Panadol extra
Ukraine
Table of Contents
INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT PANADEXTRA (PANADOLEXTRA)
Composition:
Active substances: 1 tablet contains 500 mg of paracetamol and 65 mg of caffeine;
Excipients: pregelatinized starch, corn starch, povidone, potassium sorbate, talc, stearic acid, sodium croscarmellose, hypromellose, glycerol triacetate.
Pharmaceutical form. Coated tablets.
Main physicochemical properties: white, capsule-shaped coated tablets with flat edges, with a triangular logo and the symbol "+" embossed on one side and no embossing on the other side.
Pharmacotherapeutic group.
Analgesics and antipyretics. Paracetamol combinations without psychotropic agents.
ATC code N02BE51.
Pharmacological properties.
Pharmacodynamics.
Paracetamol is an analgesic and antipyretic agent. Its effect is based on the inhibition of prostaglandin synthesis in the central nervous system. Paracetamol is partially suitable for patients contraindicated for salicylates.
Caffeine acts as a stimulant, increasing the effectiveness of paracetamol.
Pharmacokinetics.
Paracetamol and caffeine are rapidly absorbed in the gastrointestinal tract and distributed into most body tissues. Plasma protein binding of paracetamol is minimal when administered at therapeutic doses.
Paracetamol and caffeine are primarily metabolized in the liver and excreted in urine as metabolites.
Clinical characteristics.
Indications.
Symptomatic treatment of pain and fever of mild to moderate severity, for example, headache, including migraine, toothache, neuralgia, rheumatic pain, menstrual pain; for relief of symptoms of cold and flu, sore throat.
Contraindications.
Hypersensitivity to paracetamol, caffeine, or any other component of the drug in medical history; severe impairment of liver and/or kidney function; congenital hyperbilirubinemia; glucose-6-phosphate dehydrogenase deficiency; alcoholism; blood disorders, pronounced anemia, leukopenia; conditions of increased excitation, sleep disorders, epilepsy; marked increase in blood pressure, organic cardiovascular diseases, including severe atherosclerosis, severe hypertension; decompensated heart failure, acute myocardial infarction, paroxysmal tachycardia, hyperthyroidism, acute pancreatitis, severe forms of diabetes mellitus, glaucoma; age over 60 years.
Do not use concomitantly with monoamine oxidase inhibitors (MAOIs) and within 2 weeks after discontinuation of MAOIs.
Contraindicated in patients taking tricyclic antidepressants or beta-blockers.
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.
Long-term concurrent use of the drug with acetylsalicylic acid or other nonsteroidal anti-inflammatory agents may lead to kidney damage.
The anticoagulant effect of warfarin and other coumarins, with an increased risk of bleeding, may be enhanced due to prolonged regular use of paracetamol. Single doses do not show a 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 formation of hepatotoxic metabolites. Concurrent use of paracetamol with hepatotoxic agents may increase the likelihood of paracetamol accumulation, as well as increase the hepatotoxic effects of both paracetam0l and these agents. Concurrent use of high doses of paracetamol with isoniazid increases the risk of developing hepatotoxic syndrome. Paracetamol reduces the effectiveness of diuretics.
Paracetamol increases plasma levels of acetylsalicylic acid and chloramphenicol. Probenecid affects the plasma concentration of paracetamol and its excretion.
Inducers of hepatic microsomal enzymes (rifampicin and phenobarbital) increase the toxicity of paracetamol, since during its biotransformation a larger amount of toxic epoxide is formed. Paracetamol may reduce the bioavailability of lamotrigine, possibly reducing its effect due to likely induction of its hepatic metabolism. Concurrent use of paracetamol and zidovudine increases the risk of developing neutropenia.
Paracetamol should be used with caution when administered concomitantly with floxacillin, as concurrent use has been associated with metabolic acidosis with a high anion gap as a result of pyroglutamic acidosis, especially in patients with risk factors (see section "Special precautions").
Do not use concomitantly with alcohol.
Concurrent use of caffeine with MAO inhibitors may cause dangerous elevation of blood pressure. Caffeine enhances the effect (improves bioavailability) of analgesic-antipyretic agents, potentiates the effects of xanthine derivatives, alpha- and beta-adrenergic agonists, psychostimulants.
Cimetidine, hormonal contraceptives, isoniazid enhance the action of caffeine.
