Efferalgan

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT EFERALGAN (EFFERALGAN)

Composition:

Active substance: paracetamol;

One effervescent tablet contains 500 mg of paracetamol;

Excipients: anhydrous citric acid, anhydrous sodium carbonate, sodium hydrogen carbonate, sorbitol (E 420), sodium saccharin, sodium docusate, povidone, sodium benzoate (E 211).

Pharmaceutical form. Effervescent tablets.

Main physicochemical properties: white tablets with bevelled edges and a score line for division, which dissolve in water with effervescence; minor chipping is acceptable.

Pharmacotherapeutic group.

Analgesics and antipyretics. ATC code N02BE01.

Pharmacological properties.

Pharmacodynamics.

Paracetamol has analgesic, antipyretic, and anti-inflammatory effects.

Pharmacokinetics.

Paracetamol is rapidly and almost completely absorbed in the gastrointestinal tract. Maximum plasma concentration is reached within 30–60 minutes. The half-life is 1–4 hours. It is uniformly distributed in all body fluids. Plasma protein binding is variable. It is excreted primarily by the kidneys in the form of conjugated metabolites.

Clinical characteristics.

Indications.

Symptomatic treatment of diseases accompanied by mild to moderate pain and/or elevated body temperature (infectious and inflammatory diseases, headache, toothache, muscle pain, painful menstruation).

Contraindications.

Hypersensitivity to paracetamol or to other components of the drug.

Severe impairment of liver and/or kidney function, congenital hyperbilirubinemia, glucose-6-phosphate dehydrogenase deficiency, blood disorders, Gilbert’s syndrome, severe anemia, leukopenia.

Fructose intolerance (since the drug contains sorbitol).

Alcoholism.

Special precautions.

The tablet must be completely dissolved in a glass of water (150–200 mL) before administration (single dose may vary from ½ to 2 tablets of Efferalgan).

Patients on a salt-free or low-salt diet should be aware that each effervescent tablet contains 412.4 mg of sodium.

Patients who abuse alcohol should consult a physician before taking the drug, as the risk of hepatotoxic effects of paracetamol increases. In elderly patients, elimination of paracetamol from the body may be reduced.

Paracetamol may affect laboratory test results: in assays for uric acid determination using the phosphotungstic acid method, and in blood glucose measurements using the glucose oxidase-peroxidase method.

Interaction with other medicinal products and other types of interactions.

The absorption rate of paracetamol may be increased by concomitant administration with metoclopramide and domperidone, and decreased by cholestyramine. The anticoagulant effect of warfarin and other coumarins may be enhanced by long-term, regular daily use of paracetamol, increasing the risk of bleeding. Occasional use has no 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 formation of hepatotoxic metabolites. Concomitant use of paracetamol with isoniazid increases the risk of hepatotoxic syndrome. Paracetamol reduces the efficacy of diuretics.

Do not use concurrently with alcohol.

Paracetamol should be used with caution concomitantly with flucloxacillin, as co-administration is associated with metabolic acidosis with a high anion gap due to pyroglutamic acidosis, particularly in patients with risk factors ("Special instructions for use").

Special precautions.

Consult a physician before taking this medication if the patient has liver or kidney disease. Consult a physician prior to use if the patient is taking warfarin or similar anticoagulant agents.

In patients with severe infections such as sepsis, which are associated with reduced glutathione levels, administration of paracetamol increases the risk of metabolic acidosis.

Symptoms of metabolic acidosis include deep, rapid, or labored breathing, nausea, vomiting, and loss of appetite. Medical attention should be sought immediately if these symptoms occur.

Do not exceed the recommended doses. If symptoms persist, consult a physician.

Do not take this medication concurrently with other products containing paracetamol.

When paracetamol is used in children at a dose of 60 mg/kg per day, combination with other antipyretic agents is justified only if ineffective. Use with caution in patients with body weight below 50 kg, chronic undernutrition (low hepatic glutathione stores), dehydration, or mild to moderate hepatic impairment.

Discontinue treatment if acute viral hepatitis is diagnosed.

Cases of high anion gap metabolic acidosis (HAGMA) due to 5-oxoproline (pyroglutamic acid) accumulation 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 paracetamol at therapeutic doses for prolonged periods or in combination with flucloxacillin. If HAGMA due to pyroglutamic acidosis is suspected, immediate discontinuation of paracetamol is recommended, along with close monitoring. 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.

Use during pregnancy or breastfeeding.

Pregnancy. This medication may be used during pregnancy only if the expected benefit to the mother outweighs the potential risk to the fetus or infant.

A substantial amount of data from pregnant women does not indicate teratogenic effects or fetal/neonatal toxicity. Epidemiological studies on neurodevelopmental outcomes in children exposed to paracetamol in utero have shown inconclusive results. When clinically necessary, paracetamol may be used during pregnancy at the lowest effective dose, for the shortest duration, and with the least possible frequency.

Traditional reproductive and developmental toxicity studies conducted according to current regulatory standards are lacking.

Breastfeeding period. Paracetamol passes into breast milk, but in clinically insignificant amounts. Available published data do not contraindicate breastfeeding.

