McNeil Healthcare (Ireland) Ltd

CALPOL 120 mg/5 ml Sugar Free Infant Oral Suspension

CALPOL Sugar Free Infant Oral Suspension contains 120 mg Paracetamol in each 5 ml.

Excipients: also includes the following substances in each 5 ml:

For a full list of excipients, see section 6.1

Oral Suspension.

A pink suspension with a strawberry colour .

CALPOL Sugar Free Infant Suspension is indicated for the treatment of pain (including teething pain), and as an antipyretic.

CALPOL Sugar Free Infant Suspension is indicated for the relief of headache, migraine, neuralgia, toothache and teething pains, sore throat, rheumatic aches and pains, influenza, feverishness and feverish colds.

4.2.1 Posology

Infants aged 2-3 months:

Children aged 3 months – 6 years:

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.

Heptatic / renal dysfunction

Caution should be exercised when administrating the product to patients with severe hepatic or renal impairment.

CALPOL Sugar Free Infant Suspension is contra-indicated in patients with known hypersensitivity to paracetamol, or any of the other components.

CALPOL Sugar Free Infant Suspension should be used with caution in moderate to severe renal impairment or severe hepatic impairment.

The label contains the following statements:

Store below 25°C. Protect from light.

Contains paracetamol.

Do not exceed the stated dose.

Keep out of reach of children.

Do not take more than 4 doses in 24 hours.

Dose 4 times a day.

Do not repeat doses more frequently than 4 hourly.

Do not give for more than 3 days without consulting a doctor.

If symptoms persist consult your doctor.

If you child is taking any other medicine, consult your doctor or pharmacist before taking this product.

Immediate medical advice should be sought in the event of an overdose, even if you feel well. (label)

Immediate medical advice should be sought in the event of an overdose, even if you feel well, because of the risk of irreversible liver damage. (leaflet)

Do not take with any other paracetamol containing products.

The following precautions should be followed when taking this medicine:

Do not take with any other paracetamol-containing products

Never give more medicine than shown in the table

Do not overfill the spoon

Always use the spoon supplied with the pack.

Do not give to babies less than 2 months of age

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 medicine consult your doctor or pharmacist before taking this product

Keep out of reach and sight of children

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.

The use of drugs that induce hepatic micosomal enzymes, such as anticonvulsants and oral contraceptives, may increase the extent of metabolism of paracetamol, resulting in reduced plasma concentrations of the drug and a faster elimination rate.

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.

The safe use of CALPOL Sugar Free Infant Suspension during pregnancy has not been established. There is epidemiological evidence of the safety of paracetamol in human pregnancy.

A pharmacokinetic study in 12 nursing mothers revealed that less than 1% of the dose ingested by a nursing mother appears in human breast milk, therefore maternal ingestion of therapeutic doses does not present a risk to the infant.

No special comment - unlikely to produce an effect.

Paracetamol has been widely used and, when taken at the usual recommended dosage, side effects are mild and infrequent and reports of adverse reactions are rare. Skin rash and other allergic reactions occur rarely.

Most reports of adverse reactions to paracetamol relate to overdosage with the drug.

Isolated cases of thrombocytic purpura, haemolytic anaemia and agranulocytosis 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.

Nephrotoxic effects following therapeutic doses of paracetamol are uncommon. Papillary necrosis has been reported after prolonged administration.

Symptoms and signs

Pallor, anorexia, nausea and vomiting are frequent early symptoms of paracetamol overdosage, although in many cases there are no symptoms for many hours.

Hepatic necrosis is a dose-related complication of paracetamol overdose. Hepatic enzymes may become elevated and prothrombin time prolonged within 12 to 48 hours but clinical symptoms may not be apparent for 1 to 6 days after ingestion. Toxicity is likely in subjects who have taken single doses of 10 g.

Treatment

To protect the patient against delayed hepatotoxicity, paracetamol overdosage should be treated promptly by gastric lavage followed by intravenous N-acetylcysteine or oral methionine. Additional therapy (further methionine or intravenous cysteamine or intravenous N-acetylcysteine) is normally considered in th elight of blood paracetamol content and the time elapsed since ingestion. Fulminant hepatic failure which may follow paracetamol overdosage requires specialised management.

