Gripflu

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT GRIPFLU (GRIPFLU)

Composition:

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

Excipients: maize starch, sodium methylparaben (E 219), sodium propylparaben (E 217), colloidal anhydrous silicon dioxide, magnesium stearate, talc.

Pharmaceutical form. Tablets.

Main physicochemical properties: tablets are white or almost white, round, flat, with a score line and beveled edges on both sides.

Pharmacotherapeutic group. Analgesics and antipyretics. Paracetamol combinations without psychotropic agents. ATC code N02BE51.

Pharmacological properties.

Pharmacodynamics.

The pharmacological activity of the drug is determined by the properties of paracetamol, caffeine, phenylephrine hydrochloride, and chlorpheniramine maleate contained in the drug. Paracetamol has antipyretic, analgesic, and anti-inflammatory effects. The mechanism of action is associated with inhibition of prostaglandin synthesis.

Phenylephrine hydrochloride exerts a vasoconstrictive effect, reducing swelling of the nasal mucosa and paranasal sinuses.

Chlorpheniramine maleate has antihistaminic and anticholinergic effects. By blocking H1-receptors, it exerts an antiallergic effect, reduces vascular permeability of the mucous membranes of the upper respiratory tract, and decreases lacrimation, as well as itching in the eyes and nose.

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

Clinical characteristics.

Indications.

Symptomatic treatment of cold and influenza accompanied by elevated body temperature, chills, headache, runny nose and nasal congestion, sneezing, malaise, and body aches.

Contraindications.

Hypersensitivity to the components of the drug or to other xanthine derivatives (theophylline, theobromine). Severe cardiovascular diseases, including conduction disorders, marked atherosclerosis, severe form of ischemic heart disease. Severe hepatic and renal dysfunction. Congenital hyperbilirubinemia, severe arterial hypertension; prostatic adenoma with urinary retention; bladder neck obstruction; blood disorders, severe anemia, leukopenia, hyperthyroidism, pyloroduodenal obstruction, diabetes mellitus, bronchial asthma, closed-angle glaucoma, glucose-6-phosphate dehydrogenase deficiency, alcoholism, increased excitability, sleep disturbances, concomitant therapy with monoamine oxidase inhibitors (MAOIs) and within 2 weeks after discontinuation of such therapy. Advanced age.

Interaction with other medicinal products and other types of interactions.

The absorption rate of paracetamol may be increased when used with metoclopramide and domperidone, and decreased with cholestyramine. When used concomitantly with paracetamol, the following interactions may occur: excretion of antibiotics from the body may be slowed; tetracycline increases the risk of anemia and methemoglobinemia induced by acetaminophen; antacids and food reduce the absorption of acetaminophen. With prolonged concomitant use, the anticoagulant effect of coumarins (e.g., warfarin) is enhanced. Barbiturates reduce the antipyretic effect of paracetamol. Anticonvulsants (phenytoin, barbiturates, carbamazepine) that stimulate hepatic microsomal enzymes, as well as isoniazid, may enhance the hepatotoxicity of paracetamol. Paracetamol reduces the efficacy of diuretics.

Do not use concomitantly with alcohol.

Caution should be exercised 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 for use").

Interaction of phenylephrine hydrochloride with monoamine oxidase inhibitors (MAOIs) causes a hypertensive effect; with tricyclic antidepressants (amitriptyline) – increases the risk of cardiovascular adverse effects; with digoxin and cardiac glycosides – may lead to arrhythmias and infarction. Phenylephrine combined with other sympathomimetics increases the risk of adverse cardiovascular reactions. It may reduce the effectiveness of β-blockers and other antihypertensive agents (reserpine, methyldopa), increasing the risk of arterial hypertension and adverse cardiovascular reactions. Combination with indomethacin and bromocriptine may cause severe arterial hypertension. Alkaloids of Rauwolfia reduce the therapeutic effect of phenylephrine hydrochloride.

Concomitant administration of chlorpheniramine maleate with hypnotics, barbiturates, sedatives, neuroleptics, tranquilizers, anesthetics, narcotic analgesics, and alcohol may significantly enhance its depressant effects. Chlorpheniramine maleate enhances the anticholinergic effects of atropine, spasmolytics, tricyclic antidepressants, and antiparkinsonian agents.

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 anesthetic agents and other drugs that depress the CNS, and as a competitive antagonist of adenosine and ATP preparations. When caffeine is used concomitantly with ergotamine, absorption of ergotamine in the gastrointestinal tract is improved; with thyrotropic agents – the thyroid effect is enhanced. Caffeine reduces blood lithium concentration.

