Solpadeine active

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT SOLPADEINE ACTIVE (SOLPADEINE ACTIVE)

Composition:

Active substances: paracetamol, caffeine;

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

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

Pharmaceutical form. Effervescent tablets.

Main physicochemical characteristics: flat white tablets with bevelled edges, smooth on one side and with a break line on the other.

Pharmacotherapeutic group.

Analgesics and antipyretics. ATC code N02BE51.

Pharmacological Properties.

Pharmacodynamics.

Paracetamol is an analgesic and antipyretic agent. 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. They are uniformly distributed throughout all body fluids. Plasma protein binding is minimal when administered at therapeutic doses.

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

Clinical characteristics.

Indications.

Moderate to severe pain (headache, migraine, musculoskeletal pain, muscle pain, dental pain, pain after tooth extraction and dental procedures, 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 medical 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 together with monoamine oxidase inhibitors (MAOIs) or 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. The anticoagulant effect of warfarin and other coumarins, with an increased risk of bleeding, may be enhanced by long-term regular use of paracetamol. Single doses do not exhibit 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.

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

Do not use simultaneously with alcohol.

Concomitant use of caffeine with MAO inhibitors may cause a dangerous increase in blood pressure. Caffeine enhances the effect (improves bioavailability) of analgesic-antipyretic agents, potentiates the effects of xanthine derivatives, alpha- and beta-adrenergic agonists, and 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 anesthetics and other central nervous system (CNS) depressants, and a competitive antagonist of adenosine and ATP preparations. Concurrent use of caffeine with ergotamine improves the absorption of ergotamine from the gastrointestinal tract; concurrent use with thyroid-stimulating agents increases the thyroid effect.

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 in combination with other medications containing paracetamol, which are used, for example, to reduce fever, relieve pain, treat flu and cold symptoms, or insomnia. Concurrent use with other paracetamol-containing products may result in overdose.

Consult a physician before use if you are taking warfarin or similar anticoagulant agents. It should be noted that patients with alcoholic non-cirrhotic liver disease have an increased risk of hepatotoxic effects of paracetamol.

Cases of high anion gap metabolic acidosis (HAGMA) due to pyroglutamic acidosis have been reported in patients with severe underlying conditions such as severe renal insufficiency and sepsis, or in patients with malnutrition or other sources of glutathione deficiency (e.g., chronic alcoholism, severe cachexia, anorexia, low body mass index, or sepsis) 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 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.

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, tremors, palpitations with discomfort behind the sternum, tension, irritability, and restlessness.

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. 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.

One tablet contains 427 mg of sodium. This should be taken into account by patients on a sodium-controlled diet. The product contains 50 mg of sorbitol per tablet. Patients with rare hereditary fructose intolerance should not take this medicinal product.

Keep the product out of sight and reach of children.

Use during pregnancy or breastfeeding.

Use during pregnancy is not recommended, as it may increase the risk of spontaneous abortion associated with caffeine intake.

Use of this medicinal product is not recommended during breastfeeding. Paracetamol and caffeine pass into breast milk. Caffeine in breast milk may have a stimulant effect on infants, but significant toxicity has not been observed.

Ability to influence reaction speed when driving or operating machinery.

The likelihood of any effect is negligible.

Method of Administration and Dosage

The medicine 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 12 years and older: 1–2 tablets should be dissolved 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. Not recommended for children under 12 years of age.

Overdose

Paracetamol

Paracetamol overdose can cause liver failure, which may lead to the need for liver transplantation or result in death. Acute pancreatitis has been observed, usually concurrent with liver function abnormalities and hepatotoxicity. Liver damage is possible 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 depletion (digestive disorders, cystic fibrosis, HIV infection, fasting, cachexia)], ingestion of 5 g or more of paracetamol may lead to liver damage.

Immediate medical assistance is required in case of overdose. Treatment should be initiated immediately. 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. 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 present. If overdose is confirmed or suspected, the patient must be taken to the nearest medical facility capable of providing emergency medical care and appropriate treatment. This should be done even in the absence of symptoms due to the risk of delayed liver damage. 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 after ingestion (earlier concentrations 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 appropriate alternative in remote areas outside hospital settings.

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 with 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, blood-forming organs may develop aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, and thrombocytopenia. High-dose intake may affect the central nervous system, causing dizziness, psychomotor agitation, and disorientation. Effects on the urinary system may include nephrotoxicity (renal colic, interstitial nephritis, cortical necrosis).

Caffeine

Caffeine overdose may cause epigastric pain, vomiting, diuresis, rapid breathing, tachycardia or cardiac arrhythmia, and affect the central nervous system (insomnia, restlessness, nervous excitation, anxiety, agitation, dizziness, irritability, affective disturbances, tremor, seizures). Clinically significant symptoms of caffeine overdose may also be associated with severe paracetamol-induced liver damage, which may occur when doses sufficient to cause caffeine overdose are ingested. There is no specific antidote, but supportive measures such as beta-adrenergic antagonists may help alleviate cardiotoxic effects. Gastric lavage is required; oxygen therapy is recommended; diazepam should be administered in case of seizures. Symptomatic therapy.

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.

Side effects

The information on the side effects listed below was obtained from post-marketing surveillance. These reports were submitted voluntarily, and the population of patients is of unknown size; therefore, the frequency of these side effects is unknown, but they are likely to be rare (< 1/10000).

Side effects associated with paracetamol

Blood and lymphatic system disorders: thrombocytopenia, agranulocytosis.

Immune system disorders: anaphylaxis, skin hypersensitivity reactions, including rash, angioneurotic edema, Stevens-Johnson syndrome, toxic epidermal necrolysis.

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

Hepatobiliary disorders: liver function abnormalities.

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 as a result of pyroglutamic acidosis have been observed in patients with risk factors who were treated with paracetamol (see section "Special precautions"). Pyroglutamic acidosis may occur due to low glutathione levels in these patients.

Side effects associated with caffeine

Central nervous system disorders: dizziness, headache.

Cardiovascular disorders: tachycardia.

Gastrointestinal disorders: gastrointestinal discomfort.

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

Concomitant use of the medicinal product at recommended doses with caffeine-containing products may lead to increased caffeine intake, which may intensify caffeine-related side effects such as dizziness, increased excitability, insomnia, restlessness, anxiety, irritability, headache, gastrointestinal disturbances, and tachycardia.

Shelf life. 4 years.

Storage conditions. Store at temperatures not exceeding 25 °C. Keep out of the reach and sight of children.

Packaging. 2 tablets in a multilayer strip, 6 strips in a cardboard box; 4 tablets in a multilayer strip, 3 strips in a cardboard box.

Pharmaceutical category. Over-the-counter (without prescription).

Manufacturer.

Famar A.V.E. Anthoussa plant / Famar A.V.E. Anthoussa plant.

GlaxoSmithKline Dungarvan Limited.

Manufacturer's address.

Anthoussa Avenue 7, Anthoussa Attiki, 15349, Greece / Anthoussa Avenue 7, Anthoussa Attiki, 15349, Greece.

Knockbrack, Dungarvan, Co. Waterford, Ireland / Knockbrack, Dungarvan, Co. Waterford, Ireland.