Keep out of reach of children.
Read the directions carefully before use.
QUALITATIVE AND QUANTITATIVE COMPOSITION
Active ingredient
Paracetamol ............................ 150 mg
Excipients q.s …………………….. 1 tablet
PHARMACEUTICAL FORM: Effervescent powder.
Product description: A dry, loose, orange powder with an aroma.
Box of 24 sachets x 1.5 g of effervescent powder.
Pharmacotherapeutic group: Other analgesics and antipyretics. ATC code: N02BE01.
Mechanism of action
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 distributes quickly in all tissues. Concentrations are comparable in blood, saliva and plasma. Binding to plasma proteins is weak.
Biotransformation
Paracetamol is mainly metabolized in the liver following two major metabolic pathways: glucuronic acid conjugation and sulfuric acid conjugation. The latter route is rapidly saturable at doses higher than therapeutic doses. A minor pathway, catalyzed 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.
On the other hand, during massive intoxications, the quantity of this toxic metabolite is increased.
Elimination
Elimination is mainly urinary. 90% of the ingested dose is eliminated by the kidneys in 24 hours, mainly as glucuronide (60 to 80%) and sulfonide (20 to 30%). Less than 5% is eliminated unchanged.
The elimination half-life is approximately 2 hours.
Special populations
Renal impairment
In the event of renal impairment, the elimination of paracetamol and its metabolites is delayed.
Paracetamol has no or negligible influence on the ability to drive and use machines.
Pregnancy
Animal studies have not shown any evidence of teratogenic or foetotoxic effects from paracetamol.
A large amount of data from pregnant women demonstrates the absence of any malformation or fetal/neonatal toxicity. Epidemiological studies on the neurodevelopment of children exposed to paracetamol in utero have produced inconclusive results. If clinically necessary, paracetamol can be used during pregnancy; however, it should be used at the lowest effective dose for the shortest possible time and at the lowest possible frequency.
Breast-feeding
Paracetamol is eliminated in small amounts in breast milk following oral administration. Skin rash has been reported in breastfed infants.
At therapeutic doses, the administration of this medicinal product is possible during breast-feeding.
Fertility
Not applicable.
Combinations requiring precautions for use
+ Antivitamins K
Risk of an increased effect of antivitamin K and risk of bleeding if paracetamol is taken at maximum doses (4 g/day) for at least 4 days.
More frequent monitoring of INR. Possible adjustment of the antivitamin K dosage during treatment with paracetamol and after its discontinuation.
+ Flucloxacillin
Caution is advised when paracetamol is co-administered with flucloxacillin due to an increased risk of high anion gap metabolic acidosis (HAGMA), especially in patients with a risk factor for glutathione deficiency such as severe kidney failure, sepsis, malnutrition or chronic alcoholism. Close monitoring is recommended in order to detect the appearance of HAGMA by testing for urinary 5-oxoproline.
Interactions with paraclinical examinations
Use of paracetamol can interfere with blood glucose determination by the glucose oxidase-peroxidase method in case of abnormally high concentrations.
Use of paracetamol can interfere with the dosage of blood uric acid by the phosphotungstic acid method.
Some rare cases of hypersensitivity reactions such as anaphylactic shock, hypotension (as a symptom of anaphylaxis), angioedema, erythema, urticaria, skin rash have been reported. Their occurrence requires a definitive discontinuation of this medicinal product and related drugs.
Very rare cases of severe skin reactions (e.g. acute generalized exanthematous pustulosis, toxic epidermal necrolysis and Stevens-Johnson syndrome) have been reported and require discontinuation of treatment.
Very exceptional cases of thrombocytopenia, leukopenia and neutropenia have been reported.
Cases of diarrhea, abdominal pain, increased liver enzymes, increased or decreased INR have been reported.
Please inform your doctor of all undesirable effects upon drug administration.
The risk of severe poisoning may be particularly high in the elderly, in young children, in patients with liver damage, in chronic alcoholism, in patients with chronic malnutrition and in patients receiving enzymatic inducers. In these cases, poisoning can be fatal. The clinical symptoms of liver damage are usually seen after two days, and peak after 4 to 6 days.
Symptoms
Symptoms of overdose include nausea, vomiting, anorexia, pallor, malaise, sweating, abdominal pain generally appear within the first 24 hours.
An overdose, starting from 10 g of paracetamol in a single dose in adults and 150 mg/kg of body weight in a single dose in children, causes hepatocellular damage which can lead to complete and irreversible necrosis resulting in liver insufficiency, metabolic acidosis, and encephalopathy which can go as far as coma and death.
At the same time, this may also cause an increase in liver transaminases, lactate dehydrogenase, bilirubin and a decrease in the prothrombin level which can appear 12 to 48 hours after ingestion. The clinical symptoms of liver damage are usually seen after 1 to 2 days and peak after 3 to 4 days.
Management
- Immediate transfer to hospital.
- Collect a blood tube to make an initial plasma assay for paracetamol as soon as possible from the 4th hour after ingestion.
- Rapid evacuation of the ingested product by gastric lavage.