Special precautions.

Do not exceed the recommended dose.

Avoid concomitant use with other medications intended for symptomatic treatment of cold and flu, as well as with medicinal products containing paracetamol.

This medicinal product is not recommended for concomitant use with sedatives, hypnotics, or alcoholic beverages.

The physician should prescribe the drug only after assessing the risk/benefit ratio in the following cases: arterial hypertension; epilepsy; prostate adenoma; cardiac arrhythmias; pheochromocytoma; urinary disorders.

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

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

If the drug is used long-term as directed by a physician, monitoring of liver function and peripheral blood picture is required.

Note that in patients with alcoholic liver disease, the risk of hepatotoxic effects of paracetamol is increased; the drug may affect laboratory test results for blood glucose and uric acid levels.

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 the patient is taking warfarin or similar anticoagulant agents. Patients who take analgesics daily for mild forms of arthritis should consult a physician. If headaches become persistent, medical advice should be sought.

If symptoms persist, consult a physician.

Use during pregnancy or breastfeeding. Contraindicated.

Ability to affect reaction speed when driving or operating machinery.

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

Dosage and Administration.

For adults and children aged 12 years and older, the recommended dose is 1 tablet. The interval between doses should be at least 4 hours, but no more than 4 tablets per day should be taken.

The duration of treatment is determined by a physician. The maximum duration of use without medical consultation is 3 days.

Children. This medication is indicated for treatment of children aged 12 years and older.

Overdose.

Paracetamol overdose: Hepatic damage may occur in adults who have ingested 10 g or more of paracetamol, and in children who have received more than 150 mg/kg body weight. Ingestion of 5 g or more of paracetamol may lead to liver injury 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 alcohol consumption; glutathione depletion due to malnutrition, cystic fibrosis, HIV infection, fasting, or cachexia).

With prolonged use at high doses: aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, thrombocytopenia. High doses may cause dizziness, psychomotor agitation, and disorientation. Urinary system disorders may include nephrotoxicity (renal colic, interstitial nephritis, papillary necrosis).

Overdose symptoms include pallor, anorexia, nausea, vomiting, abdominal pain, hepatonecrosis, elevated activity of liver transaminases, and increased prothrombin index. Additional manifestations may include excessive sweating, psychomotor agitation or central nervous system (CNS) depression, somnolence, impaired consciousness, cardiac arrhythmias, tachycardia, extrasystoles, tremor, hyperreflexia, and seizures. Liver damage may become evident 12–48 hours after overdose. Glucose metabolism disturbances and metabolic acidosis may also occur. In severe poisoning, liver dysfunction may progress to encephalopathy with impaired consciousness, hemorrhage, hypoglycemia, cerebral edema, and in some cases, death. Acute kidney injury with acute tubular necrosis may present with severe lumbar pain, hematuria, proteinuria, and may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have also been reported.

Treatment: The patient must be immediately hospitalized, even if early symptoms of overdose are absent. Symptoms may be limited to nausea and vomiting and 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. 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 of paracetamol ingestion, but maximum protective effect is achieved when administered within 8 hours. The efficacy of the antidote decreases significantly after this time. If required, intravenous N-acetylcysteine should be administered according to the established dosing regimen. In the absence of vomiting, oral methionine may be used as an alternative in remote areas outside hospital settings.

Phenylephrine hydrochloride overdose: Symptoms include hyperhidrosis, psychomotor agitation or CNS depression, headache, dizziness, somnolence, impaired consciousness, arrhythmias, tremor, hyperreflexia, seizures, nausea, vomiting, irritability, restlessness, arterial hypertension, tachycardia, and extrasystoles.

Chlorpheniramine maleate overdose: Anticholinergic-like (atropine-like) symptoms may occur, including mydriasis, photophobia, dry skin and mucous membranes, elevated body temperature, and intestinal atony. CNS depression may be accompanied by respiratory depression and cardiovascular disturbances (decreased pulse rate, reduced arterial pressure up to circulatory collapse).

Large doses of caffeine may cause epigastric pain, vomiting, diuresis, increased respiratory rate, extrasystoles, tachycardia or cardiac arrhythmia, and effects on the central nervous system (dizziness, insomnia, nervous excitation, irritability, emotional lability, anxiety, tremor, convulsions).

Treatment: Gastric lavage should be performed within the first 6 hours after suspected overdose, followed by hospitalization; symptomatic therapy; in cases of severe hypertension, use of α- and β-adrenergic blockers.

