SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Paracetamol 500 mg Tablets

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains paracetamol 500 mg.

For the full list of excipients, see section 6.1

3 PHARMACEUTICAL FORM

Tablet for oral administration.

White, round, flat tablet debossed with BPL on one side and NAT and score line on the other side.

The score line is not intended for breaking the tablet.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

For the symptomatic treatment of fever and mild to moderate pain including headache, migraine, neuralgia, toothache, sore throat, period pain, relief of rheumatic pain and of pain associated with colds/influenza.

4.2 Posology and method of administration Adults aged 16 and over:

Two tablets to be taken every four hours as required, up to a maximum of eight tablets in any 24-hour period.

Adolescents aged 12 to 15 years:

One tablet to be taken every four to six hours as required, up to a maximum of six tablets in any 24-hour period.

Children under 12 years:

Paracetamol 500 mg tablets are not recommended for children under 12 years of age.

4.3 Contraindications

Hypersensitivity to the active substance and/or to any of the excipients listed in section 6.1.

4.4 Special warnings and precautions for use

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 noncirrhotic alcoholic liver disease.

Do not take more medicine than the label tells you to. If you do not get better, talk to your doctor.

Contains Paracetamol.

Do not take anything else containing paracetamol while taking this medicine.

Talk to your doctor at once if you take too much of this medicine, even if you feel well. This is because too much paracetamol can cause delayed, serious liver damage.

4.5 Interaction with other medicinal products and other forms of interaction

Colestyramine: Speed of absorption is reduced by colestyramine, therefore the colestyramine should not be taken within one hour if maximal analgesia is required.

Domperidone/Metoclopramide: The speed of absorption of paracetamol is increased by concurrent use of metoclopramide or domperidone. However, concurrent use need not be avoided.

Warfarin: 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.

Chloramphenicol: Increased plasma concentration of chloramphenicol.

4.6 Fertility, pregnancy and lactation

Pregnancy

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.

Lactation

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

Fertility

There are insufficient fertility data available to indicate paracetamol has any effect on fertility.

4.7 Effects on ability to drive and use machines

Paracetamol 500mg tablets has no known influence on the ability to drive and use machines

4.8 Undesirable effects

Adverse effects of paracetamol are rare (> 1/10,000 to < 1/1,000) but hypersensitivity including skin rash may occur. There have been reports of blood dyscrasias including thrombocytopenia pupura, methaemoglobenaemia and agranulocytosis, but these were not necessarily related to paracetamol.

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 Yellow Card Scheme, Website: www.mhra.gov.uk/yellowcard.

4.9 Overdose

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 patients have risk factors (see below).

Risk Factors

If the patients

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 over dosage 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.

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 24 hours from ingestion should be discussed with the NPIS or a liver unit.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: other Analgesic and Antipyretics- Anilides ATC Code - N02BE01

Paracetamol is a peripherally acting analgesic with antipyretic activity. It is an effective analgesic and antipyretic agent but has only weak anti-inflammatory properties

Mechanisms of Action/Effect

Analgesic - the mechanism of analgesic action has not been fully determined. Paracetamol may act predominantly by inhibiting 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-regulation 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

Paracetamol is readily absorbed from the gastro-intestinal tract with peak plasma concentrations occurring about 30 minutes to 2 hours after ingestion. Paracetamol is metabolized in the liver and excreted in the urine mainly as the glucuronide and sulphate conjugates, with about 10% as glutathione 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, although this is dose dependent.

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 pre-clinical data of relevance to the prescriber which are additional to that already included in other section of the SPC.

6    PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Pregelatinized Starch

Sodium Starch Glycolate Stearic Acid Magnesium Stearate Colloidal Anhydrous Silica

6.2 Incompatibilities

None known

6.3 Shelf life

2 Years

6.4 Special precautions for storage

Do not store above 25 degrees C.

6.5 Nature and contents of container

PVC-PVC/Adhesive/Aluminium Blister Pack of 16 Tablets

6.6 Special precautions for disposal

Not applicable

7 MARKETING AUTHORISATION HOLDER

Beximco Pharma UK Ltd.

102 College Road Harrow HA1 1ES, UK

8    MARKETING AUTHORISATION NUMBER(S)

PL 36760/0002

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

20/11/2014

10    DATE OF REVISION OF THE TEXT

20/11/2014