TheraFlu^® (Powder) Instructions for Use

Marketing Authorization Holder

Cheleon Rus, JSC (Russia)

Manufactured By

Haleon US, Inc. (USA)

Contact Information

CHELEON RUS JSC (Russia)

ATC Code

N02BE51 (Paracetamol in combination with other drugs, excluding psycholeptics)

Dosage Form

TheraFlu

Powder for oral solution (forest berries): pkt. 10 pcs.

Dosage Form, Packaging, and Composition

Powder for preparation of oral solution [forest berries] granulated, light purple in color, consisting of purple and white granules with inclusions of yellowish-brownish granules; the presence of soft lumps that crumble with light pressure is allowed.

Excipients: sucrose, acesulfame potassium, Allura Red AC (E129) (FD&C Red No. 40), Brilliant Blue (E133) (FD&C Blue No. 1), maltodextrin, silicon dioxide, Natural Raspberry Flavor WONF Durarome (860385 TD0994), Natural Cranberry Flavor Durarome (861149 TD2590), anhydrous citric acid, sodium citrate dihydrate, tricalcium phosphate, magnesium stearate.

11.6 g – seven-layer sachets (10) – cardboard packs.

The secondary packaging may have a first-opening control.

Clinical-Pharmacological Group

Drug for symptomatic therapy of acute respiratory diseases

Pharmacotherapeutic Group

Analgesics; other analgesics and antipyretics; anilides

Pharmacological Action

A combined drug, the action of which is due to its constituent components. It has antipyretic, analgesic, vasoconstrictive action, and relieves cold symptoms. It constricts blood vessels and relieves swelling of the nasal mucosa and nasopharynx.

Paracetamol

Paracetamol has an analgesic and antipyretic effect by suppressing the synthesis of prostaglandins mainly in the CNS. It does not affect platelet function and hemostasis.

Phenylephrine Hydrochloride

Phenylephrine hydrochloride is a sympathomimetic agent; when taken orally, it has a moderate vasoconstrictive effect (due to stimulation of α₁-adrenergic receptors), reduces swelling and hyperemia of the nasal mucosa.

Pheniramine Maleate

Pheniramine maleate is an antiallergic agent, a blocker of histamine H₁-receptors. It has a moderate sedative effect and also exhibits antimuscarinic activity.

Pharmacodynamic Effects

Paracetamol

The absence of suppression of peripheral prostaglandin synthesis gives the drug significant pharmacological properties, such as the preservation of protective prostaglandins in the gastrointestinal tract. Therefore, Paracetamol is particularly suitable for patients with a history of diseases or simultaneously taking drugs for which suppression of peripheral prostaglandin synthesis would be undesirable (for example, patients with a history of gastrointestinal bleeding or elderly patients).

Phenylephrine Hydrochloride

Phenylephrine hydrochloride reduces swelling of the nasal mucosa.

Pheniramine Maleate

It leads to the relief of common allergic symptoms associated with respiratory disorders.

Pharmacokinetics

Paracetamol

Absorption

Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract. After oral administration of the drug, C_max of paracetamol in plasma is reached within 10-60 minutes.

Distribution

Paracetamol is distributed in most body tissues, crosses the placental barrier and is present in breast milk. In therapeutic concentrations, binding to plasma proteins is insignificant, increasing with increasing concentration.

Metabolism

It undergoes metabolism during the “first pass” through the liver, and is excreted mainly in the urine as glucuronide and sulfate conjugates.

Excretion

Less than 5% of the administered dose is excreted as unchanged paracetamol. T_1/2 is 1-3 hours.

Phenylephrine Hydrochloride

Absorption

Phenylephrine hydrochloride is unevenly absorbed from the gastrointestinal tract and undergoes presystemic metabolism by MAO in the intestine and liver. C_max in plasma is reached in the interval from 45 minutes to 2 hours. Thus, phenylephrine hydrochloride has reduced bioavailability when taken orally.

Distribution

Relevant data are not available.

Metabolism

It undergoes presystemic metabolism by MAO in the intestine and liver.

Excretion

It is excreted in the urine almost completely as sulfate conjugates. T_1/2 is 2-3 hours.

Pheniramine Maleate

Absorption

C_max of pheniramine in plasma is reached in approximately 1-2.5 hours.

Distribution, Metabolism

Relevant data are not available.

Excretion

T_1/2 of pheniramine is 16-19 hours. 70-83% of the administered dose is excreted from the body in the urine as metabolites or unchanged.

Indications

For adults (including the elderly) and children 12 years and older

• Symptomatic treatment of infectious and inflammatory diseases: acute respiratory viral infections, including influenza and colds, accompanied by high fever, chills, headache, sore throat, runny nose, nasal congestion, sneezing and muscle pain.

