Source: Medicines & Healthcare Products Regulatory Agency (GB) Revision Year: 2020 Publisher: Alliance Pharmaceuticals Limited, Avonbridge House, Bath Road, Chippenham, Wiltshire, SN15 2BB
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Hypoprothrombinaemia, haemophilia, haemorrhagic disease or a history of bleeding disorders, cerebral haemorrhage, and active peptic ulceration or a history of peptic ulceration.
Doses >100mg/day during the third trimester of pregnancy (see section 4.6).
In women who are breastfeeding (see section 4.6).
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).
Aspirin can reduce uric acid excretions and therefore should be used with care in patients with gout or a history of gout.
Before commencing long-term aspirin therapy for the management of cerebrovascular or cardiovascular disease patients should consult their doctor who can advise on the relative benefits versus the risks for the individual patient.
Aspirin decreases platelet adhesiveness and increases bleeding time. Haematological and haemorrhagic effects can occur and may be severe. Patients should report any unusual bleeding symptoms to their physician.
Salicylates should be used with caution in patients with inflammatory bowel disease or coagulation abnormalities as they may also induce gastro-intestinal haemorrhage, occasionally major.
They may also precipitate bronchospasm or induce attacks of asthma in susceptible subjects.
High doses of aspirin may precipitate acute haemolytic anaemia in patients with glucose 6-phosphate dehydrogenase (G6PD) deficiency.
Aspirin should be used with caution in patients with impaired renal or hepatic function (avoid if severe), or in patients who are dehydrated.
Patients with hypertension should be carefully monitored.
Nu-Seals should be discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity.
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.
Salicylates may enhance the effect of oral hypoglycaemic agents, phenytoin and sodium valproate. They inhibit the uricosuric effect of probenecid and may increase the toxicity of sulphonamides.
Angiotensin converting enzyme inhibitors (ACE) in combination with acetylsalicylic acid at higher doses lead to decreased glomerular filtration via inhibition of vasodilatory prostaglandins and therefore, decreased antihypertensive effect.
Diuretics can increase the risk of nephrotoxicity of NSAIDs via decreased renal prostaglandin synthesis.
Aspirin may potentiate the effect of heparin and increases the risk of bleeding with oral anticoagulants, antiplatelet agents and fibrinolytics.
Plasma salicylate concentrations may be reduced by concurrent use of corticosteroids, and salicylate toxicity may occur following withdrawal of the corticosteroids. The risk of gastrointestinal ulceration and bleeding may be increased when aspirin and corticosteroids are co-administered.
Concurrent use of aspirin and other NSAIDs should be avoided. Use of two or more NSAID preparations increases the risk of serious gastrointestinal haemorrhage.
Concurrent administration of carbonic anhydrase inhibitors such as acetazolamide and salicylates may result in severe acidosis and increased central nervous system toxicity.
In large doses, salicylates may also decrease insulin requirements.
Patients using gastro-resistant aspirin should be advised against ingesting antacids simultaneously to avoid premature drug release.
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).
Concomitant use of excessive alcohol with aspirin may increase the risk of gastrointestinal bleeding.
Methotrexate: decreased elimination of methotrexate.
Cyclosporin, tacrolimus: increased risk of nephrotoxicity with NSAIDs.
Gold: risk of increased hepatotoxicity with aspirin.
Thiopental: Aspirin may potentiate the effects of thiopental anaesthesia.
Aspirin can interfere, to varying degrees, with some urine tests for catecholamines, dopa, glucose, ketones, hippuric acid, homogentisic acid, homovallinic acid, 17-hydroxycorticosteroids, 5-hydroxyindoleacetic acid, urine pregnancy tests and with some serum or plasma tests for albumin, barbiturates, calcium, propylthiouracil, tyrosine and uric acid.
Anti-platelet agents and selective serotonin reuptake inhibitors (SSRIs): increased risk of gastrointestinal bleeding.
Findings from a variety of animal models with a number of NSAIDs including aspirin indicate that these active substances block blastocyst implantation which may have an impact on female fertility
Clinical studies indicate that doses up to 100 mg/day for restricted obstetrical use, which require specialised monitoring, appear safe.
There is insufficient clinical experience regarding the use of doses above 100 mg/day up to 500 mg/day. Therefore, the recommendation below for doses of 500 mg/d and above apply also for this dose range.
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 prostaglandin synthesis inhibitor has been shown to results 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:
the mother and the neonate, at the end of pregnancy, to:
Consequently, acetylsalicylic acid at doses of 100 mg/day and higher is contraindicated during the third trimester of pregnancy.
As aspirin is excreted into breast milk, Nu-Seals 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.
None known.
The most commonly observed adverse events are gastrointestinal in nature.
Undesirable effects are listed by MedDRA System Organ Classes.
Assessment of undesirable effects is based on the following frequency groupings: 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, Not known cannot be estimated from the available data.
Not known: Anaemia1, Bleeding disorders2, Thrombocytopenia
Not known: Hypersensitivity reactions including skin rashes, urticaria, angioedema, asthma, bronchospasm and anaphylaxis.
Not known: Cerebral haemorrhage
Not known: Tinnitus
Not known: Haematoma, Haemorrhage
Not known: Epistaxis, Haemoptysis
Not known: Gastrointestinal irritation, Nausea, Vomiting, Dyspepsia, Gastritis, Gastrointestinal erosions, Gastrointestinal ulcer, Gastrointestinal bleeding
Not known: Purpura, Ecchymoses
Not known: Urate kidney stones, Haematuria
Not known: Bleeding time prolonged2, Transaminases increased
1 may occur following chronic gastrointestinal blood loss or acute haemorrhage.
2 fatalities have occurred.
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, Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.
None known.
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