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SUMMARY OF PRODUCT CHARACTERISTICS

1    NAME OF THE MEDICINAL PRODUCT

Aspirin 75mg Gastro-resistant Tablets

Boots Aspirin75mg Gastro-resistant Tablets

Lloyds Pharmacy Aspirin Enteric Coated Tablets 75mg

2    QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains aspirin 75mg For excipients see section 6.1

3    PHARMACEUTICAL FORM

Gastro-resistant tablet

White circular tablet, plain on both sides.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

For the secondary prevention of thrombotic cerebrovascular or cardiovascular disease and following by-pass surgery.

4.2 Posology and method of administration

Aspirin 75 mg is for oral administration to adults only.

Take the tablet with water, do not cut, chew or crush the tablet. Swallow whole.

The advice of a doctor should be sought before commencing therapy for the first time.

The usual dosage, for long term use, is 75mg-150mg once daily. In some circumstances a higher dose may be appropriate, especially in the short term, and up to 300mg a day may be used on the advice of a doctor.

In Elderly: The risk-benefit ratio of the antithrombotic action of aspirin has not been fully established.

Children: Do not give to children aged under 16 years, unless specifically indicated (e.g. for Kawasaki’s disease). See Section 4.4

4.3 Contraindications

•    Hypersensitivity to aspirin or any other NSAIDs, or any of the excipients (see section 6.1)

•    Active peptic ulceration or history of peptic ulceration

•    Haemophilia, other coagulopathies, including hypoprothrombinaemia or concurrent anticoagulant therapy

•    Gout

•    Do not give to children aged under 16 years, unless specifically indicated (e.g. for Kawasaki’s disease).

4.4 Special warnings and precautions for use

Caution should be exercised in patients with allergic disease, impairment of hepatic or renal function (avoid if severe) and dehydration.

Aspirin may also precipitate bronchospasm or induce attacks of asthma in susceptible subjects.

The elderly may be more susceptible to the toxic effects of salicylates. Continuous prolonged use of aspirin should be avoided in the elderly because of the risk of gastrointestinal bleeding.

Caution should be taken in patients with glucose-6-phosphate dehydrogenase deficiency as haemolytic anaemia may occur.

Aspirin may interfere with insulin and glucagon in diabetes.

Aspirin prolongs bleeding time, mainly by inhibiting platelet aggregation and therefore it should be discontinued several days before scheduled surgical procedures. Haematological & haemorrhagic effects can occur, and may be severe. Patients should report any unusual bleeding symptoms to their physician.

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 aged under 16 years unless specifically indicated (e.g. for Kawasaki’s disease).

Salicylates should not be used in patients with a history of coagulation abnormalities as they may also induce gastro-intestinal haemorrhage, occasionally major. (see section 4.3)

Aspirin should not be taken by patients with a stomach ulcer or a history of stomach ulcers. (see section 4.3)

Before commencing long term aspirin therapy for the management of cardiovascular or cerebrovascular disease patients should consult their doctor who can advise on the relative benefits versus the risks for the individual patient.

Patients with hypertension should be carefully monitored.

4.5 Interaction with other medicinal products and other forms of interaction

Anticoagulants: Aspirin may potentiate the effect of heparin and increases the risk of bleeding with oral anticoagulants, antiplatelet agents and fibrinolytics. _Concomitant use is not recommended (see Section 4.3)

Other non-steroidal anti-inflammatory drugs (NSAIDs): Concurrent administration can increase side effects. Use of two or more NSAIDs increases risk of gastrointestinal haemorrhage. 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)

Corticosteroids: The risk of gastrointestinal bleeding and ulceration is increased. Corticosteroids reduce the plasma salicylate concentration and salicylate toxicity may occur following withdrawal of corticosteroids.

Carbonic anhydrase inhibitors: Reduced excretion of acetazolamide; salicylate intoxication has occurred in patients on high dose salicylate regimes and carbonic anhydrase inhibitors. Concurrent administration of carbonic anhydrase inhibitors such as acetazolamide and salicylates may result in severe acidosis and increased central nervous system toxicity.

Antacids and adsorbents: The excretion of aspirin is increased in alkaline urine; kaolin possibly reduces absorption. Patients should be advised against ingesting antacids simultaneously to avoid premature drug release.

Mifepristone: The manufacturer of mifepristone recommends that aspirin should be avoided until eight to twelve days after mifepristone has been discontinued.

Antimetabolites: The activity of methotrexate may be markedly enhanced and its toxicity increased.

Antibacterials: The toxicity of sulfonamides may be increased.

Alcohol: Some of the effects of aspirin on the gastrointestinal tract are enhanced by alcohol.

Antiemetics: Metoclopramide enhances the effects of aspirin by increasing the rate of absorption.

ACE inhibitors: Aspirin may reduce the antihypertensive effect of ACE inhibitors.

Anti-epileptics: May enhance the effects of phenytoin and sodium valproate.

Diuretics: Antagonism of the diuretic effect of spironolactone.

Hypoglycaemic agents: Aspirin may enhance the effects of insulin and oral hypoglycaemic agents.

Leukotriene antagonists: The plasma concentration of zafirlukast is increased.

Immune system disorders: Hypersensitivity reactions include skin rashes, urticaria, angioedema, asthma, bronchospasm, rhinitis and rarely, anaphylaxis.

Ear & Labyrinth disorders: Tinnitus.

Gastrointestinal disorders: Gastrointestinal irritation is common in patients taking aspirin preparations, and nausea, vomiting, dyspepsia, gastritis, gastrointestinal erosions and ulceration have been reported. Anaemia may occur following chronic gastrointestinal blood loss or acute haemorrhage.

