Instructions for Theraflu Extra with lemon flavor powder for oral solution, package No. 10
Composition
active ingredients: 1 packet contains paracetamol 650 mg, pheniramine maleate 20 mg, phenylephrine hydrochloride 10 mg;
excipients: sucrose, anhydrous citric acid, natural lemon flavors, sodium citrate dihydrate, calcium phosphate, maltodextrin, acesulfame potassium, silicon dioxide, D&C yellow dye No. 10 (E 104), FD&C yellow dye No. 6 (E 110).
Dosage form
Powder for oral solution.
Main physicochemical properties: loose granular powder with white and yellow large granules, the presence of soft lumps is possible; solution: cloudy yellow solution with a lemon odor.
Pharmacotherapeutic group
Analgesics and antipyretics. Paracetamol, combinations without psycholeptics. ATX code N02B E51.
Pharmacological properties
Pharmacodynamics
A combination drug for the treatment of flu and cold symptoms.
Paracetamol has analgesic, antipyretic and weak anti-inflammatory effects, which are mainly mediated by inhibition of prostaglandin synthesis in the central nervous system. It does not affect platelet function and hemostasis. The lack of peripheral inhibition of prostaglandins determines important properties of the drug, such as maintaining protective prostaglandins in the gastrointestinal tract. Therefore, paracetamol can be taken in patients for whom peripheral inhibition of prostaglandins is undesirable (for example, patients with a history of gastrointestinal bleeding or elderly patients).
Phenylephrine hydrochloride is a sympathomimetic amine that acts primarily directly on alpha-adrenergic receptors. When used in therapeutic doses for nasal congestion, the drug has no significant stimulating effect on beta-adrenergic receptors of the heart and no significant effect on the central nervous system. It is a well-known nasal decongestant and acts by vasoconstriction, reducing swelling and hyperemia of the nasal mucosa.
Pheniramine maleate is an H1-receptor blocker, has an antiallergic effect, reduces the severity of local exudative manifestations, reduces lacrimation, rhinorrhea, itching in the eyes and nose. Reduction of general allergic symptoms associated with respiratory diseases, which causes a moderate sedative effect. It also has an antimuscarinic effect.
Pharmacokinetics
After oral administration, paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract. Peak plasma concentrations are reached within 10–60 minutes.
Paracetamol is distributed into most body tissues. It crosses the placental barrier and is excreted in breast milk. At usual therapeutic doses, paracetamol binds to plasma proteins to a negligible extent, but the degree of binding increases with increasing concentrations.
Paracetamol is mainly metabolized in the liver by two pathways: glucuronidation and sulfation. It is excreted in the urine, mainly as glucuronide and sulfate conjugates. Less than 5% of a dose of paracetamol is excreted unchanged. The half-life is 1 to 3 hours.
The maximum concentration of pheniramine maleate in the blood plasma is reached after 1-2.5 hours; the half-life is 16-19 hours. 70-83% of the oral dose is excreted in the urine in unchanged form or in the form of metabolites.
Phenylephrine hydrochloride is unevenly absorbed from the gastrointestinal tract and undergoes presystemic metabolism by monoamine oxidase (MAO) in the intestine and liver; thus, phenylephrine has a reduced bioavailability when taken orally. It is excreted in the urine almost entirely as the sulfate conjugate. Peak plasma concentrations are achieved within 45 minutes to 2 hours, and the plasma half-life is 2 to 3 hours.
Indication
Treating symptoms of flu and colds, including fever and chills, headache, runny nose, nasal and sinus congestion, sneezing, and body aches.
Contraindication
Hypersensitivity to any of the components of the drug. Severe cardiovascular diseases, severe liver and/or kidney dysfunction, congenital hyperbilirubinemia, hyperthyroidism, pheochromocytoma, glucose-6-phosphate dehydrogenase deficiency, severe forms of diabetes mellitus, alcoholism, acute pancreatitis, prostatic hypertrophy with urinary retention, bladder neck obstruction, pyloroduodenal obstruction, bronchial asthma, epilepsy, blood diseases (including severe anemia, leukopenia), thrombosis, thrombophlebitis, angle-closure glaucoma, arterial hypertension, sleep disorders. Do not use during treatment with MAO inhibitors and within 2 weeks after stopping such treatment.
Concomitant treatment with tricyclic antidepressants, beta-blockers, and other sympathomimetics is contraindicated.
Interaction with other medicinal products and other types of interactions
The drug interactions of each individual component of the drug are well known. There is no reason to assume that the use of these components in combination would affect the drug interaction profile.
