4.1. Therapeutic indications

To relieve mild to moderate pain and reduce fever in many conditions including headache, toothache, feverishness, colds and influenza.

4.2. Posology and method of administration

For oral use only.

It is important to shake the bottle for at least 10 seconds before use.

Child's Age

How Much

How Often (in 24 hours)

6-8 years

5 ml

4 times

8-10 years

7.5 ml

4 times

10-12 years

10 ml

4 times

Do not give more than 4 doses in any 24 hour period.

Leave at least 4 hours between doses.

Do not give this medicine to your child for more than 3 days without speaking to your doctor or pharmacist.

Do not give to children under the age of 6 years.

Children aged 12-16 years: 10-15 ml up to 4 times a day.

Adults and children over 16 years: 10-20 ml up to 4 times a day.

Elderly: In the elderly the rate and extent of paracetamol absorption is normal but plasma half-life is longer and paracetamol clearance is lower than in young adults. Dosage may need to be reduced.

4.3. Contraindications

Hypersensitivity to paracetamol or any of the other ingredients.

4.4. Special warnings and precautions for use

Do not exceed the recommended dose. Taking more than the recommended dose (overdose) may cause liver damage. In case of overdose, get medical help straight away. Quick medical attention is critical for adults as well as children even if signs or symptoms are not noticed.

Caution in patients with severely impaired liver or kidney function. The hazards of overdose are greater in those with noncirrhotic alcoholic liver disease. Chronic alcohol users should consult a doctor before use.

This medicine should not be diluted. Where a dilution of this medicine is required, Paracetamol 120mg/5ml Oral Suspension should be recommended.

Patients should be informed about the signs of serious skin reactions and use of the drug should be discontinued at the first appearance of skin rash or any other sign of hypersensitivity.

Taking this product with other paracetamol-containing medicines could lead to overdose and should therefore be avoided.

The label should contain the following statements:

Contains paracetamol.

Do not give this medicine with any other paracetamol-containing product.

For oral use only.

Never give more medicine than shown in the table.

Always use the syringe supplied with the pack.

Do not give to children under 6 years of age.

Do not give more than 4 doses in any 24 hour period.

Leave at least 4 hours between doses.

Do not give this medicine to your child for more than 3 days without speaking to your doctor or pharmacist.

As with all medicines, if your child is currently taking any medicine consult your doctor or pharmacist before taking this product.

Do not store above 25°C. Store in the original package.

Shake the bottle for at least 10 seconds before use.

Keep out of the reach and sight of children.

Immediate medical advice should be sought in the event of an overdose, even if the child seems well.

Do not exceed the stated dose.

If symptoms persist consult your doctor.

Leaflet or combined label/leaflet:

Immediate medical advice should be sought in the event of an overdose, even if the child seems well, because of the risk of delayed, serious liver damage.

Cases of high anion gap metabolic acidosis (HAGMA) due to pyroglutamic acidosis have been reported in patients 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 the underlying cause of HAGMA in patients with multiple risk factors.

Glutathione deficiency can also increase the risk of hepatotoxicity with paracetamol use, even at therapeutic doses. Caution is advised for patients at risk of glutathione depletion (See section 4.9).

Hepatotoxicity at therapeutic dose

Cases of paracetamol induced hepatotoxicity, including fatal cases, have been reported in patients taking paracetamol at doses within the therapeutic range. These cases were reported in patients with one or more risk factors for hepatotoxicity including low body weight (adults <50 kg), renal and hepatic impairment, chronic alcoholism, concomitant intake of hepatotoxic drugs and in acute and chronic malnutrition (low reserves of hepatic glutathione). Paracetamol should be administered with caution to patients with these risk factors. Caution is also advised in patients on concomitant treatment with drugs that induce hepatic enzymes and in conditions which may predispose to glutathione deficiency (see section 4.9).

Dosage adjustment of paracetamol should be considered where there are risk factors for glutathione deficiency or hepatotoxicity and for those of low weight (for adults those weighing less than 50kg).

Very rare cases of serious skin reactions have been reported. Symptoms may include:

- Skin reddening

- Blisters

- Rash

If skin reactions occur or existing skin symptoms worsen, stop use and seek medical help right away.

Important information about some of the ingredients of this medicine

This medicine contains 1.1g of sorbitol in each 5ml dose, which is equivalent to 220mg/ml. Sorbitol may cause gastrointestinal discomfort and have a mild laxative effect. Patients with hereditary fructose intolerance (HFI) should not take/be given this medicine.

Methyl hydroxybenzoate (E218) may cause allergic reactions (possibly delayed).

This medicine contains 0.06 mg of benzyl alcohol in each 5ml dose, which is equivalent to 0.012mg/ml. Benzyl alcohol may cause allergic reactions. High volumes should be used with caution and only if necessary, especially in patients who are pregnant or breast-feeding or subjects with liver or kidney impairment because of the risk of accumulation and toxicity (metabolic acidosis).

This medicine contains 17.8mg propylene glycol (E1520) in each 5ml dose, which is equivalent to 3.56mg/ml.

This medicine contains less than 1mmol sodium (23mg) per 5ml dose, that is to say essentially 'sodium-free'.

