4.1. Therapeutic indications

For the treatment of mild to moderate pain and as an anti-pyretic. It can be used in many conditions including headache, toothache, earache, sore throat, colds and influenza, aches and pains and post-immunisation fever.

4.2. Posology and method of administration

Child's Age

How Much

How often

(in 24 hours)

6 – 8 years

One 5 ml spoonful (large end)

4 times

8 – 10 years

One 5.0 ml spoonful (large end) and

one 2.5 ml spoonful (small end)

4 times

10 – 12 years

Two 5 ml spoonfuls (large end)

4 times

• Do not give more than 4 doses in any 24 hour period

• Leave at least 4 hours between doses

• Do not give this medicine to your child for more than 3 days without speaking to your doctor or pharmacist

• Do not give to children under the age of 6 years

Children aged 12 - 16 years: Two – three 5 ml spoonfuls (large end) up to 4 times a day.

Adults and children over 16 years: Two – four 5 ml spoonfuls (large end) up to 4 times a day.

The Elderly:

In the elderly, the rate and extent of paracetamol absorption is normal but plasma half-life is longer and paracetamol clearance is lower than in young adults.

It is important to shake the bottle for at least 10 seconds before use.

4.3. Contraindications

Hypersensitivity to Paracetamol or any of the other constituents.

Patients with rare hereditary problem of fructose intolerance should not take this medicine.

4.4. Special warnings and precautions for use

Paracetamol Oral Suspension 250mg/5ml should be used with caution in severe renal or severe hepatic impairment. The hazards of overdose are greater in those with non-cirrhotic alcoholic liver disease

Hydrogenated glucose syrup may have a laxative effect. Each 5 ml spoonful of this product contains 3.93g of hydrogenated glucose syrup. Calorific value 2.3 kcal/g of hydrogenated glucose syrup.

Cases of high anion gap metabolic acidosis (HAGMA) due to pyroglutamic acidosis have been reported in patients with severe illness such as severe renal impairment and sepsis, or in patients with malnutrition and other sources of glutathione deficiency (e.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.

The label should contain the following statements:

• Contains paracetamol.

• Do not give this medicine with any other paracetamol-containing product.

• For oral use only.

• Never give more medicine than shown in the table.

• Do not overfill the spoon.

• Always use the spoon supplied with the pack.

• Do not give more than 4 doses in any 24 hour period.

• Leave at least 4 hours between doses.

• Do not give this medicine to your child for more than 3 days without speaking to your doctor or pharmacist.

• As with all medicines, if your child is currently taking any medicine consult your doctor or pharmacist before taking this product.

• Do not store above 25°C. Store in the original package.

• Keep all medicines out of the reach and sight of children.

• Immediate medical advice should be sought in the event of an overdose, even if the child seems well (label).

• Immediate medical advice should be sought in the event of an overdose, even if the child seems well, because of the risk of delayed, serious liver damage (leaflet).

4.5. Interaction with other medicinal products and other forms of interaction

The speed of absorption of Paracetamol may be increased by metoclopramide or domperidone and absorption reduced by cholestyramine.

The anti-coagulant effect of warfarin and other coumarins may be enhanced by prolonged regular use of Paracetamol with increased risk of bleeding; occasional doses have no significant effect.

Chronic alcohol intake can increase the hepatotoxicity of paracetamol overdose and may have contributed to the acute pancreatitis reported in one patient who had taken an overdose of paracetamol. Acute alcohol intake may diminish an individual's ability to metabolise larger doses of paracetamol, the plasma half-life of which can be prolonged.

The use of drugs which induce hepatic microsomal enzymes such as anti-convulsants or oral contraceptives may increase the extent of metabolism of paracetamol, resulting in reduced plasma concentration of the drug and a faster elimination rate.

