PARACETAMOL ADULT

Posology Adults and adolescents over 16 years: 500mg (5ml) or 1000mg (10ml) up to three to four times a day, as required. Maximum daily dose should not exceed 4g (40ml). The dose should not be repeated more frequently than every four hours, and not more than four doses should be taken in any 24 hour period.

Special Populations Renal impairment:

When a 500 mg administration is possible: It is recommended, when giving paracetamol to patients with renal impairment, to reduce the dose and to increase the minimum interval between each administration to at least 6 hours unless directed otherwise by a physician.

See Table below:

Adults: Glomerular filtration rate Dose 10-50 ml/min 500mg every 6 hours <10ml/min 500mg every 8 hours Hepatic impairment: In patients with hepatic impairment or Gilbert’s Syndrome, the dose should be reduced or the dosing interval prolonged.

The daily dose should not exceed 2g/day unless directed by a physician.

The elderly:

Experience has indicated that normal adult dosage is usually appropriate. However in frail, immobile, elderly subjects or in elderly patients with renal or hepatic impairment, a reduction in the amount or frequency of dosing may be appropriate.

The maximum daily dose should not exceed 60mg/kg/day (up to a maximum of 2g per day) in the following situations, unless directed by a physician: • Weight less than 50kg • Chronic alcoholism • Dehydration • Chronic malnutrition Method of administration For oral administration only

The following convention has been utilised for the classification of the frequency of adverse reactions: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1,000, <1/100), rare (≥1/10,000, <1/1000), very rare (<1/10,000), not known (cannot be estimated from available data).

Adverse effects of paracetamol are rare but hypersensitivity including skin rash may occur. There have been reports of blood dyscrasias including methaemoglobenaemia and agranulocytosis, but these were not necessarily causally related to paracetamol.

Very rare:

Thrombocytopaenia. Very rare cases of serious skin reactions have been reported.

Very rare:

Cutaneous hypersensitivity reactions including, among others, skin rashes, angioedema, Stevens Johnson syndrome and Toxic Epidermal Necrolysis. Cases of acute pancreatitis have been reported. Paracetamol has been widely used and reports of adverse reactions are rare, and are generally associated with overdosage.

Allergic reactions occur occasionally.

Very rare:

Anaphylaxis.

Very rare:

Bronchospasm in patients sensitive to aspirin and other NSAIDs.

Very rare:

Hepatic dysfunction.

Uncommon:

Nephrotoxic effects have not been reported in association with therapeutic doses, except after prolonged administration. High Anion Gap Metabolic Acidosis (HAGMA) may occur with an unknown frequency. 4). Pyroglutamic acidosis may occur as a consequence of low glutathione levels in these patients.

2 where relevant): • Hepatic impairment • Renal impairment (GFR≤50ml/min) • Gilbert’s Syndrome (familial non-haemolytic jaundice) • Concomitant treatment with medicinal products affecting hepatic function • Glucose-6-phosphate dehydrogenase deficiency (may lead to methaemoglobinaemia and haemolytic anaemia) • Haemolytic anaemia • Elderly Cases of hepatic dysfunction/ failure have been reported in patients with depleted glutathione levels, such as those who are severely malnourished, anorexic, have a low body mass index, dehydrated, are chronic heavy users of alcohol or have sepsis.

In patients with glutathione-depleted states the use of paracetamol may increase the risk of metabolic acidosis. In general, medicinal products containing paracetamol should be taken for only a few days without the advice of a physician or dentist and not at high doses.

If high fever or signs of secondary infection occur or if symptoms persist for longer than 3 days, a physician should be consulted. Prolonged or frequent use is discouraged. Patients should be advised not to take other paracetamol containing products concurrently.

Taking multiple daily doses in one administration can severely damage the liver; in such case medical assistance should be sought immediately. Care is advised in the administration of paracetamol to patients with severe renal or severe hepatic impairment.

The hazards of overdose are greater in those with non-cirrhotic alcoholic liver disease. g. chronic alcoholism) who were treated with paracetamol at therapeutic dose for a prolonged period or a combination of paracetamol and flucloxacillin.

If HAGMA due to pyroglutamic acidosis is suspected, prompt discontinuation of paracetamol and close monitoring is recommended. The measurement of urinary 5-oxoproline may be useful to identify pyroglutamic acidosis as underlying cause of HAGMA in patients with multiple risk factors.

1. Patients with severe hepatic dysfunction. Do not use this medicine in children and adolescents under 16 years.