Caffeine reduces the effect of opioid analgesics, anxiolytics, hypnotics and sedatives; it is an antagonist of anesthetic agents and other drugs that suppress the CNS, a competitive antagonist of adenosine and ATP preparations. Concurrent use of caffeine with ergotamine improves absorption of ergotamine from the gastrointestinal tract; with thyroid-stimulating agents – increases thyroid effect.
Caffeine may enhance lithium excretion from the body. Therefore, concomitant use of the drug with lithium preparations is not recommended.
Special precautions for use
The product contains paracetamol; therefore, it should not be used in combination with other medicinal products containing paracetamol, such as those used for fever reduction, pain relief, cold and flu symptoms, or insomnia. Concurrent use with other paracetamol-containing products may lead to overdose. Paracetamol overdose can cause liver failure, which may necessitate liver transplantation or result in fatal outcomes.
Patients with liver or kidney disease should consult a physician before using this product. Restrictions on use in such patients are primarily due to the presence of paracetamol. In patients with liver disease, the risk of hepatotoxic effects of paracetamol is increased.
Alcoholic beverages must not be consumed during treatment. Paracetamol may be hepatotoxic at doses exceeding 6–8 g per day; however, adverse effects on the liver may also occur at significantly lower doses when alcohol is consumed, when hepatic enzyme inducers or other hepatotoxic substances are used, or in patients with non-cirrhotic alcoholic liver disease. Chronic alcohol consumption significantly increases the risk of hepatotoxic effects of paracetamol. In patients with impaired liver function and in those taking high doses of paracetamol over a prolonged period, regular monitoring of liver function tests is recommended.
When treating patients on oral anticoagulants, monitoring of prothrombin time is required if high doses of paracetamol are taken concomitantly.
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 Panadol Extra.
Cases of impaired liver function/liver failure have been reported in patients with reduced glutathione levels, such as those with severe malnutrition, anorexia, low body mass index, chronic alcoholism, or sepsis.
In patients 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.
If symptoms persist, medical advice should be sought.
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, or in patients with malnutrition or other sources of glutathione deficiency (e.g., chronic alcoholism), who were treated with paracetamol at therapeutic doses over a prolonged period 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. Measurement of 5-oxoproline levels in urine may be useful in identifying pyroglutamic acidosis as the underlying cause of HAGMA in patients with multiple risk factors.
During treatment with this product, excessive consumption of beverages containing caffeine (such as coffee, tea, and certain other drinks) is not recommended. This may lead to sleep disturbances, tremor, palpitations, nervousness, irritability, and discomfort behind the sternum.
Keep the product out of sight and reach of children.
Use during pregnancy or breastfeeding
The use of this product during pregnancy is not recommended due to an increased risk of spontaneous abortion associated with caffeine use.
The use of this product during breastfeeding is not recommended. Paracetamol and caffeine pass into breast milk, but in clinically insignificant amounts when taken at recommended doses. Caffeine in breast milk may have a stimulating effect on infants during breastfeeding, although significant toxicity has not been observed.
Ability to affect reaction speed when driving or operating machinery
The likelihood of effect is negligible.
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 for the shortest possible duration.
The interval between doses should be at least 4 hours.
Adults (including elderly patients) and children aged 15 years and older: 1–2 tablets every 4–6 hours as needed (one tablet for patients weighing 34–60 kg; 2 tablets for patients weighing more than 60 kg).
Do not take more than 8 tablets (4000 mg paracetamol / 520 mg caffeine) within 24 hours.
During prolonged therapy (more than 10 days), the daily dose should not exceed 2.5 g of paracetamol.
The maximum single dose is 1 g of paracetamol (2 tablets).
Children aged 12–15 years: 1 tablet as needed, up to a maximum of 6 times daily, with a minimum interval of 4–6 hours.
Do not take more than 6 tablets (3000 mg paracetamol / 390 mg caffeine) within 24 hours. The maximum single dose is 1 tablet.
Children
The product is not recommended for children under 12 years of age.
Overdose
Paracetamol
Paracetamol overdose can cause liver failure, which may require liver transplantation or result in death. Acute pancreatitis has been reported, usually occurring concurrently with liver dysfunction and hepatotoxicity. Liver damage may occur in adults who have ingested 6–8 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 (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 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. Clinical experience shows that signs of liver damage typically become apparent 24–48 hours after overdose and peak usually between 4 and 6 days. Metabolic disturbances such as hypoglycemia 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 present as severe flank pain, hematuria, proteinuria, and may develop even in the absence of severe liver damage. Cardiac arrhythmias have also been reported.
