Dispersible Aspirin Tablets 75 mg – Summary of Product Characteristics (SmPC) for healthcare professionals

1 NAME OF THE MEDICINAL PRODUCT

Dispersible Aspirin Tablets 75 mg

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Each tablet contains Aspirin 75 mg.

Excipients with known effect:

Lactose:

Each tablet contains 27.5mg of lactose anhydrous.

Sodium:

Each tablet contains 0.09mg of sodium.

For the full list of excipients, see section 6.1.

3 PHARMACEUTICAL FORM

Dispersible tablet.

White, flat, circular tablet with C on one side and ll on the other side.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Dispersible Aspirin is indicated for the secondary prevention of thrombotic cerebrovascular or cardiovascular disease and following by-pass surgery.

4.2 Posology and method of administration

For the management of cardiovascular or cerebrovascular disease:

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 75-150 mg once daily. In some circumstances a higher dose may be appropriate, especially in the short term, and up to 300 mg 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 or over:

As for adults and the elderly.

Children under 16 years:

Do not give to children aged under 16 years. See 4.4 Special Warnings and Precautions for Use.

Method of administration: Dispersible Aspirin Tablets should be dissolved in a glass of water and taken orally.

4.3 Contraindications

Hypersensitivity to the acetylsalicylic acid or to any of the excipients listed in section 6.1.

Not to be given to children under 16 years unless specifically indicated (eg. 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 precautions for use

Aspirin Tablets 75mg is not suitable for use as an anti-inflammatory/analgesic/ antipyretic.

Recommended for use in adults and adolescents from 16 years of age. This medicinal product is not recommended for use in adolescents/children under 16 years unless the expected benefits outweigh the risks. Acetylsalicylic acid may be a contributory factor in the causation of Reye's Syndrome in some children.

Acetylsalicylic acid should be used with caution in patients with moderately impaired renal or hepatic function (contraindicated if severe), or in patients who are dehydrated, since the use of NSAIDs may result in deterioration of renal function. Liver function tests should be preformed regularly in patients presenting slight or moderate hepatic insufficiency.

Recommended for use in adults and adolescents from 16 years of age. This medicinal product is not recommended for use in adolescents/children under 16 years unless the expected benefits outweigh the risks. Acetylsalicylic acid may be a contributory factor in the causation of Reye's Syndrome in some children.

There is an increased risk of haemorrhage particularly during or after operative procedures (even in cases of minor procedures, e.g. tooth extraction). Use with caution before surgery, including tooth extraction. Temporary discontinuation of treatment may be necessary.

Aspirin Tablets 75mg is not recommended during menorrhagia where it may increase menstrual bleeding.

Acetylsalicylic acid may promote bronchospasm and asthma attacks or other hypersensitivity reactions. Risk factors are existing asthma, hay fever, nasal polyps or chronic respiratory diseases. The same applies for patients who also show allergic reaction to other substances (e.g. with skin reactions, itching or urticaria).

Serious skin reactions, including Steven Johnsons syndrome, have rarely been reported in association with the use of acetylsalicylic acid (see section 4.8). Aspirin Tablets 75 mg should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.

Aspirin should be avoided in late pregnancy and during breastfeeding (see section4.6).

Dispersible Aspirin Tablets 75mg contain lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Elderly patients are particularly susceptible to the adverse effects of NSAIDs, including acetylsalicylic acid and more likely to experience gastrointestinal side effects especially gastrointestinal bleeding and perforation which may be fatal (see section 4.2). Where prolonged therapy is required, patients should be reviewed regularly.

Aspirin may induce gastro-intestinal haemorrhage, occasionally major. Aspirin is to be used with caution in cases of hypertension and when patients have a past history of gastric or duodenal ulcer or haemorrhagic episodes or are undergoing therapy with anticoagulants.

Patients should report any unusual bleeding symptoms to their physician. If gastrointestinal bleeding or ulceration occurs the treatment should be withdrawn.