Skin and subcutaneous tissue disorders: Skin reactions may occur in susceptible patients. Renal and Urinary disorders: urate kidney stones

4.9 Overdose

Salicylate poisoning is usually associated with plasma concentrations >350mg/L (2.5mmol/L) Most adult deaths occur in patients whose concentrations exceed 700mg/L (5.1mmol/L). Single doses less than 100mg/kg are unlikely to cause serious poisoning.

Symptoms

Common features include vomiting, dehydration, tinnitus, vertigo, deafness, sweating, warm extremities with bounding pulses, increased respiratory rate and hyperventilation. Some degree of acid-base disturbance is present in most cases.

A mixed respiratory alkalosis and metabolic acidosis with normal or high arterial pH ( normal or reduced hydrogen ion concentration) is usual in adults or children over the age of four years. In children four years or less, a dominant metabolic acidosis with low arterial pH (raised hydrogen ion concentration) is common. Acidosis may increase salicylate transfer across the blood brain barrier.

Uncommon features include haematemesis, hyperpyrexia, hypoglycaemia, hypokalaemia, thrombocytopaenia, increased INR/PTR, intravascular coagulation, renal failure and noncardiac pulmonary oedema.

Central nervous system features including confusion, disorientation, coma and convulsions are less common in adults than in children.

Treatment

Give activated charcoal if an adult presents within one hour of ingestion of more than 250mg/kg. The plasma salicylate concentration should be measured, although the severity of poisoning cannot be determined from this alone and the clinical and biochemical features must be taken into account. Elimination is increased by urinary alkalinisation, which is achieved by the administration of 1.26% sodium bicarbonate. The urine pH should be monitored. Correct metabolic acidosis with intravenous 8.4% sodium

bicarbonate (first check serum potassium). Forced diuresis should not be used since it does not enhance salicylate excretion and may cause pulmonary oedema.

Haemodialysis is the treatment of choice for severe poisoning and should be considered in patients with plasma salicylate concentrations >700mg/L (5.1mmol/L) or lower concentrations associated with severe clinical or metabolic features. Patients under ten years or over 70 have increased risk of salicylate toxicity and may require dialysis at an earlier stage.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

B01A C (blood and blood forming organs — antithrombotic agents)

Aspirin has analgesic, anti-inflammatory and anti-pyretic activity. It also has an antithrombotic action, mediated through inhibition of platelet activation, which has been shown to be useful in secondary prophylaxis following myocardial infarction and in patients with unstable angina or ischaemic stroke including cerebral transient attacks.

In the body it is rapidly converted to the salicylate form which has similar activity and works via the inhibition of the enzyme cyclo-oxygenase inhibiting prostaglandin synthesis.

The enteric coat is intended to resist gastric fluid whilst allowing disintegration in the intestinal fluid. Owing to the delay that the coating imposes on the release of the active ingredient, enteric coated tablets are unsuitable for the short-term relief of pain.

Experimental data suggest 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 30min after immediate release aspirin dosing (81 mg), 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.

5.2 Pharmacokinetic properties

Absorption: Aspirin is rapidly absorbed after oral administration, with some hydrolysis to salicylate before absorption. Absorption is delayed by the presence of food and is impaired in patients suffering migraine attacks. Absorption is more rapid in patients with achlorhydria and also following administration of polysorbates and antacids.

Blood concentration: Single and multiple 100 mg doses of enteric- coated aspirin give systemic bioavailabilities of between 15% and 20% of that seen with immediate release aspirin preparations. Cmax of aspirin for several enteric - coated preparations has been shown to be approximately 100 - 200 ng/ml with a half - life of approximately 1.7 hours. Plasma concentrations of salicylic acid increase disproportionately with dose - a 325 mg dose having a half-life of 2-3 hours and higher doses showing lower plasma concentrations in the presence of an increased half-life due to a disproportionate increase in volume of distribution.

Distribution: Aspirin is found in the saliva, milk, plasma and synovial fluid at concentrations less than blood and crosses the placenta.

Salicylate - extensive protein binding.

Aspirin - protein binding to a small extent.

Metabolism: In the blood, rapid hydrolysis to salicylic acid; glucuronic acid/ glycine conjugation to form glucuronides and salicyluronic acid; oxidation of a small proportion.

Excretion: Excreted in the urine mainly as salicyluronic acid. Salicylate reabsorbed by renal tubules in acid urine, and alkaline diuresis will increase the rate of excretion; 85% of dose excreted as free salicylate.

5.3 Preclinical safety data

None applied on the basis of the active ingredient being a well known and marketed compound with an established efficacy and side effect profile.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Potato starch

Calcium hydrogen phosphate dihydrate E341

Microcrystalline cellulose E460 Talc E553b

Methacrylic acid - ethylacrylate -copolymer (1: 1) (also contains: Sodium lauryl sulphate and polysorbate 80)

Macrogol

30% Simeticone emulsion

6.2 Incompatibilities

Not applicable

6.3    Shelf life

3 years

6.4    Special precautions for storage

Do not store above 25°C.

Store in the original package.

6.5    Nature and contents of container

32, 56 or 84 tablets in a blister pack.

Blister strips consist of a 35gsm paper/9^ soft tempered aluminium foil lid and 250^ PVC film base in cartons.

or

Child resistant Aluminium/PVC blister packs: 20um hard aluminium foil laminated to 15um rigid PVC and 250u PVC film base in cartons

Special precautions for disposal

None

7 MARKETING AUTHORISATION HOLDER

Bristol Laboratories Ltd Unit 3, Canalside,

Northbridge Road Berkhamsted HP4 1EG UK

8 MARKETING AUTHORISATION NUMBER(S)

PL 17907/0157

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

19/02/1998 / 07/12/2005

10 DATE OF REVISION OF THE TEXT

23/09/2014