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

The speed of absorption of paracetamol may be increased by metoclopramide or domperidone and absorption reduced by cholestyramine.

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 who have taken barbiturates, tricyclic antidepressants and alcohol may show diminished ability to metabolise large doses of paracetamol, the plasma half-life of which can be prolonged.

Alcohol can increase the hepatotoxicity of paracetamol overdosage and may have contributed to the acute pancreatitis reported in one patient who had taken an overdose of paracetamol.

Chronic ingestion of anticonvulsants or oral steroid contraceptives induce liver enzymes and may prevent attainment of therapeutic paracetamol levels by increasing first pass metabolism or clearance.

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 risk 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.

When given to the mother in therapeutic doses (1 g single dose), paracetamol crosses the placenta into foetal circulation as early as 30 minutes after ingestion and is metabolised in the foetus by conjugation with sulfate and increasingly with glutathione.

Breastfeeding

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

Fertility

There is no information relating to the effects of this medicine on fertility.

4.7. Effects on ability to drive and use machines

No adverse effects known.

4.8. Undesirable effects

Adverse drug reactions (ADRs) identified during clinical trials and postmarketing experience with paracetamol are listed below by System Organ Class (SOC). The frequencies are defined according to the following convention:

Very common

Common

Uncommon

Rare

Very rare

Not known

≥1/10

≥1/100 and <1/10

≥1/1,000 and <1/100

≥1/10,000 and <1/1,000

<1/10,000

(cannot be estimated from the available data)

ADRs are presented by frequency category based on 1) incidence in adequately designed clinical trials or epidemiology studies, if available, or 2) when incidence is unavailable, frequency category is listed as 'Not known'.

System Organ Class (SOC)

Frequency

Adverse Drug Reaction (Preferred Term)

Blood and lymphatic system disorders

Not known

Blood disorder (including thrombocytopenia and agranulocytosis)1

Immune system disorders

Very rare

Anaphylactic reaction

Very rare

Hypersensitivity

Hepatobiliary disorders

Not known

Liver injury2

Skin and subcutaneous tissue disorders

Very rare

Rash

Not known

Fixed eruption

Not known

Rash pruritic

Not known

Urticaria

Renal and urinary disorders

Uncommon

Nephropathy toxic

Not known

Renal papillary necrosis3

Investigations

Not known

Transaminases increased4

Metabolism and nutrition disorders

Not known

High anion gap metabolic acidosis5

1 Reported following paracetamol use, but not necessarily causally related to the drug

2 Chronic hepatic necrosis has been reported in a patient who took daily therapeutic doses of paracetamol for about a year

3 Reported after prolonged administration.

4 Low level transaminase elevations may occur in some patients taking therapeutic doses of paracetamol; these elevations are not accompanied with liver failure and usually resolve with continued therapy or discontinuation of paracetamol.

5 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.

Very rare cases of serious skin reactions have been reported.

Chronic hepatic necrosis has been reported in a patient who took daily therapeutic doses of paracetamol for about a year and liver damage has been reported after daily ingestion of excessive amounts for shorter periods. A review of a group of patients with chronic active hepatitis failed to reveal differences in the abnormalities of liver function in those who were long-term users of paracetamol nor was the control of their disease improved after paracetamol withdrawal.

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

Liver damage is possible in patients who have taken more than recommended doses of paracetamol. It is considered that excess quantities of a toxic metabolite (usually adequately detoxified by glutathione when normal doses of paracetamol are ingested), become irreversibly bound to liver tissue.

Ingestion of paracetamol at therapeutic doses may lead to liver damage if the patient has risk factors. These include if:

• They are undergoing long-term treatment with drugs that induce liver enzymes

Or

• They regularly consume ethanol in excess of recommended amounts

Or

• They are likely to be glutathione deplete e.g. diet (malnutrition, fasting, dietary restrictions, eating disorders and starvation), catabolic states (sepsis), cachexia and chronic illness (cystic fibrosis, liver disease, HIV and muscular dystrophy).

Symptoms:

Symptoms of paracetamol overdosage in the first 24 hours include pallor, nausea, hyperhidrosis, malaise, vomiting, anorexia and abdominal pain. Liver damage may become apparent 12 to 48 hours after ingestion as liver function tests become abnormal. This may include hepatomegaly, liver tenderness, jaundice, acute hepatic failure and hepatic necrosis, Abnormalities of glucose metabolism and metabolic acidosis may occur. Blood bilirubin, hepatic enzymes, INR, prothrombin time, blood phosphate and blood lactate may be increased. In severe cases poisoning, hepaticliver failure may lead to encephalopathy, haemorrhage, hypoglycaemia, cerebral oedema coma and death. Acute renal failure with acute tubular necrosis, strongly suggested by loin pain, haematuria and proteinuria, may develop with or withouteven in the absence of severe liver damage. Cardiac arrhythmias and pancreatitis have been reported.

Haemolytic anaemia (in patients with glucose-6-phosphate dehydrogenase [G6PD] deficiency): Haemolysis has been reported in patients with G6PD deficiency, with use of paracetamol in overdose.

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.