Concomitant treatment with Aspirin Tablets 75 mg and other drugs that alter haemostasis (i.e. anticoagulants such as warfarin, thrombolytic and antiplatelet agents, anti-inflammatory drugs and selective serotonin reuptake inhibitors) is not recommended, unless strictly indicated, because they may enhance the risk of haemorrhage (see section 4.5). If the combination cannot be avoided, close observation for signs of bleeding is recommended.

Caution should be advised in patients receiving concomitant medications which could increase the risk of ulceration, such as oral corticosteroids, selective serotonin reuptake inhibitors and deferasirox (see section 4.5).

Acetylsalicylic acid in low doses reduces uric acid excretion. Due to this fact, patients who tend to have reduced uric acid excretion may experience gout attacks (see section 4.5).

Aspirin should be avoided in late pregnancy and generally during breast feeding (see section 4.6).

Patients with rare hereditary problems of galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

The risk of hypoglycaemic effect with sulfonylureas and insulins may be potentiated with Aspirin Tablets 75 mg taken at over dosage (see section 4.5).

This medicine contains less than 1mmol sodium (23mg) per tablet. It is essentially `sodium-free´.

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 >15 mg/week) with Aspirin Tablets 75 mg 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 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 – acetylsalycilic 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 and including 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 above 100mg/day and up to 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.

From the 20th week of pregnancy onward, acetylsalicylic acid use may cause oligohydramnios resulting from foetal renal dysfunction. This may occur shortly after treatment initiation and is usually reversible upon discontinuation. In addition, there have been reports of ductus arteriosus constriction following treatment in the second trimester, most of which resolved after treatment cessation. Therefore, 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. Antenatal monitoring for oligohydramnios and ductus arteriosus constriction should be considered after exposure to acetylsalicylic acid for several days from gestational week 20 onward. acetylsalicylic acid should be discontinued if oligohydramnios or ductus arteriosus constriction are found.

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 (see above);

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 higher than 100 mg/day and higher is contraindicated during the third trimester of pregnancy (see sections 4.3). Doses up to and including 100 mg/day may only be used under strict obstetric monitoring.

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 breastfeeding. In cases of long term use and/or administration of higher doses, breastfeeding should be discontinued.

4.7 Effects on ability to drive and use machines

Not relevant.

4.8 Undesirable effects

Side effects are grouped on the basis of System Organ Class. Within each system organ class the frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000) and not known (cannot be estimated from the available data)

breast disorders

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 or search for MHRA Yellow Card in the Google Play or Apple App Store.

4.9 Overdose

Although considerable inter-individual variations are involved, it can be considered that the toxic dose is about 200mg/kg in adults and 100mg/kg in children. The lethal dose of acetylsalicylic acid is 25-30 grams. Salicylate poisoning is usually associated with plasma concentrations >300 mg/L (2.5 mmol/L). Plasma concentrations above 500mg/l in adults and 300mg/l in children generally cause severe toxicity. 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.

Overdose may harmful for elderly patients and particularly for small children (therapeutic overdose or frequent accidental intoxications may be fatal).

Symptoms of moderate intoxications:

Common features of salicylate poisoning include abdominal pain, dehydration, tinnitus, headache, vertigo, deafness, sweating, warm extremities with bounding pulses, nausea and vomiting.

Symptoms of severe intoxications:

Some degree of acid-base disturbance is present in most cases. In the first instance hyperventilation occurs, which results in respiratory alkalosis. Respiratory acidosis ensues due to suppression of the respiratory centre.

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, hyperthermia and perspiration, resulting in dehydration: feelings of restlessness, convulsions and halluciations.

Central nervous system features including confusion, disorientation, coma and convulsions, cardiovascular collapse or respiratory arrest are less common in adults than in children.

Treatment of overdose:

If a toxic dose has been ingested, hospital admission is required. In the event of moderate intoxication, inducing the patient to vomit should be attempted.

If this fails, gastric lavage may be attempted during the first hour after ingestion of a substantial amount of the medicine.

