SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Paracetamol Capsules Paracetamol 500 mg Capsules.

Spar Paracetamol 500 mg Capsules

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

INGREDIENT    QTY UNIT DOSE

Paracetamol    500 mg    capsule

3    PHARMACEUTICAL FORM

Capsule

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

For the treatment of mild to moderate pain including headache, migraine, neuralgia, toothache, sore throat, period pains, symptomatic relief of sprains, strains, rheumatic pain, sciatica, lumbago, fibrositis, muscular aches and pains, joint swelling and stiffness, influenza, feverishness and feverish colds.

4.2 Posology and method of administration

Route of administration: Oral.

Adults, the elderly and children over 12 years of age: 2 capsules up to 4 times daily as required.

The dose should not be repeated more frequently than every 4 hours and not more than 4 doses should be given in any 24 hour period.

4.3 Contraindications

Hypersensitivity to paracetamol and/or other constituents.

4.4 Special warnings and precautions for use

If symptoms persist consult your doctor

Do not exceed the stated dose

Keep all medicines out of reach and sight of children

Do not take with any other paracetamol-containing products.

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.

Care is advised in the administration of paracetamol to patients with severe renal or severe hepatic impairment. The hazards of overdose are greater in those with (non-cirrhotic) alcoholic liver disease.

Care is advised in the administration of paracetamol to patients who are alcohol dependent.

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 colestyramine.

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.

Patients receiving enzyme inducing drugs such as carbamazepine are considered at high risk of overdose. In cases of overdose an antidote should be administered even if their plasma-paracetamol concentrations are up to 50% below the standard reference line.

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.

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

4.7 Effects on ability to drive and use machines

None stated.

4.8 Undesirable Effects

Adverse events of paracetamol from historical clinical trial data are both infrequent and from small patient exposure. Accordingly, events reported from extensive post-marketing experience at therapeutic/labelled dose and considered attributable are tabulated below by system class. Due to limited clinical trial data, the frequency of these adverse events is not known (cannot be estimated from available data), but post-marketing experience indicates that adverse reactions to paracetamol are rare and serious reactions are very rare.

Post marketing data

Body System	Undesirable effect
Blood and lymphatic	Thrombocytopenia
system disorders	Agranulocytosis
Immune system disorders	Anaphylaxis
	Cutaneous hypersensitivity reactions including skin rashes, angioedema and Stevens Johnson syndrome/toxic epidermal necrolysis
Respiratory, thoracic and mediastinal disorders	Bronchospasm*
Hepatobiliary disorders	Hepatic dysfunction

* There have been cases of bronchospasm with paracetamol, but these are more likely in asthmatics sensitive to aspirin or other NSAIDs.

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

Paracetamol

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 (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.

Or

b,    Regularly consumes ethanol in excess of recommended amounts.

Or

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 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 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 section.

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 the NPIS or a liver unit.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

ANALGESIC:

The mechanism of analgesic action has not been fully determined. Paracetamol may act predominantly by inhibiting a prostaglandin synthesis in the central nervous system (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.

ANTIPYRETIC:

Paracetamol probably produces antipyresis by acting centrally 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.

5.2 Pharmacokinetic properties

Absorption and Fate

Paracetamol is readily absorbed from the gastro-intestinal tract with peak plasma concentrations occurring about 30 minutes to 2 hours after ingestion. It is metabolised in the liver 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 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.

5.3 Preclinical safety data

There are no preclinical data of relevance to the prescriber additional to that already covered in other sections of the SPC.

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Capsule Contents Maize Starch Croscarmellose Sodium Sodium Laurilsulfate Magnesium Stearate

Capsule

Gelatin

Titanium Dioxide E171 Indigo Carmine E132 Erythrosine E127

6.2 Incompatibilities

None stated.

6.3 Shelf life

3 years.

6.4 Special precautions for storage

Do not store above 25°C.

6.5 Nature and contents of container

35gsm glassine (Pergamin) paper/9 micron soft tamper aluminium foil/250 micron PVC in cartons of 8, 12, 16, 24, 48, 96.