Paracetamol

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT PARACETAMOL

Composition:

Active ingredient: paracetamol;

1 tablet contains 325 mg of paracetamol;

Excipients: maize starch, powdered cellulose, pregelatinized starch, sodium starch glycolate, magnesium stearate.

Pharmaceutical form. Tablets.

Main physico-chemical properties: intact, regular, round cylindrical tablets with flat upper and lower surfaces, beveled edges, a dividing line, white or almost white in color. A greyish tint is acceptable.

Pharmacotherapeutic group.

Analgesics and antipyretics. Paracetamol. ATC code N02BE01.

Pharmacological properties.

Pharmacodynamics.

The drug contains paracetamol, an analgesic and antipyretic (pain-relieving and fever-reducing agent).

Pharmacokinetics.

Paracetamol is rapidly and almost completely absorbed in the gastrointestinal tract. Maximum plasma concentration is reached within 30–60 minutes. The half-life elimination ranges from 1 to 4 hours. It is evenly distributed throughout all body fluids. Plasma protein binding is variable. It is excreted primarily by the kidneys in the form of conjugated metabolites.

Clinical characteristics.

Indications.

Headache, toothache, muscle pain, back pain, moderate pain in arthritis, menstrual pain; relief of fever and pain symptoms associated with cold and flu.

Contraindications.

Hypersensitivity to the components of the drug, severe impairment of liver and/or kidney function, congenital hyperbilirubinemia, glucose-6-phosphate dehydrogenase deficiency, alcoholism, blood disorders, Gilbert's syndrome, marked anemia, leukopenia.

Interaction with other medicinal products and other forms of interaction.

The absorption rate of paracetamol may be increased when used 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 by prolonged simultaneous use of paracetamol. Occasional use does not show a significant effect.

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 conversion of the drug into hepatotoxic metabolites. Concurrent use of paracetamol with hepatotoxic agents increases the hepatotoxic effects of the drugs.

Concomitant use of high doses of paracetamol with isoniazid increases the risk of developing hepatotoxic syndrome.

Caution is advised when using paracetamol concomitantly with flucloxacillin, as this combination is associated with metabolic acidosis with a high anion gap due to pyroglutamic acidosis, particularly in patients with risk factors (see section "Special precautions for use").

Paracetamol reduces the effectiveness of diuretics.

Do not use concurrently with alcohol.

Special precautions for use

The product contains paracetamol; therefore, it should not be used together with 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 products may lead to overdose. Paracetamol overdose may cause liver failure, which could result in liver transplantation or death.

In patients with liver or kidney disease, consult a physician before using this product.

It should be noted that patients with liver disease have an increased risk of hepatotoxic effects of paracetamol. The 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 before using paracetamol.

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

In patients with reduced glutathione levels, for example due to severe infections such as sepsis, 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.

If symptoms persist, consult a physician.

If headaches become persistent, 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 and sepsis, as well as in patients with inadequate nutrition or other causes 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 high anion gap metabolic acidosis due to pyroglutamic acidosis is suspected, immediate discontinuation of paracetamol is recommended, along with close monitoring of the patient. Measurement of urinary 5-oxoproline levels may be helpful in identifying pyroglutamic acidosis as the underlying cause of high anion gap metabolic acidosis in patients with multiple risk factors.

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

Do not exceed the recommended dosage.

Keep the product out of sight and reach of children.

Use during pregnancy or breastfeeding

Before using this product during pregnancy or breastfeeding, consult a physician.

The product may be used during this period only if the expected benefit to the mother outweighs the potential risk to the fetus or infant.

Paracetamol passes into breast milk, but in clinically insignificant amounts. Available published data do not contain contraindications to breastfeeding.

Effect on ability to drive or operate machinery

No effect.

Dosage and Administration

The product is intended for oral use.

Do not exceed the recommended dose. The lowest effective dose required to achieve the therapeutic effect should be used.

Adults and children aged 12 years and older: 2 tablets every 4–6 hours, but not more than 10 tablets per day.