Adverse reactions.

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

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

Neurological disorders: headache, dizziness, psychomotor agitation and disorientation, restlessness, nervousness, feeling of fear, irritability, sleep disturbances, insomnia, somnolence, confusion, hallucinations, depressive states, tremor, sensations of tingling and heaviness in the extremities, tinnitus, in isolated cases – coma, seizures, dyskinesia, behavioral changes, general weakness.

Respiratory system disorders: bronchospasm in patients sensitive to acetylsalicylic acid and other NSAIDs.

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, loss of appetite.

Hepatobiliary disorders: liver function abnormalities, increased 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: thrombocytopenia, agranulocytosis, bruising or bleeding, anemia, including hemolytic anemia, sulfhemoglobinemia and methemoglobinemia (cyanosis, dyspnea, chest pain).

Renal and urinary system disorders: nephrotoxicity, interstitial nephritis, papillary necrosis, urinary disorders, difficulty in urination, dysuria, urinary retention.

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

Metabolism and nutrition disorders: metabolic acidosis with high anion gap (frequency of cases – unknown).

Description of selected adverse reactions

Metabolic acidosis with high anion gap.

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

Reporting of adverse reactions

Reporting of adverse reactions after drug registration is important. It allows continuous monitoring of the benefit-risk balance of the drug. Medical and pharmaceutical professionals, as well as 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. 3 years.

Storage conditions.

Store in the original packaging, in a place inaccessible to children, at a temperature not exceeding 25 °C.

Packaging.

4 tablets per strip; 1 strip per envelope.

4 tablets per strip; 1 strip per envelope; 50 envelopes per cardboard box.

10 tablets per blister, 1 blister per box.

Prescription status.

Over-the-counter – tablets No. 4, No. 10.

By prescription only – tablets No. 200.

Manufacturer.

Artura Pharmaceuticals Pvt. Ltd.

Manufacturer’s address and location of its business operations.

1505 Portia Road, Sri City SEZ, Sityavedu Mandal, Chittoor District – 517 588, Andhra Pradesh State, India.

Marketing Authorization Holder.

Ananta Medikare Ltd.

Address of the Marketing Authorization Holder and/or its representative.

Suite 1, 2 Station Court, Imperial Wharf, Townmead Road, Fulham, London, United Kingdom.

INSTRUCTION

for medical use of the medicinal product

GRIPFLU

(GRIPFLU)

Composition:

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

Excipients: maize starch, sodium methylparaben (E 219), sodium propylparaben (E 217), colloidal anhydrous silicon dioxide, magnesium stearate, talc.

Pharmaceutical form. Tablets.

Main physicochemical properties: white or almost white, round, flat tablets with a score line and bevelled edges on both sides.

Pharmacotherapeutic group. Analgesics and antipyretics. Paracetamol combinations without psychotropic agents. ATC code N02BE51.

Pharmacological Properties.

Pharmacodynamics.

The pharmacological activity of the drug is due to the properties of paracetamol, caffeine, phenylephrine hydrochloride, and chlorpheniramine maleate contained in the formulation. Paracetamol has antipyretic, analgesic, and anti-inflammatory effects. Its mechanism of action is associated with inhibition of prostaglandin synthesis.

Phenylephrine hydrochloride exerts a vasoconstrictive effect, reducing swelling of the nasal mucosa and paranasal sinuses.

Chlorpheniramine maleate has antihistaminic and anticholinergic effects. By blocking H1-receptors, it produces an antiallergic effect, reduces vascular permeability of the mucous membranes of the upper respiratory tract, and decreases lacrimation, as well as itching in the eyes and nose.

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 and the sensation of fatigue, and attenuates the effects of agents that suppress the central nervous system.

Clinical characteristics.

Indications.

Symptomatic treatment of cold and influenza accompanied by elevated body temperature, chills, headache, runny nose and nasal congestion, sneezing, malaise, and body aches.

Contraindications.

Hypersensitivity to the components of the drug or other xanthine derivatives (theophylline, theobromine). Severe cardiovascular disorders, including conduction disturbances, pronounced atherosclerosis, severe form of ischemic heart disease. Marked impairment of liver or kidney function. Congenital hyperbilirubinemia, severe arterial hypertension; prostatic adenoma with difficult urination; bladder neck obstruction; blood disorders, marked anemia, leukopenia, hyperthyroidism, pyloroduodenal obstruction, diabetes mellitus, bronchial asthma, closed-angle glaucoma, glucose-6-phosphate dehydrogenase deficiency, alcoholism, increased excitability, sleep disorders, concomitant therapy with monoamine oxidase inhibitors (MAOIs) and within 2 weeks after discontinuation of their use. Advanced age.

