Summary of Product Characteristics (SmPC) - Dispersible Aspirin tablets BP 75 mg
1 NAME OF THE MEDICINAL PRODUCT
Dispersible Aspirin Tablets BP 75mg.
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each tablet contains aspirin BP 75mg.
Excipient(s) with known effect
Lactose
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Dispersible tablet.
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
Posology
The advice of a doctor should be sought before commencing therapy for the first time.
Adults and the elderly:
The usual dosage, for long term use, is 75-150mg 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 general, acetylsalicylic acid should be used with caution in elderly patients who are more prone to adverse events. The usual adult dose is recommended in the absence of severe renal or hepatic insufficiency (see sections 4.3 and 4.4). Treatment should be reviewed at regular intervals.
Paediatric population
Children 16 years and over:
As for adults and the elderly
Children under 16 years:
Do not give to children aged under 16 years, unless specifically indicated (e.g. for Kawasaki’s disease) (see section 4.4).
Method of administration:
Dispersible Aspirin Tablets should be dissolved in a glass of water and taken orally.
4.3 Contraindications
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Not to be given to children under 16 years unless specifically indicated (e.g. for Kawasaki's disease).
Other contraindications include active peptic ulceration, or a history of recurrent peptic ulceration, and/or gastric/intestinal haemorrhage or other kinds of bleeding such as cerebrovascular haemorrhages, gout, haemorrhagic diathesis, haemophilia or other clotting disorders, thrombocytopenia, hypersensitivity to salicylic acid compounds or prostaglandin synthetase inhibitors (e.g. certain asthma patients who may suffer an attack or faint and certain patients who may suffer from bronchospasm, rhinitis and urticaria) or to any of the other ingredients or non-steroidal anti-inflammatory drugs, and severe renal or hepatic impairment.
Doses >100 mg/day during the third trimester of pregnancy (see section 4.6).
Methotrexate used at doses >15 mg/week (see section 4.5).
4.4 Special Warnings and Special Precautions for Use
Administer with caution in the presence of allergic disease, renal or hepatic impairment, or dehydration. Acetylsalicylic acid may trigger haemolysis in patients with glucose-6-phosphate dehydrogenase deficiency.
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).
Elderly patients may be more susceptible to the toxic effects of salicylates.
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.
Aspirin may also precipitate bronchospasm or induce attacks of asthma in susceptible subjects.
Continuous prolonged use of aspirin should be avoided in the elderly because of the risk of gastrointestinal bleeding.
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)
Rare cases of acute myocardial ischemia with or without myocardial infarction as part of a hypersensitivity reaction (Kounis syndrome) have been reported in patients treated with acetylsalicylic acid. In the event of confirmed Kounis syndrome due to acetylsalicylic acid, Dispersible Aspirin Tablets BP 75mg, should be discontinued immediately.
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
Contraindicated combinations
Methotrexate (used at doses >15 mg/week):
The combined drugs, methotrexate and acetylsalicylic acid, enhance haematological toxicity of methotrexate due to the decreased renal clearance of methotrexate by acetylsalicylic acid. Therefore, the concomitant use of methotrexate (at doses >15mg/week) with Dispersible Aspirin Tablets is contraindicated (see section 4.3).
Not recommended combinations
Uricosuric agents, e.g. probenecid
Inhibits the effect of uricosurics (probenecid and sulfinpyrazone) The combination should be avoided.
Combinations requiring precautions for use or to be taken into account
Anticoagulants e.g. coumarin, heparin, warfarin and phenindione
Increased risk of bleeding due to inhibited thrombocyte function, injury of the duodenal mucosa and displacement of oral anticoagulants from their plasma protein binding sites. The bleeding time should be monitored (see section 4.4).
Antiplatelet agents (e.g. clopidogrel and dipyridamole) and selective serotonin reuptake inhibitors (SSRIs; such as sertraline or paroxetine)
Increased risk of gastrointestinal bleeding (see section 4.4)
Antidiabetics e.g. Sulfonylureas
Salicylics may increase the hypoglycaemic effect of sulfonylureas.
Digoxin and lithium
Acetylsalicylic acid impairs the renal excretion of digoxin and lithium, resulting in increased plasma concentrations. Monitoring of plasma concentrations of digoxin and lithium is recommended when initiating and terminating treatment with acetylsalicylic acid. Dose adjustment may be necessary.
