Aspirin Enteric Coated Tablets 75mg
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Aspirin Enteric Coated Tablets 75mg.
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains aspirin BP 75mg.
3 PHARMACEUTICAL FORM
Enteric-coated tablet for oral administration.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
For the secondary prevention of thrombotic cerebrovascular or cardiovascular disease and following by-pass surgery. Owing to the delayed release of the aspirin imposed by the enteric coating, these tablets are not suitable for short term pain relief.
4.2 Posology and method of administration
The advice of a doctor should be sought before commencing therapy for the first time.
Adults including the elderly:
The usual dosage for long term use is one to two tablets (75-150mg) to be taken once daily. In some circumstances a higher dose may be appropriate, especially in the short term, and up to 4 tablets (300mg) a day may be used on the advice of a doctor.
Children under 16 years:
Do not give to children aged under 16 years, unless specifically indicated (e.g. for Kawasaki’s disease). (see 4.4 ‘Special Warnings and Special Precautions for Use’).
4.3 Contraindications
Hypersensitivity to aspirin, or other NSAIDs, or any of the other ingredients. Patients with asthma or allergic reactions to other non-steroidal anti- inflammatory drugs.
Patients with active or a history of gastric or duodenal ulcers.
Patients with haemorrhagic disease such as haemophilia and other coagulopathies including hypoprothrombinaemia or concurrent anticoagulant therapy.
Patients with severe renal and liver disorders.
Children under 16 years of age, unless specifically indicated (e.g. for
Kawasaki's
disease).
The last 3 months of pregnancy.
Gout
4.4 Special warnings and precautions for use
Before commencing long-term therapy for the management of cardiovascular or cerebrovascular disease patients should consult their doctor who can advise on the relative benefits versus the risks of the individual patient.
Care is advised in the administration of aspirin to patients with non-cirrhotic alcohol liver disease as the hazards of overdose are greater in these patients.
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).
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.
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)
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 zafirlukst is increased.
Uricosurics: Effect of probenecid and sulfinpyrazone may be reduced.
Thyroid function tests: Aspirin may interfere with thyroid function tests.
4.6 Fertility, Pregnancy and lactation
Pregnancy: Although clinical and epidemiological evidence suggests the safety of aspirin for use in pregnancy, caution should be exercised when considering use in pregnant patients. Maternal use of aspirin prior to birth may increase the risk of intracranial haemorrhage in premature or low birth weight infants and may contribute to maternal and neonatal bleeding. Regular use of high doses could impair platelet function and produce hypoprothrombinaemia in the infant if neonatal Vitamin K stores are low.
Prolonged pregnancy & labour, with increased bleeding before & after delivery, decreased birth weight and increased rate of stillbirth have been reported with high blood salicylate levels. With high doses there may be premature closure of the ductus arteriosus and possible persistent pulmonary hypertension in the newborn. Analgesic doses of aspirin should be avoided during the last trimester of pregnancy.
Lactation: As aspirin is excreted in breast milk, Aspirin should not be taken by patients who are breast-feeding, as there is a risk of Reye’s syndrome in the infant. High maternal doses may impair platelet function in the infant.
4.7 Effects on ability to drive and use machines
None.
4.8 Undesirable effects
Side effects are generally mild and infrequent:
Blood and the lymphatic system disorders: Aspirin prolongs bleeding time, decreases platelet adhesiveness and, in large doses, may cause hypoprothrombinaemia. Thrombocytopenia may also occur. Bleeding disorders such as epistaxis, haematuria, purpura, ecchymoses, haemoptysis, gastrointestinal bleeding, haematoma and cerebral haemorrhage have occasionally been reported. Fatalities have occurred. Haemolytic anaemia can occur in patients with glucose-6-phosphate dehydrogenase (G6PD) deficiency.
Immune system disorder: Hypersensitivity reactions include skin rashes, urticaria, angioedema, asthma, bronchospasm, rhinitis and rarely,
anaphylaxis.
Ear & Labyrinth disorder:
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
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
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
Symptoms of mild aspirin overdosage (chronic and acute) include nausea, vomiting, dizziness, mental confusion, tinnitus, perspiration, troubled vision, headache and thirst. In children, drowsiness and metabolic acidosis commonly occur and hypoglycaemia may be severe.
Symptoms of more severe chronic or acute overdosage include hyperventilation, vasodilation, sweating, hypothermia, deafness, ketosis and respiratory alkalosis and metabolic acidosis. Depression of the central nervous system leading to loss of consciousness; cardiovascular collapse and respiratory failure may result.
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
If overdosage is suspected the patient should be kept under observation for at least 24 hours as symptoms and salicylate blood levels may not become apparent for several hours. Gastric lavage should always be carried out and haemodialysis may be necessary in severe cases. Hospitalisation in severe cases is essential where plasma salicylate, pH and electrolytes can be monitored.
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.
Fluid losses should be replaced and forced alkaline diuresis considered when the plasma salicylate concentration is greater than:
500mg/litre (3.6 mmol/litre) in adults, or
300mg/litre (2.2 mmol/litre) in children.
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 (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.
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/mlwith 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
No additional data provided. The pre-clinical safety of aspirin is already well documented.
6.1 List of excipients
Lactose, starch, sucrose, talc, Eudragit L100-55, polyethylene glycol, hydroxypropyl methylcellulose and titanium dioxide (E171).
6.2 Incompatibilities
None.
6.3 Shelf life
2 years.
6.4 Special precautions for storage
Store below 25°C in a dry place.
6.5 Nature and contents of container
HDPE containers with HDPE lids (OTC packs, child resistant) containing 100
tablets,
or
Blister packs comprised of aluminium/PVC strips enclosed in an outer carton containing 28 or 56 tablets.
6.6 Special precautions for disposal
Not applicable.
7 MARKETING AUTHORISATION HOLDER
Ennogen Pharma Limited Unit G4,
Riverside Industrial Estate,
Riverside Way,
Dartford DA1 5BS
8 MARKETING AUTHORISATION NUMBER(S)
PL 40147/0008
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
27 January 1998
10 DATE OF REVISION OF THE TEXT
17/06/2015