drug at recommended doses with products containing caffeine may enhance caffeine-related adverse effects such as dizziness, increased excitability, insomnia, restlessness, anxiety, irritability, headache, gastrointestinal disturbances, and tachycardia.

Reporting suspected adverse reactions

Reporting of suspected adverse reactions after drug registration is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, as well as their legal representatives, are encouraged to report all suspected adverse reactions and lack of drug efficacy via the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life.

4 years.

Storage conditions.

Store in the original packaging, out of reach of children, at a temperature not exceeding 25 °C.

Packaging.

4 or 10 tablets per blister, 1 blister per cardboard pack; 10 packs of 4 tablets per group cardboard box (No. 40), 20 packs of 4 tablets per group cardboard box (No. 80), 10 packs of 10 tablets per group cardboard box (No. 100).

Supply category.

Over-the-counter.

Manufacturer.

MediTop Pharmaceuticals Ltd.

Manufacturer’s location and address of place of business.

Hungary, Edvard Endre Str. 1, Pilisborosjenő, 2097.

Marketing authorization holder: TOV "Movi Health"

Address of the marketing authorization holder:

162 A, Shevchenka St., Shevchenkove village, Kyiv-Sviatoshyn district, Kyiv region, 08140, Ukraine