McNeil Healthcare (Ireland) Ltd

CALPOL SIX PLUS 250mg/5ml SUGAR/COLOUR FREE ORAL SUSPENSION

CALPOL SIX PLUS SUGAR/COLOUR FREE SUSPENSION contains Paracetamol 250 mg per 5 ml.

Excipients: Also contains

Maltitol 2040mg per 5ml

Sorbitol 1400mg

Methyl parahydroxybenzoate 5.0mg per 5ml

Propyl parahydroxybenzoate 1.0mg per 5ml

For a full list of excipients, see section 6.1

Oral Suspension.

An off-white oral suspension with an odour of strawberries.

Calpol products are indicated for the treatment of mild to moderate pain and as antipyretics.

Calpol is indicated for the symptomatic relief of headache, migraine, neuralgia, toothache and teething pains, sore throat, influenza, feverishness and feverish colds.

For oral administration

Children aged 6 years – 12 years:

Children aged 12 – 16 years:

Two – three 5ml spoonfuls (large end) up to 4 times a day.

Adults and children over 16 years:

Two – four 5ml spoonfuls (large end) up to 4 times a day.

Calpol is contra-indicated in patients with a known hypersensitivity to paracetamol.

Calpol should be used with caution in patients with severe hepatic or renal dysfunction.

There is no evidence of paracetamol dependence.

Contains 2.04g Maltitol and 1.4g Sorbitol per 5ml

Patients with rare hereditary problems of fructose intolerance should not take this medicine. May have mild laxative effect. Calorific value 2.3kcal/g maltitol and 2.6 kcal/g sorbitol.

Methyl and propyl parahydroxybenzoates may cause allergic reactions (possibly delayed).

The following precautions should be followed when taking this medicine:

Do not give 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 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

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.

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 during pregnancy has not been established directly. There is epidemiological evidence of safety of paracetamol in human pregnancy.

A pharmacokinetic study in 12 nursing mothers revealed that less than 1% of a 650 mg oral dose of paracetamol ingested by a nursing mother appears in human breast milk, therefore maternal ingestion of therapeutic doses does not present a risk to the infant.

None known

Paracetamol is well tolerated when taken at the usual recommended dosages, with most reports of adverse reactions to paracetamol relating to overdosage with the drug. At normal therapeutic doses, side effects are mild and infrequent with reports of adverse reactions rare. Skin rashes have been documented occasionally, as have case reports of hypersensitivity and idiosyncratic reactions (e.g. thrombocytopenic purpura, haemolytic anaemia and agranulocytosis).

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.

Nephrotoxicity following therapeutic doses of paracetamol is uncommon, but papillary necrosis has been reported after prolonged administration.

Signs & Symptoms

Pallor, anorexia, nausea and vomiting are frequent early symptoms of paracetamol overdosage. Hepatic necrosis is a dose-related complication of paracetamol overdosage. Hepatic enzymes may become elevated and prothrombin time prolonged within 12-48 hours, but clinical symptoms may not be apparent until 1 to 6 days after ingestion. Toxicity is likely in adults who have taken more than 10g, but may also occur at lower doses in certain patients (see treatment section).

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. Peak plasma paracetamol concentrations may be delayed by up to 4 hours following overdose. Additional therapy (further methionine or intravenous N-acetylcysteine) is normally considered in the light of blood paracetamol content and 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 in ¹⁴CO₂ excretion after oral 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. Concomitant renal failure due to acute tubular necrosis may accompany paracetamol-induced fulminant hepatic failure. The incidence is however, no more frequent in these patients than in others with fulminant hepatic failures from other causes.

It has been proposed that the threshold for treatment with N-acetylcysteine should be reduced by 30-50% in patients taking drugs which reduce hepatic enzymes, who abuse alcohol long term, or who are chronically malnourished, as these patients may be more susceptible to the toxic effects of paracetamol.

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 the 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.

The active ingredients of Calpol are well known constituents of medicinal products and their safety profile is well documented.

Maltitol Liquid (E965)

Sorbitol Liquid (noon-crystallising) (E420)

Glycerol

Dispersible Cellulose

Xanthan Gum

Methyl Parahydroxybenzoate (E218)

Propyl Parahydroxybenzoate (E216)

Acesulfame Potassium

Polysorbate 80

Sodium Saccharin

Flavour, Strawberry Cream 11407-33

Flavour, Strawberry 500286E

Purified Water

None known

3 years.

Do not store above 25^ºC.

Store in original package in order to protect from light. Keep the bottle tightly closed..

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

Or

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

Or

Amber glass bottle closed with a two-piece screw child resistant, tamper evident closure fitted with a polyethylene laminate faced wad

Or

Amber glass bottle closed with a plastic screw closure or a metal Roll-on-pilfer-proof closure fitted with a polyethylene or polyvinylidene chloride (PVDC) faced wad.

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

Pack sizes: 60ml, 70 ml, 100 ml, 140 ml, 500 ml or 1000 ml

Not all pack sizes may be marketed

Shake well before use.

McNeil Healthcare (Ireland) Limited

Airton Road

Tallaght

Dublin 24

Ireland

PA 823/10/4

14^th October 1994 / 14 October 2009.

December 2011