Tylophen® hot

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT TAILOLFEN® HOT

Composition:

Active substances: paracetamol, chlorpheniramine maleate, phenylephrine hydrochloride;

Each sachet contains: paracetamol 500 mg, chlorpheniramine maleate 4 mg, phenylephrine hydrochloride 10 mg;

Excipients: citric acid anhydrous, tartaric acid, sodium hydrogencarbonate, sodium carbonate anhydrous, sodium benzoate (E 211), lemon flavor, confectionery sugar, povidone, quinoline yellow (E 104).

Pharmaceutical form. Powder for oral solution.

Main physicochemical properties: granular free-flowing powder consisting of white, light yellow and yellow granules with a lemon odor.

Pharmacotherapeutic group.

Analgesics and antipyretics. Paracetamol combinations without psycholeptics.

ATC code N02B E51.

Pharmacological properties.

Pharmacodynamics.

The drug is based on a combination of active substances acting on the main components in the pathogenesis of colds. Paracetamol exerts antipyretic and analgesic effects; chlorpheniramine maleate, an H1-histamine receptor blocker, exerts a desensitizing effect manifested as a reduction in inflammatory response of the mucous membranes of the upper respiratory tract (improvement in nasal breathing, reduction in rhinorrhea, cessation of sneezing and lacrimation); phenylephrine hydrochloride reduces edema and hyperemia of the mucous membranes of the upper respiratory tract and sinuses.

Pharmacokinetics.

Not studied.

Clinical characteristics.

Indications.

Symptomatic treatment of influenza and colds in adults and children aged 12 years and older, accompanied by fever, headache, and rhinitis.

Contraindications.

Hypersensitivity to any component of the drug or to other antihistamines; severe impairment of liver and/or kidney function; congenital hyperbilirubinemia; glucose-6-phosphate dehydrogenase deficiency; alcoholism; blood disorders (including anemia, leukopenia); severe cardiovascular diseases, including severe conduction disorders, advanced atherosclerosis, severe coronary artery disease, severe arterial hypertension, decompensated heart failure, arrhythmias, epilepsy, sleep disorders; pheochromocytoma, hyperthyroidism, closed-angle glaucoma, urethral disorders and prostate hyperplasia with difficult urination, bladder neck obstruction; peptic ulcer disease of the stomach and duodenum in the acute phase, pyloroduodenal obstruction, acute pancreatitis; bronchial asthma, patients at risk of developing respiratory failure; thrombosis; thrombophlebitis; diabetes mellitus.

Do not use concomitantly with monoamine oxidase inhibitors (MAOIs) or within 2 weeks after discontinuation of MAOIs; do not use simultaneously with tricyclic antidepressants or β-adrenergic blockers, or other sympathomimetics.

Interaction with other medicinal products and other forms of interaction.

Drug interactions for each individual component of the drug are well known. There is no reason to assume that the use of these substances in combination may affect the profile of drug interactions.

Paracetamol.

The absorption rate of paracetamol may be increased by metoclopramide and domperidone, and decreased by cholestyramine; however, the reduction in absorption is insignificant if cholestyramine is administered 1 hour apart. Paracetamol may reduce the bioavailability of lamotrigine, possibly diminishing its effect due to potential induction of its hepatic metabolism. 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 caused by paracetamol; antacids and food reduce paracetamol absorption. The anticoagulant effect of warfarin and other coumarins may be enhanced by long-term, regular daily use of paracetamol, increasing the risk of bleeding. Occasional use does not show a significant effect.

Barbiturates and alcohol may enhance the hepatotoxic and nephrotoxic effects of paracetamol; barbiturates reduce the antipyretic effect of paracetamol.

Anticonvulsants (including phenytoin, barbiturates, carbamazepine), isoniazid, and rifampicin, which stimulate hepatic microsomal enzyme activity, may enhance the hepatotoxic effect of paracetamol due to increased conversion of the drug into hepatotoxic metabolites. Concomitant use of paracetam0l with hepatotoxic agents increases the risk of liver toxicity. Regular concomitant use of paracetamol with zidovudine may lead to neutropenia and increased risk of liver damage.

Simultaneous use of high-dose paracetamol with isoniazid increases the risk of hepatotoxic syndrome. Paracetamol reduces the effectiveness of diuretics.

