Source: Health Products and Food Branch (CA) Revision Year: 2022
ASA is one of the most frequent causes of accidental poisonings in toddlers and infants. Tablets or caplets should be kept well out of the reach of children.
ASA should be administered cautiously to patients with:
ASA may precipitate bronchospasm and induce asthma attacks or other hypersensitivity reactions. Risk factors are present bronchial asthma, hay fever, nasal polyps, or chronic respiratory disease. This applies also for patients showing allergic reactions (e.g. cutaneous reactions, itching, urticaria) to other substances.
Due to effect on platelet aggregation, ASA may be associated with an increased risk of bleeding. Caution is necessary when salicylates and anticoagulants are prescribed concurrently, as salicylates can depress the concentration of prothrombin in the plasma.
Due to its inhibitory effect on platelet aggregation which persists for several days after administration, ASA may lead to an increased bleeding tendency during and after surgical operations (including minor surgeries, e.g. dental extractions).
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 as possible and duration of treatment as short as possible.
Based on the limited published data available, the studies in humans showed no consistent effect of acetylsalicylic acid on impairment of fertility and there is no conclusive evidence from animal studies.
Acetylsalicylic acid inhibits prostaglandin synthesis. Inhibition of prostaglandin synthesis may adversely affect the pregnancy and/or the embryo/foetal 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 (1st - 4th month) of about 14,800 mother-child pairs has not yielded any association with an elevated rate of malformations.
During the third trimester of pregnancy, all prostaglandin synthesis inhibitors may expose the foetus to:
Use of any prostaglandin synthesis inhibitors at the end of pregnancy may expose the mother and the child to:
Consequently, acetylsalicylic acid is contraindicated in the third trimester of pregnancy.
ASA and its metabolites pass into breast milk in small quantities. Since no adverse effects on the infant have been observed 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.
A possible association between Reye’s syndrome and the use of salicylates has been suggested but not established. Reye’s syndrome has also occurred in many patients not exposed to salicylates. ASA should not be used in children and teenagers for viral infections with or without fever without consulting a physician. In certain viral illnesses, especially influenza A, influenza B and varicella, there is a risk of Reye’s syndrome, a very rare but possibly lifethreatening illness requiring immediate medical action. The risk may be increased when ASA is given concomitantly; however, no causal relationship has been proven. Should persistent vomiting occur with such diseases; this may be a sign of Reye’s syndrome.
At low doses, ASA reduces excretion of uric acid. This can trigger gout in patients who already tend to have low uric acid excretion.
In patient suffering from glucose-6-phosphate dehydrogenase (G6PD) deficiency, ASA may induce hemolysis or haemolytic anemia. Factors that may increase the risk of haemolysis are high dosage, fever, or acute infections.
In general, ASA should be used with caution in elderly patients (≥60 years of age), as these patients may be more susceptible to adverse reactions.
Salicylates can produce changes in thyroid function tests.
Isolated cases of liver function disturbances (transaminases increase) have been described.
Many adverse reactions due to ASA ingestion are dose-related. The following is a list of adverse reactions that have been reported in the literature and from both clinical and post-marketing experience.
Gastrointestinal (the frequency and severity of these adverse effects are dose-related): nausea, vomiting, diarrhea, gastrointestinal bleeding and/or ulceration, dyspepsia, heartburn, hematemesis, melena, abdominal pain, rarely gastrointestinal inflammation, and intestinal diaphragm disease with frequency not known (especially in long-term treatment).
Bleeding: Due to platelet inhibition, bleedings e.g. perioperative haemorrhage, hematomas, epistaxis, urogenital bleedings, and gingival bleedings may occur.
Serious bleedings, such as gastrointestinal tract hemorrhages, and cerebral hemorrhages are rare. Isolated cases of potentially life threatening bleedings have been reported, especially in patients with uncontrolled hypertension and/or concomitant antihemostatic agents.
Ear: dizziness, tinnitus, vertigo, hearing loss. Dizziness and tinnitus have been reported, which may be indicative of an overdose.
