COMPOSITION: Each sachet 1.5 g contains:

Composition of active ingredient: Acetaminophen ………….80 mg

Composition of excipients: Sugar RE, lactose DC, tuiti fruit flavor, aspartame, microcrystalline cellulose & sodium carboxymethyl cellulose.

DOSAGE FORM:

Powder for oral suspension.

Homogeneous powder, not clotted, white or ivory, mixed fruit flavor, sweetness.

INDICATIONS:

Reduces fever.

For the treatment of mild to moderate pain due to: the common cold, flu, headache, sore throat, teething, immunization and tonsillectomy.

Treatment for children with weight from 6 – 20 kg.

DOSAGE AND ADMINISTRATION:

Administration:

Oral route. Stirring the powder into an appropriate amount of water and drink immediately.

If the child’s temperature exeeds 38.5⁰C, the following steps will improve the efficacy of the drug treatment.

– Take off the child’s clothes.

– Give the child more drinks.

– Do not leave the child in an excessively warm place.

– If necessary, bathe the child with warm water of 2°C lower than the child’s body temperature.

Dosage:

This presentation is restricted to children weighing from 6 to 20 kg (about 1 to 7 years).

DOSAGE MUST BE DETERMINED BY THE PATIENT’S WEIGHT.

Approximate ages related to weight are given below as guidance only. To avoid the risk of overdose, check that concomitant medications (including prescription and non-prescription) do not contain acetaminophen (see “Warnings and precautions for use”).

TYDOL 80 should be administered as 10 to 15 mg/kg/dose, every 4 to 6 hours, up to a maximum total daily dose of 60 mg/kg/day. The maximum daily dose must not exceed 3 grams.

* Approximate age ranges relative to weight are given as guidance only.

Renal impairment:

In patients with severe renal impairment, the minimum interval between each administration should be modified according to the following schedule:

Hepatic impairment:

In patients with chronic or compensated active hepatic disease, especially those with hepatocellular insufficiency, chronic alcoholism, chronic malnutrition (low reserves of hepatic glutathione), and dehydration, the dose should not exceed 3 g/day.

Frequency of timing administration:

In children, there should be an interval between administration, during both day and night, preferably of 6 hours, or at least 4 hours. This administration frequency avoids changes in pain or fever levels.

In case of serious kidney disease (severe renal insufficiently), see “Dosage and Administration, renal impairment”.

CONTRAINDICATIONS:

This medicine must not be used in the following cases:

• Known allergy to acetaminophen or to propacetamol hydrochloride (prodrug of acetaminophen) or to any the components of this medicine.
• Severe liver disease or active liver disease.
• Glucose-6-Phosphate Dehydrogenase (G6PD)

WARNINGS AND PRECAUTIONS FOR USE:

Warnings:

Consult your doctor immediately in the event of overdose or accidental administration of an excessively high dose.

This medicine contains acetaminophen. Other medicines may also contain this substance. Do not combine such medicines in order not to exceed the recommended daily dosage (see “Dosage and Administration”).

Administration of acetaminophen doses higher than recommended entails the risk for very serious liver damage. Clinical symptoms of liver damage are usually first seen after 1 to 2 days following acetaminophen overdose. Maximum liver damage symptoms are usually observed after 3 to 4 days. Treatment with antidote should be given as soon as possible (see “Overdose and treatment“).

Acetaminophen should be used with caution in cases of:

• Hepatocellular insufficiency.
• Severe renal insufficiency (Clearance of creatinine ≤ 30 mL/min).
• Anorexia, bulimia or cachexia, chronic malnutrition (low reserves of hepatic glutathione)
• Dehydration, hypovolemia.

Doctors need to warn patients about the signs of serious skin reactions such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), Lyell’s syndrome, acute generalized exanthematous pustulosis (AGEP).

Precautions for use:

If the pain persists for more than 5 days, or fever for more than 3 days, or if the drug is insufficiently effective, or if any other symptom develops, do not continue the treatment without consulting your doctor.

In case of severe liver or kidney disease, you must consult your doctor before taking acetaminophen.

