EFFERALGAN 250 mg Effervescent powder for oral solution in sachet 12Sachet

Paracetamol..................................................................................................................................................250 mg

Per sachet.

Excipients with known effect: one sachet contains 13 mg of aspartame (E951) (source of phenylalanine), 26 mg of sodium benzoate (E211), 93 mg of sodium, 60 mg of sorbitol (E420), and in the flavouring, 0,00016 mg of benzyl alcohol and 0,0002 mg of sulphur dioxide (E220).

Symptomatic treatment of mild to moderate pain and/or fever in children weighing 13 to 50 kg (approximately 2 to 15 years).

Dosage

Paediatric population

In children, it is imperative to observe the dosages defined according to weight of the child and therefore choose a suitable presentation. Approximate ages according to weight are given for information only.

The recommended daily dose of paracetamol is approximately 60 mg/kg/day, to be divided into 4 or 6 doses, i.e. approximately 15 mg/kg every 6 hours or 10 mg/kg every 4 hours.

For children, the total dose of paracetamol must not exceed 80 mg/kg/day (see section Overdose).

Recommended maximum doses : see section Warnings and precautions.

Warning: Take into account all medicines containing paracetamol to avoid overdose, including those obtained without a prescription.

Special populations

The maximum daily dose must not exceed 60 mg/kg/day nor 3000 mg per day (3 g/day) in the following situations: 

•          In case of low reserves or deficiency of hepatic glutathione (e.g., chronic malnutrition, fasting, recent weight loss, anorexia, cachexia),

•          Dehydration.

Hepatic insufficiency (mild to moderate), chronic alcoholism and Gilbert's syndrome (familial non-haemolytic jaundice)

It is recommended to reduce the dose and increase the minimum interval between two doses. The daily dose of paracetamol must not exceed 2000 mg/day (2 g/day).

Renal impairment

In case of renal impairment and unless medically advised otherwise, it is recommended to reduce the maximum daily dose and to increase the minimum interval between 2 doses according to the table below:

Method of administration

Oral use.

Pour the contents of the sachet into a glass, then add a small amount of drink (for example water, milk, fruit juice). Drink immediately after complete dissolution.

Duration of treatment

Frequent or prolonged use without medical supervision is not recommended.

If symptoms persist beyond 5 days in the case of pain or 3 days in the case of fever, if symptoms worsen or if new symptoms appear, treatment should be re-evaluated.

Hypersensitivity to the active substance or to any of the excipients listed in section Composition.

Severe hepatic insufficiency.

Special warnings

Patients must be informed that they must not take other medicines containing paracetamol. Taking several doses at one administration can seriously damage the liver; if this occurs, the patient must immediately call a doctor.

In a child treated with 60 mg/kg/day of paracetamol, the combination with another antipyretic is only justified in case of ineffectiveness.

In case of acute viral hepatitis, treatment should be stopped.

Special warnings

To avoid a risk of overdose:

• check the absence of paracetamol in the composition of other medicines (medicines obtained with or without prescription),

• respect the recommended maximum doses.

Recommended maximum doses :

• in children under 40 kg, the total dose of paracetamol must not exceed 80 mg/kg/day (see section Overdose).

Precautions for use

Paracetamol must be administered with caution in the following situations (see section Dosage and administration) :

• Mild to moderate hepatic insufficiency

• Chronic alcoholism and recent withdrawal

• Renal impairment

• Gilbert's syndrome

• Concomitant treatment with medicines affecting liver function (e.g. potentially hepatotoxic medicines or cytochrome P450 enzyme-inducing medicines such as phenobarbital, phenytoin, carbamazepine, topiramate, rifampicin)

• Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency (which may lead to haemolytic anaemia)

• Dehydration

• In cases of low reserves or hepatic glutathione deficiency (e.g. chronic malnutrition, fasting, recent weight loss, anorexia, cachexia)

Consumption of alcoholic beverages during treatment is not recommended.

In case of long-term use, high doses, or incorrect use of analgesics in patients with chronic headaches, headaches may appear or worsen; they should not be treated with higher doses of this medicine. In such cases, use of analgesics should be discontinued on medical advice.