With regular long-term use of paracetamol, the anticoagulant effect of warfarin or other coumarin derivatives may be enhanced, as well as the risk of bleeding may increase. With occasional use of paracetamol, this effect is not pronounced.
Hepatotoxic drugs may increase the likelihood of paracetamol accumulation and overdose. The risk of developing hepatotoxic effects of paracetamol may increase in patients receiving drugs that induce liver microsomal enzymes, such as barbiturates and antiepileptic drugs (phenytoin, phenobarbital, carbamazepine), and the antituberculosis drugs rifampicin and isoniazid.
Metoclopramide increases the rate of absorption of paracetamol and causes an increase in its maximum plasma levels. Similarly, domperidone may increase the rate of absorption of paracetamol.
Paracetamol may prolong the half-life of chloramphenicol.
Paracetamol may reduce the bioavailability of lamotrigine with a decrease in its effect due to possible induction of its metabolism in the liver.
The absorption of paracetamol may be reduced when co-administered with cholestyramine, but the reduction in absorption is insignificant if cholestyramine is administered 1 hour later.
Regular use of paracetamol simultaneously with zidovudine may lead to the development of neutropenia and an increased risk of liver damage. Paracetamol reduces the effectiveness of diuretics.
Probenecid affects the metabolism of paracetamol. The dose of paracetamol should be reduced in patients taking probenecid concomitantly. The hepatotoxicity of paracetamol may be increased by prolonged or excessive alcohol consumption.
Paracetamol may affect the results of tests for determining uric acid levels using the phosphotungstic acid method.
Pheniramine maleate.
First-generation antihistamines, such as pheniramine maleate, may enhance the central nervous system depressant effects of certain other drugs (e.g., monoamine oxidase inhibitors, tricyclic antidepressants, hypnotics and sedatives, neuroleptics, alcohol, antiparkinsonian drugs, barbiturates, anesthetics, tranquilizers, and narcotic analgesics).
Pheniramine enhances the anticholinergic effects of atropine, antispasmodics, other antihistamines, antiparkinsonian drugs and phenothiazine neuroleptics. Pheniramine maleate may also inhibit the effects of anticoagulants.
Phenylephrine hydrochloride.
The use of the drug is contraindicated in patients undergoing therapy with monoamine oxidase inhibitors (MAOIs) and in patients who have used MAOIs within the last 2 weeks. Phenylephrine may potentiate the effects of MAO inhibitors and provoke a hypertensive crisis.
Concomitant use of phenylephrine with other sympathomimetic agents or tricyclic antidepressants (e.g. amitriptyline) may lead to an increased risk of cardiovascular side effects.
Phenylephrine may reduce the effectiveness of beta-blockers and other antihypertensive drugs (e.g. debrisoquine, guanethidine, reserpine, methyldopa). The risk of developing arterial hypertension and other cardiovascular side effects may increase.
Concomitant use of phenylephrine with digoxin and cardiac glycosides may increase the risk of heart rhythm disturbances or heart attack.
Concomitant use of phenylephrine with ergot alkaloids (ergotamine and methysergide) may increase the risk of developing ergotism.
Application features
The medicine should be used with caution in the following cases:
renal and/or hepatic impairment; acute hepatitis; hemolytic anemia; chronic malnutrition and dehydration; cardiovascular disease; diabetes mellitus; prostatic hypertrophy, as patients may be predisposed to developing urinary retention; stenosing peptic ulcer.
As this medicinal product contains paracetamol, concomitant use of other medicinal products containing paracetamol should be avoided due to the risk of severe liver damage in the event of overdose. Overdose of paracetamol may cause liver failure, which may require liver transplantation or be fatal. The medicinal product is not recommended for use with vasoconstrictors. Do not exceed the indicated doses.
When using the drug, you should avoid drinking alcoholic beverages, since ethyl alcohol, when used simultaneously with paracetamol, can cause liver dysfunction. Paracetamol should be used with caution in patients with Raynaud's disease, heart disease (including arrhythmia, bradycardia), thyroid disease, glaucoma, chronic lung disease, as well as patients taking medications that affect the liver and the elderly. Elderly patients with confusion should avoid taking the drug. There is a known risk of premature closure of the ductus arteriosus in the fetus when using paracetamol during pregnancy.
if they have breathing problems such as asthma, emphysema or chronic bronchitis; if symptoms do not improve within 5 days or if symptoms are accompanied by high fever, fever lasting more than 3 days, rash or prolonged headache; regarding the possibility of using the drug in cases of impaired kidney and liver function.
These phenomena may be symptoms of a more serious illness.
The drug may affect the results of laboratory tests for blood glucose.
