Coldrex hotrem with lemon

I N S T R U C T I O N for medical use of the medicinal product COLDREX HOTREM with lemon flavour

Composition:

Active substances: paracetamol, ascorbic acid, phenylephrine hydrochloride;

One sachet contains: paracetamol 750 mg, ascorbic acid 60 mg (coated with 1.5 mg ethylcellulose), phenylephrine hydrochloride 10 mg;

Excipients: sucrose, anhydrous citric acid, sodium citrate, sodium saccharin, lemon flavorings, quinoline yellow (E 104).

Pharmaceutical form. Powder for oral solution.

Main physicochemical properties: pale-yellow powder with a characteristic lemon odor.

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

Pharmacological properties.

Pharmacodynamics.

Paracetamol exerts analgesic and antipyretic effects. It has the ability to inhibit prostaglandin synthesis by suppressing cyclooxygenase of arachidonic acid in the central nervous system (CNS). As a result, sensitivity of the CNS to the effects of kinins and serotonin is reduced, leading to decreased pain perception. In addition, reduced prostaglandin concentrations in the hypothalamus produce an antipyretic effect. Paracetamol does not affect platelet aggregation.

Phenylephrine hydrochloride belongs to sympathomimetic amines and primarily acts directly on adrenergic receptors, predominantly affecting α-adrenergic receptors, which leads to reduction of nasal mucosa hyperemia.

Ascorbic acid (vitamin C) is an essential vitamin, deficiency of which may occur at the onset of acute viral infections.

The sedative effect of the active ingredients of the drug has not been established.

Pharmacokinetics.

Paracetamol is rapidly and almost completely absorbed in the gastrointestinal tract and evenly distributed throughout all body fluids. The rate of absorption decreases when paracetamol is taken with food. At therapeutic doses, paracetamol is only minimally bound to plasma proteins. The drug is metabolized in the liver and is almost entirely excreted in the urine, primarily as glucuronide and sulfate conjugates.

A potentially hepatotoxic intermediate metabolite, N-acetyl-p-benzoquinoneimine (NAPQI), which is formed in small amounts (~5%), is eliminated after conjugation with glutathione via cysteine or mercapturic acid. When large doses of paracetamol are administered, glutathione stores in the liver become depleted, leading to accumulation of toxic metabolites in the liver. This may result in hepatocyte damage, cell death, and acute liver failure.

Less than 5% of the administered paracetamol dose is excreted unchanged.

The average elimination half-life of paracetamol ranges from 1 to 4 hours.

Patients with impaired liver function. The elimination half-life of paracetamol in individuals with compensated liver insufficiency is the same as in healthy individuals. In cases of severe liver failure, the elimination half-life of paracetamol may be prolonged. The clinical significance of prolonged elimination half-life in patients with liver disease is unknown. However, no accumulation, hepatotoxicity, or impairment of glutathione conjugation has been observed.

Patients with impaired kidney function. Over 90% of a therapeutic dose of paracetamol is normally excreted in the urine as metabolites within 24 hours. In patients with chronic renal insufficiency, the ability to excrete polar metabolites is limited, which may lead to their accumulation. Patients with chronic renal insufficiency should have extended intervals between doses of paracetamol.

Ascorbic acid (vitamin C) is rapidly absorbed in the gastrointestinal tract and delivered to all body tissues; 25% is bound to plasma proteins. Excess ascorbic acid exceeding the body's requirements is excreted in the urine as metabolites.

Phenylephrine hydrochloride is readily and rapidly absorbed in the gastrointestinal tract. It undergoes first-pass metabolism by monoamine oxidase in the intestine and liver, resulting in a bioavailability of approximately 40%. Maximum plasma concentration is reached within 1–2 hours. The elimination half-life ranges from 2 to 3 hours. It is excreted in the urine primarily as sulfates.

Clinical characteristics.

Indications.

Short-term relief of symptoms of colds and influenza, including headache, fever, nasal congestion, sinus pain, sore throat, and body aches.

Contraindications.

Hypersensitivity to any component of the drug, severe cardiac failure, 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, prostate hypertrophy, diabetes mellitus, epilepsy, hyperthyroidism, pheochromocytoma, closed-angle glaucoma, arterial hypertension, severe forms of atherosclerosis, ischemic heart disease; sleep disorders.

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

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 regimen. Barbiturates reduce the antipyretic effect of paracetamol.

Anticonvulsant drugs (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.

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

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

Concomitant use of phenylephrine with ergot alkaloids (ergotamine and 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.

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

Special precautions for use

Before using the medicine, consult a doctor.