Give activated charcoal if an adult (50g for an adult, 1g/kg body weight for a child up to 12 years) 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 (5.1 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.

Other symptoms to be treated symptomatically.

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Antithrombotic agents: platelet aggregation inhibitors excl. heparin, ATC code: B01A C06

Aspirin inhibits platelet aggregation. Blocking the platelet cyclooxygenase by acetylation, it inhibits thromboxane A2 synthesis, a physiological activating substance released by the platelets and which would play a role in the complications of the atheromatosic lesions. Inhibition of TXA2-synthesis is irreversible, because thrombocytes, which have no nucleus, are not capable (due to lack of protein synthesis capability) to synthesise new cyclooxygenase, which had been acetylated by acetylsalicylic acid.

The repeated doses from 20 to 325 mg involve an inhibition of the enzymatic activity from 30 to 95%. Due to the irreversible nature of the binding, the effect persists for the lifespan of a thrombocyte (7-10 days). The inhibiting effect does not exhaust during prolonged treatments and the enzymatic activity gradually begins again upon renewal of the platelets 24 to 48 hours after treatment interruption. Acetylsalicylic acid extends bleeding time on average by approximately 50 to 100%, but individual variations can be observed.

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 30 min after immediate release aspirin dosing (81mg), a decreased effect of aspirinon 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:

After oral administration, acetylsalicylic acid is rapidly absorbed from the gastrointestinal tract. However, a significant portion of the dosage is already hydrolysed to salicylic acid in the intestinal wall during the absorption process.

Distribution:

Acetylsalicylic acid as well as the main metabolite salicylic acid, are extensively bound to plasma proteins, primarily albumin, and distributed rapidly into all parts of the body. Maximum plasma concentration is reached after 0.3 - 2 hours (total salicylate). The volume of distribution of acetylsalicylic acid is ca. 0.16 l/kg of body weight.

Biotransformation:

Acetylsalicylic acid is rapidly metabolised to salicylic acid, with a half-life of 15- 30 minutes. Salicylic acid is subsequently predominantly converted into glycine and glucuronic acid conjugates. Elimination kinetics of salicylic acid is dose dependent, because the metabolism is limited by liver enzyme capacity. Thus, elimination half-time varies and is 2-3 hours after low doses (75 mg – 160 mg).

Elimination:

Salicylic acid and its metabolites are predominantly excreted via the kidneys.

5.3 Preclinical safety data

The nonclinical safety profile of acetylsalicylic acid is well documented. In experimental animal studies, salicylates have shown no other organ injury than renal damage. In rat studies, fetotoxicity and teratogenic effects were observed with acetylsalicylic acid at maternotoxic doses. Clinical relevance is unknown as the doses used in non-clinical studies are much higher (7 times at least) than the maximal recommended doses in targeted cardiovascular indications. Acetylsalicylic acid was extensively investigated with regard to mutagenic and carcinogenic effects. The results as a whole show no relevant signs for any mutagenic or carcinogenic effects in mice and rat studies.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Maize starch

Saccharin sodium

Lactose

Citric acid

Calcium carbonate

Talc

Sodium laurilsulfate

6.2 Incompatibilities

None known.

6.3 Shelf life

36 months, as packaged for sale.

6.4 Special precautions for storage

Do not store above 25°C.

Protect from heat, light and moisture

6.5 Nature and contents of container

Dispersible Aspirin Tablets 75mg

Opaque plastic containers composed of either high density polypropylene or high density polyethylene with a child resistant tamper evident closure composed of high density polyethylene with polyether foam or polyethylene or polypropylene filler or cotton coil filler.

Pack sizes of 24, 25, 28, 32 and 100.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

No special requirements for disposal

7 MARKETING AUTHORISATION HOLDER

Crescent Pharma Ltd

Key House

Sarum Hill,

Basingstoke

RG21 8SR,

United Kingdom

8 MARKETING AUTHORISATION NUMBER(S)

PL 20416/0230

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE

AUTHORISATION

26 November 2004

10 DATE OF REVISION OF THE TEXT

09/07/2026