Coldrex maxgrip with lemon flavour

I N S T R U C T I O N for medical use of the medicinal product COLDREX MAXGRI P with lemon flavour (COLDREX MAXGRI P with lemon flavour)

Composition:

Active substances: paracetamol, phenylephrine hydrochloride, ascorbic acid;

1 sachet contains paracetamol 1000 mg, phenylephrine hydrochloride 10 mg, ascorbic acid 40 mg;

Excipients: sucrose, citric acid anhydrous, sodium citrate, maize starch, sodium cyclamate, sodium saccharin, colloidal anhydrous silicon dioxide, lemon flavour, curcumin (E 100).

Pharmaceutical form. Powder for oral solution.

Main physicochemical properties: inhomogeneous, free-flowing powder of light yellow colour with lemon 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, primarily within the central nervous system. The absence of inhibition of peripheral prostaglandin synthesis preserves protective prostaglandins in the gastrointestinal tract. Therefore, paracetamol is particularly suitable for patients with a history of diseases or concomitant therapies in which suppression of peripheral prostaglandin synthesis would be undesirable (e.g., in patients with a history of gastrointestinal bleeding or in elderly individuals).

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 included in the formulation to compensate for the loss of vitamin C that may occur at the onset of a viral infection.

Pharmacokinetics.

Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract. Plasma protein binding at therapeutic concentrations is minimal. Paracetamol is metabolized in the liver and excreted in the urine primarily as glucuronide and sulfate conjugates. Less than 5% is excreted unchanged.

Phenylephrine is irregularly absorbed from the gastrointestinal tract. It undergoes presystemic metabolism by monoamine oxidase in the intestine and liver, resulting in reduced bioavailability following oral administration. It is almost entirely excreted in the urine as sulfate conjugates.

Ascorbic acid is rapidly absorbed from the gastrointestinal tract and widely distributed throughout the body. Plasma protein binding is approximately 25%. Excess ascorbic acid is excreted from the body in the urine as metabolites.

Clinical characteristics.

Indications.

Short-term relief of symptoms of colds and influenza, such as headache, sore throat, nasal congestion, sinus pressure and associated pain, body aches and pains, 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 excitation, 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, with tricyclic antidepressants, beta-blockers, or other antihypertensive drugs.

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, with long-term, regular, daily use of paracetamol. These interactions are not clinically significant when paracetamol is used short-term according to the recommended dosage regimen.

Barbiturates reduce the antipyretic effect of paracetamol.

Anticonvulsants (including phenytoin, barbiturates, carbamazepine), which stimulate hepatic microsomal enzyme activity, 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.

Caution should be exercised when using paracetamol concomitantly with flucloxacillin, as co-administration has been associated with metabolic acidosis with a high anion gap, particularly in patients with risk factors (see section "Special precautions").

Interaction of phenylephrine with MAO 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. Phenylephrine may reduce the effectiveness of beta-blockers and other antihypertensive agents (including debrisoquin, guanethidine, reserpine, methyldopa), increasing the risk of arterial hypertension and other cardiovascular adverse reactions. Concomitant use with ergot alkaloids (e.g., ergotamine, methysergide) may increase the risk of ergotism.

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 beverages.

Ascorbic acid may be taken only 2 hours after deferoxamine injection, as their concomitant use increases iron toxicity, especially in the myocardium.

Prolonged intake of high doses in individuals treated with disulfiram inhibits the disulfiram-alcohol reaction.

Special precautions for use.

Before taking the medicine, consult a doctor. Contains paracetamol.

Concomitant use with other medicines containing paracetamol may lead to overdose. Paracetamol overdose can cause liver failure, which may necessitate liver transplantation or result in death.

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

Patients suffering from arterial hypertension, cardiovascular diseases, diabetes, hyperthyroidism, closed-angle glaucoma, pheochromocytoma, benign prostatic hyperplasia, Raynaud's disease, or with impaired liver or kidney function should consult a doctor before using the medicine. Underlying liver disease increases the risk of liver damage associated with paracetamol.

