COMPOSITION: Each sachet of 1.5 g contains:
Composition of active ingredient:
Acetaminophen……………………………………….. 250 mg
(as microencapsulated acetaminophen)
Composition of excipients:
Sugar RE, flowlac 100, tuiti fruit flavor, aspartam, microcrystalline cellulose & sodium carboxymethyl cellulose.
DOSAGE FORM:
Powder for oral suspension
White or ivory-white powder, specific fragrance, sweet taste.
INDICATIONS:
Reduces fever.
For the treatment of mild to moderate pain due to the common cold, flu, headache, sore throat, teething, immunization, and tonsillectomy.
DOSAGE AND ADMINISTRATION:
Dosage:
Pediatric population
In children, it is imperative to respect the dosages defined according to the child’s weight. So choose a suitable presentation. The approximate ages based on weight are given as information.
The recommended daily dose of acetaminophen is approximately 60 mg/kg/day, divided into 4 or 6 doses, approximately 15 mg/kg every 6 hours or 10 mg/kg every 4 hours.
| Weight (kg) | Age | Dose |
| 13 kg – 20 kg | approximately 2 to 7 years | 1 sachet every 6 hours,
not exceed 4 sachets/24 hours |
| 21 kg – 25 kg | approximately 6 to 10 years | 1 sachet every 4 hours,
not exceed 6 sachets/24 hours |
| 26 kg – 40 kg | approximately 8 to 13 years | 2 sachets every 6 hours,
not exceed 8 sachets/24 hours |
| 41 kg – 50 kg | approximately 12 to 15 years | 2 sachets every 4 hours,
not exceed 12 sachets/24 hours |
For children, the total dose of acetaminophen should not exceed 80 mg/kg/day.
The maximum recommended dose: see Warnings and precautions for use.
Renal failure
In case of renal insufficiency and except medical advice, it is recommended to reduce the dose and increase the minimum interval between 2 doses according to the following table:
| Clearance of creatinine | Administration interval |
| ≥ 50 mL/min | 4 hours |
| 10 – 50 mL/min | 6 hours |
| < 10 mL/min | 8 hours |
The total dose of acetaminophen should not exceed 3 g/day.
Hepatic failure
In patients with chronic or active compensated liver disease, particularly those with hepatocellular insufficiency, chronic alcoholism, chronic malnutrition (low liver glutathione reserves), Gilbert’s syndrome (non-hemolytic familial jaundice), and dehydration, a dose of acetaminophen should not exceed 3 g/day.
Administration:
Oral administration.
Stirring the powder into an appropriate amount of water and drink immediately.
Frequency of administration:
The frequency helps to avoid oscillations of pain or fever:
- In children, the doses should be regularly spaced, including at night, preferably 6 hours and at least 4 hours
- In adults, the doses should be spaced at least 4 hours.
CONTRAINDICATIONS:
- Hypersensitivity to acetaminophen, or to any component of this medicine.
- Severe hepatocellular insufficiency or active decompensated liver disease.
WARNINGS AND PRECAUTIONS FOR USE:
Special warnings
To avoid the risk of overdose:
- Do not use with other drugs containing acetaminophen (including prescription and non-prescription drugs),
- Respect the maximum recommended doses.
The maximum recommended doses:
- In children weighing less than 40 kg, the total dose of acetaminophen should not exceed 80 mg/kg/day.
- In children from 41 kg to 50 kg, the total dose of acetaminophen should not exceed 3 g/day.
- In adults and children over 50 kg, the total dose of acetaminophen should not exceed 4 g/day.
Acetaminophen may cause severe skin reactions such as acute generalized exanthematous pustulosis (AGEP), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN), which can be life-threatening. Patients should be informed of the early signs of these serious skin reactions, and the onset of a rash or any other sign of hypersensitivity requires discontinuation of treatment.
Precautions for use
In a child treated with 60 mg/kg/day acetaminophen, the combination of another antipyretic is justified only in the case of ineffectiveness.
Acetaminophen should be used with caution in case:
- weight <50 kg
- mild to moderate hepatocellular insufficiency,
- renal failure,
- Gilbert’s syndrome (non-hemolytic familial jaundice),
- deficiency of Glucose-6-Phosphate Dehydrogenase (G6PD) (which can lead to anemia hemolytic)
- chronic alcoholism, excessive alcohol consumption (3 or more alcoholic beverages each day),
- anorexia, bulimia or cachexia,
- chronic malnutrition (low liver glutathione reserves),
- dehydration, hypovolemia.
If acute viral hepatitis is found, the treatment should be discontinued.
This drug contains:
- Lactose and sucrose. Patients with rare hereditary problems of galactose intolerance, fructose intolerance, total lactase deficiency, sucrase-isomaltase insufficiency, or glucose-galactose malabsorption should not take this drug.
- Aspartame: This medicine contains 40 mg aspartame in each sachet 1.5 g which is equivalent to 67 mg/g. Aspartame is a source of phenylalanine. It may be harmful if you have phenylketonuria (PKU), a rare genetic disorder in which phenylalanine builds up because the body cannot remove it properly.
PREGNANCY AND LACTATION:
Pregnancy:
Studies in animals have not shown any teratogenic or fetotoxic effect of acetaminophen.
Clinically, the results of epidemiological studies seem to exclude a particular malformation or fetotoxic effect of acetaminophen.
Prospective data on pregnant women exposed to acetaminophen overdose did not show an increased risk of malformation.
The recommended dosage and duration of treatment should be strictly followed.
Therefore, acetaminophen, under normal conditions of use, maybe prescribed throughout pregnancy.