ICD codes

Dosage Regimen

1 sachet every 4-6 hours, as needed, but no more than 4 doses within 24 hours.

TheraFlu can be taken at any time of the day, but the best effect is achieved by taking the drug before bedtime, at night.

If no relief of symptoms is observed within 3 days after starting the drug, it is necessary to consult a doctor.

Patients should not take TheraFlu for more than 5 days. Do not exceed the recommended dose.

The lowest dose necessary to achieve the effect should be taken for the shortest possible treatment duration.

Patients with impaired renal function. In the presence of renal failure (CrCl<10 ml/min), the interval between doses of TheraFlu should be at least 8 hours.

Patients with impaired liver function. Patients with impaired liver function or Gilbert’s syndrome should reduce the dose or increase the interval between doses of TheraFlu.

Elderly patients. No dose adjustment is necessary in elderly patients.

Children

The dosage regimen for children 12 years and older does not differ from the dosage regimen for adults.

TheraFlu is contraindicated in children under 12 years of age.

Method of Administration

Orally.

One sachet is dissolved in a glass of hot, but not boiling water, and stirred. Take while hot. Description of the prepared solution: an opaque purple solution with a berry smell.

Adverse Reactions

The adverse reactions listed below are presented according to the affected organs and organ systems and frequency of occurrence. Frequency is defined as follows: very common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/1,000 and <1/100), rare (≥1/10,000 and <1/1,000), very rare (<1/10,000, including isolated cases). Frequency categories were formed based on post-marketing surveillance.

Blood and lymphatic system disorders very rare – thrombocytopenia, agranulocytosis, leukopenia, pancytopenia; frequency unknown – hemolytic anemia.

Immune system disorders rare – hypersensitivity reactions (rash, dyspnea, anaphylactic shock), angioedema and skin rash, urticaria, allergic dermatitis; frequency unknown – anaphylactic reaction, Stevens-Johnson syndrome, toxic epidermal necrolysis.

Psychiatric disorders rare – increased excitability, sleep disturbance; frequency unknown – hallucinations, confusion.

Nervous system disorders common – drowsiness; rare – dizziness, headache; frequency unknown – anticholinergic symptoms, impaired coordination of movements, tremor, memory loss or impaired concentration (more common in elderly patients), balance disorder (more common in elderly patients), dizziness (more common in elderly patients), sedative reactions (more pronounced at the beginning of treatment), drowsiness (more pronounced at the beginning of treatment).

Eye disorders: rare – mydriasis, accommodation paresis, intraocular pressure disturbance, acute angle-closure glaucoma (most likely to occur in individuals with angle-closure glaucoma).

Cardiac disorders rare – tachycardia, palpitations.

Vascular disorders rare – increased blood pressure; frequency unknown – orthostatic hypotension.

Gastrointestinal disorders common – nausea, vomiting; rare – dry mouth, constipation, abdominal pain, diarrhea.

Hepatobiliary disorders rare – increased activity of liver enzymes.

Skin and subcutaneous tissue disorders rare – eczema, rash, itching, erythema, purpura.

Renal and urinary disorders rare – difficulty urinating (most often occur in patients with bladder outlet obstruction, for example, due to prostatic hyperplasia), dysuria.

General disorders and administration site conditions rare – malaise; frequency unknown – dryness of the mucous membrane.

Contraindications

• Hypersensitivity to the active substances or to any of the excipients included in the drug;
• Concomitant use of tricyclic antidepressants;
• Concomitant use of beta-blockers;
• Concomitant use of other sympathomimetic drugs (such as decongestants, appetite suppressants and amphetamine-like agents);
• Concomitant or within the preceding 2 weeks use of MAO inhibitors;
• Portal hypertension;
• Alcoholism;
• Diabetes mellitus;
• Severe cardiovascular diseases;
• Arterial hypertension;
• Hyperthyroidism;
• Angle-closure glaucoma;
• Pheochromocytoma.
• Sucrase/isomaltase deficiency, fructose intolerance, glucose-galactose malabsorption;
• Pregnancy;
• Breastfeeding period;
• Children under 12 years of age.

With caution

In severe atherosclerosis of the coronary arteries, cardiovascular diseases, acute hepatitis, hemolytic anemia, bronchial asthma, severe liver or kidney diseases, prostatic hyperplasia, difficulty urinating due to prostatic hyperplasia, blood diseases, glucose-6-phosphate dehydrogenase deficiency, congenital hyperbilirubinemia (Gilbert’s, Dubin-Johnson and Rotor syndromes), chronic malnutrition (calorie deficiency) and dehydration, pyloroduodenal obstruction, stenosing gastric and/or duodenal ulcer, epilepsy, with simultaneous use of digoxin and cardiac glycosides, ergot alkaloids (for example, ergotamine and methysergide), as well as drugs that can negatively affect the liver (barbiturates, phenytoin, phenobarbital, carbamazepine, rifampicin, isoniazid, zidovudine and other inducers of liver microsomal enzymes).

