4.1. Therapeutic indications

For the treatment of mild to moderate pain including headache, migraine, neuralgia, toothache, sore throat, period pains, aches and pains, symptomatic relief of rheumatic aches and pains and of influenza, feverishness and feverish colds.

4.2. Posology and method of administration

Adults, the elderly, and children aged 16 years and over:

One or two tablets up to four times daily as required.

Children:

Aged 10 - 15 years: One tablet up to four times daily as required.

Not suitable for children under 10 years of age. Children should not be given Panadol Original Tablets for more than 3 days without consulting a doctor.

These doses should not be repeated more frequently than every four hours nor should more than four doses be given in any 24-hour period.

Oral administration only.

4.3. Contraindications

Hypersensitivity to paracetamol or any of the constituents.

4.4. Special warnings and precautions for use

Contains Paracetamol.

Do not take anything else containing paracetamol while taking this medicine. The concomitant use with other products containing paracetamol may lead to an overdose

Underlying liver disease increases the risk of paracetamol-related liver damage. Patients who have been diagnosed with hepatic or renal impairment must seek medical advice before taking this medication. The hazards of overdose are greater in those with non-cirrhotic alcoholic liver disease.

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

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.

Cases of high anion gap metabolic acidosis (HAGMA) due to pyroglutamic acidosis have been reported in patients with with severe illness such as severe renal impairment and sepsis, or in patients with malnutrition or other sources of glutathione deficiency (e.g. chronic alcoholism) who were treated with paracetamol at therapeutic dose for a prolonged period or a combination of paracetamol and flucloxacillin. If HAGMA due to pyroglutamic acidosis is suspected, prompt discontinuation of paracetamol and close monitoring is recommended. The measurement of urinary 5-oxoproline may be useful to identify pyroglutamic acidosis as underlying cause of HAGMA in patients with multiple risk factors.

This medicine contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially "sodium free".

Cases of hepatic dysfunction/ failure have been reported in patients with depleted glutathione levels, such as those who are severely malnourished, anorexic, have a low body mass index, dehydrated, are chronic heavy users of alcohol or have sepsis. In patients with glutathione-depleted states the use of paracetamol may increase the risk of metabolic acidosis.

If symptoms persist, medical advice must be sought.

Keep out of sight and reach of children.

4.5. Interaction with other medicinal products and other forms of interaction

Cholestyramine: The speed of absorption of paracetamol is reduced by cholestyramine. Therefore, the cholestyramine should not be taken within one hour if maximal analgesia is required.

Metoclopramide and Domperidone: The absorption of paracetamol is increased by metoclopramide and 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.

Caution should be taken when paracetamol is used concomitantly with flucloxacillin as concurrent intake has been associated with high anion gap metabolic acidosis due to pyroglutamic acidosis, especially in patients with risks factors (see section 4.4)

4.6. Fertility, pregnancy and lactation

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.

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

4.7. Effects on ability to drive and use machines

None known.

4.8. Undesirable effects

The following convention has been utilised for the classification of the frequency of adverse reactions: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1,000, <1/100), rare (≥1/10,000, <1/1000), very rare (<1/10,000), not known (cannot be estimated from available data).

Adverse reactions from historical clinical trial data are both infrequent and from small patient exposure. Accordingly, events reported from extensive post-marketing experience at therapeutic/labeled dose and considered attributable are tabulated below by MedDRA System Organ Class. As these reactions are reported voluntarily from a population of uncertain size, the frequency of these reactions is not known but likely to be rare or very rare (<1/1000).

MedDRA SOC

Adverse Reaction

Frequency

Blood and lymphatic system disorders

Thrombocytopaenia

Very rare

Immune system disorders

Anaphylaxis

Cutaneous hypersensitivity reactions including, among others, skin rashes, angioedema, Stevens Johnson syndrome and Toxic Epidermal Necrolysis

Very rare

Respiratory, thoracic and mediastinal disorders

Bronchospasm in patients sensitive to aspirin and other NSAIDs

Very rare

Hepatobiliary disorders

Hepatic dysfunction

Very rare

Metabolism and nutrition disorders

High anion gap metabolic acidosis

Cases of high anion gap metabolic acidosis due to pyroglutamic acidosis have been observed in patients with risk factors using paracetamol (see section 4.4). Pyroglutamic acidosis may occur as a consequence of low glutathione levels in these patients.

Not known

There have been reports of blood dyscrasias including methaemoglobenaemia and agranulocytosis, but these were not necessarily causality 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 the Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9. Overdose

Symptoms and Signs

Experience following overdose with paracetamol indicates that the clinical signs of liver injury occur usually after 24 to 48 hours and peak after 4 to 6 days.

Overdose may cause liver failure which may require liver transplant or lead to death. Acute pancreatitis has been observed, usually with hepatic dysfunction and liver toxicity.

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 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.