Lactation:
A small quantity acetaminophen is passed through into breast milk following oral administration. Cases of skin rash have been reported in breastfed infants. At therapeutic doses, administration of this drug is possible during breastfeeding.
EFFECTS ON ABILITY TO DRIVE AND OPERATE MACHINERY:
Acetaminophen has no or negligible effect on the ability to drive and operate machines.
INTERACTIONS AND INCOMPATIBILITIES:
Interactions:
- Phenytoin: phenytoin administered in combination may cause a decrease in the efficacy of acetaminophen and an increased risk of hepatotoxicity. Patients who are receiving phenytoin treatment should avoid large and/or chronic doses of acetaminophen. Patients will be monitored for signs of hepatotoxicity.
- Probenecid: probenecid results in a decrease of almost half the clearance of acetaminophen by inhibiting its conjugation to glucuronic acid. A decrease in the dose of acetaminophen should be considered when co-administered with probenecid.
- Salicylamide: salicylamide may prolong the elimination half-life of acetaminophen.
- Enzyme-inducing agents: caution in combination use acetaminophen and enzyme-inducing agents. These substances include barbiturates, isoniazid, carbamazepine, rifampicin, and ethanol.
- Caution when combined with oral anticoagulants: the risk of an increase in the effect of oral anticoagulant and hemorrhagic risk when taking acetaminophen at maximum doses
(4 g/day) for at least 4 days. Regular control of the INR. The possible adjustment of oral anticoagulant dosage during acetaminophen treatment and after discontinuation. - Interactions with paraclinical examinations: taking acetaminophen may interfere with the determination of glucose by the glucose oxidase-peroxidase method in cases of abnormally high concentrations. Taking acetaminophen may interfere with the determination of blood uric acid by the phosphotungstic acid method.
Incompatibilities:
Not applicable.
SIDE EFFECTS:
- Few cases of hypersensitivity reactions such as anaphylactic shock, hypotension (as a symptom of anaphylaxis), Quincke edema, erythema, urticaria, skin rash have been reported. Their occurrence imposes the definitive discontinuation of this drug and related drugs.
- Very rare cases of serious skin reactions (acute generalized exanthematous pustulosis, toxic epidermal necrolysis and Stevens-Johnson Syndrome) have been reported, and require cessation 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.
Immediately inform doctors or physicians of any adverse drug reactions that happened when using this drug.
OVERDOSE AND TREATMENT:
The risk of severe intoxication may be particularly high in the elderly, in young children, in patients with liver injury, in chronic alcoholism, in patients suffering from chronic malnutrition, and in patients receiving enzyme-inducing agents. In these cases, intoxication can be fatal.
Symptoms:
Nausea, vomiting, anorexia, paleness, malaise, sweating, abdominal pain usually appear in the first 24 hours.
Overdose, starting with 10 g of acetaminophen in a single dose in adults or 150 mg/kg of body weight in a single dose in children, causes hepatic cytolysis which may result in complete and irreversible necrosis, hepatocellular insufficiency, metabolic acidosis, and encephalopathy that can lead to coma and death. At the same time, there is an increase in hepatic transaminases (AST, ALT), lactate dehydrogenase, bilirubin, and a decrease in the prothrombin level that may occur 12 to 48 hours after oral administration. Clinical symptoms of liver damage are usually seen after 1 to 2 days, and peak after 3 to 4 days.
Treatment:
- Immediate transfer to hospital.
- Collect a tube of blood to do the initial plasma acetaminophen assay as soon as possible from the 4th hour after ingestion.
- Rapid evacuation of the ingested drug by gastric lavage.
- Treatment of overdose typically involves as early as possible administration of the antidote N-acetylcysteine by I.V. or oral route if possible before the tenth hour.
- Symptomatic treatment.
- Liver tests should be performed at the beginning of treatment and repeated every 24 hours. In most cases, hepatic transaminases return to normal in 1 to 2 weeks with complete restitution of liver function. However, in very severe cases, liver transplantation may be necessary.
PHARMACODYNAMICS:
Pharmacotherapeutic group: Analgesic; antipyretic.
ATC code: N02B E01
Action mechanism: Acetaminophen has a central and peripheral mechanism of action.
PHARMACOKINETICS:
Absorption:
Oral acetaminophen absorption is complete and rapid. Maximum plasma concentrations are reached 30 to 60 minutes after oral administration.
Distribution:
Acetaminophen is rapidly distributed in all tissues. The concentration is similar in blood, saliva, and plasma. Plasma protein binding is low.
Biotransformation:
Acetaminophen is metabolized mainly in the liver. The two major metabolic pathways are glucuronic acid conjugation and sulfuric acid conjugation. The latter route is rapidly saturable at doses that exceed the therapeutic doses. A small fraction is catalyzed by cytochrome P 450 to 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. However, during massive intoxications, the quantity of this toxic metabolite is increased.
Elimination:
The elimination is mainly urine. 90% of the administered dose is eliminated by the kidney in 24 hours, mainly as glucuronide (60 to 80%) and sulfate (20 to 30%) conjugates. Less than 5% is eliminated as unchanged drug. The elimination half-life is about 2 hours.
Renal impairment:
In case of severe renal impairment, the elimination of acetaminophen and its metabolites are delayed.
Elderly:
Conjugation capacity is not changed.
DESCRIPTION OF PACKAGING:
Box of 12 sachets x 1.5 g powder for oral suspension.
STORAGE, SHELF-LIFE, SPECIFICATION OF DRUG:
Storage: Store at temperature below 30oC, in a dry place, protect from light.
Shelf-life: 36 months from manufacturing date. Do not use after expiry date.
Specification of drug: Manufacturer’s