This medicine contains:

Lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Sucrose. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

40 mg aspartame/sachet. Aspartame is a source of phenylalanine. It may be harmful if patients have phenylketonuria (PKU), a rare genetic disorder in which phenylalanine builds up because the body cannot remove it properly.

PREGNANCY AND LACTATION:

Not applicable

EFFECTS ON ABILITY TO DRIVE AND OPERATE MACHINERY:

Not relevant.

INTERACTIONS AND INCOMPATIBILITIES:

Interactions:

If the doctor prescribes an assay of blood uric acid or sugar levels, you should inform him that your child is taking this drug.

In order to avoid potential interactions between different medicines you should always inform your doctor or pharmacist if other medicines are being taken.

Effects of TYDOL 80 on other drugs

• TYDOL 80 may increase the chance of unwanted effects when administered with other drugs.
• Oral anticoagulants: acetaminophen may enhance the effect of anticoagulants.

Effects of other drugs on TYDOL 80

• Phenytoin administered concomitantly may result in decreased acetaminophen effectiveness and an increased risk of hepatotoxicity. Patients receiving phenytoin therapy should avoid large and/or chronic doses of acetaminophen. Patients should be monitored for evidence of hepatotoxicity.
• Probenecid causes an almost two-fold reduction in clearance of acetaminophen by inhibiting its conjugation with glucuronic acid. A reduction of the acetaminophen dose should be considered when administered concomitantly with probenecid.
• Salicylamide may prolong the elimination half-life of acetaminophen.
• Enzyme-inducing substances: caution should be exercised when acetaminophen is taken concomitantly with enzyme-inducing substances. These substances include barbiturates, isoniazid, carbamazepine, rifampicin, and ethanol (see “Overdose and treatment”).

Incompatibilities: Not applicable.

SIDE EFFECTS:

Like all medicines, this product may, in certain individuals, bring about effects of greater or lesser severity.

The following adverse reactions have been reported during post-marketing surveillance but the incidence rate (frequency) is not known.

Blood and lymphatic system disorders: thrombocytopenia, neutropenia, leukopenia.

Gastrointestinal disorders: diarrhoea, abdominal pain.

Hepatobiliary disorders: hepatic enzyme increased.

Immune system disorders: anaphylaxis shock, Quincke’s edema, hypersensitivity reaction.

Investigations: INR value increased, INR value decreased.

Skin and subcutaneous tissue disorders: urticarial, erythema, rash, acute generalized exanthematous pustulosis, toxic epidermal necrolysis, Stevens-Johnson Syndrome.

Vascular disorders: hypotension (as a symptom of anaphylaxis).

Immediately inform doctors or physicians on any adverse drug reactions happened when using this drug.

OVERDOSE AND TREATMENT:

Inform immediately to doctor in case of overdose or poinson.

Signs and symptoms

There is a risk of poisoning, particularly in patients with liver disease, in patients with chronic malnutrition, and in patients receiving enzyme inducer. Overdosing may be fatal, especially in these cases (see “Warnings and Precautions for use” and “Interactions and Incompatibilities”).

Symptoms that generally appear within the first 24 hours include nausea, vomiting, anorexia, pallor, malaise, and diaphoresis.

Overdose with an acute ingestion of 7.5 g or more of acetaminophen in adults, or 140 mg/kg of body weight in children, causes cytolytic hepatitis likely to induce complete and irreversible necrosis, resulting in hepatocellular insufficiency, metabolic acidosis, and encephalopathy, which may lead to coma and death.

Simultaneously, increased levels of hepatic transaminases (AST, ALT), lactate dehydrogenase and bilirubin are observed together with decreased prothrombin levels that may appear 12 to 48 hours after ingestion. Clinical symptoms of liver damage are usually evident initially after 1 to 2 days, and reach a maximum after 3 to 4 days.

Treatment:

Immediate hospitalisation.

Before beginning treatment, obtain a tube of blood for plasma acetaminophen assay, as soon as possible, but no sooner than 4 hours after acetaminophen ingestion.

Elimination of ingested medicine by gastric lavage.