Children aged 6 to 12 years: 1 tablet every 4–6 hours, but not more than 5 tablets per day.

The single dose of paracetamol is 10–15 mg/kg body weight; the maximum daily dose is 60 mg/kg body weight.

The interval between doses should be at least 4 hours.

The maximum duration of treatment without medical advice is 3 days.

Do not take together with other medicinal products containing paracetamol.

Children.

Not recommended for children under 6 years of age.

Overdose.

Paracetamol overdose may cause liver failure, which can lead to liver transplantation or death. 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, which is the maximum daily dose taken from other paracetamol-containing products.

In patients with risk factors (chronic use of carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. John’s wort, or other drugs inducing liver enzymes; alcohol abuse; glutathione system deficiency (e.g., malnutrition, cystic fibrosis, HIV infection, fasting, cachexia)), ingestion of 5 g or more of paracetamol may lead to liver damage.

In case of overdose, immediate medical attention is required. Treatment should be initiated without delay. The patient should be taken to hospital even if early symptoms of overdose are absent.

Symptoms within the first 24 hours: pallor, nausea, vomiting, loss of appetite, and abdominal pain. Liver damage may become apparent 12–48 hours after overdose. Glucose metabolism disturbances and metabolic acidosis may occur. In severe poisoning, liver failure may progress to encephalopathy, hemorrhage, hypoglycemia, coma, and may be fatal. Acute renal failure 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 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. With high-dose intake, dizziness, psychomotor agitation, and disorientation may occur from the central nervous system; from the urinary system – nephrotoxicity (renal colic, interstitial nephritis, capillary necrosis).

Symptoms may be limited to nausea and vomiting or may not reflect the severity of overdose or risk of organ damage. Treatment with activated charcoal should be considered if the excessive dose of paracetamol was ingested 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 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, methionine may be used as an appropriate alternative in remote areas outside hospital settings.

Side effects

Allergic reactions: anaphylaxis, hypersensitivity reactions including skin itching, rashes on the skin and mucous membranes (usually generalized rashes, erythematous rashes, urticaria), angioneurotic edema, multiform exudative erythema (including Stevens–Johnson syndrome), Lyell’s syndrome.

Gastrointestinal system disorders: nausea, epigastric pain.

Endocrine system disorders: hypoglycemia, up to hypoglycemic coma.

Blood and lymphatic system disorders: thrombocytopenia, agranulocytosis, anemia, sulfhemoglobinemia and methemoglobinemia (cyanosis, dyspnea, chest pain), hemolytic anemia, bruising or bleeding.

Respiratory system disorders: bronchospasm in patients sensitive to acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs.

Hepatobiliary system disorders: liver function abnormalities, increased liver enzyme activity, usually without development of jaundice.

Metabolism and nutrition disorders: metabolic acidosis with high anion gap (frequency unknown).

Description of selected side effects

Metabolic acidosis with high anion gap. Cases of metabolic acidosis with high anion gap due to pyroglutamic acidosis have been observed in patients with risk factors who were taking paracetamol (see section "Special precautions"). Pyroglutamic acidosis may occur due to low glutathione levels in these patients.

Reporting suspected adverse reactions

Reporting suspected adverse reactions after drug registration is highly important. It allows continuous monitoring of the benefit-risk balance of the medicinal product. Medical and pharmaceutical professionals, as well as patients or their legal representatives, should report all suspected adverse reactions and lack of drug efficacy via the Automated Pharmacovigilance Information System at: https://aisf.dec.gov.ua.

Shelf life. 3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach and sight of children.

Packaging.

10 tablets in blisters;

10 tablets in a blister, 5 or 10 blisters per pack.

Release category.

Over-the-counter: tablets № 10.

By prescription only: tablets № 50 (5×10), № 100 (10×10).

Manufacturer: JSC "Lubnipharm".

Manufacturer's address and location of business activity:

16, Barvinkova Street, Lubny, Poltava region, 37500, Ukraine.