Paracetamol 500mg Tablets

Paracetamol 500mg For excipients see Section 6.1

Tablets. White round flat bevelled edge tablet with a break line on one side.

For the relief of mild to moderate pain including headache, migraine, neuralgia, toothache, sore throat and dysmenorrhoea.

For the symptomatic relief of rheumatic and muscular aches and pains, sciatica, fibrositis, lumbago, joint swelling and stiffness.

For the symptomatic relief of influenza, feverish colds and feverishness.

For all indications:

Adults, the elderly and children aged 12 years and over:One or two tablets up to four times a day, as required.Maximum daily dose is 4 g in divided doses.

Children 6 to 12 years:Half to one tablet up to four times a day, as required.

Children under 6 years:Not to be used unless recommended by a doctor.

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.

Dosage should not be continued for longer than 3 days without consulting a doctor.

Contra-indicated in patients with a known hypersensitivity to Paracetamol and/or any of the other constituents.

Care is advised in the administration of paracetamol to patients with severe renal or severehepatic impairment. The hazard of overdose is greater in those with non-cirrhotic alcoholicliver disease.

The label/leaflet will state:Immediate medical advice should be sought in the event of an overdose, even if you feel well,because of the risk of delayed, serious liver damage.Do not take with any other paracetamol-containing products.

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

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

The anticoagulant 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.

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, however, hypersensitivity 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.

Potentially fatal liver damage is likely in adults who have taken 15g or more of paracetamol. As little as 10g may lead to liver necrosis. Patients taking enzyme-inducing drugs or with a history of alcoholism may have an increased susceptibility. It is considered that excess quantities of a toxic metabolite (usually adequately detoxified by glutathione when normal doses of paracetamol are employed), become irreversibly bound to liver tissue.

Symptoms of paracetamol overdosage in the first 24 hours are pallor, nausea, vomiting, diarrhoea, anorexia, abdominal pain and increased sweating. 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, coma, and death. Acute renal failure with acute tubular necrosis may develop even in the absence of severe liver damage. Cardiac arrhythmias have been reported.

Prompt treatment is essential in the management of paracetamol overdosage. Any patient who has ingested about 7.5g or more of paracetamol in the preceding 4 hours should undergo gastric lavage or induced emesis. Specific therapy with an antidote such as acetylcysteine or methionine may be necessary. Acetylcysteine may be given either intravenously or by mouth or methionine may be given by mouth within 10 -12 hours of ingestion of the overdose. Generally treatment is required if the blood-paracetamol concentration is higher than a line (the '200' line) drawn on semi-log/linear paper joining the points 200 mg/litre (1.32 mmol/litre) at 4 hours and 30 mg/litre (0.20 mmol/litre) at 15 hours following ingestion.

Determination of the concentration before 4 hours is not considered to give a reliable measurement. 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. Liver function tests should be performed at 24 hour intervals for at least 96 hours post-ingestion if the plasma paracetamol concentration indicates a potential for hepatotoxicity. Renal and cardiac function should be monitored and supportive treatment should be directed at maintaining fluid and electrolyte balance and correcting hypo-glycaemia. Haemodialysis and haemoperfusion have been used with some success but peritoneal dialysis is ineffective.

Paracetamol is an effective analgesic and antipyretic agent but has only weak anti-inflammatory properties. Its mechanism of action is not fully understood. It has been suggested that it may act predominantly by inhibiting prostaglandin synthesis in the CNS and to a lesser extent through a peripheral action by blocking pain-impulse generation. The peripheral action may also be due to inhibition of prostaglandin synthesis or to inhibition of the synthesis or actions of other substances that sensitise pain receptors to mechanical or chemical stimulation.

Paracetamol probably produces an antipyretic action by a central effect on the hypothalamic heat-regulating centre to produce peripheral vasodilation resulting in increased blood flow through the skin, sweating and heat loss. The central action probably involves inhibition of prostaglandin synthesis in the hypothalamus. The drug has no effect on the cardiovascular and respiratory systems, and unlike salicylates it does not cause gastric irritation or bleeding.

Paracetamol is readily absorbed from the gastrointestinal tract with peak plasma concentrations occurring about 30 minutes to 2 hours after ingestion; the time to peak effect 1 to 3 hours and the duration of action 3 to 4 hours. It is metabolised in the liver (90 -95%) and excreted in the urine mainly as the glucuronide and sulphate conjugates. Less than 5% is excreted as unchanged paracetamol. The elimination half-life varies from about 1 to 4 hours. Plasma-protein binding is negligible at usual therapeutic concentrations but increases with increasing concentrations.

A minor hydroxylated metabolite (n-acetyl-p-benzoquinoneimine) which is usually produced in very small amounts by mixed-function oxidases in the liver and which is usually detoxified by conjugation with liver glutathione may accumulate following paracetamol overdosage and cause liver damage.

There are no pre-clinical data of relevance to the prescriber which are additional to that already included in other sections of the SPC.

Pregelatinised Maize Starch

Sodium Metabisulphite

Magnesium Stearate

Not applicable

3 years – Polypropylene or HDPE containers.3 years – Blister packs.3 years – Polypropylene blister packs.

None

Blister strips comprised of 30micron hard temper Aluminium lidding foil with 250 –300micron PVC base material.or

Blister strips comprised of 30micron hard temper Aluminium lidding foil with 250 micron PVC/PVdC (40-90gsm) base material. or Blister strips comprised of 20micron Aluminium/15micron PVC lidding foil with 250 – 300micron PVC base material. or Blister strips comprised of 20micron Aluminium/15micron PVC lidding foil with 250micron PVC/PVdC (40-90gsm) base material. or Blister strips comprised of 35-41gsm Glassine paper/9micron Aluminium lidding foil with 250 –300micron PVC base material. or Blister strips comprised of 35-41gsm Glassine paper/9micron Aluminium lidding foil with 250micron PVC/PVdC (40-90gsm) base material.

Blister pack sizes of 16 or 32 tablets.

Polypropylene or HDPE containers with Polypropylene or HDPE screw caps containing 16, 32, 100, 500 or 1000 tablets.

Not applicable

Galpharm Healthcare Limited Hugh House Upper Cliffe Road Dodworth Business Park Dodworth South Yorkshire S75 3SP

PL 16028/0053

8 October 2001

April 2006 (Change to section 6.5).