Reckitt Benckiser Ireland Limited

Disprin Direct 300mg Chewables Tablets

Aspirin 300 mg/tablet.

For excipients see 6.1.

Dispersible tablet.

A white circular tablet with odour and taste of lemon. On one surface indented with 'sword' motif, the other plain.

For the relief of mild to moderate pain such as is associated with headache, toothache and neuralgia. Reduction of temperature. Reduction of inflammation such as in lumbago.

Disprin Direct Chewables disperse on the tongue without water, and are then swallowed.

Adults and children 16 years and over: One to two tablets to a maximum of twelve tablets in 24 hours. The dose may be repeated after 4 hours, but the maximum dose in 24 hours must not be exceeded.

Do not give to children and adolescents aged under 16 years, except on medical advice, where the benefit outweighs the risk.

Elderly: Non-steroidal anti-inflammatory drugs should be used with particular caution in elderly patients who are more prone to adverse events. The lowest dose compatible with adequate safe clinical control should be employed. See also Section 4.4.

Severe heart failure.

History of gastrointestinal bleeding or perforation related to previous NSAIDs therapy. Active, or history of recurrent peptic ulcer/haemorrhage (two or more distinct episodes of proven ulceration or bleeding).

Should not be given to patients hypersensitive (e.g. bronchospasm, rhinitis, urticaria) to aspirin or to other non-steroidal anti-inflammatory drugs. Do not use in patients suffering from peptic ulceration or a coagulation deficiency disorder.

The use with concomitant NSAIDs including cyclooxygenase-2 selective inhibitors should be avoided.

Caution (discussion with doctor or pharmacist) is required prior to starting treatment in patients with a history of hypertension and/or heart failure as fluid retention and oedema have been reported in association with NSAID therapy.

Undesirable effects may be minimised by using the minimum effective dose for the shortest duration necessary to control symptoms (See section 4.2, and GI and cardiovascular risks below).

Gastrointestinal bleeding, ulceration and perforation: GI bleeding, ulceration or perforation, which can be fatal, has been reported with all NSAIDs at any time during treatment, with or without any warning symptoms or a previous history of serious GI events.

The risk of GI bleeding, ulceration or perforation is higher with increasing NSAID doses, in patients with a history of ulcer, particularly if complicated with haemorrhage or perforation (see section 4.3), and in the elderly. These patients should commence treatment on the lowest dose available. Combination therapy with protective agents (e.g. misoprostol or proton pump inhibitors) should be considered for these patients, and also for patients requiring concomitant low dose aspirin, or other drugs likely to increase gastrointestinal risk (see below and 4.5).

Patients with a history of GI toxicity, particularly when elderly, should report any unusual abdominal symptoms (especially GI bleeding) particularly in the initial stages of treatment.

Caution should be advised in patients receiving concomitant medications which could increase the risk of ulceration or bleeding, such as oral corticosteroids, anticoagulants such as warfarin, selective serotonin reuptake inhibitors or anti-platelet agents such as aspirin (see section 4.5).

When GI bleeding or ulceration occurs in patients receiving Disprin Direct, the treatment should be withdrawn.

NSAIDs should be given with care to patients with a history of gastrointestinal disease (ulcerative colitis, Crohn's Disease) as their condition may be exacerbated (see section 4.8 – undesirable effects).

Cardiovascular and cerebrovascular effects: Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke). There are insufficient data to exclude such a risk for aspirin when given at a daily dose of 3600mg

Serious skin reactions, some of them fatal, including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis, have been reported very rarely in association with the use of NSAIDs (see 4.8). Patients appear to be at highest risk of these reactions early in the course of therapy, the onset of the reaction occurring in the majority of cases within the first month of treatment. Disprin Direct should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

There is some evidence that drugs which inhibit cyclo-oxygenase/prostaglandin synthesis may cause impairment of female fertility by an effect on ovulation. This is reversible on withdrawal of treatment.

Elderly: The elderly have an increased frequency of adverse reactions to NSAIDs especially gastrointestinal bleeding and perforation which may be fatal (see section 4.2)

Elderly patients are particularly susceptible to the adverse effects of non-steroidal anti-inflammatory drugs. Unsupervised prolonged use of non-steroidal anti-inflammatory drugs in the elderly is not recommended.