Interaction with other medicinal products and other types of interactions.

The absorption rate of paracetamol may be increased when used with metoclopramide and domperidone, and decreased with cholestyramine. When used concomitantly with paracetamol, the following interactions may occur: elimination of antibiotics from the body may be slowed; tetracycline increases the risk of anemia and methemoglobinemia caused by acetaminophen; antacids and food reduce the absorption of acetaminophen. With prolonged concomitant use, the anticoagulant effect of coumarins (e.g., warfarin) is enhanced. Barbiturates reduce the antipyretic effect of paracetamol. Anticonvulsant drugs (phenytoin, barbiturates, carbamazepine) that stimulate hepatic microsomal enzymes and isoniazid may enhance the hepatotoxicity of paracetamol. Paracetamol reduces the effectiveness of diuretics.

Do not use concomitantly with alcohol.

Caution should be exercised when using paracetamol concomitantly with flucloxacillin, as such concomitant administration 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 for use").

Interaction of phenylephrine hydrochloride with monoamine oxidase inhibitors (MAOIs) causes a hypertensive effect; with tricyclic antidepressants (amitriptyline) – increases the risk of cardiovascular adverse effects; with digoxin and cardiac glycosides – may lead to arrhythmias and infarction. Phenylephrine combined with other sympathomimetics increases the risk of adverse cardiovascular reactions. It may reduce the effectiveness of β-blockers and other antihypertensive agents (reserpine, methyldopa), increasing the risk of arterial hypertension and cardiovascular adverse effects. Combination with indomethacin and bromocriptine may cause severe arterial hypertension. Alkaloids of Rauwolfia reduce the therapeutic effect of phenylephrine hydrochloride.

Concomitant use of the drug with sedatives, barbiturates, tranquilizers, neuroleptics, anesthetics, narcotic analgesics, and alcohol may significantly enhance the depressant effect of chlorpheniramine maleate. Chlorpheniramine maleate enhances the anticholinergic effects of atropine, spasmolytics, tricyclic antidepressants, and antiparkinsonian agents.

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 to anesthetic agents and other drugs that depress the CNS, as a competitive antagonist to adenosine and ATP preparations. When used concomitantly with ergotamine, caffeine improves the absorption of ergotamine in the gastrointestinal tract; with thyrotropic agents – increases the thyroid effect. Caffeine reduces blood lithium concentration.

Special precautions for use.

Do not exceed the recommended dose.

Avoid concomitant use with other medicinal products intended for symptomatic treatment of cold and flu, or with medicines containing paracetamol.

This medicine should not be used concomitantly with sedatives, hypnotics, or alcoholic beverages.

The physician should prescribe this medicine only after assessing the risk/benefit ratio in the following conditions: arterial hypertension; epilepsy; prostate adenoma; cardiac arrhythmias; pheochromocytoma; urinary retention disorders.

Medical advice should be sought regarding the possibility of using this medicine in patients with renal or hepatic impairment.

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 insufficiency and sepsis, or in patients with malnutrition or other causes of glutathione deficiency (e.g., chronic alcoholism), who received paracetamol at therapeutic doses for prolonged periods or a combination of paracetamol and 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.

If the medicine is used for prolonged periods as directed by a physician, monitoring of liver function and peripheral blood picture is necessary.

Note that patients with alcoholic liver disease have an increased risk of hepatotoxic effects of paracetamol; the medicine may interfere with laboratory tests for blood glucose and uric acid levels.

When using this medicine, 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 use if the patient is taking warfarin or similar anticoagulant medicines. Patients who take analgesics daily for mild forms of arthritis should consult their physician. If headaches become persistent, medical advice should be sought.

If symptoms do not resolve, consult a physician.

Use during pregnancy or breastfeeding. Contraindicated.

Ability to affect reaction speed when driving or operating machinery.

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

Dosage and Administration.

For adults and children aged 12 years and older: 1 tablet per dose; the interval between doses should be at least 4 hours, but not more than 4 tablets per day.

The duration of treatment should be determined by a physician. The maximum duration of use without medical consultation is 3 days.

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

Overdose.

Paracetamol overdose: liver damage may occur in adults who have ingested 10 g or more of paracetamol, and in children who have received more than 0.15 g/kg body weight. Ingestion of 5 g or more of paracetamol may lead to hepatotoxicity 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 alcohol consumption; glutathione depletion due to malnutrition, cystic fibrosis, HIV infection, fasting, or cachexia).