Ability to affect reaction speed when driving or operating machinery.

No effect.

Dosage and Administration

The medicine is intended for adults and children with body weight above 15 kg (aged 3 years and older). For children with body weight below 15 kg, other dosage forms of paracetamol should be used. The dose of paracetamol in children is determined by body weight. If body weight is unknown, the child must be weighed before starting treatment. The daily dose of paracetamol must not exceed 60 mg/kg/day, which should be divided equally into 4 or 6 doses (15 mg/kg every 4 hours or 10 mg/kg every 6 hours).

Children with body weight from 15 to 21 kg (usually aged 3 to 6 years) – ½ tablet; if necessary, repeat doses every 6 hours, but not more than 2 tablets per day.

Children with body weight from 21 to 25 kg (usually aged 6 to 10 years) – ½ tablet; if necessary, repeat doses every 4 hours, but not more than 3 tablets per day.

Children with body weight from 26 to 40 kg (usually aged 8 to 13 years) – 1 tablet; if necessary, repeat doses every 4 hours, but not more than 4 tablets per day.

Children with body weight from 41 to 50 kg (usually aged 12 to 15 years) – 1 tablet; if necessary, repeat doses every 4 hours, but not more than 6 tablets per day.

Adults and children with body weight over 50 kg (from 15 years of age) – 1–2 tablets per dose; if necessary, repeat the dose after 4 hours. The average daily dose is 3 g of paracetamol per day (6 tablets). However, in cases of severe pain, the maximum daily dose of 4 g of paracetamol (8 tablets) may be taken, with intervals between doses of at least 4 hours.

Duration of treatment – no more than 3 days.

Children

Do not use in children under 3 years of age.

Overdose

There is a risk of severe poisoning in elderly individuals, young children, patients with liver disease, chronic alcoholism, or chronic malnutrition.

To prevent overdose, do not use other paracetamol-containing medicines concomitantly with Efferalgan.

A single dose of 10 g in adults or 150 mg/kg body weight in children may cause hepatocellular insufficiency, impaired glucose metabolism, metabolic acidosis, hemorrhage, hypoglycemia, encephalopathy, coma, and even death. In such cases, levels of liver transaminases, lactate dehydrogenase, and bilirubin increase, and prothrombin levels decrease within 12–48 hours.

Acute renal failure with acute tubular necrosis may manifest as severe lumbar pain, hematuria, and proteinuria, and may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have also been reported. With prolonged use of high doses, aplastic anemia, pancytopenia, agranulocytosis, neutropenia, leukopenia, and thrombocytopenia may develop from the hematopoietic system. High-dose intake may cause dizziness, psychomotor agitation, and disorientation from the central nervous system; nephrotoxicity (renal colic, interstitial nephritis, papillary necrosis) from the urinary system; and hepatonecrosis from the digestive system.

In patients with risk factors (long-term use of carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St. John's wort, or other hepatic enzyme-inducing agents; chronic alcohol abuse; glutathione system deficiency, e.g., due to poor nutrition, AIDS, fasting, cystic fibrosis, cachexia), ingestion of 5 g or more of paracetamol may lead to liver damage. Liver injury may become apparent 12–48 hours after overdose.

In case of overdose, the patient must be immediately taken to hospital, even if early symptoms of overdose are absent. Symptoms of overdose may appear within the first 24 hours: nausea, vomiting, loss of appetite, pallor, abdominal pain, or may not reflect the severity of overdose or risk of organ damage.

Emergency measures: immediate hospitalization, determination of plasma paracetamol concentration, gastric lavage, administration of the antidote N-acetylcysteine intravenously or oral methionine within the first 10 hours, and symptomatic therapy.

Adverse reactions.

Very rare:

Allergic reactions: anaphylaxis, skin itching, rashes on the skin and mucous membranes (usually generalized rash, erythematous rash, urticaria), angioneurotic edema, multiform exudative erythema (including Stevens-Johnson syndrome), toxic epidermal necrolysis (Lyell's syndrome);

Gastrointestinal disorders: nausea, epigastric pain, increased activity of liver enzymes (usually without development of jaundice), liver function disorders;

Endocrine system disorders: hypoglycemia, up to hypoglycemic coma;

Blood and lymphatic system disorders: anemia, thrombocytopenia, leukopenia, neutropenia, sulfhemoglobinemia and methemoglobinemia (cyanosis, dyspnea, chest pain), hemolytic anemia, bruising or bleeding;

Respiratory system disorders: bronchospasm in patients sensitive to acetylsalicylic acid and other NSAIDs.

Occasionally malaise and decrease in blood pressure, renal colic may occur.

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

Description of individual 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 as a consequence of low glutathione levels in these patients.

Shelf life.

3 years.

Storage conditions.

Store at temperatures not exceeding 30 °C, in a place inaccessible to children.

Packaging.

4 effervescent tablets per strip, 4 strips per cardboard box.

Pharmaceutical classification.

Over-the-counter (without prescription).

Manufacturer.

UPSA SAS, France.

Manufacturer's address and location of business activity.

979, avenue des Pyrenees, 47520 Le Passage, France.

304, avenue du Docteur Jean Bru, 47000 Agen, France.