DAFALGAN 600 mg Suppos adulte Plq/10

For a suppository:

Paracetamol: 600 mg

Excipient with known effect: one suppository contains lecithin derived from soybean oil (contained in the semi-synthetic glycerides).

Symptomatic treatment of mild to moderate pain and/or fever in adults and children weighing more than 30 kg (approximately 10 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 doses, i.e. approximately 15 mg/kg every 6 hours.

Due to the risk of local toxicity, administration of a suppository is not advised more than 4 times per day, and the duration of rectal treatment should be as short as possible.

In case of diarrhea, administration of the suppository is not recommended.

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

Maximum recommended 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: 

• Adults weighing less than 50 kg,

•          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:

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

Rectal route.

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.

Due to the presence of lecithin derived from soybean oil, this medicine is contraindicated in case of allergy to peanut or soy.

Severe hepatic insufficiency.

Recent history of proctitis, anitis, or rectal bleeding.

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).

• in children from 41 kg to 50 kg, the total dose of paracetamol must not exceed 3 g per day (see section Overdose).

• in adults and children over 50 kg, THE TOTAL DOSE OF PARACETAMOL MUST NOT EXCEED 4 GRAMS PER DAY (see section Overdose).

With suppositories, there is a risk of local toxicity, which is more frequent and intense the longer the duration of treatment, the higher the frequency of administration and the higher the dosage.

Precautions for use

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

• Adult weighing less than 50 kg

• 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)

• Elderly

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.

In case of diarrhoea, the suppository form is not suitable.

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)

RELATED TO PARACETAMOL

RELATED TO THE PHARMACEUTICAL FORM

• Rectal and anal irritation.

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 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.

• 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

Rectally, the absorption of paracetamol is slower than orally.

It is however complete. Maximum plasma concentrations are reached 2 to 3 hours after administration.

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 dosages 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 intoxications, the amount of this toxic metabolite is increased.

Elimination

Elimination is primarily urinary. 90 % of the administered dose is eliminated by the kidney in 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 4 to 5 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).

Elderly subject: the conjugation capacity is not modified (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.

To be stored at a temperature not exceeding 30°C.

No special requirements.