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

-          Paracetamol 60 mg suppository is indicated in children aged up to 1 year.

-          Paracetamol 125 mg suppository is indicated in children aged 1 to 5 years.

-          Paracetamol 250 mg suppository is indicated in children aged 6 to 12 years.

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

Posology

-          Children under 3 months of age (60 mg suppositories)

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.

-          Children 3 months to 1 year (60 mg suppositories)

-          Children 1 to 5 years (125 mg suppositories)

-          Children 6 to 12 years (250 mg suppositories)

 Method of administration

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.

Revanin 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.

Doses higher than those recommended involve a risk of very severe liver damage. Liver damage is also associated with certain risk factors (see also Section 4.5 Interaction with other medicinal products and other forms of interaction, and Section 4.9 Overdose). If liver damage is suspected then liver function tests should be performed.

Do not exceed the recommended dose. If symptoms persist consult your doctor. Keep out of the sight and reach of children.

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.

Probenicid inhibits the glucuronidation of paracetamol which can affect the clearance of paracetamol. This should be considered when these medicines are administered concomitantly.

Paracetamol may affect the pharmacokinetics of chloramphenicol. This interaction should be considered when these medications are administered concomitantly, especially in malnourished patients.

Enzyme-inducing medicines, such as some antiepileptic drugs (phenytoin, phenobarbital, carbamazepine, primidone) 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.

Not relevant.

Side-effects at therapeutic doses are rare.

Very rare cases of serious skin reactions have been reported.

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).

Reporting of suspected adverse reactions

• Saudi Arabia:

The National Pharmacovigilance and Drug Safety Centre (NPC)

Fax: +966-11-205-7662

Call NPC at +966-11-2038222, Exts: 2317-2356-2353-2354-2334-2340.

Toll free phone: 8002490000

E-mail: npc.drug@sfda.gov.sa

Website: www.sfda.gov.sa/npc

• Other GCC States: Please contact the relevant competent authority

Toxicity

Liver damage is possible in adults who have taken 10 g or more of 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

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

or

-          Is likely to be glutathione depleted 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 administration and clinical symptoms generally culminate after 4 to 6 days. Abnormalities of glucose metabolism and metabolic acidosis may occur.

In severe poisoning, hepatic failure may progress to encephalopathy, haemorrhage, hypoglycaemia, cerebral oedema, and death. Acute renal failure with acute tubular necrosis, strongly suggested by loin pain, haematuria and proteinuria, may develop even in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have been reported.

Management

Immediate treatment is essential in the management of paracetamol overdose. Despite a lack of clinically significant early symptoms, patients should be referred urgently to hospital for immediate medical attention. This is because early 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.

As concentrations soon after paracetamol ingestion are unreliable, plasma paracetamol concentration should be measured at 4 hours or later after the initial administration. Treatment with N-acetylcysteine may be used for up to 24 hours after administration of paracetamol; however, the maximum protective effect is only obtained up to 8 hours post-administration. The effectiveness of this antidote declines sharply after this 8 hour time period. If required, the patient should be given intravenous N-acetylcysteine, in line with the established dosage schedule. If vomiting is not a problem, then oral methionine may be a suitable alternative for remote areas, outside hospital.

Management of those patients presenting with serious hepatic dysfunction 24 hours after paracetamol administration should be discussed with the national poisons information centre or a liver unit.

Pharmacotherapeutic group: Anilides

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.

Absorption

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.

Biotransformation

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.

Elimination

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.

White beeswax

Witepsol H-15

Not applicable.

Store below 30°C, away from light.

Opaque white plastic laminated PVC/PE foil.

Each pack contains 5 or 100 suppositories.

Not all pack sizes may be marketed.

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