In paracetamol overdosage with liver cell damage, paracetamol half-life is often prolonged from around 2 hours in normal adults to 4 hours or longer.

However liver cell damage has been found in patients with a paracetamol half life less than 4 hours. Diminution of ¹⁴CO₂ excretion after ¹⁴C-aminopyrine has been reported to correlate better with liver cell damage in paracetamol overdosage than do either plasma paracetamol concentration or half-life, or conventional liver function test measurements. Renal failure due to acute tubular necrosis may follow paracetamol-induced fulminant hepatic failure. The incidence of this is, however, no more frequent in these patients than in others with fulminant hepatic failure from other causes.

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 half-life 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.

Mutagenicity

There are no studies relating to the mutagenic potential of CALPOL Sugar Free Infant Suspension.

In vivo mutagencicity tests of paracetamol in mammals are limited and show conflicting results. Therefore, there is insufficient information to determine whether paracetamol poses a mutagenic risk to man.

Paracetamol has been found to be non-mutagenic in bacterial mutagenicity assays, although a clear clastogenic effect has been observed in mammalian cells in vitro following exposure to paracetamol (3 and 10 mM for 2 hr).

Carcinogenicity

There are no studies relating to the carcinogenic potential of CALPOL Sugar Free Infant Suspension.

There is inadequate evidence to determine the carcinogenic potential of paracetamol in humans. A positive association between the use of paracetamol and cancer of the ureter (but not of other sites in the urinary tract) was observed in a case-control study in which approximate lifetime consumption of paracetamol (whether acute or chronic) was estimated . However, other similar studies have failed to demonstrate a statistically significant association between paracetamol and cancer of the urinary tract, or paracetamol and renal cell carcinoma.

There is limited evidence for the carcinogenicity of paracetamol in experimental animals. Liver cell tumours can be detected in mice and liver and bladder carcinomas can be detected in rats following chronic feeding of 500 mg/kg/day paracetamol.

Teratogenicity

There is no information relating to the teratogenic potential of CALPOL Sugar Free Infant Suspension. In humans, paracetamol crosses the placenta and attains concentrations in the foetal circulation similar to those in the maternal circulation. Intermittent maternal ingestion of therapeutic doses of paracetamol is not associated with teratogenic effects in humans.

Paracetamol has been found to be fetotoxic to cultured rat embryo.

Fertility

There is no information relating to the effects of CALPOL Sugar Free Infant Suspension. A significant decrease in testicular weight was observed when male Sprague-Dawley rats were given daily high doses of paracetamol (500 mg/kg body weight/day) orally for 70 days.

Maltitol Liquid

Sorbitol solution (70% non crystallising) (E420)

Glycerol

Dispersible cellulose

Xanthan gum

Ethyl Parahydroxybenzoate (E214)

Methyl Parahydroxybenzoate (E218)

Propyl Parahydroxybenzoate (E216)

Polysorbate 80

Strawberry flavour 50086E

Carmoisine (E122)

Purified water

Not applicable

3 years

Do not store above 25C. Keep in original container.

5 ml sachet composed of a complex made of paper/PE/aluminium/Surlyn.

Pack sizes: 10 x 5 ml , 12 x 5 ml and 20 x 5 ml.

A spoon with a 5 ml and 2.5 ml measure is supplied with this pack.

Amber glass bottle with a two-piece plastic child resistant, tamper evident closure fitted with a polyethylene or polvinylidine chloride (PVDC) laminate faced wad

or

Amber glass bottle with a three-piece plastic child resistant, tamper evident closure fitted with a polyethylene or polvinylidine chloride (PVDC) laminate faced wad

Pack sizes: 30 ml, 60 ml, 70 ml, 100ml and 140 ml.

A spoon with a 5 ml and 2.5 ml measure is supplied with all packs of this product.

1000 ml amber glass bottle with an aluminium cap fitted with a polyethylene wad.

Not all pack sizes may be marketed.

No special requirements.

McNeil Healthcare (Ireland) Ltd

Airton Road

Tallaght

Dublin 24

Ireland

PA 823/10/5

Date of first authorisation: 22 March1988

Date of last renewal: 22 March 2008

December2011