Diuretics and antihypertensives
NSAIDs may decrease the antihypertensive effects of diuretics and other antihypertensive agents. As for other NSAIDs concomitant administration with ACE inhibitors increases the risk of acute renal insufficiency.
Diuretics: Risk of acute renal failure due to the decreased glomerular filtration via decreased renal prostaglandin synthesis. Hydrating the patient and monitoring renal function at the start of the treatment is recommended.
Carbonic anhydrase inhibitors (acetazolamide)
May result in severe acidosis and increased risk of central nervous system toxicity.
Systemic corticosteroids
The risk of gastrointestinal ulceration and bleeding may be increased when acetylsalicylic acid and corticosteroids are co-administered (see section 4.4).
Methotrexate (used at doses <15 mg/week)
The combined drugs, methotrexate and acetylsalicylic acid, may increase haematological toxicity of methotrexate due to decreased renal clearance of methotrexate by acetylsalicylic acid. Weekly blood count checks should be done during the first weeks of the combination. Enhanced monitoring should take place in the presence of even mildly impaired renal function, as well, as in the elderly.
Other NSAIDs
Aspirin may also potentiate the effects and side effects of other non-steroidal anti-inflammatory drugs. Increased risk of ulcerations and gastrointestinal bleeding due to synergistic effects.
Ibuprofen
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).
Ciclosporin, tacrolimus
Concomitant use of NSAIDs and ciclosporin or tacrolimus may increase the nephrotoxic effect of ciclosporin and tacrolimus. The renal function should be monitored in case of concomitant use of these agents and acetylsalicylic acid.
Valproate
Acetylsalicylic acid has been reported to decrease the binding of valproate to serum albumin, thereby increasing its free plasma concentrations at steady state.
Phenytoin (an antiepileptic)
Salicylate diminishes the binding of phenytoin to plasma albumin. This may lead to decreased total phenytoin levels in plasma, but increased free phenytoin fraction. The unbound concentration, and thereby the therapeutic effect, does not appear to be significantly altered.
Alcohol
Concomitant administration of alcohol and acetylsalicylic acid increases the risk of gastrointestinal bleeding.
Antacids will reduce the effect of aspirin. Principle incompatibilities are iron salts, carbonates and alkali hydroxides.
Metamizole – acetylsalicylic acid interaction
Metamizole may reduce the effect of acetylsalicylic acid on platelet aggregation, when taken concomitantly. Therefore, this combination should be used with caution in patients taking low dose aspirin for cardioprotection.
4.6 Fertility, Pregnancy and lactation
Pregnancy
Low doses (up to 100 mg/day):
Clinical studies indicate that doses up to 100 mg/day for restricted obstetrical use, which require specialised monitoring, appear safe.
Doses of 100-500mg/day:
There is insufficient clinical experience regarding the use of doses above 100 mg/day up to 500 mg/day. Therefore, the recommendations below for doses of 500 mg/day and above apply also for this dose range.
Doses of 500 mg/day and above:
Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal development. Data from epidemiological studies suggest an increased risk of miscarriage and of cardiac malformation and gastroschisis after use of a prostaglandin synthesis inhibitor in early pregnancy. The absolute risk for cardiovascular malformation was increased from less than 1%, up to approximately 1.5%. The risk is believed to increase with dose and duration of therapy.
In animals, administration of a prostaglandin synthesis inhibitor has been shown to result in increased pre- and post-implantation loss and embryo-foetal lethality. In addition, increased incidences of various malformations, including cardiovascular, have been reported in animals given a prostaglandin synthesis inhibitor during the organogenetic period.
During the first and second trimester of pregnancy, acetylsalicylic acid should not be given unless clearly necessary. If acetylsalicylic acid is used by a woman attempting to conceive, or during the first and second trimester of pregnancy, the dose should be kept as low and duration of treatment as short as possible.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to:
- Cardiopulmonary toxicity (with premature closure of the ductus arteriosus and pulmonary hypertension)
Renal dysfunction, which may progress to renal failure with
oligohydroamniosis
the mother and the neonate, at the end of pregnancy, to:
- Possible prolongation of bleeding time, an anti-aggregating effect which may occur even at very low doses.
- Inhibition of uterine contractions resulting in delayed or prolonged labour.
Consequently, acetylsalicylic acid at doses of 100 mg/day and higher is contraindicated during the third trimester of pregnancy.
