This information is intended for use by health professionals

1. Name of the medicinal product

Paracetamol Tablets 500mg

2. Qualitative and quantitative composition

Each tablet contains 500 mg of paracetamol. Each tablet also contains sodium metabisulphite 0.56 mg.

For a list of excipients, see section 6.1.

3. Pharmaceutical form

Tablet

White to off white, circular flat bevelled edge tablet with breakline on one side and plain on other.

4. Clinical particulars
4.1 Therapeutic indications

For the treatment of mild to moderate pain, including headache, neuralgia, toothache, period pains, aches and pains.

Symptomatic relief of rheumatic aches and pains.

Symptomatic relief of influenza, feverishness, feverish colds.

4.2 Posology and method of administration

These tablets are for oral administration

Adults, the elderly and children over 15 years:

Single dose: 0.5 g to 1 g (one to two tablets).

Maximum daily dose: 4 g (eight tablets) in divided doses.

Children:

Age 12 years to under 15 years: one tablet to one and a half tablet.

Age 10 years to under 12 years: one tablet

Age 6 years to under 10 years: half tablet

Not for use in under 6 year olds.

Dosage instruction:

Take every 4 to 6 hours, as required. Do not take more frequently than every 4 hours. Not more than 4 doses should be administered in any 24 hour period. Dosage should not be continued for more than three days without consulting a doctor.

4.3 Contraindications

Hypersensitivity to paracetamol or any other ingredients. Alcoholics could be at risk in taking paracetamol.

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 alcohol 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.

Patients should be advised that paracetamol may cause severe skin reactions. If a skin reaction such as skin reddening, blisters, or rash occurs, they should stop use and seek medical assistance right away.

Contains sodium metabisulphite which may rarely cause severe hypersensitivity reactions and bronchospasm.

4.5 Interaction with other medicinal products and other forms of interaction

Alcohol reduces liver capacity to deal with paracetamol. Chronic use of paracetamol enhances effect of warfarin and other coumarins with increased risk of bleeding; occasional doses have no significant effect. Cholestyramine reduces absorption of paracetamol. Metoclopramide and Domperidone accelerate absorption of paracetamol.

May interact with Chloramphenicol causing increased plasma levels.

4.6 Fertility, pregnancy and lactation

Epidemiological studies in human pregnancy have shown no ill effects due to paracetamol being 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 clinically significant quantities. Available published data do not contraindicate breast- feeding.

A large amount of data on pregnant women indicate neither malformative, nor feto/neonatal toxicity. Epidemiological studies on neurodevelopment in children exposed to paracetamol in utero show inconclusive results. If clinically needed, paracetamol can be used during pregnancy however it should be used at the lowest effective dose for the shortest possible time and at the lowest possible frequency

4.7 Effects on ability to drive and use machines

None.

4.8 Undesirable effects

The information below lists reported adverse reactions, ranked using the following frequency classification:

Very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000);

very rare (<1/10,000), not known (cannot be estimated from the available data).

Immune system disorders

Hypersensitivity including skin rash may occur.

Not known: anaphylactic shock, angioedema

Blood and lymphatic system disorders

Not known: blood dyscrasias including thrombocytopenia and agranulocytosis

Gastrointestinal

Not known: acute pancreatitis

Skin and subcutaneous disorders

Very rare cases of serious skin reactions such as Toxic Epidermal Necrolysis (TEN), Stevens-Johnson syndrome (SJS), acute generalised exanthematous pustulosis, fixed drug eruption have been reported.

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 at: www.mhra.gov.uk/yellowcard.

4.9 Overdose

Liver damage is possible in adults who have taken 10 g or more of paracetamol. Ingestion of 5 g 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.

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.

5. Pharmacological properties
5.1 Pharmacodynamic properties

ATC code: N02BE01, Other analgesics and antipyretics

Paracetamol is an effective analgesic and antipyretic agent but has only weak antiinflammatory properties. Its mechanism of action is not fully understood, as it is only a weak inhibitor of prostaglandin bio-synthesis, but it has been suggested that it is more effective against enzymes in the CNS than those in the periphery. 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 hypothalmic heat-regulating centre to produce peripheral vasodilatation 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 it does not cause gastric irritation or bleeding like salicylates.

5.2 Pharmacokinetic properties

Paracetamol is readily absorbed from the gastrointestinal tract with peak plasma concentrations occurring 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 1-4 hours.

Plasma-protein binding is negligible at usual therapeutic concentrations but increases with increasing concentration.

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. The time to peak plasma concentration of paracetamol is 0.5 to 2 hours, the time to peak effect 1 to 3 hours and the duration of action 3 to 4 hours.

5.3 Preclinical safety data

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

Conventional studies using the currently accepted standards for the evaluation of toxicity to reproduction and development are not available.

6. Pharmaceutical particulars
6.1 List of excipients

Pregelatinised starch (maize)

Sodium metabisulphite

Stearic acid (E570)

Magnesium stearate (E572)

6.2 Incompatibilities

None stated.

6.3 Shelf life

5 years.

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

Paracetamol 500mg Tablets are available in child-resistant packs (Glassine paper foil/ Aluminium or PVC I Aluminium foil) of 4,6,12 and 16tablets.

Specification details of blister packs:

PVC/Aluminium foil

- PVC (white, rigid, opaque): 250 microns

- PVC/Aluminium foil (hard tempered): 15/20 microns

- Primer (nitrocellulose): 1.5 to 2.5 gsm

- Heat seal lacquer: 6.5 to 8.5 gsm

PVC/Glassine paper – Aluminium foil

- PVC (white, rigid, opaque): 250 microns

- Glassine paper/Aluminium foil : 35±3.50/25±2.0 gsm

6.6 Special precautions for disposal and other handling

No special precautions required.

7. Marketing authorisation holder

Flamingo Pharma UK Ltd

1st Floor, Kirkland House,

11-15 Peterborough Road,

Harrow, Middlesex,

HA1 2AX,

United Kingdom

8. Marketing authorisation number(s)

PL 43461/0006

9. Date of first authorisation/renewal of the authorisation

16th March 2011

Renewal: Pending

10. Date of revision of the text

23/07/2019