Panadol

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT PANAДOL (PANADOL)

Composition:

Active ingredient: paracetamol;

1 tablet contains 500 mg of paracetamol;

Excipients: maize starch, pregelatinized starch, povidone, potassium sorbate, talc, stearic acid, hypromellose, glyceryl triacetate, carnauba wax.

Pharmaceutical form. Coated tablets.

Main physicochemical properties: white coated tablets with flat edges, with a triangular logo imprint on one side and a break line on the other.

Pharmacotherapeutic group. Analgesics and antipyretics. Anilides. Paracetamol.

ATC code N02B E01.

Pharmacological properties.

Pharmacodynamics.

Panadol tablets contain 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 doses.

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

Clinical characteristics.

Indications.

Short-term treatment of headache, toothache, muscle pain, menstrual pain, moderate pain associated with osteoarthritis, and symptoms of fever and pain due to 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, pronounced anemia, leukopenia. Age under 6 years.

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 concurrent use of paracetamol. Occasional use does not have 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. 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 concurrently with alcohol.

Paracetamol should be used with caution when administered concomitantly with flucloxacillin, as such concurrent use 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 for use").

Special precautions for use

The medicine contains paracetamol; therefore, it should not be used together with other medicines containing paracetamol, which are used, for example, to reduce fever, relieve pain, treat flu or cold symptoms, or for insomnia. Concurrent use with other paracetamol-containing medicines may lead to overdose. Paracetamol overdose can cause liver failure, which may require liver transplantation or result in death.

Patients with liver or kidney disease should consult a physician before using this medicine.

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

Cases of impaired liver function/liver failure have been reported in patients with reduced glutathione levels, such as in severe malnutrition, anorexia, low body mass index, chronic alcoholism, or sepsis. Prolonged use without medical supervision may be hazardous.

Cases of high anion gap metabolic acidosis (HAGMA) due to pyroglutamic acidosis have been reported in critically ill patients, such as those with severe renal failure or 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 in combination with flucloxacillin. 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 high anion gap metabolic acidosis due to pyroglutamic acidosis is suspected, immediate discontinuation of paracetamol is recommended, along with careful monitoring of the patient. Measurement of 5-oxoproline levels in urine may be useful in identifying pyroglutamic acidosis as the underlying cause of high anion gap metabolic acidosis in patients with multiple risk factors.

The medicine should be used only when clearly necessary.

Keep the medicine out of sight and reach of children.

Use during pregnancy or breastfeeding

As with any other medicinal product, consult a physician before using paracetamol during pregnancy. Extensive data in pregnant women do not indicate any malformative 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, but it should be administered at the lowest effective dose, for the shortest possible duration, and with the least possible frequency.

Paracetamol is excreted into breast milk, but in clinically insignificant amounts when used at recommended doses. Available published data do not contraindicate the use of the medicine during breastfeeding.

Ability to affect reaction speed when driving or operating machinery

No effect.

Method of Administration and Dosage.

The product is intended for oral administration.

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

Adults and children aged 12 years and older: 1–2 tablets up to 4 times daily (every 4–6 hours) as needed.

The interval between doses should be at least 4 hours.

Do not take more than 8 tablets (4000 mg) within 24 hours.

Children (6–11 years of age): ½–1 tablet up to 4 times daily (every 4–6 hours) as needed.

Maximum duration of use in children without medical consultation is 3 days.

Do not take more than 4 doses within 24 hours.

The interval between doses should be at least 4 hours.

Children.

Not recommended for children under 6 years of age.

Overdose.

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

There is an increased risk of paracetamol poisoning, particularly in elderly patients, children, patients with liver disease, chronic alcoholism, and chronic malnutrition.

Symptoms of overdose within the first 24 hours: pallor, nausea, vomiting, loss of appetite, and abdominal pain; however, overdose may also be asymptomatic.

Paracetamol overdose following a single ingestion by adults or children may cause reversible or irreversible necrosis of liver cells, leading to disturbances in glucose metabolism, metabolic acidosis, hepatocellular failure, encephalopathy, hemorrhages, hypoglycemia, coma, and potentially fatal outcomes. Concurrently, elevated levels of liver transaminases (AST, ALT), lactate dehydrogenase, bilirubin, and prolonged prothrombin time may occur 12–48 hours after ingestion. Liver damage is likely in adults who have taken more than the recommended amount of paracetamol. It is believed that an increased amount of a paracetamol metabolite (normally neutralized by glutathione when standard doses are used) irreversibly binds to liver tissue.

Acute kidney 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 accompanied by liver function abnormalities and hepatotoxicity.

With prolonged use of the drug in high doses, hematological side effects may include aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, and thrombocytopenia. High-dose intake may also affect the central nervous system, causing dizziness, psychomotor agitation, and disorientation. Effects on the urinary system may include 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.

Risk factors for paracetamol overdose include:

• Long-term treatment with carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. John’s wort, and other drugs that induce liver enzyme synthesis;
• Chronic alcohol abuse;
• Reduced glutathione levels, for example, due to malnutrition, fasting, cachexia, cystic fibrosis, or HIV.

In case of overdose, immediate medical assistance is required. Treatment for overdose or even suspected overdose should be initiated immediately by transporting the patient to a hospital, even if early symptoms are absent, because liver damage may not develop immediately. Plasma paracetamol concentration should be measured at least 4 hours after ingestion (earlier concentrations are unreliable).

Treatment with activated charcoal should be considered if an excessive dose of more than 150 mg/kg has been ingested within 1 hour. Treatment with N-acetylcysteine or methionine should also be considered. Symptomatic treatment is also necessary.

Side effects.

Blood and lymphatic system disorders: (rare: < 1/10000) – thrombocytopenia.

Immune system disorders: (rare: < 1/10000) – anaphylaxis, skin hypersensitivity reactions including rash, angioedema, Stevens-Johnson syndrome, and toxic epidermal necrolysis.

Respiratory, thoracic and mediastinal disorders: (rare: < 1/10000) – bronchospasm in patients sensitive to acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs.

Hepatobiliary disorders: (rare: < 1/10000) – liver function disturbances.

Metabolism and nutrition disorders: (frequency not known: cannot be estimated from available data) 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 taking paracetamol (see section "Special precautions for use"). Pyroglutamic acidosis may occur due to low glutathione levels in these patients.

Additionally, the following adverse reactions may occur after administration of paracetamol-containing products: skin itching, multiform exudative erythema, nausea, epigastric pain, hypoglycemia up to hypoglycemic coma, agranulocytosis, anemia, sulfhemoglobinemia and methemoglobinemia (cyanosis, dyspnea, chest pain), hemolytic anemia, bruising or bleeding, increased liver enzyme activity, usually without development of jaundice.

Shelf life.

5 years.

Storage conditions.

Store at temperatures not exceeding 25 °C, in a place inaccessible and out of sight of children.

Packaging.

12 tablets in a blister pack, 1 blister pack in a cardboard box.

Prescription status.

Over-the-counter.

Manufacturer.

Haleon Ireland Dungarvan Limited.

Manufacturer's address and place of business.

Knockbrack, Lisfennel, Dungarvan, X35 RY76, Ireland.