Alvedon Suppositories 60, 125, 250 mg.

Each suppository contains Paracetamol 60, 125 or 250 mg.

For excipients see 6.1.

Suppositories.

For the treatment of mild to moderate pain and pyrexia in children:

up to the age of 1 year - 60 mg suppositories

aged 1-5 years - 125 mg suppositories

aged 6-12 years - 250 mg suppositories

Alvedon suppositories may be especially useful in patients unable to take oral forms of paracetamol, e.g. post-operatively or with nausea and vomiting.

60 mg suppositories

Children 3 months to 1 year, 1-2 suppositories:

The dosage should be based on age and weight i.e.

3 months (5 kg) - 60mg (1 suppository)

1 year (10 kg) - 120mg (2 suppositories)

Infants under 3 months:

One suppository (60 mg) is suitable for babies who develop a fever following immunisation at 2 months. Otherwise only use in babies aged less than 3 months on a doctor's advice.

125 mg suppositories

Children 1-5 years, 1-2 suppositories:

The dosage should be based on age and weight i.e.

1 year (10 Kg) - 125mg (1 suppository)

5 years (20 Kg) -250mg (2 suppositories)

250 mg suppositories

Children 6 to 12 years 1-2 suppositories:

The dosage should be based on age and weight i.e.

6 years (20 Kg) - 250mg (1 suppository)

12 years (40 Kg) - 500mg (2 suppositories)

These doses may be repeated up to a maximum of 4 times in 24 hours. The dose should not be repeated more frequently than every 4 hours. The recommended dose should not be exceeded. Higher doses do not produce any increase in analgesic effect. Only whole suppositories should be administered – do not break suppository before administration.

Hypersensitivity to paracetamol or hard fat

Alvedon Suppositories should not be combined with other analgesic medications that contain paracetamol. Paracetamol should be given with care to patients with impaired kidney or liver function.

Label and Leaflet will state the following warnings:

Label:

“Immediate medical advice should be sought in the event of an overdose, even if the child seems well”.

“Do not give with any other Paracetamol-containing products.”

Leaflet:

“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.”

Drugs which induce hepatic microsomal enzymes such as alcohol, barbiturates and other anticonvulsants, may increase the hepatotoxicity of paracetamol, particularly after overdosage.

The anti-coagulant effect of warfarin and other coumarins may be enhanced by prolonged regular use of paracetamol with increased risk of bleeding. The effect appears to increase as the dose of paracetamol is increased, but can occur with doses as low as 1.5 – 2 g paracetamol per day for at least 5 – 7 days. Occasional doses have no significant effect.

Enzyme-inducing medicines, such as some antiepileptic drugs (phenytoin, phenobarbital, carbamazepine) have been shown in pharmacokinetic studies to reduce the plasma AUC of paracetamol to approx. 60 %. Other substances with enzyme-inducing properties, e.g. rifampicin and St. John's wort (hypericum) are also suspected of causing lowered concentrations of paracetamol. In addition, the risk of liver damage during treatment with maximum recommended doses of paracetamol will be higher in patients being treated with enzyme-inducing agents.

Not applicable.

None known.

Side-effects at therapeutic doses are rare.

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

Hepatic necrosis may occur after overdosage (see below).

Immediate treatment is essential in the management of paracetamol overdose. Despite a lack of significant early symptoms, patients should be referred to a hospital urgently for immediate medical attention. Administration of oral methionine or intravenous N-acetylcysteine which may have a beneficial effect up to at least 48 hours after the overdose, may be required. General supportive measures must be available.

Symptoms of paracetamol overdose in the first 24 hours are pallor, nausea, vomiting, anorexia and abdominal pain. Liver damage may become apparent 12 to 48 hours after ingestion ingestion and clinical symptoms generally culminate after 4-6 days.

Abnormalities of glucose metabolism and metabolic acidosis may occur. In severe poisoning, hepatic failure may progress to encephalopathy, coma and death. Acute renal failure with acute tubular necrosis may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have been reported.

Toxicity: 5 g during 24 hours in a child aged 3 ½ years,15-20 g in adults, caused fatal intoxication. The toxic dose for children and adults is generally>140 mg/kg. Malnutrition, dehydration, medication with enzyme-inducing drugs such as some antiepileptic drugs (phenytoin, phenobarbital, carbamazepine), rifampicin and St. John's wort (hypericum are risk factors, and even slight overdosage can then cause marked liver damage. Even subacute “therapeutic” overdose has resulted in severe intoxication with doses varying from 6 g/24 hours for a week, 20 g for 2-3 days, etc.

ATC code: N02BE01

Paracetamol is an aniline derivative with analgesic and antipyretic actions similar to those of aspirin but with no demonstrable anti-inflammatory activity. Paracetamol is less irritant to the stomach than aspirin. It does not affect thrombocyte aggregation or bleeding time. Paracetamol is generally well tolerated by patients hypersensitive to acetylsalicylic acid.

Paracetamol is well absorbed by both oral and rectal routes. Peak plasma concentrations occur about 2 to 3 hours after rectal administration. The plasma half life is about 2 hours.

Paracetamol is primarily metabolised in the liver by conjugation to glucuronide and sulphate. A small amount (about 3-10% of a therapeutic dose) is metabolised by oxidation and the reactive intermediate metabolite thus formed is bound preferentially to the liver glutathione and excreted as cystein and mercapturic acid conjugates. Excretion occurs via the kidneys. 2-3% of a therapeutic dose is excreted unchanged; 80-90% as glucuronide and sulphate and a smaller amount as cystein and mercapturic acid derivatives.

Not applicable

Hard fat (Witepsol H12)

None known.

3 years.

Do not store above 25°C.

PVC/polyethylene blister strips each containing 5 suppositories. Packs of 5 or 10 suppositories.

PVC/polyethylene blister strips each containing 1 suppository. Packs of 10 suppositories.

PVC/polyethylene blister strips each containing 1 suppository packed in high density polyethylene (HDPE) bottles with tamper-proof, child resistant, polypropylene (PP) lids. Packs of 10 suppositories.

Not all pack sizes may be marketed.

Peel the wrapper apart to remove the suppository, gently push into the rectum pointed end first.

AstraZeneca UK Ltd.,

600 Capability Green,

Luton,

LU1 3LU,

UK

PL 17901/0096, 0097, 0098

16^th June 2002

14^th September 2005