Coldrex maxgrip with forest berries flavour

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT COLDREX MAXGRIP WITH FOREST BERRIES FLAVOUR (COLDREX MAXGRIP WITH FOREST BERRIES FLAVOUR)

Composition:

Active substances: paracetamol, phenylephrine hydrochloride, ascorbic acid;

1 sachet contains: paracetamol 1000 mg, ascorbic acid 70 mg, phenylephrine hydrochloride 10 mg;

Excipients: sucrose, tartaric acid, sodium citrate anhydrous, aspartame (E 951), fruit-berry flavouring, Euroblend Black Currant.

Pharmaceutical form. Oral soluble powder.

Main physicochemical properties: light pink powder with a characteristic fruity-menthol odour.

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 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 swelling of the nasal mucosa.

Ascorbic acid is an essential vitamin added to the formulation to compensate for the loss of vitamin C that may occur at the onset of a viral infection.

Pharmacokinetics.

Paracetamol is rapidly absorbed in the gastrointestinal tract, metabolized in the liver, and excreted in the urine mainly as glucuronide and sulfate conjugates. Ascorbic acid is rapidly absorbed in the gastrointestinal tract; 25% binds to plasma 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.

Short-term relief of symptoms of colds and influenza, such as headache, sore throat, nasal congestion, sinus pain and associated pain, muscle aches, and fever.

Contraindications.

Hypersensitivity to any component of the drug, severe cardiovascular insufficiency, severe hepatic and/or renal dysfunction, congenital hyperbilirubinemia, glucose-6-phosphate dehydrogenase deficiency, alcoholism, blood disorders (including severe anemia, leukopenia), thrombosis, thrombophlebitis, states of increased excitement, acute pancreatitis, benign prostatic hyperplasia with urinary retention, severe forms of diabetes mellitus, epilepsy, pheochromocytoma, hyperthyroidism, closed-angle glaucoma, severe forms of: arterial hypertension, atherosclerosis, ischemic heart disease; sleep disorders.

Do not use concomitantly with monoamine oxidase inhibitors (MAOIs) or within 2 weeks after discontinuation of MAOIs, tricyclic antidepressants, beta-blockers or other antihypertensive drugs, or other sympathomimetics (decongestant medications).

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 forms of interaction.

The absorption rate of paracetamol may be increased when used concomitantly with metoclopramide and domperidone, and decreased with cholestyramine.

The anticoagulant effect of warfarin and other coumarins may be enhanced, increasing the risk of bleeding, during prolonged daily use of paracetamol. These interactions are not clinically significant when paracetamol is used short-term according to the recommended regimen.

Barbiturates reduce the antipyretic effect of paracetamol. Anticonvulsants (including phenytoin, barbiturates, carbamazepine), which stimulate hepatic microsomal enzymes, may enhance the hepatotoxic effect of paracetamol due to increased formation of hepatotoxic metabolites.

Concomitant use of high doses of paracetamol with isoniazid increases the risk of hepatotoxic syndrome. Paracetamol reduces the effectiveness of diuretics. Do not use concomitantly with alcohol.

If paracetamol is administered concomitantly with zidovudine, toxicity of both drugs may increase (neutropenia and hepatotoxicity). When taken concomitantly with probenecid, the dose of paracetamol should be reduced, as probenecid reduces paracetamol clearance by almost half by inhibiting its conjugation with glucuronic acid.

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 pyroglutamic acidosis, especially in patients with risk factors (see section "Special precautions for use").

Interaction of phenylephrine with monoamine oxidase inhibitors causes a hypertensive effect; with tricyclic antidepressants (e.g., amitriptyline) and other sympathomimetics – increases the risk of cardiovascular adverse effects; with digoxin and cardiac glycosides – may lead to cardiac arrhythmias or myocardial infarction.

Concomitant use with ergot alkaloids (e.g., ergotamine and methysergide) may increase the risk of ergotism.

