ASPIRIN Effervescent tablet Ref.[116531] Active ingredients: Acetylsalicylic acid

Aspirin should be used with particular caution in the following cases:

• hypersensitivity to analgesics/anti-inflammatory agents/anti-rheumatics and in the presence of other allergies,
• history of gastro-intestinal ulcers including chronic or recurrent ulcer disease or history of gastro-intestinal bleedings,
• with concomitant treatment with anticoagulants (see interactions with other medicinal products and other forms of interaction),
• patients with impaired renal function or patients with impaired cardiovascular circulation (e.g. renal vascular disease, congestive heart failure, volume depletion, major surgery, sepsis or major hemorrhagic events), since acetylsalicylic acid may further increase the risk of renal impairment and acute renal failure
• impaired hepatic function.

Acetylsalicylic acid may precipitate bronchospasm and induce asthma attacks or other hypersensitivity reactions. Risk factors are pre-existing asthma, hay fever, nasal polyps, or chronic respiratory disease. This also applies to patients exhibiting allergic reactions (e.g. cutaneous reactions, itching, urticaria) to other substances.

Due to its inhibitory effect on platelet aggregation which persists for several days after administration, acetylsalicylic acid may lead to an increased bleeding tendency during and after surgical operations (including minor surgeries, e.g. dental extractions).

At low doses, acetylsalicylic acid reduces the excretion of uric acid. This can possibly trigger gout attacks in predisposed patients.

In patients suffering from severe glucose-6-phosphate dehydrogenase (G6PD) deficiency, acetylsalicylic acid may induce haemolysis or haemolytic anaemia. Factors that may increase the risk of haemolysis are high dosage, fever, or acute infections, for example.

Elderly patients are particularly susceptible to the adverse effects of NSAIDs. Prolonged use of NSAIDs in the elderly is not recommended. Where prolonged therapy is required, patients should be reviewed regularly.

Undesirable effects may be reduced by using the minimum effective dose for the shortest possible duration. Patients treated with NSAIDs long-term should undergo regular medical supervision to monitor for adverse events.

There is 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 and adolescents aged under 16 years unless specifically indicated.

There is some evidence that drugs which inhibit cyclo-oxygenase /prostaglandin synthesis may cause impairment of female fertility by an effect on ovulation. This is reversible on withdrawal of treatment.

Prolonged use, except under medical supervision, can be harmful.

If symptoms persist, the physician should be consulted.

This medicinal product contains 150 mg sodium per tablet, equivalent to 7.5% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

Contra-indicated Interactions

Methotrexate used at doses of 15 mg/week or more

Increased haematological toxicity of methotrexate (decreased renal clearance of methotrexate by anti-inflammatory agents in general and displacement of methotrexate from its plasma protein binding by salicylates) (see Section 4.3 Contraindications).

Combinations requiring precautions for use

Methotrexate, used at doses of less than 15 mg/week

Increased haematological toxicity of methotrexate (decreased renal clearance of methotrexate by anti‑inflammatory agents in general and displacement of methotrexate from its plasma protein binding by salicylates).

Anticoagulants, thrombolytics/other inhibitors of platelet aggregation/haemostasis

Increased risk of bleeding.

Other non‑steroidal anti‑inflammatory drugs with salicylates at higher doses

Increased risk of ulcers and gastrointestinal bleeding due to synergistic effect.

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).

Selective Serotonin Re-uptake Inhibitors (SSRIs)

Increased risk of upper gastrointestinal bleeding due to possibly synergistic effect.

Digoxin

Plasma concentrations of digoxin are increased due to a decrease in renal excretion.

Antidiabetics, e.g. insulin, sulphonylureas

Increased hypoglycaemic effect by high doses of acetylsalicylic acid via hypoglycaemic action of acetylsalicylic acid and displacement of sulfonylurea from its plasma protein binding.

Diuretics in combination with acetylsalicylic acid

Decreased glomerular filtration via decreased renal prostaglandin synthesis.

Systemic glucocorticoids, except hydrocortisone used as replacement therapy in Addison's disease

Decreased blood salicylate levels during corticosteroid treatment and risk of salicylate overdose after this treatment is stopped via increased elimination of salicylates by corticosteroids.