The medicine contains phenylephrine, which may cause angina attacks.
Cases of hepatic dysfunction/failure have been reported in patients with reduced glutathione levels, such as those who are severely malnourished, anorexic, have a low body mass index, or suffer from chronic alcohol dependence.
Patients with severe infections such as sepsis, which are accompanied by a decrease in glutathione levels, are at increased risk of metabolic acidosis when taking paracetamol. Symptoms of metabolic acidosis include deep, rapid or difficult breathing, nausea, vomiting, loss of appetite. You should seek immediate medical attention if these symptoms occur.
1 package of the drug contains 12.6 g of sucrose, which must be taken into account by patients with diabetes mellitus. Patients with rare hereditary diseases such as fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase deficiency should not take this drug.
The medicinal product contains FD&C Yellow No. 6 (E 110), which may cause allergic reactions. 1 sachet of the medicinal product contains 42.2 mg of sodium. Patients on a controlled sodium diet should take the sodium content into account.
Reporting suspected adverse reactions to a physician after a drug is licensed is important. This allows continued monitoring of the benefit/risk balance of the drug.
Ability to influence reaction speed when driving vehicles or other mechanisms
The drug may cause drowsiness in some patients (especially pheniramine), which may significantly affect the ability to drive or use machines. Caution should be exercised when driving or operating machinery that requires concentration.
Use during pregnancy or breastfeeding
The use of the drug is not recommended during pregnancy or breastfeeding, as its safety in such cases has not been studied.
Pregnancy.
A large amount of data on pregnant women have not revealed any congenital or feto/neonatal toxicity. Although epidemiological studies on the intrauterine development of the nervous system in children exposed to paracetamol are not conclusive. If clinically necessary, paracetamol can be used during pregnancy at the lowest effective dose for the shortest duration and with the lowest frequency.
To date, there are no adequate reproductive function studies or embryo/fetotoxicity data with pheniramine.
There are currently only limited data on the use of phenylephrine hydrochloride in pregnant women. Uterine vasoconstriction and impaired uterine blood flow associated with the use of phenylephrine may lead to fetal hypoxia. The use of phenylephrine hydrochloride should be avoided during pregnancy.
Breast-feeding.
Paracetamol is excreted in breast milk, but in amounts that are not clinically significant. Available published data do not provide grounds to recommend discontinuation of breast-feeding during therapy with the drug.
There is insufficient information regarding the excretion of pheniramine into breast milk and the amount of the drug that may enter the child's body.
There are no data on the excretion of phenylephrine into breast milk. The use of phenylephrine should be avoided in women who are breastfeeding.
Method of administration and doses
For oral use. Adults and children over 12 years of age should be prescribed 1 sachet every 4–6 hours (if necessary to relieve symptoms), but not more than 4 sachets per day. A single dose should not exceed 1 sachet. It is not recommended to use the drug for longer than 7 days without consulting a doctor. The minimum interval between doses is 4 hours. The contents of 1 sachet should be dissolved in a glass of boiled hot water (but not boiling water) and drunk hot. The lowest dose necessary to achieve effectiveness in the shortest possible time should be taken.
Patients with liver failure.
For patients with impaired liver function, it is necessary to reduce the dose or increase the interval between doses.
Elderly patients: No dose adjustment is required for elderly patients.
Children
Do not use the drug in children under 12 years of age.
Overdose
Symptoms caused by paracetamol: hepatotoxic effect, in severe cases liver necrosis develops. Overdose of paracetamol, including a high total dose received over a long period, can cause analgesic-induced nephropathy with irreversible liver function impairment. Liver damage is possible in adults who have taken 10 g or more of paracetamol, and in children who have taken more than 150 mg/kg of body weight. In patients with risk factors: regular excessive use of ethanol, glutathione cachexia (including digestive disorders, cystic fibrosis, HIV infection, cachexia) - the use of 5 g or more of paracetamol can lead to liver damage.
There is a risk of poisoning, especially in elderly patients, young children, patients with liver disease, in cases of chronic malnutrition and in patients receiving inducers of liver enzymes (long-term treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. John's wort). In severe poisoning, liver failure can progress to encephalopathy, coma and death.
With prolonged use of the drug in high doses, aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, thrombocytopenia may develop from the hematopoietic system. When taking large doses, from the central nervous system - dizziness, psychomotor agitation and disorientation; from the urinary system - nephrotoxicity (renal colic, interstitial nephritis, capillary necrosis).