Do not use concomitantly with alcohol. Probenecid affects paracetamol metabolism. In patients receiving probenecid concomitantly, the dose of paracetamol should be reduced.

Caution is advised when using paracetamol concomitantly with flucloxacillin, as co-administration 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").

Phenylephrine.

Phenylephrine hydrochloride should not be used concomitantly with α-blockers, other antihypertensive agents, phenothiazine derivatives (e.g., promethazine), bronchodilator sympathomimetics, guanethidine, digitalis, Rauwolfia alkaloids, indomethacin, methyldopa, glucocorticoids; appetite suppressants, amphetamine-like psychostimulants, labor stimulants, anesthetics, ergot alkaloids, other central nervous system stimulants, theophylline.

Concomitant use of phenylephrine hydrochloride with indomethacin or bromocriptine may cause severe arterial hypertension. Simultaneous use of phenylephrine hydrochloride with sympathomimetic amines, digoxin, and cardiac glycosides increases the risk of arrhythmias and myocardial infarction.

Vasoconstrictive effects of the drug may be enhanced when used concomitantly with labor stimulants, and arrhythmias may occur when used with anesthetics. Marked increase in blood pressure may occur with intravenous administration of ergot alkaloids.

Atropine sulfate blocks reflex bradycardia caused by phenylephrine and enhances the vasopressor response to phenylephrine. Phenylephrine may reduce the effectiveness of β-adrenergic blockers and other antihypertensive agents. Concurrent use of phenylephrine with β-adrenergic blockers may lead to arterial hypertension and excessive bradycardia, possibly resulting in heart block. Use with caution with thyroid hormones and drugs affecting cardiac conduction (cardiac glycosides, antiarrhythmic agents). When used concomitantly with drugs that promote potassium excretion, such as certain diuretics like furosemide, hypokalemia may be intensified and arterial sensitivity to vasoconstrictors such as phenylephrine may be reduced.

Do not use concomitantly with other vasoconstrictive agents (regardless of the route of administration).

Concomitant use of phenylephrine and other sympathomimetics may lead to additive stimulation of the central nervous system to an extremely high level, resulting in nervousness, irritability, and insomnia. Seizure attacks are also possible. Furthermore, concomitant use of other sympathomimetics with phenylephrine may enhance vasoconstrictive or cardiovascular effects of either drug. Prolonged intake of large doses during disulfiram treatment inhibits the disulfiram-alcohol reaction.

Chlorpheniramine.

Enhances the effects of drugs that depress the central nervous system (hypnotics, sedatives, anesthetics, MAO inhibitors, tricyclic antidepressants, antiparkinsonian agents, barbiturates, tranquilizers, narcotic analgesics, as well as alcohol), and enhances the anticholinergic effects of atropine, spasmolytics, tricyclic antidepressants, and antiparkinsonian agents. May inhibit the action of anticoagulants and interact with progesterone, reserpine, and thiazide diuretics. Concomitant use of oral contraceptives may lead to reduced efficacy of the antihistamine component of the drug.

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

Special precautions for use.

Do not exceed the recommended dose or use the medication for longer than 5 days. In the evening, the medication should be taken several hours before bedtime.

If symptoms of illness have not disappeared after 5 days, treatment with the medication should be discontinued and medical advice should be sought.

If headache becomes persistent, consult a physician.

During use of this medication, do not take other medicinal products containing paracetamol.

The medication should be prescribed by a physician only after assessment of the risk/benefit ratio in the following conditions: arterial hypertension, ischemic heart disease, Raynaud's disease/syndrome, urinary disorders, increased intraocular pressure, prostate hypertrophy, pancreatitis.

Cases of high anion gap metabolic acidosis (HAGMA) due to 5-oxoproline (pyroglutamic) acidosis have been reported in patients with severe underlying conditions such as severe renal insufficiency and sepsis, or malnutrition and other sources of glutathione deficiency (e.g., chronic alcoholism), who were treated with paracetamol at therapeutic doses over a prolonged period or with 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 primary cause of HAGMA in patients with multiple risk factors.

