Panadol advans

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT PANADOL ADVANCE

Composition:

Active ingredient: paracetamol;

One tablet contains 500 mg of paracetamol;

Excipients: pregelatinized starch, povidone, calcium carbonate, alginic acid, crospovidone (type A), magnesium stearate, colloidal anhydrous silicon dioxide, Opadry White (YS-1-7003) (titanium dioxide (E 171), hypromellose, polyethylene glycol 400, polysorbate 80), carnauba wax.

Pharmaceutical form. Film-coated tablets.

Main physicochemical characteristics: film-coated tablet, capsule-shaped, white to almost white, with convex edges. On one side, the letter "P" is embossed in a circle; on the other side, there is a dividing line, with the symbol «-» embossed on both sides of the line.

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). The effect is based on inhibition of prostaglandin synthesis in the central nervous system. Clinical studies have shown that pain relief after tooth extraction begins 15 minutes after administration of 2 tablets of the drug.

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.

The drug contains a disintegration system that accelerates the absorption of active substances. Study data show that the drug begins to disintegrate in the gastrointestinal tract within 5 minutes after administration, and paracetamol is detected in blood plasma as early as 10 minutes after administration.

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

Clinical characteristics.

Indications.

The drug provides moderate analgesic and antipyretic effects and is recommended for short-term treatment of headache, including migraine and tension headache, pain associated with osteoarthritis, rheumatic pain, neuralgia, muscle pain, back pain, menstrual pain in women, fever and pain following vaccination, pain after dental procedures and tooth extraction, toothache, as well as symptoms of cold and flu such as fever, malaise, and sore throat.

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. Age under 6 years.

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 with cholestyramine. The anticoagulant effect of warfarin and other coumarins, increasing the risk of bleeding, may be enhanced during prolonged simultaneous 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 these drugs. Simultaneous use of high doses of paracetamol with isoniazid increases the risk of developing hepatotoxic syndrome.

Paracetamol reduces the efficacy of diuretics. Do not use concurrently with alcohol.

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

Special precautions for use.

The product contains paracetamol; therefore, it should not be used in combination with other medicinal products containing paracetamol, which are used, for example, to reduce fever, treat pain, symptoms of influenza and colds, or insomnia. Concurrent use with other paracetamol-containing products may lead to overdose. Paracetamol overdose can cause liver failure, which may require liver transplantation or may result in death.

In patients with liver or kidney disease, medical advice should be sought before using the product.

It should be noted that in patients with liver disease the risk of hepatotoxic effects of paracetamol is increased; 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 use.

Cases of liver function impairment / liver failure have been reported in patients with reduced glutathione levels, such as in severe malnutrition, anorexia, low body mass index, or chronic alcoholism. 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, 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. If these symptoms occur, immediate medical attention should be sought.

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's condition. 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.

If symptoms do not resolve, medical advice should be sought.

Keep the product out of sight and reach of children.

Use during pregnancy or breastfeeding.

Studies have not shown any risk to animals or humans regarding intrauterine fetal development, the course of pregnancy, lactation, or to breastfed infants. However, before using the product during pregnancy, consultation with a physician is necessary, and the recommended dosage and administration instructions should be strictly followed.

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

Effect on the 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 therapeutic effect 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): ½–1 tablet up to 4 times daily (every 4–6 hours) as needed.

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

The 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. Liver damage may occur 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 depletion (e.g., due to 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 must be initiated promptly. The patient should be taken to a hospital even if early symptoms of overdose are not present.

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. Metabolic disturbances such as glucose metabolism disorders and metabolic acidosis may occur. In severe poisoning, liver failure may progress to encephalopathy, hemorrhage, hypoglycemia, coma, and may be fatal. Acute kidney injury 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 accompanied by liver function abnormalities and hepatotoxicity.

With prolonged use of high doses, hematological disorders may include aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, and thrombocytopenia. Central nervous system effects may include dizziness, psychomotor agitation, and disorientation. Renal system effects may include nephrotoxicity (renal colic, interstitial nephritis, cortical necrosis).

Symptoms may be limited to nausea and vomiting, or may not reflect the severity of overdose or risk of organ damage. Administration of activated charcoal should be considered if the excessive dose of paracetamol was taken within the last hour. Plasma paracetamol concentration should be measured at least 4 hours after ingestion (earlier measurements are unreliable). Treatment with N-acetylcysteine may be administered within 24 hours of paracetamol ingestion, but the maximum protective effect is achieved when administered within 8 hours of ingestion. The efficacy of the antidote decreases significantly after this time. If required, N-acetylcysteine should be administered intravenously according to current guidelines. In the absence of vomiting, oral methionine may be used as an appropriate alternative in remote areas outside hospital settings.

Adverse Reactions

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

Immune system disorders: (Rare: < 1/10000) – anaphylaxis, hypersensitivity skin 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 abnormalities.

Metabolism and nutrition disorders: (Frequency unknown: cannot be estimated from available data) – metabolic acidosis with high anion gap.

Cases of high anion gap metabolic acidosis 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.

Other adverse reactions reported after administration of paracetamol-containing products include: pruritus, erythema multiforme, 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.

2 years.

Storage conditions.

Store at a temperature not exceeding 30 °C. Keep out of sight and reach of children.

Packaging.

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

Prescription status.

Over-the-counter (without prescription).

Manufacturer.

GlaxoSmithKline Dungarvan Limited, Ireland.

Manufacturer's name and address.

Knockbrack, Dungarvan, Co. Waterford, Ireland.