Symptoms of paracetamol overdose, which appear in the first 24 hours, are: pallor, nausea, vomiting and lack of appetite. The first sign of liver damage may be abdominal pain, which does not always appear in the first 24-48 hours, but may occur later, during a period of up to 4-6 days after taking the drug. Liver damage, as a rule, occurs a maximum of 72-96 hours after taking the drug. Abnormalities in glucose metabolism (hypoglycemia) and metabolic acidosis, hemorrhages may be observed. Acute renal failure with acute tubular necrosis may develop even in the absence of severe liver damage and manifest as severe back pain, hematuria, proteinuria. Cases of cardiac arrhythmias and acute pancreatitis have been reported.
Treatment: Paracetamol overdose requires immediate medical attention, even if no symptoms of overdose are present. Administer N-acetylcysteine intravenously or orally as an antidote to paracetamol in the early stages. Gastric lavage and/or oral methionine may be beneficial for at least 48 hours after overdose. Activated charcoal and monitoring of respiration and circulation may be helpful. Diazepam may be used if convulsions occur.
Symptoms caused by pheniramine maleate and phenylephrine hydrochloride
Symptoms due to mutual potentiation of the parasympatholytic effect of the antihistamine and the sympathomimetic effect of phenylephrine hydrochloride include drowsiness, which may develop into excitation (especially in children) or depression of the central nervous system, visual impairment, rash, nausea, vomiting, persistent headache, hyperhidrosis, nervousness, dizziness, tremor, insomnia, hyperreflexia, irritability, restlessness, circulatory disorders, arterial hypertension and bradycardia. In severe cases, an overdose of phenylephrine may cause impaired consciousness, arrhythmias, coma, and convulsions. Cases of atropine-like "psychosis" have been reported against the background of an overdose of pheniramine. Atropine-like symptoms may include: mydriasis, photophobia, dry skin and mucous membranes, hyperthermia, and intestinal atony.
Treatment. There is no specific antidote for antihistamine overdose. The patient should be given standard emergency care, including activated charcoal, saline laxative, and standard cardiorespiratory support. Stimulants should not be used; vasoconstrictors may be used to treat hypotension.
To eliminate hypertensive effects, an α-receptor blocker (phentolamine) can be used for intravenous administration. If seizures occur, diazepam can be used.
Adverse reactions
The adverse reactions listed below are ranked by frequency: very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1000, < 1/100), rare (≥ 1/10000, < 1/1000), very rare (< 1/10000), frequency unknown (cannot be estimated from the available data).
From the circulatory and lymphatic system: very rarely - thrombocytopenia, agranulocytosis, leukopenia, pancytopenia, anemia including hemolytic, sulfhemoglobinemia and methemoglobinemia (cyanosis, shortness of breath, heart pain), bruising or bleeding.
On the part of the immune system: rarely - hypersensitivity, Quincke's edema; frequency unknown - anaphylactic reactions, Stevens-Johnson syndrome, toxic epidermal necrolysis.
Mental disorders: rarely - nervousness, insomnia, confusion, psychomotor agitation and disorientation, anxiety, feeling of fear, irritability, sleep disturbances, hallucinations, depressive states.
On the part of the organs of vision: mydriasis, acute angle-closure glaucoma (more often in patients with glaucoma), accommodation disorders.
From the cardiovascular system: rarely - tachycardia, palpitations, arterial hypertension.
On the part of the endocrine system: rarely - hypoglycemia, up to hypoglycemic coma.
On the part of the digestive tract: often - nausea, vomiting; rarely - dry mouth, constipation, abdominal pain and discomfort, diarrhea, heartburn, decreased appetite, hypersalivation.
Respiratory system: very rarely - bronchospasm in patients sensitive to aspirin and other NSAIDs.
On the part of the liver and biliary tract: rarely - impaired liver function, increased levels of liver enzymes, usually without the development of jaundice.
From the kidneys and urinary system: rarely - dysuria, nephrotoxicity, renal colic; very rarely - urinary retention (more likely in patients with prostatic hypertrophy).
Skin and subcutaneous tissue disorders: rarely - rash, itching, erythema multiforme, urticaria, eczema, purpura, allergic dermatitis.
General disorders: rarely - general weakness, malaise.
Unlike second-generation antihistamines, the use of pheniramine is not associated with QTc interval prolongation and cardiac arrhythmia.
Expiration date
2 years.
Storage conditions
Store out of the reach of children at a temperature not exceeding 25 °C.
Packaging
10 packages in a cardboard box.
Vacation category
Without a prescription.
Producer
Delpharm Orleans.
Location of the manufacturer and its business address
5 avenue de Consir, ORLEANS CEDEX 2, 45071, France.