Aminophyllines may cause disturbances of central nervous system function and, as a result, provoke seizures. Phenylephrine, a component of the medication, may exert vasoconstrictive effects and cause cardiovascular failure manifesting as arterial hypotension. Therefore, the medication should be used with caution in patients aged 70 years and older and in patients with cardiovascular diseases.

During treatment with this medication, avoid using sedatives/hypnotics (particularly barbiturates), as they may enhance the sedative effect of antihistamines (chlorpheniramine maleate). Use with caution in patients with liver or kidney disease, acute hepatitis, hemolytic anemia, chronic malnutrition, dehydration, or stenosing peptic ulcer. The medication contains phenylephrine, which may provoke angina attacks.

Use with caution in patients with compensated heart failure; in patients at risk of seizures; in patients with chronic obstructive airway diseases, persistent or chronic cough due to smoking, or when cough is associated with excessive sputum production; in patients with congenital prolonged QT interval or those undergoing prolonged treatment with drugs that may prolong the QT interval.

If the illness is caused by a bacterial infection, concomitant treatment with antibiotics is recommended.

Alcohol consumption is prohibited during treatment with this medication.

Consult a physician before use if the patient is taking warfarin or similar anticoagulant agents.

Note that in patients with alcoholic liver disease, the risk of hepatotoxic effects of paracetamol is increased. The medication may affect laboratory test results for blood glucose and uric acid levels. 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. Seek immediate medical attention if these symptoms occur.

For professional athletes: phenylephrine may cause a false-positive result in doping tests.

This medicinal product contains less than 1 mmol (23 mg)/dose of sodium, i.e., essentially sodium-free.

When prescribing this medication to patients on a sugar-free diet, note that one sachet contains sugar. If intolerance to certain sugars is present, consult a physician before taking this medicinal product.

Use during pregnancy or breastfeeding.

Do not use.

Effect on ability to drive or operate machinery.

The medication may cause drowsiness. Exercise caution when driving or operating machinery requiring concentration.

Method of Administration and Dosage.

For adults and children aged 12 years and older, the recommended dose is 1 sachet as needed, 2–3 times daily. The contents of the sachet should be dissolved in a glass of hot water. The solution should be taken immediately after preparation. The interval between doses should be at least 4 hours. The duration of treatment is determined individually by a physician, but typically lasts 3–5 days.

Children.

Do not use in children under 12 years of age.

Overdose.

Paracetamol overdose. Liver damage is possible in adults who have ingested 10 g or more of paracetamol, and in children who have ingested more than 150 mg/kg body weight. In patients with risk factors (long-term treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. John’s wort, or other drugs that induce liver enzymes; chronic excessive alcohol consumption; glutathione depletion (due to malnutrition, cystic fibrosis, HIV infection, fasting, cachexia)), liver damage may occur after ingestion of 5 g or more of paracetamol.

Symptoms within the first 24 hours: pallor, nausea, vomiting, anorexia, and abdominal pain. After ingestion of large doses, disorientation, psychomotor agitation, dizziness, sleep disturbances, cardiac arrhythmias, pancreatitis, and hepatonecrosis may occur. The first sign of liver damage may be abdominal pain, which does not always appear within the first 12–48 hours but may develop later, up to 4–6 days after drug intake. Liver injury typically develops within 72–96 hours after ingestion. Glucose metabolism disturbances and metabolic acidosis may also occur. In severe poisoning, hepatic failure may progress to encephalopathy, hemorrhage, hypoglycemia, coma, and 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.

With prolonged use of the drug in high doses, blood disorders such as aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, and thrombocytopenia may develop. In the central nervous system, high doses may cause dizziness, psychomotor agitation, and disorientation. In the urinary system, nephrotoxicity may occur (renal colic, interstitial nephritis, capillary necrosis).

Treatment. The patient should 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. Administration of 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 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 after ingestion. The efficacy of the antidote decreases sharply after this time. If necessary, 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. Treatment is symptomatic.

