Coldrex menthol active

I N S T R U C T I O N for medical use of the medicinal product COLDREX MENTHOL ACTIVE (COLDREX MENTHOL ACTIVE)

Composition:

Active substances: paracetamol, phenylephrine hydrochloride, ascorbic acid;

1 sachet contains 600 mg of paracetamol, 40 mg of ascorbic acid, 10 mg of phenylephrine hydrochloride;

Excipients: sucrose, sodium citrate, anhydrous citric acid, corn starch, menthol powder E41580, lemon flavor 610399E, honey flavor PFWIS PHS-050860, honey flavor F7624/P, caramel simple 626E150A, aspartame (E 951), sodium saccharin.

Pharmaceutical form. Powder for oral solution.

Main physicochemical properties: almost white/beige, free-flowing, heterogeneous powder with a smell of honey, lemon, and menthol.

Pharmacotherapeutic group. Analgesics and antipyretics. Paracetamol combinations without psychotropic agents. ATC code N02B E51.

Pharmacological properties.

Pharmacodynamics.

Paracetamol is an analgesic and antipyretic. Its mechanism of action is explained by inhibition of prostaglandin synthesis, primarily in the central nervous system. Phenylephrine hydrochloride is a sympathomimetic agent. Its action is primarily associated with direct stimulation of adrenergic receptors, mainly alpha-adrenergic receptors. Phenylephrine hydrochloride reduces nasal mucosal edema. Ascorbic acid is an essential vitamin added to the medicinal product to compensate for vitamin C loss that may occur at the onset of viral infection. It is known that ascorbic acid plays an important role in mediating the body's defense function against infection and is necessary for normal functioning of T-lymphocytes and effective phagocytic activity of leukocytes.

Pharmacokinetics.

Paracetamol is well absorbed from the gastrointestinal tract, metabolized in the liver, and excreted in the urine primarily as glucuronide and sulfate conjugates. Ascorbic acid is readily absorbed in the gastrointestinal tract; 25% binds to blood proteins. Excess ascorbic acid beyond the body's requirements is excreted in the urine as metabolites.

Phenylephrine hydrochloride is metabolized by monoamine oxidase in the intestine and liver. It is excreted in the urine as sulfate conjugates.

Clinical characteristics.

Indications.

For relief of symptoms of colds and influenza, including headache, sore throat, body aches and pains, nasal congestion, sinusitis and associated pain, acute catarrhal rhinitis, and fever.

Contraindications.

Hypersensitivity to any component of the drug. Concomitant use of other sympathomimetic decongestants (even those of local action). Severe hepatic and/or renal function impairment, severe forms of diabetes mellitus, benign prostatic hyperplasia with urinary retention, hyperthyroidism, severe cardiovascular disorders, severe arterial hypertension.

Pheochromocytoma, glucose-6-phosphate dehydrogenase deficiency, blood disorders (including marked anemia, leukopenia), acute pancreatitis, epilepsy, closed-angle glaucoma.

Do not use concomitantly with monoamine oxidase inhibitors (MAOIs) or within 2 weeks after discontinuation of MAOIs, as well as with tricyclic antidepressants, beta-blockers, and other antihypertensive agents.

Do not use in patients with phenylketonuria due to the presence of aspartame (E 951) in the formulation.

Interaction with other medicinal products and other types of interactions.

The absorption rate of paracetamol may be increased when used concomitantly with metoclopramide and domperidone, and decreased when used with cholestyramine. The anticoagulant effect of warfarin and other coumarins may be enhanced, increasing the risk of bleeding, during prolonged, regular daily use of paracetamol. However, such interactions are not clinically significant when paracetamol is used short-term according to the recommended regimen. Anticonvulsant drugs (including phenytoin, barbiturates, carbamazepine), which stimulate hepatic microsomal enzyme activity, may enhance the hepatotoxic effects of paracetamol due to increased formation of hepatotoxic metabolites. Concomitant use of high doses of paracetamol with isoniazid increases the risk of developing hepatotoxic syndrome. Do not use concomitantly with alcohol.

Paracetamol should be used with caution when administered concomitantly with flucloxacillin, as co-administration has been associated with metabolic acidosis with a high anion gap due to 5-oxoproline (pyroglutamic acid) accumulation, particularly in patients with risk factors (see section "Special precautions").

Caution is required when combining phenylephrine with the following drugs:

Vitamin C, when taken orally, enhances the absorption of penicillin and iron, reduces the effectiveness of heparin and indirect anticoagulants, and increases the risk of developing crystalluria during treatment with salicylates. Antidepressants, antiparkinsonian and antipsychotic drugs, phenothiazine derivatives increase the risk of urinary retention, dry mouth, and constipation. Ascorbic acid can be taken only 2 hours after deferoxamine injection, as their simultaneous use increases iron toxicity, especially in the myocardium. Prolonged intake of high doses in patients treated with disulfiram inhibits the disulfiram-alcohol reaction.

Special precautions for use.