Phenylephrine may reduce the effectiveness of beta-blockers and other antihypertensive drugs (including debrisoquin, guanethidine, reserpine, methyldopa), increasing the risk of arterial hypertension and other cardiovascular adverse reactions. Concomitant use of tricyclic antidepressants and phenylephrine may increase the risk of cardiovascular adverse reactions.

Ascorbic acid, when taken orally, enhances the absorption of penicillin and iron, reduces the effectiveness of heparin and indirect anticoagulants, and increases the risk of crystalluria during salicylate therapy. Antidepressants, antiparkinsonian and antipsychotic drugs, phenothiazine derivatives increase the risk of urinary retention, dry mouth, and constipation. Glucocorticoids increase the risk of glaucoma. High doses of the drug reduce the effectiveness of tricyclic antidepressants.

Absorption of vitamin C is reduced when used concomitantly with oral contraceptives, fruit or vegetable juices, or alkaline drinks. Ascorbic acid should be taken only 2 hours after deferoxamine injection, as their concomitant use increases iron toxicity, especially in the myocardium. Prolonged use of high doses in patients treated with disulfiram inhibits the disulfiram-alcohol reaction.

Special precautions.

Before using the medicine, consult a physician. Contains paracetamol.

Concomitant use with other medicines containing paracetamol may lead to overdose. Paracetamol overdose can cause liver failure, which may require liver transplantation or result in death. The risk of overdose is higher in patients with non-cirrhotic alcoholic liver disease.

Cases of liver dysfunction/failure have been reported in patients with reduced glutathione levels, such as those suffering from severe malnutrition, anorexia, low body mass index, or chronic alcoholism.

Patients with arterial hypertension, cardiovascular diseases, diabetes, hyperthyroidism, closed-angle glaucoma, benign prostatic hyperplasia, Raynaud's disease, or impaired liver or kidney function should consult a physician before using the medicine. Underlying liver disease increases the risk of liver injury associated with paracetamol. In patients with severe infections such as sepsis, which are accompanied by reduced glutathione levels, the use of paracetamol may increase 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.

Cases of high anion gap metabolic acidosis (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 sources of glutathione deficiency (e.g., chronic alcoholism), who were treated with paracetamol at therapeutic doses for prolonged periods or in combination with 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.

This medicine should not be used in patients taking other sympathomimetics, such as decongestants, cold and flu remedies, appetite suppressants, or amphetamine-like psychostimulants. The medicine contains phenylephrine, which may provoke angina attacks.

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

One sachet (1 dose) contains 5 g of sucrose. This should be taken into account by patients with diabetes mellitus. The medicine contains the colorants Sunset Yellow (E 110) and carmoisine (E 122) as part of the "Black Currant" colour blend, which may cause allergic reactions. Contains 117 mg of sodium per dose, which should be considered by patients on a low-sodium diet.

Contains a source of phenylalanine, which may be harmful to individuals with phenylketonuria.

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

Use during pregnancy or breastfeeding.

This medicine should not be used during pregnancy except when the expected benefit to the mother outweighs the potential risk to the fetus. It should be used at the lowest effective dose and for the shortest duration possible. Use only under medical supervision.

Paracetamol and phenylephrine may be excreted in breast milk. During breastfeeding, use only under medical supervision.

Effect on ability to drive or operate machinery.

If dizziness occurs, driving or operating complex machinery is not recommended.

Method of Administration and Dosage

The product is intended for oral administration.

The contents of 1 sachet should be poured into a glass and mixed with hot water to half-fill the glass. Stir until completely dissolved. Cold water may be added if necessary.

Adults and children aged 12 years and older: 1 sachet every 4–6 hours as needed. Do not take more frequently than every 4 hours. Maximum daily dose – 4 sachets.

Treatment duration – no longer than 7 days. Do not exceed the recommended treatment duration without medical consultation. Do not exceed the stated doses. If the patient's condition does not improve with treatment, medical advice should be sought. The lowest effective dose should be used.

Children

The product is not recommended for children under 12 years of age.

Overdose

The risk of overdose is increased in patients with liver disease.

