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Paracetamol Tablets 500mg

Document: spc-doc_PL 43461-0006 change

SUMMARY OF PRODUCT CHARACTERISTICS

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 12 years:

Single dose: 0.5 g to 1 g (1 to 2 tablets).

Maximum daily dose: 4 g (8 tablets) in divided doses.

Children:

Age 6 years to under 12 years: half tablet to one 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

i)    Do not exceed the stated

dose.

ii)    Consult a doctor if symptoms persist. Do not continue to use for longer than 3 days without consulting your doctor or pharmacist.

iii)    Ask the doctor or pharmacist about taking the tablets if pregnant or already on a course of medication.

iv)    This product contains

paracetamol.

v)    The label shall say: “Do not take with any other paracetamol-containing products” and “Immediate medical advice should be sought in the event of an overdose, even if you feel well”.

vi)    The leaflet shall say: “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”.

vii)    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.

viii)    Keep out of the sight and reach of children.

ix)    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.

Fertility, Pregnancy and lactation

4.6


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.

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.

5.1 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.

Preclinical safety data

5.3


Pregelatinised starch (maize) Sodium metabisulphite Stearic acid (E570) Magnesium stearate (E572)

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

Store below 25°C. Store in the original package.

6.5 Nature and contents of container

Paracetamol Tablets 500mg are available in child-resistant packs of 24 and 32 tablets.

Specification details of blister packs:

-    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

6.6 Special precautions for disposal

No special precautions required.

7    MARKETING AUTHORISATION HOLDER

Flamingo Pharma UK Ltd 1st Floor, Kirkland House,

11-15 Peterborough Road,

Harrow, Middlesex,

HA1 2 AX,

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

04/09/2015