This product should be taken only when necessary.

Prolonged use except on medical advice can be harmful.

Undesirable effects may be reduced by using the minimum effective dose for the shortest possible duration.

The doctor should be consulted if there is no improvement in 24 hours.

If the patient is on any medication consult the doctor or pharmacist before using.

If the patient suffers from asthma, has renal or hepatic impairment, or a history of peptic ulceration or inflammatory bowel disease, then a doctor should be consulted before taking the product.

There is a possible association between aspirin and Reye's syndrome when given to children. Reye's syndrome is a very rare disease, which affects the brain and liver, and can be fatal. For this reason aspirin should not be given to children and adolescents aged under 16 years unless specifically indicated.

Anti-coagulants: NSAIDs may enhance the effects of anticoagulants, such as warfarin (see section 4.4).

It is considered unsafe to take non-steroidal anti-inflammatory drugs in combination with warfarin or heparin unless under direct medical supervision.

Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding (see section4.4).

Aspirin may enhance the effects of anticoagulants, inhibit the effects of uricosurics and reduce the excretion of methotrexate (increasing its toxicity).

Diuretics: Reduced diuretic effect. Diuretics can increase the risk of nephrotoxicity of non-steroidal anti-inflammatory drugs.

Other non-steroidals: Avoid concomitant use of two or more non-steroidal anti-inflammatory drugs.

Corticosteroids: Increased risk of gastrointestinal bleeding.

Antihypertensives: Reduced antihypertensive bleeding.

Cardiac glycosides: Non-steroidal anti-inflammatory drugs may exacerbate cardiac failure, reduce GFR and increase plasma cardiac glycoside levels.

Lithium: Decreased elimination of lithium.

Methotrexate: Decreased elimination of methotrexate.

Cyclosporin: Increased risk of nephrotoxicity with non-steroidal anti-inflammatory drugs.

Aminoglycosides: Reduction in renal function in susceptible individuals, decreased elimination of aminoglycosides and increased plasma concentration.

Probenecid: Reduction in metabolism and elimination of NSAID and metabolites.

Experimental data suggest that ibuprofen may inhibit the effect of low dose aspirin on platelet aggregation when they are dosed concomitantly. However, the limitations of these data and the uncertainties regarding extrapolation of ex vivo data to the clinical situation imply that no firm conclusions can be made for regular ibuprofen use, and no clinically relevant effect is considered to be likely for occasional ibuprofen use (see section 5.1).

As with all other drugs, aspirin should be taken during pregnancy only after strict risk-benefit evaluation.

In the last three months of pregnancy, the prolonged administration of aspirin (>300 mg/day) can lead to delayed onset and increased duration of labour, premature closure of the ductus arteriosus and inhibition of uterine contractions. An increased haemorrhagic tendency has been observed in both the mother and child. Administration of aspirin in high doses shortly before birth can lead to intracranial haemorrhages, particularly in premature babies.

Salicylates pass into breast milk in small quantities. As no adverse effects on the infant have been observed after occasional use, interruption of breast feeding is usually unnecessary. However, if high doses (>300 mg/day) are used regularly, breast feeding should be discontinued as toxicity to the new-born cannot be ruled out.

None stated.

Adverse effects occurring with aspirin include gastro-intestinal disturbance, peptic ulceration and gastro-intestinal bleeding. Other less frequent adverse effects to aspirin include headache, skin rash, oedema, blurred vision, hypersensitivity, thrombocytopenia, abnormal liver function and impaired renal function.

Gastrointestinal: The most commonly observed adverse events are gastrointestinal in nature. Peptic ulcers, perforation or GI bleeding, sometimes fatal, particularly in the elderly, may occur (see section 4.4). Nausea, vomiting, diarrhoea, flatulence, constipation, dyspepsia, abdominal pain, melaena, haematemesis, ulcerative stomatitis, exacerbation of colitis and Crohn's disease (see section 4.4 –Special warnings and precautions for use) have been reported following administration. Less frequently, gastritis has been observed. Gastrointestinal blood losses leading to anaemia have been reported with non-steroidal anti-inflammatory drugs such as aspirin.