Angiotensin converting enzyme inhibitors (ACE) in combination with acetylsalicylic acid

Decreased glomerular filtration via inhibition of vasodilatory prostaglandins. Further-more, decreased antihypertensive effect.

Valproic acid

Increased toxicity of valproic acid due to displacement from protein binding sites.

Alcohol

Increased damage to gastro-intestinal mucosa and prolonged bleeding time due to additive effects of acetylsalicylic acid and alcohol.

Uricosurics such as benzbromarone, probenecid

Decreased uricosuric effect (competition of renal tubular uric acid elimination).

Pregnancy

Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/fœtal development. Data from epidemiological studies raise concern about an increased risk of miscarriage and of malformations after the use of a prostaglandin synthesis inhibitor in early pregnancy. The risk is believed to increase with dose and duration of therapy. Available data do not support any association between intake of acetylsalicylic acid and an increased risk for miscarriage. For acetylsalicylic acid the available epidemiological data regarding malformation are not consistent, but an increased risk of gastroschisis could not be excluded. A prospective study with exposure in early pregnancy (1^st-4^th month) of about 14,800 mother-child pairs has not yielded any association with an elevated rate of malformations.

Animal studies have shown reproductive toxicity (see Section 5.3 Preclinical Safety Data).

From the 20th week of pregnancy onward, acetylsalicylic acid containing drug 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 containing drugs should not be given unless clearly necessary.

If acetylsalicylic acid containing drugs are 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 containing drugs for several days from gestational week 20 onward. Acetylsalicylic acid containing drugs 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 (premature constriction/closure of the ductus arteriosus and pulmonary hypertension);
• renal dysfunction (see above).

Prostaglandin synthesis inhibitors may expose the mother and the child, at the end of pregnancy, to:

• possible prolongation of bleeding time, an anti-aggregating effect which may occur even after very low doses;
• inhibition of uterine contractions resulting in delayed or prolonged labour.

Consequently, acetylsalicylic acid is contraindicated during the third trimester of pregnancy (see sections 4.3 and 5.3).

Breast-feeding

Salicylate and its metabolites pass into breast milk in small quantities.

Since no adverse effects on the infant have been observed so far after occasional use, interruption of breast-feeding is usually unnecessary. However, on regular use or on intake of high doses, breast feeding should be discontinued early.

Fertility

There is some evidence that drugs which inhibit cyclo-oxygenase /prostaglandin synthesis may cause impairment of female fertility by an effect on ovulation. This is reversible on withdrawal of treatment.

None stated.

The listed adverse drug reactions are based on spontaneous reports, thus an organisation according to CIOMS III categories of frequency is not possible.

Blood and lymphatic system disorders: Haemorrhagic anaemia, iron deficiency anaemia with the respective laboratory and clinical signs and symptoms. Haemolysis, haemolytic anaemia

Cardiac disorders: Cardio-respiratory distress

Ear and labyrinth disorders: Tinnitus

Gastrointestinal disorders: Dyspepsia, gastrointestinal pain, abdominal pain, gingival bleeding, gastrointestinal inflammation, gastrointestinal ulcer, gastrointestinal haemorrhage, gastrointestinal ulcer haemorrhage and perforation with the respective laboratory and clinical signs and symptoms, intestinal diaphragm disease

Hepatobiliary disorders: Liver disorder, transaminases increased

Immune system disorders: Hypersensitivity, drug hypersensitivity, allergic edema and angioedema, anaphylactic reaction, anaphylactic shock with respective laboratory and clinical manifestations

Injury, poisoning and procedural complications: See overdose section

Nervous system disorders: Cerebral and intracranial haemorrhage, dizziness

Renal and urinary disorders: Urogenital haemorrhage, renal impairment, renal failure acute

Respiratory, thoracic and mediastinal disorders: Epistaxis, analgaesic asthma syndrome, rhinitis, nasal congestion

Skin and subcutaneous tissue disorders: Rash, urticaria, pruritus

Vascular disorders: Haemorrhage, operative haemorrhage, haematoma, muscle haemorrhage

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 HPRA Pharmacovigilance; Website: www.hpra.ie.

Not applicable.