With prolonged use of high doses, hematological disorders such as aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, and thrombocytopenia may develop. High doses may also affect the central nervous system, causing dizziness, psychomotor agitation, and disorientation. Urinary system effects may include nephrotoxicity (renal colic, interstitial nephritis, capillary necrosis).
Symptoms of overdose may be limited to nausea and vomiting or may not reflect the severity of overdose or risk of organ damage. Immediate medical intervention is essential in case of overdose, even if no symptoms are present. If overdose is confirmed or suspected, the patient must be taken immediately to the nearest medical facility capable of providing emergency care and appropriate treatment. This should be done even in the absence of symptoms due to the risk of delayed liver injury. Administration of activated charcoal should be considered if excessive paracetamol was ingested within the past hour. Plasma paracetamol concentration should be measured at least 4 hours (or later) after ingestion (earlier measurements are unreliable). Treatment with N-acetylcysteine may be administered within 24 hours of paracetamol ingestion, but 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 the recommended dosage. In the absence of vomiting, oral methionine may be used as an alternative in remote areas outside hospital settings.
Caffeine
Caffeine overdose may cause epigastric pain, vomiting, diuresis, rapid breathing, tachycardia, or cardiac arrhythmia, and may affect the central nervous system (insomnia, restlessness, nervous excitation, anxiety, agitation, apprehension, dizziness, irritability, mood disturbance, tremor, seizures). Clinically significant symptoms of caffeine overdose may also be associated with severe paracetamol-induced liver injury, which may occur when such quantities of the product are ingested that lead to caffeine overdose. There is no specific antidote, but supportive measures such as beta-adrenergic blockers may help alleviate cardiotoxic effects. Gastric lavage is recommended. Oxygen therapy is advised; diazepam is indicated in case of seizures. Symptomatic treatment should be provided.
Adverse Reactions
Information on the adverse reactions listed below was obtained from post-marketing surveillance. These reports are voluntary and derived from a population of unknown size; therefore, it is not possible to reliably estimate the frequency of these adverse reactions, although they are likely to be rare (< 1/10,000).
Adverse reactions due to paracetamol
Blood and lymphatic system disorders: thrombocytopenia, neutropenia, leukopenia, agranulocytosis, pancytopenia.
Immune system disorders: anaphylaxis, hypersensitivity skin reactions, including rash, angioneurotic edema, Stevens-Johnson syndrome, toxic epidermal necrolysis, and acute generalized exanthematous pustulosis.
Respiratory, thoracic and mediastinal disorders: bronchospasm in patients sensitive to acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs.
Hepatobiliary disorders: liver function abnormalities, hepatic failure, liver necrosis, jaundice.
Metabolism and nutrition disorders: metabolic acidosis with high anion gap (frequency unknown).
Description of selected adverse reactions
Metabolic acidosis with high anion gap
Cases of metabolic acidosis with high anion gap as a result of pyroglutamic acidemia have been observed in patients with risk factors who used paracetamol (see section "Special precautions for use"). Pyroglutamic acidemia may occur due to low glutathione levels in these patients.
Adverse reactions due to caffeine
Central nervous system disorders: nervousness, dizziness.
Cardiovascular system disorders: tachycardia, edema.
Gastrointestinal disorders: gastrointestinal discomfort, abdominal pain, diarrhea, nausea, vomiting.
Psychiatric disorders: insomnia, restlessness, anxiety, irritability, nervousness.
Skin and subcutaneous tissue disorders: pruritus, rash, sweating, purpura, urticaria.
Additionally, adverse reactions reported with medications containing similar active substances include: headache, erythema multiforme, heartburn, epigastric pain, hypoglycemia up to hypoglycemic coma, anemia, sulfhemoglobinemia, and methemoglobinemia (cyanosis, dyspnea, chest pain), hemolytic anemia, bruising or bleeding, tachycardia, arrhythmia, increased blood pressure, elevated liver enzyme activity (usually without development of jaundice).
Concomitant use of this medicine at recommended doses with products containing caffeine may lead to increased caffeine intake, thereby potentiating caffeine-related adverse effects.
Shelf life. 4 years.
Storage conditions.
Store at temperatures not exceeding 25 °C, in a place inaccessible and out of sight of children.
Packaging.
12 film-coated tablets per blister, 1 blister per cardboard box.
Availability. Over-the-counter (without prescription).
Manufacturer.
GlaxoSmithKline Dungarvan Limited, Ireland.
Manufacturer's address.
Knockbrack, Dungarvan, Co. Waterford, Ireland.
Marketing Authorization Holder's Representative: Kotsiuba N.O.