Phenylephrine overdose symptoms: Overdose may intensify adverse reactions, especially with prolonged use. Possible symptoms include cardiac arrhythmias, increased blood pressure, arterial hypotension, chest pain and discomfort, palpitations, dyspnea, non-cardiogenic pulmonary edema, psychomotor agitation or central nervous system depression, seizures, headache, tremor, sleep disturbances, somnolence, impaired consciousness, arrhythmias, restlessness, anxiety, nervousness, irritability, inappropriate behavior, psychosis with hallucinations, insomnia, weakness, anorexia, nausea, vomiting, oliguria, urinary retention, painful or difficult urination, facial flushing, cold sensation in extremities, paresthesia, pallor, piloerection, increased sweating, hyperglycemia, hypokalemia, peripheral vasoconstriction, reduced blood flow to vital organs, which may lead to impaired renal perfusion, metabolic acidosis, and increased cardiac workload due to elevated systemic vascular resistance. Severe vasoconstriction complications are more likely in patients with hypovolemia and severe bradycardia.

To counteract hypertensive effects, intravenous α-adrenergic blockers may be used. Seizures may be treated with diazepam.

In case of chlorpheniramine maleate overdose, anticholinergic (atropine-like) symptoms may occur: mydriasis, photophobia, dry skin and mucous membranes, elevated body temperature, tachycardia, and intestinal atony. Typically, central nervous system excitation symptoms appear first (psychomotor agitation, impaired motor coordination, hyperreflexia, seizures), followed by depression, drowsiness, and impaired consciousness, accompanied by respiratory depression and cardiovascular disturbances (cardiac arrhythmias, extrasystoles, decreased pulse rate, decreased blood pressure up to circulatory collapse). In case of overdose (even in the absence of symptoms), immediate medical assistance and urgent hospitalization are required. CNS stimulants must not be used; vasoconstrictors may be administered to treat arterial hypotension.

Adverse reactions.

Cardiovascular system: cardiac arrhythmia, tachycardia, reflex bradycardia, increased arterial pressure (especially in patients with arterial hypertension), sensation of flushing, palpitations.

Blood system: thrombocytopenia, leukopenia, pancytopenia, agranulocytosis, anemia, sulfhemoglobinemia and methemoglobinemia (cyanosis, dyspnea, chest pain), hemolytic anemia, bruising or bleeding.

Gastrointestinal tract: nausea, vomiting, heartburn, constipation, diarrhea, dyspepsia, flatulence, dry mouth, anorexia, epigastric discomfort and pain, decreased appetite, hypersalivation.

Urinary and reproductive system: urinary retention, difficulty urinating, dysuria, aseptic pyuria, nephrotoxicity, renal colic.

Psychiatric disorders: nervousness, insomnia, confusion, psychomotor agitation and disorientation, anxiety, fear, irritability, sleep disturbances, hallucinations, depressive states.

Nervous system: headache, dizziness, insomnia, drowsiness, excitability, tremor, hallucinations, paresthesia, tinnitus, seizures/epileptic seizures, dyskinesia, coma, behavioral changes.

Hepatobiliary system: liver function abnormalities, increased liver enzyme activity, usually without development of jaundice, biliary tract dyskinesia, hepatitis, jaundice, hepatotoxicity, hepatonecrosis (dose-dependent effect).

Skin and subcutaneous tissue: skin rashes, mucosal lesions, urticaria, pruritus, pallor of the skin, exfoliative dermatitis/multiform exudative erythema (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome), purpura.

Eye disorders: dryness of ocular mucosa, mydriasis, increased intraocular pressure, acute angle-closure glaucoma, accommodation disorders.

Immune system: anaphylaxis, hypersensitivity reactions, including angioneurotic edema.

Endocrine system: fluctuations in blood glucose levels, hypoglycemia, up to hypoglycemic coma.

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

Metabolism and nutrition disorders: metabolic acidosis with high anion gap with frequency "unknown" (cannot be estimated from available data).

Other: nasal dryness, feeling of weakness.

Unlike second-generation antihistamines, pheniramine use is not associated with QT interval prolongation or cardiac arrhythmia.

Description of individual 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.

Shelf life. 2 years.

Storage conditions.

Store at a temperature not exceeding 25 °C in the original packaging.

Keep out of reach of children.

Packaging. 20 g of product in a sachet.

20 g of product in a sachet, 6 or 12 sachets in a cardboard pack.

Prescription status. Over-the-counter.

Manufacturer.

NOBEL ILAC SANAYI VE TICARET A.S.

Manufacturer's address and location of its business operations.

Sankaklar District, Eski Akcakoca Avenue, No. 299, 81100, Duzce, Turkey.