Should be used with caution in elderly patients, who are more susceptible to the development of adverse effects. Use should be avoided in elderly patients with confusion.

Use in Pregnancy and Lactation

Pregnancy

Data on the use of this drug in pregnant women are insufficient. Data obtained from reproductive toxicity studies in animals are insufficient. The use of the drug during pregnancy is contraindicated.

Breastfeeding period

The use of the drug during breastfeeding is contraindicated.

Paracetamol

Paracetamol is excreted in breast milk, but in clinically insignificant amounts when used at recommended doses.

Phenylephrine Hydrochloride

Phenylephrine may be excreted in breast milk.

Pheniramine Maleate

Animal studies and clinical data on the use of pheniramine during breastfeeding are not available.

Use in Hepatic Impairment

With caution severe liver diseases.

Use in Renal Impairment

With caution severe kidney diseases.

Pediatric Use

Contraindicated in children under 12 years of age.

Geriatric Use

No dose adjustment is necessary in elderly patients.

Should be used with caution in elderly patients, who are more susceptible to the development of adverse effects. Use should be avoided in elderly patients with confusion.

Special Precautions

To avoid toxic liver damage, the drug should not be combined with the intake of alcoholic beverages.

The drug should not be used with any other drugs containing Paracetamol. Concomitant use with other drugs containing Paracetamol may lead to overdose. Paracetamol overdose can cause the development of liver failure, which may lead to the need for liver transplantation or death.

Cases of impaired liver function/liver failure have been reported in patients with reduced glutathione levels, for example, in extremely emaciated patients suffering from anorexia, with low body mass index, in patients with severe chronic alcohol dependence or sepsis.

Concomitant use with decongestants and antihistamines should be avoided.

Patients with the following disorders should consult a doctor before taking the drug

• Impaired liver or kidney function. Concomitant liver disease increases the risk of paracetamol-related liver damage;
• Conditions accompanied by a decrease in glutathione levels, since the use of paracetamol may increase the risk of metabolic acidosis.

Patients should consult a doctor if

• They have bronchial asthma, emphysema or chronic bronchitis;
• Symptoms do not go away within 5 days or are accompanied by severe fever lasting for 3 days, rash or persistent headache.

These may be signs of more serious disorders.

The drug should not be taken from damaged sachets.

Excipients

1 sachet of TheraFlu contains

• 10 g of sucrose, which should be taken into account by patients with diabetes mellitus. Patients with rare hereditary fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase deficiency should not take this drug;
• 42.2 mg of sodium, which should be taken into account by patients on a sodium-restricted diet;
• Allura Red AC E129 (FD&C Red No. 40), which may cause allergic reactions.

Effect on ability to drive vehicles and operate machinery

Caution must be exercised when driving vehicles and operating machinery while taking TheraFlu.

TheraFlu can cause drowsiness, dizziness, blurred vision, impaired cognitive function and coordination of movements, which can significantly affect the ability to drive vehicles and operate machinery. These adverse effects may be further enhanced by the intake of alcoholic beverages or other sedatives.

Overdose

Symptoms due to paracetamol (occur after taking more than 10-15 g)

In severe cases of overdose, Paracetamol has a hepatotoxic effect, including the possibility of causing liver necrosis. Overdose can also cause liver failure, which may lead to liver transplantation or death. Clinical signs of liver damage develop mainly after 24-48 hours and reach a maximum after 4-6 days. Acute pancreatitis has been observed, usually with impaired liver function and toxic effects on the liver.

The severity of overdose depends on the dose, therefore the simultaneous use of paracetamol-containing drugs is prohibited. The risk of poisoning is especially high in elderly patients, children, patients with liver diseases, in cases of chronic alcoholism, patients with chronic malnutrition (calorie deficiency) and patients taking inducers of microsomal oxidation in the liver.

Symptoms of paracetamol overdose in the first 24 hours pale skin, nausea, vomiting, loss of appetite, convulsions. Abdominal pain may be the first sign of liver damage and sometimes does not appear for 24-48 hours and sometimes may appear later, after 4-6 days, on average after 72-96 hours after taking the drug. Impaired glucose metabolism and metabolic acidosis may also occur. Even in the absence of liver damage, acute liver failure and acute tubular necrosis may develop. Cases of cardiac arrhythmia and the development of pancreatitis have been reported.

Treatment

In case of exceeding the recommended dose, the patient should immediately seek medical help, even if feeling well, because there is a risk of delayed serious liver damage.