The principal antidotal treatment is the administration of sulfhydryl compounds (for example N-acetylcysteine or methionine), which probably act, in part, by replenishing hepatic stores of glutathione. N-acetylcysteine is effective when given orally or intravenously. The antidote should be administered immediately as soon as possible if less than 36 hours has elapsed since ingestion of acetaminophen, although treatment with N-acetylcysteine is more effective when given less than 10 hours after ingestion. When given orally, N-acetylcysteine solution is diluted with water or soft drinks to achieve a 5% solution and should be consumed within 1 hour of preparation. An oral loading dose of 140 mg/kg is given, followed by the administration of 70 mg/kg every 4 hours for 17 doses. Treatment is terminated if assays of acetaminophen in plasma indicate that the risk of hepatotoxicity is low. N-acetylcysteine can also be used intravenously: initial dose of 150 mg/kg, diluted in 200 ml of glucose 5% for intravenous injection for 15 minutes; then intravenous infusion for 4 hours with dose of 50 mg/kg diluted in 500 ml of glucose 5%; after than is 100 mg/kg in 1 liter of solution within the next 16 hours. In case do not have glucose 5% solution, sodium chloride 0.9% solution can be used. Adverse reactions to N-acetylcysteine include skin rash (including urticaria, which does not require one to discontinue treatment), nausea, vomiting, diarrhea, and anaphylactoid reactions. If N-acetylcysteine is not available, methionine should be given. If activated charcoal has been given before using methionine, firstly it should withdraw activated carbon from the stomach. In addition activated charcoal and/or saline cathartics which may reduce acetaminophen absorption should be given.

Symptomatic treatment.

Hepatic tests must be conducted at the beginning of treatment and repeated every 24 hours. In most cases, hepatic transaminases return to normal in 1 to 2 weeks with full restitution of the liver function. In very severe cases, however, liver transplantation may be necessary.

PHARMACODYNAMICS:

Pharmacotherapeutic group: Other analgesics and antipyretics

ATC code: N02BE01

Acetaminophen (paracetamol or N-acetyl-p-aminophenol), an active metabolite of phenacetine, produces analgesia and antipyresis by a mechanism similar to that produced by aspirin. However, unlike aspirin, acetaminophen does not have anti-inflammatory activity. In equal doses, the degree of analgesia and antipyresis produced by acetaminophen is similar to that produced by aspirin.

Acetaminophen lowers body temperature in patients with fever but rarely lowers normal body temperature. The drug acts on the hypothalamus to produce antipyresis, heat dissipation is increased as a result of vasodilation and increased peripheral blood flow.

Acetaminophen is chosen usually as analgesia and antipyresis, especially in elderly patients and the patients whom salicylates or other NSAIDs are contraindicated, such as patients as asthma, have a history of peptic ulcer and children.

PHARMACOKINETICS:

Absorption: Acetaminophen is rapidly and almost completely absorbed from the GI tract following oral administration. Food rich in carbohydrate reduces the absorption rate of acetaminophen. Peak plasma concentrations are attained within 30 – 60 minutes after therapeutic doses.

Distribution: Acetaminophen is rapidly and uniformly distributed into most body tissues. About 25% of acetaminophen in blood is bound to plasma proteins.

Elimination: Acetaminophen has a plasma half-life of 1.25 – 3 hours. Plasma half-life of acetaminophen may be prolonged following toxic doses or in patients with liver damage. Following therapeutic doses 90 – 100% of drug may be recovered in the urine within the first day, primarily after hepatic conjugation with glucuronic acid (about 60%), sulfuric acid (about 35%) or cysteine (about 3%); small amounts of hydroxylated and deacetylated metabolites also have been detected. Small children have less capacity for glucuronidation of the drug than do adults.

Acetaminophen is metabolized by a cytochrome P450 microsomal enzyme to form N-acetyl-benzoquinoneimine (NAPQ), a high reactive intermediate metabolite. Normally, this metabolite reacts with the sulfhydryl groups of glutathione and is thereby inactivated. However, with high doses of acetaminophen, this metabolite is formed just enough to deplete the liver glutathione; under these circumstances, NAPQ does not conjugate with glutathione which cause hepatotoxicity, leading to hepatitis and can lead to hepatic necrosis.

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 30^oC, in a dry place, protect from light

Shelf-life: 48 months from manufacturing date. Do not use after expiry date

Specification of drug: Manufacturer’s