Paracetamol extra

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

Composition:

Active substances: paracetamol, caffeine;

1 tablet contains 500 mg of paracetamol, 65 mg of caffeine;

Excipients: sodium hydrocarbonate, sodium carbonate, citric acid, sorbitol (E 420), sodium saccharin, povidone, sodium lauryl sulfate, dimethicone.

Pharmaceutical form. Effervescent tablets.

Main physicochemical properties: white-colored, round, flat tablets with beveled edges and a score line on one side. Effervescence with gas bubble release is observed when dissolved in water.

Pharmacotherapeutic group. Analgesics and antipyretics. ATC code N02B E51.

Pharmacological Properties.

Pharmacodynamics.

Paracetamol is an analgesic and antipyretic. Its effect is based on inhibition of prostaglandin synthesis in the central nervous system (CNS). Inhibition of peripheral prostaglandin synthesis is minimal; therefore, paracetamol is partially suitable for patients in whom blockade of peripheral prostaglandins is undesirable (e.g., patients with a history of gastrointestinal bleeding).

Caffeine enhances analgesic efficacy through its stimulatory effect on the CNS, which may counteract the depression often associated with pain.

Pharmacokinetics.

Paracetamol and caffeine are rapidly and almost completely absorbed in the gastrointestinal tract. Paracetamol is uniformly distributed throughout all body fluids, and its binding to plasma proteins is minimal when administered at therapeutic doses.

Paracetamol and caffeine are metabolized primarily in the liver and are excreted in the urine as metabolites.

Clinical characteristics.

Indications.

Moderate to severe pain (headache, migraine, musculoskeletal pain, muscle pain, toothache, post-extraction and dental procedure pain, sore throat, menstrual pain), fever and pain following vaccination, elevated body temperature.

Contraindications.

Hypersensitivity to paracetamol, caffeine, or any other component of the medicinal product in history; severe impairment of liver and/or kidney function; congenital hyperbilirubinemia; glucose-6-phosphate dehydrogenase deficiency; alcoholism; blood disorders, marked anemia, leukopenia; states 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 β-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. The anticoagulant effect of warfarin and other coumarins, with an increased risk of bleeding, may be enhanced by prolonged regular use of paracetamol. Single-dose administration 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. Concurrent use of high doses of paracetamol with isoniazid increases the risk of developing hepatotoxic syndrome. Paracetamol reduces the effectiveness of diuretics. Caution should be exercised when using paracetamol concomitantly with flucloxacillin, as such concurrent use is associated with metabolic acidosis with a high anion gap due to 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, α- and β-adrenergic agonists, psychostimulants.

Cimetidine, hormonal contraceptives, and isoniazid enhance the effect 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. When caffeine is used concomitantly with ergotamine, absorption of ergotamine from the gastrointestinal tract improves; when used with thyroid-stimulating agents, the thyroid effect is enhanced.

Caffeine may enhance lithium excretion from the body. Therefore, concomitant use of the medicinal product with lithium preparations is not recommended.

Special precautions for use.

The medicinal product contains paracetamol; therefore, it should not be used with other medications containing paracetamol, which are used, for example, to reduce fever, treat pain, symptoms of flu and colds, or insomnia. Concomitant 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.

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.

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, or in those with malnutrition and other causes of glutathione deficiency (e.g., chronic alcoholism), who were treated with paracetamol at therapeutic doses over a prolonged period or with a combination of paracetamol and flucloxacillin. If HAGMA 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 helpful in identifying pyroglutamic acidosis as the underlying cause of HAGMA in patients with multiple risk factors. 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.

During treatment with this medicinal 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 with discomfort behind the sternum, nervousness, and irritability.

In patients with liver or kidney disease, medical advice should be sought before using this product. Restrictions on use in such patients are primarily due to the presence of paracetamol. It should be noted that patients with alcoholic non-cirrhotic liver disease have an increased risk of hepatotoxic effects from paracetamol in cases of overdose. 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 their physician.

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

This medicinal product contains 37.14 mmol (or 854 mg)/dose (2 tablets) of sodium. Caution is advised when administering to patients on a sodium-restricted diet.

The product contains sorbitol (E 420). If the patient has been diagnosed with intolerance to certain sugars, medical advice should be sought before taking this medicinal product.

Use during pregnancy or breastfeeding.

Use during pregnancy is not recommended, as it increases the risk of spontaneous abortion associated with caffeine use.

Use of this medicinal product is not recommended during breastfeeding. Paracetamol and caffeine pass into breast milk. 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 almost negligible.

Method of Administration and Dosage

The medicinal product is intended for oral administration.

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, elderly patients, and children aged 16 years and older: 1–2 tablets should be dissolved together in half a glass of water. Take every 4–6 hours as needed. Do not take more than 8 tablets (4000 mg paracetamol / 520 mg caffeine) within 24 hours.

