Solpadeine active

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

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. Film-coated tablets.

Main physicochemical properties: white, capsule-shaped film-coated tablets with flat edges, embossed with a triangular logo and the symbol "+" on one side and no engraving 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 inhibition of prostaglandin synthesis in the central nervous system (CNS). Due to weak inhibition of peripheral prostaglandins, particularly in the gastrointestinal tract, paracetamol is partially suitable for patients for whom inhibition of peripheral prostaglandins is undesirable, e.g. when salicylates are contraindicated.

Caffeine acts as a stimulant, enhancing 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 metabolized primarily in the liver and excreted in urine as metabolites.

Clinical characteristics.

Indications.

The drug exerts moderate analgesic and antipyretic effects. Indications for use include headache, including migraine, toothache, neuralgias, rheumatic pain, menstrual pain in women; for relief of symptoms of colds and flu, sore throat.

Contraindications.

Hypersensitivity to paracetamol, caffeine, or any other component of the drug in medical history; severe liver and/or kidney impairment; congenital hyperbilirubinemia; glucose-6-phosphate dehydrogenase deficiency; alcoholism; blood disorders, marked anemia, leukopenia; conditions of increased excitation, sleep disturbances, 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.

Prolonged concomitant 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-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 likelihood of paracetamol accumulation and enhances the hepatotoxic effects of both paracetamol and these agents. Concurrent use of high doses of paracetamol with isoniazid increases the risk of 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, as a larger amount of toxic epoxide is formed during its biotransformation. Paracetamol may reduce the bioavailability of lamotrigine, thereby decreasing its effect, likely due to induction of its hepatic metabolism. Concurrent use of paracetamol and zidovudine increases the risk of neutropenia.

Paracetamol should be used with caution when administered concurrently with flucloxacillin, as concomitant 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 concurrently with alcohol.

Concurrent use of caffeine with monoamine oxidase inhibitors (MAOIs) may cause a dangerous increase in blood pressure. Caffeine enhances the effect (improves bioavailability) of analgesic-antipyretic drugs, 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 anesthetic agents and other drugs that depress the CNS, and a competitive antagonist of adenosine and ATP preparations. Concurrent use of caffeine with ergotamine improves ergotamine absorption from the gastrointestinal tract; with thyroid-stimulating agents – thyroid effect is enhanced.

Caffeine may enhance lithium excretion from the body. Therefore, concurrent use of the drug 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 medicinal products containing paracetamol, which are used, for example, to reduce fever, relieve pain, treat flu and cold symptoms, or for insomnia. Concurrent use with other paracetamol-containing products may result in overdose. Paracetamol overdose can cause liver failure, which may necessitate liver transplantation or lead to 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 should 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 use significantly increases the risk of developing hepatotoxic effects of paracetamol. In patients with impaired liver function and in those taking high doses of paracetamol for prolonged periods, regular monitoring of liver function tests is recommended.

When treating with oral anticoagulants, prothrombin time should be monitored if high doses of paracetamol are taken concurrently.

The medicinal 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 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 underlying 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 therapeutic doses of paracetamol over a prolonged period or in combination with flucloxacillin. If HAGMA due to pyroglutamic acidosis is suspected, immediate discontinuation of paracetamol is recommended, and close monitoring of the patient's condition should be initiated. Measurement of urinary 5-oxoproline levels may be helpful 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 with discomfort behind the sternum, nervousness, and irritability.

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

Use during pregnancy or breastfeeding.

The use of this medicinal product during pregnancy is not recommended, as it may increase the risk of spontaneous abortion associated with caffeine use.

The use of this medicinal 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.

Effect on ability to drive or operate machinery.

The effect is absent or negligible.

Method of Administration and Dosage.

The product is intended for oral administration.

Adults and children aged 12 years and older: 1–2 tablets every 4–6 hours as needed. Do not exceed 8 tablets (4000 mg paracetamol / 520 mg caffeine) within 24 hours.

Do not exceed the recommended dose.

The lowest effective dose should be used for the shortest duration necessary to achieve therapeutic effect.

The interval between doses should be at least 4 hours.

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 observed, 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 that induce 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, prompt medical attention is required. Treatment must be initiated immediately. 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 peak usually within 4–6 days. Glucose metabolism disturbances and metabolic acidosis may occur. In severe poisoning, liver failure may progress to encephalopathy, hemorrhage, hypoglycemia, coma, and may be fatal. Acute kidney failure with acute tubular necrosis may manifest as severe lumbar 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 such as aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, and thrombocytopenia may develop. Central nervous system effects from high doses may include dizziness, psychomotor excitation, 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 assistance is essential in case of overdose, even if no symptoms are observed. If overdose is confirmed or even suspected, the patient must be taken to the nearest medical facility where emergency medical care and appropriate treatment can be provided. This should be done even if no symptoms are present, due to the risk of delayed liver damage. Administration of activated charcoal should be considered if the excessive dose of paracetamol was ingested within the past 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 maximum protective effect is achieved when administered within 8 hours of ingestion. The efficacy of the antidote decreases sharply 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.

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, nervousness, dizziness, irritability, affective state, tremor, seizures). Clinically significant symptoms of caffeine overdose may also be associated with severe liver injury caused by paracetamol, which may occur when large amounts of the product are consumed. There is no specific antidote, but supportive measures such as beta-adrenergic antagonists may help alleviate cardiotoxic effects. Gastric lavage is recommended; oxygen therapy is advised; diazepam should be administered in case of seizures. Symptomatic therapy is indicated.

Adverse Reactions

The information on the adverse reactions listed below was obtained from post-marketing surveillance. The data are voluntarily reported and relate to a population of unknown size; therefore, the frequency of these adverse reactions is unknown and they are likely to be rare (< 1/10,000).

Adverse reactions associated with paracetamol:

Blood and lymphatic system disorders: thrombocytopenia, neutropenia, leukopenia, agranulocytosis, pancytopenia.

Immune system disorders: anaphylaxis, hypersensitivity reactions including skin rash, angioedema, 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 acidosis have been observed in patients with risk factors who used paracetamol (see section "Special precautions"). Pyroglutamic acidosis may occur due to low glutathione levels in these patients.

Adverse reactions associated with caffeine:

Central nervous system disorders: nervousness, dizziness.

Cardiovascular 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 observed after administration of drugs 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, increased liver enzyme activity, usually without development of jaundice.

Concomitant use of the drug at recommended doses with products containing caffeine may result in increased caffeine intake, which may intensify 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 category. Over-the-counter.

Manufacturer.

GlaxoSmithKline Dungarvan Limited, Ireland.

Manufacturer's address and place of business.

Knockbrack, Dungarvan, Co. Waterford, Ireland.