With prolonged use at high doses: aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, thrombocytopenia. High doses may cause dizziness, psychomotor agitation, and disorientation; urinary system disorders – nephrotoxicity (renal colic, interstitial nephritis, papillary necrosis).

Overdose symptoms include pallor, anorexia, nausea, vomiting, abdominal pain, hepatonecrosis, elevated "liver" transaminase activity, and prolonged prothrombin time. In cases of overdose, excessive sweating, psychomotor agitation or central nervous system (CNS) depression, somnolence, impaired consciousness, cardiac arrhythmias, tachycardia, extrasystoles, tremor, hyperreflexia, and seizures may occur. Liver damage may manifest 12–48 hours after overdose. Glucose metabolism disturbances and metabolic acidosis may also develop. In severe poisoning, liver dysfunction may progress to encephalopathy with impaired consciousness, hemorrhages, hypoglycemia, cerebral edema, and in some cases, death. Acute renal failure with acute tubular necrosis may present as severe lumbar pain, hematuria, proteinuria, and may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have also been reported.

Treatment: 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 an excessive dose of paracetamol was ingested within the past hour. 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. The efficacy of the antidote decreases significantly after this time. If required, N-acetylcysteine should be administered intravenously according to the established dosing regimen. In the absence of vomiting, oral methionine may be used as an alternative in remote areas outside hospital settings.

Phenylephrine hydrochloride overdose: symptoms include hyperhidrosis, psychomotor agitation or CNS depression, headache, dizziness, somnolence, impaired consciousness, arrhythmias, tremor, hyperreflexia, seizures, nausea, vomiting, irritability, restlessness, arterial hypertension, tachycardia, and extrasystoles.

Chlorpheniramine maleate overdose: anticholinergic-like symptoms may occur, including mydriasis, photophobia, dry skin and mucous membranes, elevated body temperature, and intestinal atony. CNS depression may be accompanied by respiratory depression and cardiovascular disturbances (decreased pulse rate, decreased arterial pressure up to circulatory failure).

Large doses of caffeine may cause epigastric pain, vomiting, diuresis, tachypnea, extrasystoles, tachycardia, or cardiac arrhythmias, and effects on the central nervous system (dizziness, insomnia, nervous excitation, irritability, emotional lability, anxiety, tremor, convulsions).

Treatment: within the first 6 hours after suspected overdose, gastric lavage should be performed, followed by hospitalization; symptomatic therapy; in cases of severe hypertension, α- and β-adrenergic blockers may be used.

Adverse Reactions

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

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

Nervous system disorders: Headache, dizziness, psychomotor agitation and disorientation, restlessness, nervousness, anxiety, irritability, sleep disturbances, insomnia, somnolence, confusion, hallucinations, depressive states, tremor, paresthesia and heaviness in limbs, tinnitus; in isolated cases – coma, seizures, dyskinesia, behavioral changes, general weakness.

Respiratory system disorders: Bronchospasm in patients sensitive to acetylsalicylic acid and other NSAIDs.

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.

Hepatobiliary disorders: Liver function abnormalities, elevated liver enzyme activity (usually without jaundice), hepatonecrosis (with high-dose administration).

Endocrine system disorders: Hypoglycemia, up to hypoglycemic coma.

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

Renal and urinary system disorders: Nephrotoxicity, interstitial nephritis, papillary necrosis, micturition disorders, difficulty in urination, dysuria, urinary retention.

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

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

Description of selected adverse reactions

Metabolic acidosis with high anion gap

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

Reporting of adverse reactions

Reporting suspected adverse reactions after medicinal product authorization is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals and patients, or their legal representatives, should report any suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life. 3 years.

Storage conditions.

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

Packaging.

4 tablets per strip; 1 strip per envelope.

4 tablets per strip; 1 strip per envelope; 50 envelopes per cardboard box.

Prescription status.

Over-the-counter – tablets № 4.

By prescription only – tablets № 200.

Manufacturer.

Flamingo Pharmaceuticals Ltd.

Manufacturer's address and location of operations.

E-28, Opp. Fire Brigade, M.I.D.C., Taloda, Raigad District, Maharashtra, IN–410208, India.

Marketing Authorization Holder.

Ananta Medicare Ltd.

Address of the Marketing Authorization Holder and/or its representative.

Suite 1, 2 Station Court, Imperial Wharf, Townmead Road, Fulham, London, United Kingdom.