Aspirin should not be taken by patients with the following conditions:
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 on the advice of a doctor e.g Kawasaki’s Syndrome
Aspirin should be used with caution in patients with:
Acetylsalicylic acid is not suitable for use as an anti-inflammatory/analgesic/antipyretic
The following warnings are on the OTC product labelling:
The following drug interactions should be considered when prescribing aspirin:
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 acetylsalicylic acid is contraindicated (see section 4.3).
Uricosuric agents, e.g. probenecid:
Salicylates reverse the effect of probenecid. The combination should be avoided.
Anticoagulants e.g. coumarin, heparin, warfarin:
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).
Anti-platelet 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. sulphonylureas:
Salicylics may increase the hypoglycaemic effect of sulphonylureas.
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 glomerual 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 central nervous system toxicity
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.
Increased risk of ulcerations and gastrointestinal bleeding due to synergistic effects.
Concomitant use of NSAIDs and ciclospoin 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.
Acetylsalicylic acid has been reported to decrease the binding of valproate to serum albumin, thereby increasing its free plasma concentrations at steady state.
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.
Concomitant administration of alcohol and acetylsalicylic acid increases the risk of gastrointestinal bleeding.
Experimental data suggest that ibuprofen may inhibit the effect of low dose acetylsalicylic acid 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).
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 recommendations below for doses of 500 mg/day 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 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.
Regular or high dose use of salicylates late in pregnancy may result in:
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.
Low quantities of salicylates and of their metabolites are excreted into the breast milk. Adverse effects for the infant have not been reported up to now. However, aspirin should be avoided during lactation because of the possible risk of Reye’s syndrome. In cases of long-term use and/or administration of higher doses, breastfeeding should be discontinued. Regular use of high doses of aspirin could impair platelet function and produce hypoprothrombinaemia in the infant neonatal vitamin K stores are low.
No studies on the effects on the ability to drive and use machines have been performed with Acetylsalicylic acid.
Based on the pharmacodynamic properties and the side effects of acetylsalicylic acid, no influence on the reactivity and the ability to drive or use machines is expected.
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)
Common: Increased bleeding tendencies.
Rare: Thrombocytopenia, agranulocytosis, aplastic anaemia.
Not known: Cases of bleeding with prolonged bleeding time such as epistaxis, gingival bleeding. Symptoms may persist for a period of 4–8 days after acetylsalicylic acid discontinuation. As a result there may be an increased risk of bleeding during surgical procedures.
Existing (haematemesis, melaena) or occult gastrointestinal bleeding, which may lead to iron deficiency anaemia (more common at higher doses).
Anaemia, haemolytic anaemia, hypoprothrombinaemia, pancytopenia, occult blood loss, elevated transaminase levels
Rare: Hypersensitivity reactions, angio-oedema, allergic oedema, anaphylactic reactions including shock.
Not known: Hyperuricemia.
Rare: Intracranial haemorrhage
Not known: Headache, vertigo.
Not known: Reduced hearing ability; tinnitus.
Rare: Haemorrhagic vasculitis.
Uncommon: Rhinitis, dyspnoea.
Rare: Bronchospasm, asthma attacks.
Rare: Severe gastrointestinal haemorrhage, nausea, vomiting.
Not known: Gastric or duodenal ulcers and perforation which can occasionally be major (may develop bloody or black tarry stools, severe stomach pain and vomiting blood), gastrointestinal irritation (mild stomach pain), erosions, heartburn, Fatalities have occurred.
Not known: Hepatic insufficiency, hepatitis (particularly in patients with SLE or connective tissue disease)
Rare: Steven-Johnsons syndrome, Lyells syndrome, purpura, erythema nodosum, erythema multiforme.
Not known: Impaired renal function
Not known: Salicylism – (mild chronic salicylate intoxication may occur after repeated administration of large doses, symptoms include dizziness, tinnitus, deafness, sweating, nausea, vomiting, headache and mental confusion, and may be controlled by reducing the dose)
Aspirin may be associated with the development of Reye’s Syndrome (encephalopathy and hepatic failure) in children presenting with an acute febrile illness.
Iron salts, alkalis and carbonates.