Overdose is generally caused by paracetamol and manifests as pallor, anorexia, nausea, vomiting, abdominal pain, hepatonecrosis, elevated liver transaminase activity, and increased prothrombin index.

Signs of liver damage appear within 24–48 hours after overdose and may peak at 4–6 days. Glucose metabolism disturbances and metabolic acidosis may occur. In severe poisoning, liver failure may progress to encephalopathy with impaired consciousness, hemorrhage, hypoglycemia, cerebral edema, and in individual cases, may necessitate liver transplantation or result in death.

Acute kidney dysfunction with acute tubular necrosis may present as severe flank pain, hematuria, proteinuria, and may develop even in the absence of severe liver damage. Cardiac arrhythmias have also been reported. Acute pancreatitis has been observed in patients with liver dysfunction and toxic liver injury.

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 of paracetamol.

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 drugs that induce liver enzymes; chronic excessive ethanol consumption; glutathione depletion (due to malnutrition, cystic fibrosis, HIV infection, fasting, cachexia)).

Treatment. In case of paracetamol overdose, prompt medical attention is required even if no symptoms 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.

Administration of activated charcoal should be considered if the excessive dose of paracetamol was taken within the past hour. Plasma paracetamol concentration should be measured 4 hours or later 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 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, particularly in remote areas outside hospital settings.

Overdose due to phenylephrine may result in effects similar to those described in the section "Adverse Reactions." Other symptoms may include irritability, restlessness, hypertension, and possibly reflex bradycardia. In severe cases, confusion, hallucinations, seizures, and arrhythmias may occur. However, the amount of drug required to cause serious phenylephrine toxicity is greater than the amount needed to cause paracetamol-induced hepatotoxicity.

Treatment: in case of overdose, gastric lavage, administration of activated charcoal, symptomatic therapy, and use of alpha-blockers such as phentolamine in cases of severe hypertension are required.

Overdose due to ascorbic acid (more than 3000 mg) may cause transient osmotic diarrhea and gastrointestinal disturbances such as nausea and epigastric discomfort. The consequences of ascorbic acid overdose may be attributed to those caused by severe liver damage resulting from paracetamol overdose.

Adverse Reactions

Skin and subcutaneous tissue disorders: rash, urticaria, allergic dermatitis, Stevens-Johnson syndrome, pruritus, erythema multiforme, toxic epidermal necrolysis.

Immune system disorders: allergic reactions (including angioedema), anaphylactic shock, hypersensitivity reactions.

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

Nervous system disorders: headache, dizziness, paresthesia.

Ear and labyrinthine disorders: tinnitus.

Eye disorders: mydriasis, acute angle-closure glaucoma (more frequently in patients with glaucoma), visual disturbances and accommodation disorders.

Gastrointestinal disorders: nausea, vomiting, dry mouth, hypersalivation, abdominal discomfort and pain, decreased appetite, heartburn, diarrhea.

Hepatobiliary disorders: liver function abnormalities, increased activity of *liver enzymes, hepatonecrosis (dose-dependent effect), hepatic failure.

Metabolism and nutrition disorders: metabolic acidosis with high anion gap with 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 used paracetamol (see section "Special precautions for use"). Pyroglutamic acidosis may occur due to low glutathione levels in these patients.

Blood and lymphatic system disorders: anemia (including hemolytic), sulfhemoglobinemia and methemoglobinemia, thrombocytopenia, leukopenia, agranulocytosis, pancytopenia, bruising or bleeding.

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

Cardiac disorders: increased blood pressure, tachycardia or reflex bradycardia, palpitations, dyspnea, chest pain.

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

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

The drug may have a mild laxative effect.

Shelf life.

3 years.

Storage conditions.

Store at temperatures not exceeding 30 °C, in a place inaccessible and out of sight of children.

Packaging.

5 or 10 sachets per cardboard box.

Prescription status.

Over-the-counter.

Manufacturer.

HALEON ALCALA, S.A./HALEON ALCALA, S.A.

Manufacturer's address and place of business.

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