Do not use in liver or kidney diseases without consulting a physician.

Patients with arterial hypertension, cardiovascular diseases, diabetes mellitus, benign prostatic hyperplasia, or Raynaud's disease (occlusive vascular disorders) should consult a physician before using this medicinal product.

Avoid concomitant use with other medications intended for symptomatic treatment of cold and flu, vasoconstrictor agents for the treatment of rhinitis, or medications containing paracetamol.

Since this medicinal product contains paracetamol, concomitant use with other paracetamol-containing products may lead to overdose. Paracetamol overdose can cause liver failure, which may necessitate liver transplantation or result in death.

Cases of high anion gap metabolic acidosis (HAGMA) due to pyroglutamic acidosis have been reported in patients with severe conditions such as severe renal insufficiency and sepsis, or in patients with malnutrition or other sources of glutathione deficiency (e.g., chronic alcoholism), who were treated with paracetamol at therapeutic doses for prolonged periods or 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 of the patient. 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.

Concomitant use with sympathomimetics (such as decongestants, appetite suppressants, amphetamine-like psychostimulants) should be avoided.

Each sachet contains 118 mg of sodium. This should be taken into account by patients on a sodium-controlled diet.

One sachet (1 dose) contains 3755 mg of sucrose. This should be considered in patients with diabetes mellitus.

The medicinal product contains a source of phenylalanine (aspartame, E 951), which may be harmful to individuals with phenylketonuria.

Patients with rare hereditary disorders such as fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase deficiency should not take this medicinal product.

Do not exceed the recommended doses. If symptoms do not improve or worsen after more than 7 days of treatment with the product, or are accompanied by high fever, rash, or persistent headache, consult a physician.

If the product is used for a prolonged period as directed by a physician, monitoring of liver function and peripheral blood picture is necessary. Prolonged use at high doses may lead to aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, or thrombocytopenia.

Risk of overdose exists in patients with non-cirrhotic alcoholic liver disease. Cases of impaired liver function or liver failure have been reported in patients with reduced glutathione levels, such as in patients with severe wasting, anorexia, low body mass index, or chronic alcoholism.

In patients with severe infections such as sepsis, which are associated with reduced glutathione levels, the use of paracetamol increases the risk of metabolic acidosis. Symptoms of metabolic acidosis include deep, rapid, or labored breathing, nausea, vomiting, and loss of appetite. Immediate medical attention should be sought if these symptoms occur.

Use during pregnancy or breastfeeding.

Do not use during pregnancy or breastfeeding. Phenylephrine may pass into breast milk.

Ability to affect reaction speed when driving or operating machinery.

If adverse effects such as dizziness occur, it is recommended to avoid driving vehicles or operating complex machinery.

Dosage and Administration

The medicinal product is taken orally. Empty the contents of one sachet into a cup with a capacity of 200–300 ml and add hot water (not boiling water) up to half the cup. Stir until completely dissolved. Cold water may be added if necessary. The solution should be taken warm.

Adults and children aged 16 years and older: 1 sachet every 4–6 hours, as needed. Do not take more frequently than every 4 hours. Maximum daily dose — 6 sachets. Maximum duration of treatment without consulting a physician — 7 days.

Do not exceed the recommended doses. If symptoms persist, consult a physician.

The lowest effective dose should be used.

Children.

Do not use in children under 16 years of age.

Overdose.

Paracetamol.

The risk of overdose is increased in patients with liver disease and in those who abuse alcohol. Paracetamol overdose can cause liver failure, which may necessitate liver transplantation or lead to death.

Liver damage may occur in adults who have ingested more than 10 g of paracetamol and in children who have ingested more than 150 mg/kg body weight. Ingestion of 5 g or more of paracetamol may lead to liver damage in patients with risk factors [long-term treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. John's wort, or other medicinal products that induce liver enzymes; regular consumption of excessive amounts of ethanol; glutathione depletion (digestive disorders, cystic fibrosis, HIV infection, fasting, cachexia)].

Symptoms.

Within the first 24 hours — pallor, nausea, vomiting, anorexia, abdominal pain. Liver damage develops within 12–48 hours after overdose. Metabolic disturbances such as glucose metabolism disorders and metabolic acidosis, as well as cardiac arrhythmias, may occur.

In severe poisoning, liver function disturbances may progress to encephalopathy with impaired consciousness, hemorrhages, hypoglycemia, cerebral edema, and in some cases, may be fatal. Acute renal failure with acute tubular necrosis may present with severe flank pain, hematuria, proteinuria, and may develop even in the absence of severe liver damage. Acute pancreatitis has also been observed, usually in patients with liver dysfunction and toxic liver injury.

Treatment.

