Ricesteele Manufacturing Ltd

Paralink 500mg Suppositories

Each suppository contains Paracetamol 500mg

For a full list of excipients see section 6.1

Suppository

White, tapered cylindrical suppositories.

Indicated in the management of pain and fever associated with such conditions as influenza, the common cold, headache, rheumatism, teething, post-operative pain

For rectal use only

Dose may be repeated every six hours as directed by the physician.

Hypersensitivity to Paracetamol or any of the other constituents.

Paralink suppositories should be administered with caution to patients with known liver or renal impairment.

The hazard of overdose is greater in those with non-cirrhotic alcoholic liver disease.

Do not exceed the recommended dose.

Do not take any other paracetamol-containing products.

If symptoms persist, consult your doctor.

Keep out of the reach and sight of children.

Prolonged use except on doctor's advice can be harmful.

Maximum duration of continued use without medical advice: 3 days.

Immediate medical advice should be sought in the event of overdosage, because of the risk of irreversible liver damage.

This product should be used only when clearly necessary.

The anticoagulant effect of warfarin and other coumarins may be enhanced by prolonged regular use of paracetamol with increased bleeding; occasional doses have no significant effect.

The rate of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption reduced by colestyramine.

Chronic alcohol intake can increase the hepatotoxicity of paracetamol overdose. Acute alcohol intake may diminish an individual's ability to metabolise large doses of paracetamol, the plasma half-life of which can be prolonged.

The use of drugs that induce hepatic micosomal enzymes, such as anticonvulsants and oral contraceptives, may increase the extent of metabolism of paracetamol, resulting in reduced plasma concentrations of the drug and a faster elimination rate.

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.

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

None

Adverse effects of paracetamol are rare but hypersensitivity including skin rash may occur. There have been a few reports of blood dyscrasias including thrombocytopoenia and agranulocytosis but these were not 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.

Nephrotoxic effects following therapeutic doses of paracetamol are uncommon. Papillary necrosis has been reported after prolonged administration.

Liver damage is possible in adults who have taken 10g or more of paracetamol. Ingestion of 5g or more of paracetamol may lead to liver damage if the patient has risk factors, including the following ones:

Risk factors

a) Long term treatment with carbamazepine, phenobarbitone, phenytoin, primidone, rifampicin, St John's Wort or other drugs that induce liver enzymes, or

b) regular consumption of ethanol in excess of recommended amounts, or

c) likely glutathione depletion, 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 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.

Treatment

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.

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 concentrations 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 a suitable alternative for remote areas, outside hospital. Management of patients who present with serious hepatic dysfunction beyond 24h from ingestion should be discussed with a liver unit.

Analgesic, Antipyretic: N02 BE01

Paracetamol is an antipyretic and analgesic proven in paediatric use. Paracetamol produces antipyresis through action on the hypothalmic heat-regulation centre and analgesia by elevation of the pain threshold. Paracetamol has analgesic and antipyretic actions similar to those of aspirin but it has no useful anti-inflammatory properties.

Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract. Peak plasma concentrations occur within 30 to 60 minutes, with slightly faster absorption of liquid preparations. Usual analgesic doses produce total serum concentrations of 5 to 20mcg/ml. A good correlation between serum concentration and analgesic effect has not been found.

Paracetamol is distributed into most body tissues, it crosses the placenta and it is present in breast milk. Serum protein binding varies from 20 to 50% at toxic serum concentrations.

Paracetamol is metabolised predominantly in the liver and excreted in the urine mainly as glucuronide and sulfate conjugates. Less than 5% is excreted as unchanged paracetamol. The elimination half-life varies from about 1 to 3 hours and is prolonged in neonates and in patients with hepatic impairment.

The overall elimination rate constant for paracetamol in children, from birth to 12 years of age, is the same as for adults but neonates have diminished capacity to form glucuronide conjugates of paracetamol.

Paracetamol is a well established drug substance whose pre-clinical profile has been investigated thoroughly and is established.

Hard Fat

Macrogol stearate

Not applicable

3 years.

Store below 25°C.

Strips of five peel-apart, plastilaminate moulds consisting of a contact layer of polyethylene, an outer layer of polyvinylchloride and a polyurethane adhesive layer.

Two strips (ten suppositories) are packed into a cardboard carton.

No special requirements.

Ricesteele Manufacturing Limited

Cookstown Industrial Estate

Tallaght

Dublin 24

Ireland

PA 95/7/4

May 2010