- Treatment of overdose conventionally includes administration as early as possible of the antidote N-acetylcysteine by IV route or by oral route if possible before the 10th hour.
- Symptomatic treatment.
- Liver tests should be done at the start of treatment and repeated every 24 hours. In most cases, liver transaminases return to normal within 1 to 2 weeks with complete restoration of liver function. However, in very severe cases, a liver transplant may be necessary.
Store in dry places, not exceeding 30°C, protect from light.
Special warnings
To avoid a risk of overdose:
- Check the absence of paracetamol in the composition of other medicines (including prescription and over-the-counter medications).
- Respect the maximum recommended doses.
Maximum recommended doses:
- In children weighing less than 40 kg, the total dose of paracetamol should not exceed 80 mg/kg/day (see section Overdose).
- In children weighing 41 kg to 50 kg, the total dose of paracetamol should not exceed 3 g per day (see section Overdose).
- In adults and children weighing over 50 kg, THE TOTAL DOSE OF PARACETAMOL SHOULD NOT EXCEED 4 GRAMS PER DAY (see section Overdose).
Paracetamol can cause serious skin reactions such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), Lyell’s syndrome and acute generalized exanthematous pustulosis (AGEP) which can be fatal. Patients should be informed of early signs of these serious skin reactions and an appearance of a rash or any other sign of hypersensitivity requires discontinuation of treatment.
Precautions for use
In children treated with 60 mg/kg/day of paracetamol, the combination of another antipyretic is only justified in the event of ineffectiveness.
Paracetamol should be used with caution in the event of:
- mild to moderate hepatocellular insufficiency,
- kidney failure,
- Gilbert syndrome (non-hemolytic familial jaundice),
- Glucose-6-phosphate dehydrogenase (G6PD) deficiency (which can lead to hemolytic anemia),
- chronic alcoholism, excessive alcohol consumption (3 or more alcoholic drinks each day),
- anorexia, bulimia or cachexia,
- chronic malnutrition (low reserves of hepatic glutathione),
- dehydration, hypovolemia.
If acute viral hepatitis is discovered, treatment should be discontinued.
Excipients
Sodium: This medicine contains 49.2 mg of sodium per sachet, equivalent to 2.46% of the WHO recommended maximum daily intake of 2 g in adults.
Aspartame: This medicine contains aspartame, which is a source of phenylalanine and so should not be given to patients with phenylketonuria, a rare genetic disorder in which phenylalanine builds up because the body cannot remove it properly.
Sucrose: Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.
Sunset yellow may cause allergic reactions.
Symptomatic treatment of mild to moderate pain and/or febrile conditions.
This presentation is reserved for children weighing 8 to 30 kg (approximately 6 months to 11 years).
Hypersensitivity to the active substance or to any of the excipients listed in this formulation.
Severe hepatocellular insufficiency or active decompensated liver disease.
POSOLOGY
Pediatric population
In children, it is important to follow the dosages defined according to the weight of the child and therefore to choose a suitable presentation. Approximate ages by weight are given for information.
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.
|
Body weight (age) |
Dose per administration |
Interval between each dose |
Maximum daily dose |
|
8 kg - 12 kg (about 6 to 24 months) |
150 mg (1 sachet) |
6 hours |
600 mg daily (4 sachets) |
|
13 kg - 15 kg (about 2 to 5 years old) |
150 mg
|
4 hours |
900 mg daily (6 sachets) |
|
16 kg - 24 kg (about 4 to 9 years old) |
300 mg
|
6 hours |
1200 mg daily
|
|
25 kg - 30 kg (about 8 to 11 years old) |
300 mg (2 sachets) |
4 hours |
1800 mg daily
|
For children, the total dose of paracetamol should not exceed 80 mg/kg/day (see section Overdose).
Maximum recommended doses: see section Special warnings and precautions for use.
Renal failure
In case of renal failure and unless medical advice, it is recommended to reduce the dose and increase the minimum interval between 2 doses according to the following table:
|
Creatinine clearance |
Interval between each dose |
|
≥50 mL/min |
4 hours |
|
10 - 50 mL/min |
6 hours |
|
<10 mL/min |
8 hours |
The total dose of paracetamol should not exceed 60 mg/kg/day.
Hepatic insufficiency
In patients with active or compensated chronic liver disease, especially those with hepatocellular insufficiency, chronic alcoholism, chronic malnutrition (low reserves of hepatic glutathione), Gilbert's syndrome (non-hemolytic familial jaundice) and dehydration, dose of paracetamol should not exceed 60 mg/kg/day.
Special clinical situations
The lowest possible effective daily dose should be considered, without exceeding 60 mg/kg/day (not more than 3 g/day) in the following conditions:
METHOD OF ADMINISTRATION
Oral use only.
Pour the contents of the sachet into a glass then add a small amount of liquid (for example water, milk, fruit juice). Drink immediately after complete dissolution.
FREQUENCY OF ADMINISTRATION
Observing the appropriate dose schedule avoids fluctuations in the control of pain and fever.
In children, the dose schedule must be regularly spaced, including at night at least 4 hours apart, preferably 6 hours apart.
Or as directed by the physician.
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