Paracetamol Capsules

Paracetamol 500 mg Capsules.

Capsule

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.

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.

Not recommended for children under 12 years of age.

Hypersensitivity to paracetamol and/or other constituents.

- 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.

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.

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.

None stated.

Adverse effects of paracetamol are rare but hypersensitivity including skin rash may occur. There have been reports of rare blood dyscrasias including thrombocytopenia and agranulocytosis, but these were not necessarily causally related to paracetamol.

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.

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 center 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.

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.

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

Capsule Contents

Maize Starch

Croscarmellose Sodium

Sodium Laurilsulfate

Magnesium Stearate

Capsule

Gelatin

Titanium Dioxide E171

Indigo Carmine E132

Erythrosine E127

None stated.

3 years.

None.

UPVC/aluminium foil blisters in cartons of 8, 12, 16, 24, 32, 48, 96 capsules.

Polypropylene drums with HDPE child resistant caps: 25, 50, 100 capsules/drum.

HDPE drums with polyethylene tamper evident and child resistant caps:

25, 50, 100 capsules/drum, fitted with expanded polyethylene wads.

30 micron pyamidally embossed hard temper aluminium (with 250 micron PVC blisters), in cartons of 8,12,16,24,48,96.

OR

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

None.

Wrafton Laboratories Limited

Wrafton

Braunton

North Devon EX33 2DL

PL 12063/0006.

First Authorisation 24 August 1993

20 January 2012