4.1. Therapeutic indications

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

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.

Babies over 2 months in age

For the relief of fever after vaccination at 2, 3 and 4 months 2.5 ml. This dose may be given up to 4 times a day at the time of vaccination. Don't give more than 4 doses in any 24 hour period. Leave at least 4 hours between doses. If your baby still needs this medicine two days after receiving the vaccine talk to your doctor or pharmacist. Do not give to babies less than 2 months of age.

For other causes of pain and fever:

Child's age

How much

2-3 months

2.5 ml – usually once, if necessary, after 4-6 hours, a second 2.5 ml dose may be given

Do not give to babies less than 2 months of age. Only give if your baby weighs over 4 kg and was born after 37 weeks. Do not give more than 2 doses. Leave at least 4 hours between doses. This is to ensure that fever that may be due to a serious infection is quickly diagnosed. If your child is still feverish after two doses, talk to your doctor or pharmacist.

Child's age

How much

How often (in 24 hours)

3-6 months

2.5 ml

4 times

6-24 months

5 ml

4 times

2-4 years

7.5 ml

4 times

4-6 years

10 ml

4 times

Don't 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.

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.

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 non-cirrhotic alcoholic liver disease. Chronic alcohol users should consult a doctor before use.

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

Carmoisine (E122) may cause allergic reactions.

This medicine contains maltitol liquid and sorbitol. Patients with rare hereditary problems of fructose intolerance (HFI) should not take this medicine.

This medicine contains benzyl alcohol. There is an increased risk due to accumulation in young children. High volumes should be used with caution and only if necessary, especially in subjects with liver or kidney impairment because of the risk of accumulation and toxicity (metabolic acidosis).

Very rare cases of serious skin reactions have been reported. 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 labelling should contain the following statements:

Contains paracetamol.

Do not give anything else containing paracetamol while giving this medicine.

Give this medicine to your child to swallow.

Do not give more medicine than the label tells you to. If your child does not get better talk to your doctor.

Always use the syringe supplied with the pack.

Do not give to babies less than 2 months of age.

Do not give if your child is between 2-3 months old and is taking this medicine for other causes of pain and fever and weighs less than 4 kg or was born before 37 weeks. For infants 2-3 months no more than 2 doses should be given.

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 other medicine consult your doctor or pharmacist before using this product.

Do not store above 25°C. Store in the original package. Keep the lid tightly closed.

Keep all medicines out of the sight and reach of children.

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

Talk to a doctor at once if your child takes too much of this medicine, even if they seem well.

Never give more medicine than shown in the table.

Leaflet or combined label/leaflet:

Talk to a doctor at once if your child takes too much of this medicine even if they seem well. This is because too much paracetamol can cause delayed, serious liver damage.

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

Carmoisine (E122) may cause allergic reactions.

This medicine contains 0.8 g sorbitol and 1.3 g maltitol per 5 ml spoonful. This provides 5 kcal per 5 ml spoonful.

Don't give more than 4 times in any 24 hours.

Leave at least 4 hours between doses.

For the relief of fever after vaccination at 2, 3 and 4 months, if your baby still needs this medicine 2 days after receiving the vaccine talk to your doctor or pharmacist.

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.

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).

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 colestyramine.

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

Pregnancy:

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.

Breast-feeding:

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 post-marketing 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 to <1/10

≥1/1,000 to <1/100)

≥1/10,000 to <1/1,000

<1/10,000

(cannot be estimated from 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

Very rare

Anaphylactic reaction

Hypersensitivity

Hepatobiliary disorders

Not known

Liver injury2

Skin and Subcutaneous Tissue disorders

Very rare

Not known

Not known

Not known

Rash

Fixed eruption

Rash pruritic

Urticaria

Renal and urinary disorders

Uncommon

Not known

Nephropathy toxic

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

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 the disease improved after paracetamol withdrawal.

Very rare cases of serious skin reactions 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 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 (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 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 first 24 hours are pallor, nausea, hyperhidrosis, malaise, vomiting, anorexia and abdominal pain. Liver damage may become apparent 12 to 48 hours after ingestion. 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 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.

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-acetylcystine 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.