Caution should be taken when paracetamol is used concomitantly with flucloxacillin as concurrent intake has been associated with high anion gap metabolic acidosis due to pyroglutamic acidosis , especially in patients with risks factors (see section 4.4)

4.6. Fertility, pregnancy and lactation

Epidemiological studies in human pregnancy have shown no ill effects due to Paracetamol used in the recommended dosage, but patients should follow the advice of their doctor regarding its use. A large amount of data on pregnant women indicate neither malformative, nor feto/neonatal toxicity. Epidemiological studies on neurodevelopment in children exposed to paracetamol in utero show inconclusive results. If clinically needed, 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.

Paracetamol is excreted in breast milk but not in a clinically significant amount. Available published data does not contraindicate breast-feeding.

4.8. Undesirable effects

Adverse effects of Paracetamol are rare. Very rare cases of serious skin reactions have been reported. Very rarely hypersensitivity and anaphylactic reactions including skin rash may occur.

There have been reports of blood dyscrasias including thrombocytopenia and agranulocytosis, but these were not necessarily causally related to Paracetamol.

Chronic hepatic necrosis has been reported in a patient who took daily therapeutic doses of paracetamol for about a year and liver damage has been reported after daily ingestion of excessive amounts for shorter periods. A review of a group of patients with chronic active hepatitis failed to reveal differences in the abnormalities of liver function in those who were long-term users of paracetamol nor was the control of the disease improved after paracetamol withdrawal.

SOC Metabolism and nutrition disorders

“High anion gap metabolic acidosis'' with frequency ''Not known'' (cannot be estimated from the available data)

Description of selected adverse reactions

High anion gap metabolic acidosis

Cases of high anion gap metabolic acidosis due to pyroglutamic acidosis have been observed in patients with risk factors using paracetamol (see section 4.4). Pyroglutamic acidosis may occur as a consequence of low glutathione levels in these patients.

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 reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard.

4.9. Overdose

Liver damage is possible in adults who have taken 10 g or more Paracetamol. Ingestion of 5 g or more of paracetamol may lead to liver damage if the patient has risk factors (see below).

Risk factors:

If the patient

a. Is on long term treatment with carbamazepine, phenobarbitone, phenytoin, primidone, rifampicin, St John's Wort or other drugs that induce liver enzymes.

b. Regularly consumes ethanol in excess of recommended amounts.

c. Is likely to be glutathione deplete e.g. eating disorders, cystic fibrosis, HIV infection, starvation, cachexia.

Symptoms:

Symptoms of Paracetamol overdosage in the first 24 hours are pallor, nausea vomiting, anorexia and abdominal pain. Liver damage may become apparent 12 to 48 hours after ingestion. Abnormalities of glucose metabolism and metabolic acidosis may occur. In serve poisoning, hepatic failure may progress to encephalopathy, haemorrhage, hypoglycaemia, cerebral oedema and death. Acute renal failure with acute tubular necrosis, strongly suggest by loin pain, haematuria and proteinuria, may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatits have been reports.

Management:

Immediate treatment is essential in the management of Paracetamol overdose. Despite a lack of significant early symptoms, patients should be referred to hospital urgently for immediate medical attention. Symptoms may be limited to nausea or vomiting and may not reflect the severity of overdose or the risk of organ damage, Management should be in accordance with established treatment guidelines, See BNF overdose

Treatment with activated charcoal should be considered if the overdose has been taken within 1 hour.

Plasma paracetamol concentration should be measured at 4 hours or later after ingestion (earlier concentration are unreliable). Treatment with N-acetylcysteine may be used up to 24 hours after ingestion of paracetamol; however, the maximum protective effect is obtained up to 8 hours post-ingestion. The effectiveness of the antidote declines sharply after this time. If required the patient should be given intravenous N-acetylcysteine, in line with the established dosage schedule. If vomiting is not a problem, oral methionine may be suitable alternative for remote areas, outside hospital. Management of patients who present with serious hepatic dysfunction beyond 24 hours form ingestion should be discussed with the NPIS or a liver unit.