Paracetamol

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

Composition:

Active ingredient: paracetamol;

5 ml of syrup contains 120 mg of paracetamol;

Excipients: sorbitol solution, non-crystallizing (E 420), glycerol, propylene glycol, sodium saccharin, potassium sorbate, aspartame (E 951), flavoring "Orange ASE 896", azo dye "Yellow FCF" (E 110), purified water.

Pharmaceutical form. Syrup.

Main physicochemical properties: orange-colored liquid with a characteristic orange odor, sweet to taste.

Pharmacotherapeutic group. Analgesics and antipyretics. Anilides. Paracetamol.

ATC code N02B E01.

Pharmacological properties.

Pharmacodynamics.

The drug contains paracetamol – an analgesic and antipyretic (pain-relieving and fever-reducing agent). The effect is based on inhibition of prostaglandin synthesis in the central nervous system.

Pharmacokinetics.

Paracetamol is rapidly and almost completely absorbed in the gastrointestinal tract and distributed into most body tissues. Plasma protein binding of paracetamol is minimal when administered at therapeutic concentrations.

Paracetamol is primarily metabolized in the liver and excreted in the urine as metabolites. The mean elimination half-life in plasma after oral administration is approximately 2.3 hours.

Clinical characteristics.

Indications.

Pain associated with teething, toothache, sore throat, fever in colds, influenza and childhood infections such as chickenpox, whooping cough, measles, mumps.

The drug is also recommended for the treatment of post-vaccination hyperthermia in infants aged 3 months and older.

Contraindications.

Hypersensitivity to any component of the drug, severe impairment of liver and/or kidney function, congenital hyperbilirubinemia, glucose-6-phosphate dehydrogenase deficiency, alcoholism, blood disorders, severe anemia, leukopenia, Gilbert's syndrome, phenylketonuria. Patients with rare hereditary fructose intolerance. Age under 3 months.

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, with an increased risk of bleeding, may be enhanced during prolonged concomitant use of paracetamol. Occasional use has no significant effect. Barbiturates reduce the antipyretic effect of paracetamol.

Anticonvulsant drugs (including phenytoin, barbiturates, carbamazepine), which stimulate the activity of hepatic microsomal enzymes, may enhance the hepatotoxic effect of paracetamol due to increased conversion of the drug into hepatotoxic metabolites. Concomitant use of paracetamol with hepatotoxic agents increases the hepatotoxic effects of the drugs. Concurrent use of high doses of paracetamol with isoniazid increases the risk of developing hepatotoxic syndrome.

Paracetamol reduces the effectiveness of diuretics. Do not use concomitantly with alcohol.

High concentrations of paracetamol may interfere with laboratory test results for blood glucose using the oxidase-peroxidase method, and for uric acid when using the method with phosphotungstic acid.

Paracetamol should be used with caution 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").

Special precautions for use.

Do not use this medicinal product together with any other medicinal products containing paracetamol, such as those used for fever reduction, pain relief, flu and cold symptoms, or insomnia. Concurrent use with other paracetamol-containing medicinal products may lead to overdose. Paracetamol overdose can cause liver failure, which may necessitate liver transplantation or result in death.

Consult a physician before using this medicinal product in cases of liver or kidney disease, or in patients with reduced glutathione levels.

Hepatic function impairment/liver failure has been reported in patients with reduced glutathione levels, such as those with severe malnutrition, anorexia, low body mass index, chronic alcoholism, or sepsis.

If glomerular filtration rate is below 10 mL/min, the dosing interval should be extended to 8 hours.

Consult a physician before using this product if the patient is taking warfarin or similar anticoagulant agents.

It should be noted that patients with liver disease have an increased risk of hepatotoxic effects of paracetamol. Treatment should be discontinued if acute viral hepatitis is diagnosed.

The medicinal product may affect laboratory test results for blood glucose and uric acid levels.

Patients who take analgesics daily for mild forms of arthritis should consult a physician.

Cases of high anion gap metabolic acidosis (HAGMA) due to 5-oxoproline (pyroglutamic) acidosis have been reported in patients with severe conditions such as severe renal failure or sepsis, or in patients with poor nutrition or other sources of glutathione deficiency (e.g., chronic alcoholism), who were treated with therapeutic doses of paracetamol for prolonged periods or in combination with flucloxacillin. If HAGMA due to pyroglutamic acidosis is suspected, immediate discontinuation of paracetamol and close monitoring are recommended. Measurement of urinary 5-oxoproline levels may be helpful in identifying pyroglutamic acidosis as the underlying cause of HAGMA in patients with multiple risk factors.

If symptoms do not improve or worsen after 3 days of treatment, consult a physician. Consult a physician before using paracetamol if a child is taking any other medicinal products.

The medicinal product contains aspartame, a phenylalanine source, which may be harmful for patients with phenylketonuria.

The medicinal product contains sorbitol. If a child has intolerance to certain sugars, consult a physician before using Paracetamol.

The product contains the azo dye "Yellow Sunset FCF" (E 110), which may cause allergic reactions.

Prolonged use without medical consultation may be hazardous. Excessively long-term use of the medicinal product or use in high doses may lead to liver and kidney function disorders, as well as blood abnormalities.