Cardiovascular: Oedema, hypertension and cardiac failure have been reported in association with NSAID treatment. Cardiovascular and cerebrovascular effects: Clinical trial and epidemiological data suggest that use of some NSAIDs (particularly at high doses and in long term treatment) may be associated with a small increased risk of arterial thrombotic events (for example myocardial infarction or stroke) (see section 4.4).

Skin reactions: Bullous reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis (very rare).

Non-steroidal anti-inflammatory drugs including aspirin may precipitate bronchospasm, rhinitis or urticaria, or induce attacks of asthma in susceptible subjects.

Isolated cases of liver (increased transaminases) and kidney dysfunction and severe skin reactions have been described.

Acute salicylate poisoning is usually manifested as hypokalaemia with metabolic acidosis and respiratory alkalosis. Nausea, vomiting, tinnitus, hyperpnoea, hyperpyrexia, confusion, disorientation, dizziness, coma and/or convulsions are common. Gastrointestinal haemorrhage is frequent. However, alkalaemia or acidaemia, alkaluria or aciduria, hyperglycaemia or hypoglycaemia, and water and electrolyte imbalances, can occur.

Chronic salicylate intoxication is commonly associated with daily headaches, nausea, tinnitus, dizziness, lethargy and confusion; coma may occur. The symptoms can mimic those resulting from illness for which the drug was given. Irritability, lethargy, delayed unresponsiveness and encephalopathy may be seen one to three days following withdrawal of aspirin. At the same time the concentration of salicylate in the CNS may be high, with non-toxic values in the serum.

Serum salicylate levels above 3.6 mmol/l in adults (2.2 mmol/l in children) are likely to be toxic and levels of 5.4 mmol/l can be fatal.

Treatment: Fluid and electrolyte management is the mainstay of therapy; the immediate aim is to correct acidosis, hyperpyrexia, hypokalaemia and dehydration. Drug absorption can be arrested by induction of emesis or gastric lavage within an hour of ingestion. Drug excretion is enhanced by forced alkaline diuresis and by the early use of activated charcoal. Rarely, haemodialysis is necessary. Delayed encephalopathy may respond to the administration of mannitol.

Aspirin inhibits the cyclo-oxygenase enzyme involved in conversion of phospholipids to prostaglandins and its effects on the body are believed to result primarily from prevention of prostaglandin production. These effects include peripheral analgesia, fever reduction, reduction in inflammation and inhibition of platelet aggregation.

Experimental data suggests that ibuprofen may inhibit the effect of low dose aspirin on platelet aggregation when they are dosed concomitantly. In one study, when a single dose of ibuprofen 400mg was taken within 8 h before or within 30 min after immediate release aspirin dosing 81mg, a decreased effect of ASA on the formation of thromboxane or platelet aggregation occurred. However, the limitations of these data and the uncertainties regarding extrapolation of ex vivo data to the clinical situation imply that no firm conclusions can be made for regular ibuprofen use, and no clinically relevant effect is considered to be likely for occasional ibuprofen use.

Aspirin is rapidly absorbed from the stomach and upper gastrointestinal tract with peak levels after around 20-30 minutes following dissolution. It is subject to first-pass metabolism with an overall bioavailability of around 70%. Metabolism is by conversion to salicylic acid and then by further conversion to other metabolites. These are excreted by the kidneys in both free and conjugated form. The plasma half-life of aspirin is around 15-20 minutes and that of salicylic acid is 2-3 hours.

No preclinical findings of relevance have been reported.

Glycine, maize starch, microcrystalline cellulose, purified talc, saccharin and lemon flavour 51124.

Not applicable.

Three years.

Do not store above 25°C. Store in the original package.

Vinyl coated heat sealed aluminium foils, 24 tablets to a carton.

No special requirements.

Reckitt Benckiser Ireland Limited

7 Riverwalk

Citywest Business Campus

Dublin 24

Ireland

PA 979/7/1.

Date of first authorisation: 26th July, 1983

Date of last renewal: 26th July, 2008

April 2009