Cases of high anion gap metabolic acidosis (HAGMA) due to pyroglutamic acidosis have been reported in patients with serious illness such as severe renal insufficiency and sepsis, or in patients suffering from malnutrition and other sources of glutathione deficiency (for example, chronic alcoholism), who were treated with paracetamol at a therapeutic dose for a prolonged period or with a combination of paracetamol and flucloxacillin. In case of suspected HAGMA due to pyroglutamic acidosis, it is recommended to stop paracetamol immediately and carry out close monitoring. Measurement of urinary 5-oxoproline may be useful to identify pyroglutamic acidosis as the underlying cause of HAGMA in patients with multiple risk factors.

Excipients with known effect: 

This medicine contains 26 mg of sodium benzoate (E211) per sachet. This medicine contains 93 mg of sodium per sachet, equivalent to 4,66% of the maximum recommended daily dietary intake of sodium by the WHO. The maximum daily dose of this product is equivalent to 55,9% of the maximum recommended daily dietary intake of sodium by the WHO. EFFERALGAN 250 mg, effervescent powder for oral solution in sachet has a high sodium content. To be taken into account in people on a low-sodium diet.

This medicine contains 13 mg of aspartame (E951) per sachet. Aspartame contains a source of phenylalanine. May be harmful for people with phenylketonuria (PKU), a rare genetic disease characterised by the accumulation of phenylalanine that cannot be properly eliminated. rare genetic disease characterised by the accumulation of phenylalanine that cannot be properly eliminated.

This medicine contains 60 mg of sorbitol (E420) per sachet. Patients with hereditary fructose intolerance (HFI) must not receive this medicine.

This medicine contains traces of benzyl alcohol per sachet. Benzyl alcohol may cause allergic reactions. Due to a risk of accumulation and toxicity (metabolic acidosis), precautions should be taken in pregnant and breastfeeding women, and in subjects with hepatic or renal impairment.

This medicine contains traces of sulfur dioxide (E220) per sachet. May, in rare cases, cause severe hypersensitivity reactions and bronchospasm.

Associations requiring precautions for use

+ Vitamin K antagonists

Risk of increased effect of the vitamin K antagonist and of bleeding risk when paracetamol is taken at maximum doses (4 g/day) for at least 4 days.

More frequent INR monitoring. Possible adjustment of the vitamin K antagonist dose during paracetamol treatment and after its discontinuation.

+ Flucloxacillin

Precautions must be taken when paracetamol is used at the same time as flucloxacillin, as concomitant intake has been associated with high anion gap metabolic acidosis due to pyroglutamic acidosis, particularly in patients with risk factors (see section Warnings and precautions).

Interactions with paraclinical tests

Taking paracetamol may distort the blood glucose measurement by the glucose oxidase-peroxidase method when concentrations are abnormally high.

Taking paracetamol may distort the measurement of blood uric acid by the phosphotungstic acid method.

Pregnancy

A large amount of data on pregnant women shows the'absence of any malformation or fetal/neonatal toxicity. Epidemiological studies on the neurodevelopment of children exposed to paracetamol in utero produce inconclusive results. If this is'considers it necessary to'From a clinical standpoint, paracetamol may be used during pregnancy; however, it should be used at the lowest effective dose, for the shortest possible duration and at the lowest possible frequency.

Breast-feeding

After administration, paracetamol is excreted in small quantities in breast milk. At therapeutic doses, administration of this medicine is possible during breastfeeding.

Fertility

Because of its potential mechanism of action on cyclo-oxygenases and prostaglandin synthesis, paracetamol could impair fertility in women, through an effect on ovulation that is reversible upon discontinuation of treatment.

Effects on male fertility have been observed in an animal study. The relevance of these effects in humans is not known.

Paracetamol has no or negligible effect on the ability to drive vehicles and use machines.

Adverse effects are classified by system organ class. Their frequencies are defined as follows:

• Very common (≥ 1/10)

• Common (≥ 1/100 to < 1/10)

• Uncommon (≥ 1/1000 to < 1/100)

• Rare (≥ 1/10 000 to < 1/1000)

• Very rare (< 1/10 000) 

• Not known (frequency cannot be estimated from the available data)

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reaction via the national reporting system: National Agency for the Safety of Medicines and Health Products (ANSM) and the network of Regional Centres of Pharmacovigilance - Website: https://signalement.social-sante.gouv.fr/.

