Paracetamol 250 mg/5 ml Oral suspension

Paracetamol 250 mg/5 ml oral suspension is indicated for the treatment of mild to moderate pain and as an antipyretic. It can be used in many conditions including headache, toothache, earache, sore throat, colds and influenza, aches and pains and post-immunisation fever.

Children aged 6 to 12 years:

Children aged 12-16 years: 10 – 15 ml (Two to three 5 ml doses) up to 4 times a day.

Adults and children over 16 years: 10 – 20 ml (Two to four 5 ml doses) up to 4 times a day.

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

The 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.

Hypersensitivity to paracetamol or to any of the excipients listed in section 6.1.

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.

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

Paracetamol 250 mg/5 ml oral suspension should not be diluted.

Each 5 ml of this product contains 1.8g sorbitol liquid and 2.4g of maltitol liquid. Sorbitol and maltitol may cause gastrointestinal discomfort and have a mild laxative effect.

Calorific values: 2.6 kcal/g sorbitol and 2.3 kcal/g maltitol.

Due to the presence of maltitol liquid (E965) and sorbitol liquid (E420), patients with rare hereditary problems of fructose intolerance should not take this medicine.

This medicine contains propyl hydroxybenzoate (E216) and methyl hydroxybenzoate (E218) which may cause allergic reactions (possibly delayed).

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

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.

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 underlying cause of HAGMA in patients with multiple risk factors.

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

The label contains the following statements:

- Contains paracetamol.

- Do not give anything else containing paracetamol.

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

- For oral use only.

- Always use the double sided measuring spoon supplied with the pack.

- 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.

- Keep out of the sight and reach of children.

- Do not store above 25ºC. Store in the original package.

- 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.

The leaflet contains the following statements:

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.

If the child needs more than the doses shown in the table, or if fever doesn't go away, speak to your doctor as soon as possible.

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.

Drugs which induce hepatic microsomal enzymes

Metabolism of paracetamol possibly accelerated by carbamazepine, fosphenytoin, phenytoin, phenobarbital, primidone (also isolated reports of hepatotoxicity).

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.

Chronic alcohol intake can increase the hepatotoxicity of paracetamol overdose and may have contributed to the acute pancreatitis reported in one patient who had taken an overdose of paracetamol. Acute alcohol intake may diminish an individual's ability to metabolise large doses of paracetamol, the plasma half-life of which can be prolonged.

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)

Pregnancy

A large amount of data on pregnant women indicates 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.

None known.

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:

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'.

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 the 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 Yellow Card Scheme. Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store

Liver damage is possible in adults and adolescents (≥12 years of age) who have taken 7.5g or more 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 5g or more of paracetamol may lead to liver damage if the patient has risk factors (see below).

Risk Factors:

If the patient

- Is on long term treatment with carbamazepine, phenobarbitone, phenytoin, primidone, rifampicin, St John's Wort or other drugs that induce liver enzymes. Or,

- Regularly consumes ethanol in excess of recommended amounts. Or,

- 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, 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 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 Nacetylcysteine 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.

Pharmacotherapeutic group: Other Analgesics and Antipyretics (Anilides)

ATC Code: N02 BE01

Paracetamol has analgesic and antipyretic effects similar to those of aspirin and is useful in the treatment of mild to moderate pain. It has weak anti-inflammatory effects.

Paracetamol is rapidly and almost completely absorbed from the gastrointestinal tract. Peak plasma concentrations are reached 30-90 minutes post dose and the plasma halflife is in the range of 1 to 3 hours after therapeutic doses. Drug is widely distributed throughout most body fluids. Following therapeutic doses 90-100% of the drug is recovered in the urine within 24 hours almost entirely following hepatic conjugation with glucuronic acid (about 60%), sulphuric acid (about 35%) or cysteine (about 3%). Small amounts of hydroxylated and deacetylated metabolites have also been detected. Children have less capacity for glucuronidation of the drug than do adults. In overdosage there is increased N-hydroxylation followed by glutathione conjugation. When the latter is exhausted, reaction with hepatic proteins is increased leading to necrosis.

Preclinical data reveal no special hazard for humans based on conventional studies of single and repeated dose toxicity, genotoxicity, and carcinogenicity.

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

Maltitol liquid (E965)

Sorbitol liquid (E420)

Glycerol (E422)

MCC and carmellose sodium

Xanthum gum,

Polysorbate 80

Methyl hydroxybenzoate (E218)

Propyl hydroxybenzoate (E216)

Acesulfame potassium

Sodium saccharin (E954)

Strawberry flavour 502301T

Strawberry 054267A

Sodium hydroxide

Citric acid monohydrate

Purified water

None known.

3 years unopened.

60 days once opened.

Do not store above 25ºC. Store in the original package.

Amber PET bottle with a white opaque polypropylene, child-resistant closure fitted with EPE liner and temper evident ring.

Pack Size: 100 ml and 200 ml. Double ended measuring spoon (2.5 ml and 5 ml) is supplied with this product.

Not all pack sizes may be marketed.

Any unused product or waste material should be disposed of in accordance with local requirements.