In case of overdose, immediate medical attention is required. The patient should be taken to hospital immediately, even if no early symptoms of overdose are present. Symptoms may be limited to nausea and vomiting or may not reflect the severity of the overdose or the risk of organ damage. Full supportive care should be provided under all circumstances. Activated charcoal treatment should be considered if the excessive dose of paracetamol was ingested within 1 hour. Plasma paracetamol concentration should be measured at least 4 hours or later after ingestion (earlier concentrations are unreliable). Treatment with N-acetylcysteine may be administered within 24 hours after paracetamol ingestion, but the maximum protective effect is achieved when administered within 8 hours after ingestion. The efficacy of the antidote decreases significantly after this time. If necessary, N-acetylcysteine is administered intravenously according to established dosing regimens. In the absence of vomiting, oral methionine may be used as an appropriate alternative in remote areas outside the hospital setting. Treatment of severe liver function disturbances occurring more than 24 hours after ingestion should be managed under the guidance of a toxicologist or hepatologist.

Phenylephrine.

Symptoms. Phenylephrine overdose most commonly manifests with symptoms described in the section "Adverse Reactions." Additionally, it may cause irritability, restlessness, hypertension, and possibly reflex bradycardia. In severe cases, impaired consciousness, hallucinations, seizures, and arrhythmias may occur. However, a significantly larger amount of the drug is required to cause phenylephrine overdose compared to paracetamol overdose.

Treatment. Treatment should be based on clinical symptoms. In case of severe hypertension, alpha-blockers such as phentolamine should be administered.

Ascorbic Acid.

Symptoms. High doses of ascorbic acid (over 3000 mg) may cause transient osmotic diarrhea and gastrointestinal disturbances such as nausea and abdominal discomfort. Symptoms of ascorbic acid overdose are usually masked by the more pronounced symptoms of paracetamol overdose.

Adverse Reactions

Listed below are the most commonly observed adverse reactions reported during clinical trials with phenylephrine, paracetamol, and ascorbic acid.

Blood and lymphatic system disorders:
Anemia (including hemolytic), sulfhemoglobinemia and methemoglobinemia, thrombocytopenia, leukopenia, agranulocytosis, bruising or bleeding; with prolonged use of high-dose ascorbic acid — thrombocytosis, hyperprothrombinemia, thrombosis, erythrocytopenia, neutrophilic leukocytosis; in patients with glucose-6-phosphate dehydrogenase deficiency, hemolysis of erythrocytes may occur.

Immune system disorders:
Anaphylaxis, skin allergic reactions (including rash, angioedema, Stevens-Johnson syndrome / toxic epidermal necrolysis), hypersensitivity reactions. Very rare cases of severe skin reactions have been reported.

Respiratory, thoracic and mediastinal disorders:
Bronchospasm in patients sensitive to aspirin and other nonsteroidal anti-inflammatory drugs.

Hepatobiliary disorders:
Liver function disturbances, increased liver enzyme activity, hepatonecrosis (dose-dependent effect), liver failure.

Psychiatric disorders:
Restlessness, nervous excitation, irritability, sleep disturbances, sensation of warmth.

Nervous system disorders:
Headache, dizziness, insomnia, fatigue.

Ear and labyrinthine disorders:
Tinnitus.

Gastrointestinal disorders:
Nausea, vomiting, dry mouth, hypersalivation, abdominal discomfort and pain, decreased appetite, heartburn, diarrhea; when ascorbic acid is used at doses exceeding 1 g per day — irritation of the gastrointestinal mucosa, vomiting.

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

Description of selected adverse reactions

Metabolic acidosis with high anion gap

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

Cardiac and vascular disorders:
Increased blood pressure, tachycardia or reflex bradycardia, palpitations, dyspnea, myocardial dystrophy.

Endocrine disorders:
With prolonged use of high-dose ascorbic acid — damage to the islet apparatus of the pancreas (hyperglycemia, glucosuria) and impaired glycogen synthesis, potentially leading to diabetes mellitus.

The following adverse reactions have been identified during post-marketing use. The frequency of these reactions is unknown but they are likely to be rare.

Eye disorders:
Mydriasis, increased intraocular pressure, acute attack of glaucoma in patients with closed-angle glaucoma.

Skin and subcutaneous tissue disorders:
Skin allergic reactions (e.g., rash, urticaria, allergic dermatitis). Cross-sensitivity reactions with other sympathomimetics are possible.

Renal and urinary disorders:
Urinary disturbances, urinary retention (more frequently in patients with benign prostatic hyperplasia), renal colic, nephrotoxic effect.

Other:
General weakness, fever, hypoglycemia, disturbances in zinc and copper metabolism.

The medicinal product may have a mild laxative effect.

Reporting of suspected adverse reactions.

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

Shelf life.

2 years.

Storage conditions.

Store at a temperature not exceeding 30 °C, in a place inaccessible to children.

Packaging.

Powder in sachets. 10 sachets per cardboard box.

Availability.

Over-the-counter (without prescription).

Manufacturer.

HALEON ALCALA, S.A., Spain.

Manufacturer's address and location of operations.

Ctra. de Ajalvir, Km. 2,500, Alcala de Henares, 28806 Madrid, Spain.