Caution is recommended when using paracetamol concomitantly with flucloxacillin due to an increased risk of high anion gap metabolic acidosis, especially in patients with severe renal impairment, sepsis, malnutrition, and other sources of glutathione deficiency (e.g. chronic alcoholism), as well as in those taking the maximum daily doses of paracetamol. Close monitoring, including measurement of urinary 5-oxoproline, is recommended.

In patients with severe infections such as sepsis, which are associated with 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. Phenylephrine contained in the medicine may provoke angina attacks.

The medicine should not be used by patients taking other sympathomimetics (e.g. decongestants, cold and flu remedies, appetite suppressants, and amphetamine-like psychostimulants). Do not exceed the recommended doses. If symptoms do not improve or worsen within 7 days of treatment, or are accompanied by high fever, rash, or persistent headache, consult a doctor.

Patients with rare hereditary conditions such as fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase deficiency should not take this medicine. One sachet (1 dose) contains 3.725 g of sucrose. This should be taken into account by patients with diabetes mellitus. One dose contains 130 mg of sodium. This should be considered by patients on a sodium-controlled diet.

Use during pregnancy or breastfeeding.

The medicine should not be used during pregnancy except when the expected benefit to the woman outweighs the potential risk to the fetus. It should be used at the lowest effective dose and for the shortest duration necessary. Use only as prescribed by a doctor.

Paracetamol and phenylephrine may be excreted in breast milk. During breastfeeding, the medicine should be used only as prescribed by a doctor.

Effect on ability to drive or operate machinery.

If dizziness occurs during use of the medicine, driving or operating complex machinery is not recommended.

Method of Administration and Dosage

The medication is intended for oral administration.

Dissolve the contents of one sachet in half a glass of hot water. Stir until completely dissolved. Add cold water 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. The treatment course without medical consultation should not exceed 7 days. Do not exceed the recommended 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 medication 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 typically appear 24–48 hours after overdose and may peak within 4–6 days. Glucose metabolism disturbances and metabolic acidosis may also occur. In severe poisoning, liver failure may progress and lead to toxic encephalopathy with impaired consciousness, hemorrhages, hypoglycemia, cerebral edema, and in some cases, may necessitate liver transplantation or result in death.

Acute kidney injury with acute tubular necrosis may present with 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 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 drugs that induce liver enzymes; chronic excessive alcohol consumption; glutathione depletion due to malnutrition, cystic fibrosis, HIV infection, fasting, or cachexia).

Treatment. In case of paracetamol overdose, prompt medical attention is required even if no symptoms are apparent. The patient should be taken to hospital immediately, even in the absence of early symptoms. Symptoms may be limited to nausea and vomiting or may not reflect the severity of the overdose or 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 of paracetamol ingestion, but maximum protective effect is achieved when administered within 8 hours of ingestion. The efficacy of the antidote decreases sharply after this period. 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.

Overdose due to phenylephrine may result in effects similar to those described in the section "Adverse Reactions." Other symptoms may include irritability, restlessness, arterial hypertension, and possibly reflex bradycardia. In severe cases, confusion, hallucinations, seizures, and arrhythmias may occur. However, the amount of medication 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 arterial hypertension are indicated.

High doses of ascorbic acid (over 3000 mg) may cause temporary osmotic diarrhea and gastrointestinal disturbances such as nausea and abdominal discomfort. Consequences of ascorbic acid overdose may be attributed to severe liver failure caused by 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 labyrinth disorders: tinnitus.

Eye disorders: mydriasis, acute angle-closure glaucoma (more common 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 liver enzyme activity, hepatonecrosis (dose-dependent effect), hepatic failure.

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

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

Cardiovascular 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 slight laxative effect.

Shelf life.

3 years.

Storage conditions.

Store at temperatures not exceeding 25 °C. Keep out of reach and sight of children.

Packaging.

5 or 10 sachets per cardboard box.

Availability.

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.