Children aged 12 to 15 years: 1 tablet should be dissolved in half a glass of water. Take every 4–6 hours as needed (up to 4 times daily). Do not take more than 4 tablets (2000 mg paracetamol / 260 mg caffeine) within 24 hours. Do not use for more than 3 consecutive days without consulting a physician.

Children.

Not recommended for children under 12 years of age.

Overdose.

Paracetamol.

Paracetamol overdose can cause hepatic failure, which may lead to the need for liver transplantation or result in death. Acute pancreatitis has been reported, usually in conjunction with liver function abnormalities 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 inducing liver enzymes; chronic excessive alcohol consumption; glutathione depletion (due to malnutrition, cystic fibrosis, HIV infection, fasting, cachexia)], ingestion of 5 g or more of paracetamol may lead to liver injury.

In case of overdose, immediate medical assistance is required. Treatment should 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. Clinical experience shows that signs of liver damage typically become apparent 24–48 hours after overdose and usually peak within 4–6 days. Glucose metabolism disturbances and metabolic acidosis may occur.

Symptoms of overdose may not reflect the severity of overdose or the risk of organ damage. Immediate medical attention is essential in case of overdose, even if no symptoms are observed. If overdose is confirmed or suspected, the patient must be taken immediately to the nearest medical facility capable of providing emergency medical care and appropriate treatment. This is necessary even in the absence of symptoms due to the risk of delayed liver damage. Administration of activated charcoal should be considered if the excessive dose of paracetamol was taken within the previous hour. Plasma paracetamol concentration should be measured 4 hours or later after ingestion (earlier measurements are unreliable). Treatment with N-acetylcysteine may be administered within 24 hours after paracetamol ingestion, but maximum protective effect is achieved when administered within 8 hours of overdose. The efficacy of the antidote decreases sharply after this time. If necessary, intravenous N-acetylcysteine should be administered according to the recommended dosage. In the absence of vomiting, oral methionine may be used as an appropriate alternative in remote areas outside hospital settings.

In severe poisoning, hepatic failure may progress to encephalopathy, hemorrhage, hypoglycemia, coma, and may be fatal. Acute renal 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 have also been reported.

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

Caffeine.

Caffeine overdose may cause epigastric pain, vomiting, diuresis, rapid breathing, tachycardia or cardiac arrhythmia, and affect the CNS (insomnia, restlessness, nervous excitation, anxiety, agitation, dizziness, irritability, affective disturbances, tremor, seizures). Clinically significant symptoms of caffeine overdose may also be associated with severe liver injury caused by paracetamol, which may occur when such amounts of the drug are taken that lead to caffeine overdose. There is no specific antidote, but supportive measures such as administration of β-adrenergic receptor antagonists may help alleviate cardiotoxic effects. Gastric lavage is recommended; oxygen therapy is advised, and diazepam should be administered in case of seizures. Symptomatic treatment is required.

Sodium bicarbonate.

High doses of sodium bicarbonate may cause gastrointestinal disturbances such as belching and nausea, and may also lead to hypernatremia; therefore, electrolyte balance should be monitored and appropriate treatment provided to patients.

Adverse reactions.

The information on the adverse reactions listed below was obtained from post-marketing surveillance. It is reported voluntarily from a population of unknown size; therefore, the frequency of the reported adverse reactions is unknown, but they are likely to be rare (< 1/10000).

Adverse reactions associated with paracetamol

Blood and lymphatic system disorders: thrombocytopenia, agranulocytosis.

Immune system disorders: anaphylaxis, skin hypersensitivity reactions, including but not limited to skin rash, angioneurotic edema, Stevens–Johnson syndrome, toxic epidermal necrolysis.

Respiratory, thoracic and mediastinal disorders: bronchospasm in patients sensitive to acetylsalicylic acid and other non-steroidal anti-inflammatory drugs.

Hepatobiliary disorders: liver function abnormalities.

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

Cases of metabolic acidosis with high anion gap, resulting from pyroglutamic acidosis, have been observed in patients with risk factors during paracetamol use (see section "Special precautions"). Pyroglutamic acidosis may occur due to low glutathione levels in these patients.

Adverse reactions associated with caffeine

CNS disorders: dizziness, headache.

Cardiovascular disorders: tachycardia.

Gastrointestinal disorders: gastrointestinal discomfort.

Psychiatric disorders: insomnia, restlessness, anxiety, irritability, nervousness.

Concomitant use of the product at recommended doses with caffeine-containing products may result in increased caffeine intake, which can intensify caffeine-related adverse effects such as insomnia, restlessness, anxiety, irritability, headache, gastrointestinal disturbances, and tachycardia.

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

Shelf life. 2 years.

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

Keep out of reach and sight of children.

Packaging. Effervescent tablets No. 12 (2**×** 6) in a strip pack in a box.

Availability category. Over-the-counter.

Manufacturer. LIMITED LIABILITY COMPANY "CORPORATION "ZDOROV'YA".

Manufacturer's address and location of business activity. 22, Shevchenka Street, Kharkiv, Kharkiv Oblast, 61013, Ukraine.