Administration of acetylcysteine intravenously or orally as an antidote, gastric lavage, oral administration of methionine may have a positive effect for at least 48 hours after overdose.

Administration of activated charcoal, monitoring of respiration and circulation are recommended. In case of convulsions, diazepam may be prescribed.

Symptoms due to phenylephrine and pheniramine (combined due to mutual potentiation of the parasympatholytic effect of pheniramine and the sympathomimetic effect of phenylephrine in case of drug overdose)

Symptoms of overdose include drowsiness, to which anxiety (especially in children), visual disturbances, rash, nausea, vomiting, headache, increased excitability, dizziness, insomnia, circulatory disorders, coma, convulsions (especially in children), behavioral changes, increased or decreased blood pressure, bradycardia are subsequently added. Cases of atropine-like “psychosis” have been reported with pheniramine overdose. In severe cases, confusion, hallucinations, convulsions and arrhythmias may develop.

Treatment

There is no specific antidote. General supportive measures are necessary, including the administration of activated charcoal, saline laxatives, and measures to support cardiac and respiratory function. Psychostimulants (methylphenidate) should not be administered due to the risk of seizures. In case of arterial hypotension, vasopressor drugs may be used.

In case of increased blood pressure, intravenous administration of alpha-adrenergic blockers (for example, phentolamine) is possible, because Phenylephrine is a selective agonist of α₁-adrenergic receptors; therefore, the hypertensive effect in case of phenylephrine overdose should be treated by blocking α-adrenergic receptors. If seizures develop, diazepam should be used.

Drug Interactions

Paracetamol

It enhances the effects of MAO inhibitors, sedatives, and ethanol.

The risk of hepatotoxic action of paracetamol increases with simultaneous use of barbiturates, phenytoin, phenobarbital, carbamazepine, rifampicin, isoniazid, zidovudine, and other inducers of liver microsomal enzymes.

The anticoagulant properties of warfarin and other coumarins may be enhanced against the background of long-term regular use of paracetamol, increasing the risk of bleeding. A single dose of paracetamol does not have this effect.

Metoclopramide increases the absorption rate of paracetamol and increases the plasma concentration of paracetamol to the maximum level. Similarly, domperidone may increase the absorption rate of paracetamol.

With simultaneous use of chloramphenicol and paracetamol, the T_1/2 of chloramphenicol may increase.

Paracetamol may reduce the bioavailability of lamotrigine with a possible decrease in its effect due to induction of its hepatic metabolism.

The absorption of paracetamol may be reduced when taken simultaneously with cholestyramine; however, this can be avoided if cholestyramine is taken one hour after paracetamol.

Regular use of paracetamol simultaneously with zidovudine may cause neutropenia and increase the risk of liver damage.

Probenecid affects the metabolism of paracetamol. In patients taking probenecid simultaneously, the dose of paracetamol should be reduced.

The hepatotoxicity of paracetamol may be enhanced by chronic or excessive alcohol consumption.

Paracetamol may affect the results of the uric acid test using the precipitating reagent phosphotungstate.

Phenylephrine

The drug TeraFlu is contraindicated in patients who are taking or have taken MAO inhibitors within the last 2 weeks. Phenylephrine may enhance the effect of MAO inhibitors and cause an increase in blood pressure.

Simultaneous use of phenylephrine with other sympathomimetic amines (for example, decongestants, appetite suppressants, and amphetamine-like agents) or tricyclic antidepressants (for example, amitriptyline) may increase the risk of cardiovascular side effects.

Phenylephrine may reduce the effectiveness of beta-blockers and other antihypertensive drugs (for example, debrisoquine, guanethidine, reserpine, methyldopa). The risk of increased blood pressure and other cardiovascular side effects may be increased.

Simultaneous use of phenylephrine with digoxin and cardiac glycosides may increase the risk of arrhythmia or myocardial infarction.

Simultaneous use of phenylephrine with ergot alkaloids (ergotamine and methysergide) may increase the risk of ergotism.

Pheniramine

Enhancement of the influence of other substances on the CNS is possible (for example, MAO inhibitors, tricyclic antidepressants, alcohol, antiparkinsonian drugs, barbiturates, benzodiazepines, tranquilizers, and narcotic agents).

Pheniramine may inhibit the effect of anticoagulants.

Pheniramine has anticholinergic activity and may enhance the anticholinergic effects of other drugs (other antihistamines, drugs for the treatment of Parkinson’s disease, and phenothiazine antipsychotics).

Storage Conditions

The drug should be stored out of the reach of children at a temperature not exceeding 25°C (77°F).

Shelf Life

Shelf life is 2 years. Do not use after the expiration date.

Dispensing Status

The drug is available without a prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.