DAFALGAN 500 mg Cpr eff séc Film/16

For a scored effervescent tablet:

Paracetamol : 500 mg

Excipients with known effect: one tablet contains 50 mg of sodium benzoate (E211), 197 mg of sodium and 126 mg of sorbitol (E420) and in the flavouring, 0,96 mg of fructose, 0,83 mg of glucose and 0,28 mg of sucrose.

Symptomatic treatment of mild to moderate pain and/or fever.

Adults and children from 13 kg (approximately 2 years).

Dosage

Use the lowest effective dose for the shortest possible duration. Use a dose of 1000 mg for pain and/or fever not relieved by a dose of 500 mg of paracetamol.

Recommended dosage: approximately 60 mg/kg/day to be divided into several doses without exceeding the maximum doses indicated in the table below. In children, the dosage should be adjusted according to weight.

The approximate ages according to weight are given for information only.

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

Only on medical advice and in the absence of concomitant risk factors, the dose may be increased up to 4000 mg (4 g) per day, i.e. 8 tablets per day, in patients weighing at least 50 kg (from approximately 15 years).

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:

• Adults weighing less than 50 kg,

• In cases of low reserves or hepatic glutathione deficiency (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:

Adults:

Elderly

Clinical experience indicates that the recommended dosage is generally adequate in adults. However, concomitant risk factors, some of which occur more frequently in elderly subjects and which require dose adjustment, should be taken into account.

Method of administration

Oral use.

Let dissolve completely the tablet in a glass of water, if necessary after breaking it in two.

Do not swallow or chew the tablets.

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 paracetamol or to any of the excipients listed in section Composition.

Severe hepatic insufficiency.

Patients must be informed that they must not take other medicines containing paracetamol. Taking several doses at one administration may 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.

Precautions for use

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

• Adult with a weight of less than 50 kg

• Mild to moderate hepatic insufficiency

• Chronic alcoholism and recent withdrawal

• Renal insufficiency

• Gilbert's syndrome

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

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

• Dehydration

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

• Elderly people

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 diseases such as severe renal failure and sepsis, or in patients suffering from malnutrition and other sources of glutathione deficit (for example, chronic alcoholism), who have been 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 immediately stop paracetamol 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 presenting with multiple risk factors.

Excipients with known effect:

This medicine contains 50 mg of sodium benzoate (E211) per effervescent tablet.

This medicine contains 0,96 mg of fructose per effervescent tablet. The additive effect of concomitantly administered products containing fructose (or sorbitol) and dietary intake of fructose (or sorbitol) must be taken into account.

This medicine contains 0,83 mg of glucose per effervescent tablet. Patients with glucose-galactose malabsorption syndrome (a rare hereditary disease) must not take this medicine.

This medicine contains 0,28 mg of sucrose per effervescent tablet. Patients with fructose intolerance, glucose-galactose malabsorption syndrome or sucrase/isomaltase deficiency (rare hereditary diseases) must not take this medicine.

This medicine contains 197 mg of sodium per effervescent tablet, equivalent to 10 % of the maximum daily sodium intake recommended by the WHO. The maximum daily dose of this product (6 tablets) is equivalent to 60 % of the maximum daily sodium intake recommended by the WHO. DAFALGAN 500 mg, scored effervescent tablet has a high sodium content. To be taken into account in people on a low-sodium diet.

This medicine contains 126 mg of sorbitol (E420) per effervescent tablet. Patients with hereditary fructose intolerance (HFI) must not take/receive this medicine. The additive effect of concomitantly administered products containing sorbitol (or fructose) and dietary intake of sorbitol (or fructose) must be taken into account.

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 demonstrates the absence of any malformation or any fetal/neonatal toxicity. Epidemiological studies on the neurodevelopment of children exposed to paracetamol in utero produce inconclusive results. If clinically necessary, 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.

Undesirable 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)

• Frequency not known (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 elderly subjects, young children, patients with hepatic or renal impairment, in cases of chronic alcoholism, 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-inducing medicines. In these cases, poisoning may 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 lead to acute pancreatitis, hyperamylasemia, acute renal failure and pancytopenia.

Emergency management

• Discontinuation of 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)
• Treatment of overdose conventionally includes 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 a longer period.
• Symptomatic treatment.
• Liver tests should be performed at the start of treatment and repeated every 24 hours. In most cases, hepatic transaminases return to normal in 1 to 2 weeks with complete restoration of liver function. However, in very severe cases, liver transplantation may be necessary.
• Taking other measures will depend on the severity, nature and evolution 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 sulfoconjugation. The latter pathway is rapidly saturable at doses above therapeutic doses. A minor pathway, catalysed by cytochrome P 450, 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 sulfate 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 altered in patients with chronic hepatic impairment, as shown by increased plasma concentrations of paracetamol and a longer elimination half-life (see section Dosage and administration).

Elderly subject: the conjugation capacity is not modified (see section Dosage and administration).

No conventional study based on currently accepted standards for assessing reproductive and developmental toxicity is available.

3 years.

No special precautions for storage.