Seek immediate medical attention in case of overdose, even if the child feels well, due to the risk of liver damage.

Do not exceed the recommended doses.

Keep the medicinal product out of sight and reach of children.

Use during pregnancy or breastfeeding.

The medicinal product is intended for use in pediatrics.

Paracetamol may be used during pregnancy if clinically necessary. Consult a physician before using the medicinal product during pregnancy or breastfeeding.

Extensive data from pregnant women do not indicate teratogenic or fetal/neonatal toxicity. Epidemiological studies on neurodevelopmental outcomes in children exposed to paracetamol in utero have not provided conclusive evidence. If clinically necessary, paracetamol may be used during pregnancy; however, it should be administered at the lowest effective dose and for the shortest possible duration.

Paracetamol crosses the placental barrier and is excreted into breast milk.

Ability to affect reaction speed when driving or operating machinery.

The product is intended for pediatric use.

No effect on reaction speed during machine operation or use of other machinery is expected.

Method of Administration and Dosage

The dose of paracetamol depends on the child's age. Do not exceed the recommended dose. The lowest effective dose required to achieve the therapeutic effect should be used. Do not take together with other medicinal products containing paracetamol. The interval between doses should be at least 4 hours.

For relief of post-vaccination reactions. Children aged from 3 months to 12 years: the single dose of paracetamol is 10–15 mg/kg body weight; the maximum daily dose is 60 mg/kg body weight. If a second dose is needed, it may be administered no sooner than 4 hours after the first. If elevated temperature persists after the second dose, consult a physician.

For other cases of pain and fever. Children aged from 3 months to 12 years: the single dose of paracetamol is 10–15 mg/kg body weight. If a second dose is needed, it may be administered no sooner than 4 hours after the first, with a maximum daily dose of 60 mg/kg body weight. Do not take more than 4 doses within 24 hours. The maximum duration of use without consulting a physician is 3 days.

The table below provides approximate dosing recommendations based on the child's body weight and age. However, in all cases, ensure that the dosage does not exceed 10–15 mg of paracetamol per kilogram of body weight of the child.

For convenient dosing of the syrup, the dosing cup is graduated at 2.5 mL, 5 mL, 10 mL, 15 mL, and 20 mL.

The bottle should be shaken for 10 seconds before use.

If the child was born prematurely, consult a doctor before administering the medication.

If the child has impaired kidney or liver function, consult a doctor before administering this medicinal product. This is due to the presence of paracetamol in the formulation.

Children.

The medicinal product is not recommended for children under 3 months of age.

To be administered to children aged from 3 months to 12 years.

Overdose.

Paracetamol overdose may cause liver failure, which could necessitate liver transplantation or result in death. Clinical experience shows that signs of liver damage after paracetamol overdose usually appear within 24–48 hours after ingestion and peak at 4–6 days.

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. 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 deficiency (malnutrition, cystic fibrosis, HIV infection, fasting, cachexia)), ingestion of 5 g or more of paracetamol may lead to liver damage.

Symptoms within the first 24 hours: pallor, nausea, vomiting, loss of appetite, and abdominal pain. Glucose metabolism disturbances and metabolic acidosis may occur. In severe poisoning, liver failure may progress to encephalopathy, hemorrhage, hypoglycemia, coma, and death. Acute kidney failure with acute tubular necrosis may manifest as severe flank pain, hematuria, proteinuria, and may develop even in the absence of severe liver damage. Cardiac arrhythmias and acute pancreatitis have also been reported, usually associated with liver function disturbances and hepatotoxicity.

With prolonged use of the drug in high doses, aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, and thrombocytopenia may develop from the hematopoietic system. From the central nervous system – dizziness, psychomotor agitation, and disorientation; from the urinary system – nephrotoxicity (renal colic, interstitial nephritis, capillary necrosis).

In case of overdose, prompt medical assistance 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 risk of organ damage. Treatment with activated charcoal should be considered if the excessive dose of paracetamol was taken within 1 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 the maximum protective effect is achieved when 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 guidelines. In the absence of vomiting, oral methionine may be used as an appropriate alternative in remote areas outside the hospital.

Adverse reactions.

Adverse reactions to paracetamol occur very rarely. The frequency of adverse reactions is presented according to the following classification: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1000, <1/100), rare (≥1/10000, <1/1000), very rare (<1/10000), frequency not known (cannot be estimated based on available data).

*Cases of metabolic acidosis with a 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.

The medicinal product may have a slight laxative effect.

Reporting of adverse reactions following marketing authorization is of great importance. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical personnel, as well as patients or their legal representatives, are encouraged to 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. 3 years.

After first opening of the packaging, the product is suitable for 3 months.

Do not use after the expiry date stated on the packaging.

Storage conditions.

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

Packaging.

90 ml in a bottle with a dosing cup in a carton.

Supply classification. Over-the-counter.

Manufacturer.

LLC "DKP "Pharmaceutical Factory".

Manufacturer's address and location of business activity.

4, Korolova St., village Stanishivka, Zhytomyr district, Zhytomyr region, 12430, Ukraine.