The risk of severe poisoning (therapeutic overdose or accidental poisoning) may be particularly high in young children, in patients with hepatic or renal impairment, in cases of chronic alcoholism, and in patients suffering from chronic malnutrition (see section Dosage and administration), fasting, recent weight loss, familial cholemia (Gilbert's syndrome), as well as patients receiving enzyme inducers. In these cases, the poisoning can be fatal.

Symptoms

Nausea, vomiting, anorexia, pallor, malaise, sweating, abdominal pain generally appear within 24 first hours.

An overdose may cause hepatic cytolysis which may lead to hepatocellular failure that may require liver transplantation, gastrointestinal bleeding, metabolic acidosis, encephalopathy that may progress to coma and death.

Cases of disseminated intravascular coagulation have been observed in the context of paracetamol overdose.

Simultaneously, an increase in hepatic transaminases, lactate dehydrogenase, bilirubin and a decrease in prothrombin level may be observed, which may appear 12 to 48 hours after ingestion. The clinical symptoms of hepatic impairment are generally observed after 1 to 2 days, and reach a maximum after 3 to 4 days.

Overdose may also cause acute pancreatitis, hyperamylasemia, acute renal failure and pancytopenia.

Emergency management

• Stop the treatment.

• Immediate transfer to a hospital setting for emergency medical care, despite the absence of significant early symptoms.

• Rapid evacuation of the ingested product, by aspiration and gastric lavage, preferably within the 4 hours following ingestion.

• Blood sample to perform the initial plasma paracetamol assay. The plasma paracetamol concentration must be measured at least 4 hours after ingestion (an assay performed earlier is not reliable)

• Management of overdose classically involves administration of the antidote N-acetylcysteine as early as possible, by intravenous route or oral route if possible before the tenth hour. Although less effective, a protective effect of the antidote may be obtained up to 48 hours post-ingestion. In this case the antidote must be administered for longer.

• Symptomatic treatment.

• Liver tests must be performed at the start of treatment and repeated every 24 hours. In most cases, liver transaminases return to normal in 1 to 2 weeks with full restoration of liver function. However, in very severe cases, a liver transplant may be necessary.

• Further measures will depend on the severity, nature and course of the clinical symptoms of paracetamol poisoning and should follow standard intensive care protocols.

Pharmacotherapeutic class: OTHER ANALGESICS AND ANTIPYRETICS-ANILIDES.

ATC code: N02BE01.

Paracetamol has a central and peripheral mechanism of action.

Absorption

Oral absorption of paracetamol is complete and rapid. Maximum plasma concentrations are reached 30 to 60 minutes after ingestion.

Distribution

Paracetamol is rapidly distributed in all tissues. Concentrations are comparable in blood, saliva and plasma. Binding to plasma proteins is low.

Biotransformation

Paracetamol is metabolised mainly in the liver. The 2 major metabolic pathways are glucuronidation and sulphation. The latter pathway is rapidly saturable at dosages above therapeutic doses. A minor pathway, catalysed by cytochrome P450, is the formation of a reactive intermediate (N-acetyl benzoquinone imine) which, under normal conditions of use, is rapidly detoxified by reduced glutathione and eliminated in the urine after conjugation with cysteine and mercapturic acid.

In contrast, during massive overdoses, the quantity of this toxic metabolite is increased.

Elimination

Elimination is mainly urinary. 90 % of the ingested dose is eliminated by the kidney within 24 hours, mainly in glucuronide conjugated form (60 to 80 %) and sulphate conjugated form (20 to 30 %). Less than 5 % is eliminated in unchanged form.

The elimination half-life is approximately 2 hours.

Pathophysiological variations

Renal impairment (see section Dosage and administration) : elimination of paracetamol and its metabolites is delayed.

Hepatic impairment: paracetamol metabolism is impaired in patients with chronic hepatic impairment, as shown by increased plasma paracetamol concentrations and a longer elimination half-life (see section Dosage and administration).

No conventional study s'supporting the currently accepted standards for assessing reproductive and developmental toxicity n'is available.

3 years.

Store in the original package, protected from moisture.

Store at a temperature not exceeding 25°C.

No special requirements.