Breast-feeding
Low quantities of salicylates and of their metabolites are excreted into the breast milk. Since adverse effects for the infant have not been reported up to now, short term use of the recommended dose does not require suspending breast-feeding. In cases of long term use and/or administration of higher doses, breast-feeding should be discontinued.
4.7 Effects on ability to drive and use machines
None known.
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
Cardiac disorders: Kounis syndrome (acute myocardial ischemia with or without myocardial infarction as part of a hypersensitivity reaction), with frequency not known (see section 4.4).
4.9 Overdose
Overdosage is unlikely due to the low level of aspirin in the tablets.
Salicylate poisoning is usually associated with plasma concentrations >350 mg/L (2.5 mmol/L). Most adult deaths occur in patients whose concentrations exceed 700 mg/L (5.1 mmol/L). Single doses less than 100 mg/kg are unlikely to cause serious poisoning.
Symptoms
Overdose produces dizziness, dehydration, tinnitus, vertigo, deafness, sweating, warm extremities with bounding pulses, increased respiratory rate, nausea and vomiting, confusion and hyperventilation. Some degree of acid-base disturbance is present in most cases. Gastric lavage and supportive therapy, restoration of acid-base balance may be necessary.
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 of salicylate poisoning include haematemesis, hyperpyrexia, hypoglycaemia, hypokalaemia, thrombocytopaenia, 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 in children.
Management
Give activated 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 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 >700 mg/L (5.1mmol/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
Pharmacotherapeutic group: Platelet aggregation inhibitors excl. heparin, ATC code: B01AC06.
Aspirin has analgesic, anti-inflammatory and anti-pyretic activity which is considered to be due to inhibition of the synthesis of prostaglandins. 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. Aspirin also inhibits platelet aggregation by irreversible acetylation of platelet cyclo-oxygenase.
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 hours before or within 30 minutes after immediate release aspirin dosing (81mg), 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.
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.
Absorption of non-ionised aspirin occurs in the stomach and intestine. Some aspirin is hydrolysed to salicylate in the gut wall. After absorption aspirin is rapidly converted to salicylate but during the first 20 minutes following oral administration, aspirin is the predominant form of the drug in the plasma. Aspirin is bound to plasma proteins and is widely distributed. Plasma aspirin concentrations decline rapidly (half life 15-20 minutes) as plasma salicylate concentrations increase.
Distribution:
Hydrolysis to salicylic acid occurs rapidly in the intestine and in the circulation.
Salicylates are extensively bound to plasma proteins; aspirin to a lesser degree. Aspirin is found in the saliva, milk, plasma and synovial fluid at concentrations less than blood and crosses the placenta.
Biotransformation:
Aspirin and salicylates are rapidly distributed to all body tissues; they appear in the
milk and cross 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.
Elimination: Salicylate is mainly eliminated by hepatic metabolism the metabolites including salicylic acid, salicyl phenolic glucuronide, salicylic acyl glucuronide, gentisic acid and gentisuric acid. As a result of zero order kinetics, plasma steady state salicylate concentrations increase disproportionately with dose.
Salicylate is 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.
The rate of excretion of aspirin varies as the pH rises and being greatest at pH 7.5 and
above. Aspirin is also excreted as salicylic acid and as glucuronide conjugate and as
salicyluric and gentisic acids.
5.3 Preclinical safety data
| There are no preclinical data of relevance to the prescriber which are additional to | |
| that already included in other sections of the SPC. | |
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Maize starch, sodium saccharin, lactose granules, anhydrous citric acid, calcium carbonate, talc and sodium lauryl sulphate.
6.2 Incompatibilities
Not known.
6.3 Shelf life
36 months.
6.4 Special precautions for storage
Protect from heat, light and moisture.
6.5 Nature and contents of container
Blister pack: pack size: 24.
Snapsafe: pack size: 25, 50 and 100.
6.6 Special precautions for disposal
Not applicable.
7 MARKETING AUTHORISATION HOLDER
Ennogen IP Ltd
Unit G4, Riverside Industrial Estate,
Riverside Way,
Dartford,
DA1 5BS, UK
8 MARKETING AUTHORISATION NUMBER(S)
PL 55612/0115
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE
AUTHORISATION
30 July 1992
10 DATE OF REVISION OF THE TEXT
26/08/2026