Aspirin 75mg Gastro-Resistant Tablets
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Aspirin 75 mg Gastro-resistant Tablets Enprin
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Aspirin BP 75 mg
3 PHARMACEUTICAL FORM
Gastro-resistant tablets for oral administration.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
For the secondary prevention of thrombotic cerebrovascular or cardiovascular disease and following bypass 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
For oral administration.
Adults including the elderly:
The advice of a doctor should be sought before commencing therapy for the first time. The usual dosage, for long term, is 75-150 mg 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 in the advice of a doctor.
Do not give to children aged under 16 years, unless specifically indicated (e.g. for Kawasaki’s disease).
4.3. Contraindications
I. Hypersensitivity to aspirin or any other NSAIDs, or any of the other excipients (see Section 6.1).
II. In patients with asthma or allergic reactions to other non-steroidal antiinflammatory drugs.
III. Patients with active or a history of gastric or duodenal ulcers.
IV. Patients with haemorrhagic disease such as haemophilia.
V. Patients with severe renal and liver disorders.
VI. The last 3 months of pregnancy.
VII. Other coagulopathies including hypoprothrombinaemia or concurrent anticoagulant therapy
VIII. Gout.
IX. Do not give to children aged under 16 years, unless specifically indicated (e.g. Kawasaki’s disease).
4.4. Special warnings and precautions for use
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).
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 for the individual patient.
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 gastrointestinal 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 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.
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.
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.
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 ASPIRIN MAY POTENTIATE:
i) The toxicity of methotrexate by inhibiting tubular secretion of the drug.
ii) The toxicity of sulphonamides.
ASPIRIN MAY REDUCE THE EFFECT OF: i) Diuretics e.g. spironolactone and thiazides.
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).
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 does 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. Blood disorders in particular thrombocytopenia and more rarely agranulocytosis 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, dyspnoea, rhinitis and rarely, anaphylaxis.
Psychiatric disorders: mental confusion
Ear and labyrinth disorders: tinnitus, vertigo.
Gastrointestinal disorders: gastric irritation, diarrhoea, 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 Investigations: increases bleeding time Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisations 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 (2.5 mmol/L). Most adult deaths occur in patients whose concentrations exceed 700 mg/L (95.1 mmol/L). Single doses less than 100 mg/kg are unlikely to cause serious poisoning.
Symptoms
Common feature 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 and children over the age of 4 years. In children aged 4 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, thrombocytopenia, increased INR/PTR, intravascular coagulation, renal failure and non-cardiac pulmonary oedema.
Central nervous system features including confusion, disorientation, coma and convulsions are less common in adults than children.
Management
Give active charcoal if an adult presents within one hour of ingestion of more than 250 mg/kg. The plasma salicylate concentration should be measured, although the severity of the poisoning cannot be determined from this alone and the clinical and biochemical features must be taken into account. Elimination is increased by urinary alkalisation, 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 is 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 salycilate concentrations > 700 mg/L (5.1 mmol/L), or lower concentrations associated with severe clinical or metabolic features. Patients under 10 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
Aspirin is a platelet aggregation inhibitor, it also has analgesic, anti-pyretic and antiinflammatory properties.
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 400 mg was taken within 8 hours before or within 30 minutes after immediate release aspirin (81 mg), a decreased effect of aspirin 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.
Pharmacokinetic properties
5.2
Non ionised acetylsalicylic acid is absorbed from the stomach. There is also absorption of acetylsalicylates from the intestines. Aspirin appears rapidly in all body tissues. It crosses the placenta and appears in breast milk, and is moderately bound to plasma proteins. Excretion is as salicylic acid and as compounds in the urine and increases as the pH rises.
5.3 Preclinical safety data
No additional data provided. The pre-clinical safety of aspirin is already well documented.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Lactose, Starch, Sucrose, Talc, Eudragit L30D55, Talc, Polyethylene Glycol, Hydroxypropylmethylcellulose and Titanium Dioxide E171.
6.2 Incompatibilities
None.
6.3 Shelf life
2 years.
6.4
Special precautions for storage
Store below 25 0C in a dry place.
6.5 Nature and contents of container
Blister strips comprised of 30micron hard temper Aluminium lidding foil with 250 -300micron PVC base material.
or
Blister strips comprised of 30micron hard temper Aluminium lidding foil with 250 micron PVC/PVdC (40-90gsm) base material.
or
Blister strips comprised of 20micron Aluminium/15micron PVC lidding foil with 250 - 300micron PVC base material.
or
Blister strips comprised of 20micron Aluminium/15mciron PVC lidding foil with 250micron PVC/PVdC (40-90gsm) base material.
or
Blister strips comprised of 35-41gsm Glassine paper/9micron Aluminium lidding foil with 250 - 300micron PVC base material.
or
Blister strips comprised of 35-41gsm Glassine paper/9micron Aluminium lidding foil with 250micron PVC/PVdC (40-90gsm) base material.
Blister pack sizes of 12, 14 or 16 tablets.
HDPE containers with HDPE lids (OTC packs child resistant) containing 12, 14 or 16 tablets.
6.6 Special precautions for disposal
Not applicable.
7. MARKETING AUTHORISATION HOLDER
Galpharm Healthcare Limited
Wrafton
Braunton
Devon
EX33 2DL
United Kingdom
8 MARKETING AUTHORISATION NUMBER(S)
PL 16028/0026
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
6 November 1997
10 DATE OF REVISION OF THE TEXT
22/04/2016