Limontar

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT LIMONTAR (LIMONTAR)

Composition:

Active substances: paracetamol, phenylephrine hydrochloride, ascorbic acid;

One sachet contains: paracetamol 600 mg, ascorbic acid 40 mg, phenylephrine hydrochloride 10 mg;

Excipients: citric acid, sodium citrate, silicon dioxide colloidal anhydrous, sucrose, saccharin, flavor "Mint", flavor "Lemon", colorant "Quinoline yellow" (E104).

Pharmaceutical form. Powder for oral solution.

Main physicochemical characteristics: pale yellowish-white powder with a mint and lemon odor.

Pharmacotherapeutic group. Analgesics and antipyretics. Paracetamol combinations without psychotropic agents. ATC code N02BE51.

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.

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 vitamin C loss that may occur at the onset of a viral infection. It is known that ascorbic acid plays an important role in mediating the body's protective functions against infection and is necessary for normal T-lymphocyte function and effective phagocytic activity of leukocytes.

Pharmacokinetics. Paracetamol is well absorbed from the gastrointestinal tract, metabolized in the liver, and excreted in the urine mainly as glucuronide and sulfate conjugates.

Ascorbic acid is readily absorbed from the gastrointestinal tract and 25% is protein-bound in the blood. 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, malaise and body aches, nasal congestion, sinusitis and associated pain, acute catarrhal rhinitis, and fever.

Contraindications. Hypersensitivity to any component of the medicinal product. Concomitant use of other sympathomimetic decongestants (even of local action). Severe impairment of liver and/or kidney function, 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 (particularly severe anemia, leukopenia), acute pancreatitis, epilepsy, closed-angle glaucoma. Do not use concurrently or within 2 weeks after administration of monoamine oxidase inhibitors (MAOIs), as well as with tricyclic antidepressants, beta-blockers, and other antihypertensive agents.

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 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 effect of paracetamol due to increased formation of hepatotoxic metabolites. Concomitant use of high-dose paracetamol with isoniazid increases the risk of hepatotoxic syndrome. Do not use concomitantly with alcohol.

Paracetamol should be used with caution concomitantly with flucloxacillin, as co-administration has been associated with metabolic acidosis with a high anion gap as a result of pyroglutamic acidosis, particularly in patients with risk factors (see section "Special precautions for use").

Caution is required when using phenylephrine in the following combinations:

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 developing crystalluria during treatment with salicylates. Antidepressants, anti-Parkinson agents, antipsychotic drugs, and phenothiazine derivatives increase the risk of urinary retention, dry mouth, and constipation. Ascorbic acid may be taken only 2 hours after deferoxamine injection, as their simultaneous administration increases iron toxicity, especially in the myocardium. Prolonged use of high doses in patients undergoing disulfiram treatment inhibits the disulfiram-alcohol reaction.

Special precautions for use.

Do not use in liver or kidney disease 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 treatment of rhinitis, or medicinal products containing paracetamol.

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

Cases of high anion gap metabolic acidosis (HAGMA) due to 5-oxoprolinuria (pyroglutamic acidosis) have been reported in patients with severe underlying 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 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's condition. Measurement of 5-oxoproline in urine may be useful in identifying pyroglutamic acidosis as the underlying cause of HAGMA in patients with multiple risk factors.

Do not use concomitantly with sympathomimetics (such as decongestants, appetite suppressants, or amphetamine-like psychostimulants).

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

If prolonged use of the product is recommended by a physician, monitoring of liver function and peripheral blood count is required. Long-term 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 those with severe cachexia, 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.

One sachet of powder 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 by patients with diabetes mellitus. This medicinal product should not be taken by patients with rare hereditary conditions such as fructose intolerance, glucose-galactose malabsorption, or sucrase-isomaltase deficiency.

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

Effect on ability to drive or operate machinery. If adverse effects such as dizziness occur, driving vehicles or operating complex machinery should be avoided.

Method of Administration and Dosage

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. Add cold water if necessary. Take warm.

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 — 6 sachets. Maximum duration of treatment without consulting a doctor — 7 days.

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

Use the lowest effective dose.

Children. Do not use in children under 12 years of age.

Overdose

Paracetamol

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

Liver damage is possible 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; 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. Disturbances in glucose metabolism and metabolic acidosis may occur, as well as cardiac arrhythmias.

In severe poisoning, liver dysfunction may progress to encephalopathy with impaired consciousness, hemorrhages, hypoglycemia, cerebral edema, and in some cases, result in death. Acute kidney dysfunction 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 assistance is required. The patient must be taken to hospital immediately, even if early symptoms of overdose are absent. 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. Treatment with activated charcoal may be beneficial if the excessive dose of paracetamol was taken within 1 hour. Paracetamol plasma 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 the maximum protective effect is achieved when it is administered within 8 hours after ingestion. The efficacy of the antidote decreases sharply after this time. If necessary, intravenous N-acetylcysteine should be administered according to current dosing recommendations. In the absence of vomiting, oral methionine may be used as an appropriate alternative in remote areas outside hospital settings. Treatment of severe liver dysfunction occurring more than 24 hours after ingestion should be managed under the guidance of a toxicologist or hepatologist.

Phenylephrine

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

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

Ascorbic Acid

High doses of ascorbic acid (over 3000 mg) may cause temporary 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

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

Immune system disorders: anaphylaxis, skin allergic reactions (including rash, angioedema, Stevens-Johnson syndrome/toxic epidermal necrolysis), hypersensitivity reactions.

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: anxiety, nervous excitement, irritability, sleep disturbances.

Neurological disorders: headache, dizziness, insomnia.

Ear and labyrinth disorders: tinnitus.

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

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

Cardiovascular disorders: increased blood pressure, tachycardia or reflex bradycardia, palpitations, dyspnea.

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: micturition disturbances, urinary retention (more common in patients with prostatic hypertrophy), renal colic, nephrotoxic effect.

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"). Pyroglutamic acidosis may occur due to low glutathione levels in these patients.

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

The medicinal product may have a slight laxative effect.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after medicine authorization is of great importance. It allows ongoing monitoring of the benefit-risk balance of the medicine. Healthcare professionals, patients, and their legal representatives should report all suspected adverse reactions and lack of efficacy through the Automated Pharmacovigilance Information System at the following link: https://aisf.dec.gov.ua.

Shelf life. 2 years.

Storage conditions. Store in original packaging at a temperature not exceeding 25 °C.
Keep out of reach of children.

Packaging. 5 g in sachets. 10 or 30 sachets per cardboard box.

Availability. Over-the-counter.

Manufacturer. ASTRAFARM LLC, Ukraine.

Manufacturer's address and location of its business activity. 6, Kyivska St., Vyshneve, Bucha District, Kyiv Region, 08132, Ukraine.