This information is intended for use by health professionals

1. Name of the medicinal product

Calpol Six Plus Fastmelts (250 mg Orodispersible Tablets)

2. Qualitative and quantitative composition

Paracetamol 250 mg

Excipients: also contains mannitol (E421) and aspartame ((E951)) contains 8mg aspartame per tablet).

For the full list of excipients, see section 6.1.

3. Pharmaceutical form

Orodispersible tablet

Round, white, bi-convex tablets with central concave depression.

4. Clinical particulars
4.1 Therapeutic indications

Calpol Six Plus Fastmelts 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.

4.2 Posology and method of administration

Oral:

Tablets should be placed in the mouth where they melt on the tongue. The tablet will rapidly disperse to a pleasant tasting paste that can be easily ingested. Alternatively the tablet can be dispersed in a teaspoonful of water or milk.

Adults and children

Child's Age

How Much

How often (in 24 hours)

Under 6 years

Not recommended

N/A

6 - 9 years

1 tablet

4 times

9 - 12 years

2 tablets

4 times

12 – 16 years

2 to 3 tablets

4 times

Adults and children over 16 years

2 to 4 tablets

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

Use in the Elderly

Normal adult dosage is appropriate. However, a reduction in dosing may be necessary in frail, elderly subjects (see Section 5.2).

4.3 Contraindications

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

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.

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. Chronic alcohol users should consult a doctor before use.

Calpol Six Plus Fastmelts contains 8mg aspartame, which is a source of phenylalanine equivalent to 0.04 mg/250 mg tablet. The phenylalanine in the tablets may be harmful to people with phenylketonuria (PKU), a rare genetic disorder in which phenylalanine builds up because the body cannot remove it properly.

Calpol Six Plus Fastmelts contain mannitol, which may have a mild laxative effect.

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 contains the following statements:

Contains paracetamol.

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

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

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.

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.

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.

4.5 Interaction with other medicinal products and other forms of interaction

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.

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

None 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

≥1/10

Common

≥1/100 and < 1/10

Uncommon

≥1/1,000 and <1/100

Rare

≥1/10,000 and <1/1,000

Very rare

<1/10,000

Not known

(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 reactions

Very rare

Hypersensitivity

Hepatobiliary disorders

Not known

Liver injury2

Skin and subcutaneous tissue disorders

Very rare

Rash

Not known

Rash pruritic

Not known

Urticaria

Renal and urinary disorders

Uncommon

Nephropathy toxic

Not known

Renal papillary necrosis3

Investigations

Not known

Transaminases increased4

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.

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.

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 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

a)- Is on long term treatment with carbamezepine, Phenobarbital, 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 overdose 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 medical attention. Symptoms may be limited to nausea or vomiting and may not reflect the severity of the 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.

5. Pharmacological properties
5.1 Pharmacodynamic properties

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.

5.2 Pharmacokinetic properties

Paracetamol is rapidly and almost completely absorbed from the gastro-intestinal tract. Peak plasma concentrations are reached 30-90 minutes post dose.

Paracetamol is distributed rapidly throughout all tissues. Protein binding is low.

The plasma half-life is in the range of 1 to 4 hours after therapeutic doses.

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 overdose there is increased N-hydroxylation followed by glutathione conjugation. When the latter is exhausted reaction with hepatic proteins is increased leading to necrosis.

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.

5.3 Preclinical safety data

There are no preclinical data of relevance to the prescriber which are additional to those already included in other sections of the SPC.

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

6. Pharmaceutical particulars
6.1 List of excipients

Mannitol (E421)

Crospovidone

Aspartame (E951)

Strawberry flavouring E. 9620941

Magnesium stearate

Basic butylated methacrylate copolymer

Polyacrylate dispersion 30%

Colloidal anhydrous silica

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

Strip containing 24 tablets.

The blister consists of a blister complex (Polyamide/PVC/Aluminium) and either:

an aluminium sealing sheet

or

a paper/aluminium child resistant sealing sheet.

6.6 Special precautions for disposal and other handling

No special requirements for disposal.

7. Marketing authorisation holder

McNeil Products Limited

Foundation Park

Roxborough Way

Maidenhead

Berkshire

SL6 3UG

8. Marketing authorisation number(s)

PL 15513/0082

9. Date of first authorisation/renewal of the authorisation

19th March 2001/03 March 2009

10. Date of revision of the text

28 January 2020