Contains paracetamol. Avoid concomitant use with other medicines for symptomatic treatment of cold and flu, vasoconstrictor medicines for the treatment of rhinitis, or medicinal products containing paracetamol. Concomitant use with other paracetamol-containing medicines may result in overdose. Paracetamol overdose may cause liver failure, which may require liver transplantation or lead to death. The risk of overdose is higher in patients with non-cirrhotic alcoholic liver disease.

Cases of hepatic dysfunction/failure have been reported in patients with reduced glutathione levels, such as those who are severely undernourished, suffer from anorexia, have a low body mass index, or suffer from chronic alcohol dependence or sepsis.

Patients taking warfarin; those with Raynaud's disease (which may manifest as pain in fingers and toes in response to cold or stress), hypertension, cardiovascular diseases, or impaired liver or kidney function should consult a doctor before using the medicine.

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 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 urinary 5-oxoproline levels may be useful in identifying pyroglutamic acidosis as the underlying cause of HAGMA in patients with multiple risk factors.

The medicine contains phenylephrine, which may provoke angina attacks.

One sachet (1 dose) contains 2.9 g of sucrose. This should be taken into account by patients with diabetes mellitus.

Patients with rare hereditary disorders such as fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase deficiency should not take this medicine. This medicine should not be used by patients taking other sympathomimetics (e.g., decongestants, appetite suppressants, or amphetamine-type psychostimulants). Use with caution in patients taking digoxin, cardiac glycosides, or ergot alkaloids (e.g., ergotamine, methysergide).

Patients should consult a doctor if symptoms persist for more than 5 days, worsen, or are accompanied by high fever, skin rash, or persistent headache.

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.

Use during pregnancy or breastfeeding.

Do not use the medicine during pregnancy.

Paracetamol and phenylephrine may be excreted in breast milk; therefore, if use of the medicine is necessary, breastfeeding should be discontinued.

Ability to influence reaction speed while driving or operating machinery.

The medicine may affect the ability to drive or operate complex machinery if certain adverse effects such as dizziness occur.

Method of Administration and Dosage

The medication is intended for oral use. Empty the contents of 1 sachet into a cup and add hot water (but not boiling water). Stir until completely dissolved. Cold water may be added if necessary.

Adults and children aged 12 years and older: 1 sachet. The contents of 1 sachet should be taken every 4–6 hours as needed. The minimum interval between doses should be 4 hours. The maximum daily dose is 5 sachets. Do not use the medication for more than 5 days without consulting a physician.

Do not exceed the recommended doses. The lowest effective dose should be used for the shortest possible duration.

Children

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

Overdose

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

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 alcohol abuse; glutathione deficiency states such as malnutrition, cystic fibrosis, HIV infection, undernutrition, cachexia), liver damage may occur after ingestion of 5 g or more of paracetamol.

Symptoms of liver damage appear within 12–48 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 and lead to toxic encephalopathy with impaired consciousness; in some cases, liver transplantation may be required or death may occur. 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.

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

With prolonged use at high doses, aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, and thrombocytopenia are possible.

Treatment: Immediate medical attention is required in case of paracetamol overdose, even if no symptoms are apparent. Symptoms may be limited to nausea and vomiting and may not reflect the severity of overdose or risk of organ damage. Gastric lavage should be performed, activated charcoal administered (within 1 hour of overdose), and symptomatic therapy initiated. Antidotes for paracetamol—N-acetylcysteine administered intravenously and methionine given orally—may be effective within 24 hours of overdose.

Overdose due to phenylephrine may cause effects similar to those described in the section "Adverse Reactions." Additional symptoms may include irritability, restlessness, 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 that needed to cause hepatotoxic effects from paracetamol.

Treatment: In case of overdose, gastric lavage, activated charcoal, symptomatic therapy, and use of alpha-blockers such as phentolamine in cases of severe 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. The consequences of ascorbic acid overdose may be categorized similarly to those caused by severe liver damage due to paracetamol overdose.

Adverse Reactions

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

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

Psychiatric disorders: psychomotor excitation 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, abdominal discomfort and pain, hypersalivation, decreased appetite, heartburn, diarrhea.

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 result of pyroglutamic acidosis have been observed in patients with risk factors who used paracetamol (see section "Special precautions"). Pyroglutamic acidosis may occur due to low glutathione levels in these patients.

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

Cardiac disorders: arterial hypertension, 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.

Shelf life

3 years.

Storage conditions

Store at temperatures not exceeding 25 °C, in a place inaccessible to children.

Packaging

5 g of powder in a sachet; 5 or 10 sachets in a cardboard box.

Supply classification

Over-the-counter (without prescription).

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.