Hematologic: leukopenia, thrombocytopenia, purpura, anemia. Anemia with respective laboratory and clinical signs and symptoms, such as asthenia, pallor, and hypoperfusion is generally caused by bleeding (e.g. occult microbleeding, acute or chronic bleeding). Hemolysis and hemolytic anemia in patients with severe forms of glucose-6-phosphate dehydrogenase (G6PD) deficiency has been reported.
Dermatologic and hypersensitivity: urticaria, pruritus, skin eruptions, asthma, anaphylaxis, edema, nasal congestion and rhinitus. Severe allergic reactions, including anaphylactic shock are very rarely reported.
Miscellaneous: mental confusion, drowsiness, sweating, thirst. Transient hepatic impairment with increase in liver transaminases has very rarely been reported. Renal impairment and acute renal failure have been reported.
ASA should be used with caution with other products that have anticoagulation or antiplatelet effects, as these effects may be potentiated. Drugs that bind to protein binding sites should also be used cautiously since ASA may displace drugs from their protein binding site.
Methotrexate, used at doses of 15 mg/week or more: Increased hematological toxicity of methotrexate (due to decreased renal clearance of methotrexate by anti-inflammatory agents in general and displacement of methotrexate from its plasma protein binding by salicylates). See CONTRAINDICATIONS.
Methotrexate, used at 15 mg/week or less: Salicylates may retard the elimination of methotrexate by decreasing renal clearance of methotrexate, displacing methotrexate from protein binding sites, and thereby increasing its hematological toxicity.
Anti-coagulants, thrombolytics / other inhibitors of platelet aggregation / hemostasis, e.g. warfarin, heparin: Caution is necessary when salicylates and anticoagulants, thrombolytics / other inhibitors of platelet aggregation / hemostasis prescribed concurrently, as salicylates can depress the concentration of prothrombin in the plasma, leading to an increased risk of bleeding.
Oral hypoglycemics, e.g. insulin, sulfonylureas: Large doses of salicylates have a hypoglycemic action and may enhance the effect of oral hypoglycemic agents. Diabetics receiving concurrent salicylate and hypoglycemic therapy should be monitored closely; reduction of the sulfonylurea hypoglycemic drug dosage may be necessary.
Diuretics: Diuretics in combination with acetylsalicylic acid at higher doses leads to decreased glomerular filtration via decreased prostaglandin synthesis. As a result, sodium excretion may be decreased by salicylate administration.
Uricosuric Agents: Salicylates in large doses are uricosuric agents; smaller amounts may depress uric acid clearance and thus decrease the uricosuric effects of other drugs.
Valproic Acid: Salicylates may alter valproic acid (VPA) metabolism and may displace VPA from protein binding sites, possibly intensifying the effects of VPA. Caution is recommended when VPA is administered concomitantly with salicylates.
Glucocorticoids (systemic), 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. Concurrent use may increase the incidence of gastrointestinal bleeding and ulceration.
Angiotensin Converting Enzyme (ACE) Inhibitors: The hyponatremic and hypotensive effects of ACE inhibitors may be diminished by the concomitant administration of ASA due to its indirect effect on the renin-angiotensin conversion pathway (i.e. inhibition of vasodilatory prostaglandins leading to decreased glomerular filtration). The potential interaction may be related to the dose of ASA (3 g/day or more).
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.
ASA and other NSAIDs: The use of other NSAIDs with salicylates at high doses (≥3 g/day) may increase the risk of ulcers and gastrointestinal bleeding due to a synergistic effect.
Ibuprofen: Ibuprofen can interfere with the anti-platelet effect of low dose ASA (81-325 mg per day). Long-term daily use of ibuprofen may render ASA less effective when used for cardioprotection and stroke prevention. To minimize this interaction, regular users of ibuprofen and of low-dose, immediate-release ASA should take the ibuprofen at least one hour after and 11 hours before the daily ASA dose. The use of delayed-release (e.g. enteric-coated) ASA is not recommended when using ibuprofen regularly.
Naproxen: Naproxen may attenuate the irreversible platelet inhibition induced by acetylsalicylic acid. Clinical pharmacodynamic data suggest that concurrent (same day) naproxen sodium usage for more than one day consecutively inhibits the effect of low-dose acetylsalicylic acid on platelet activity and this inhibition may persist for up to several days after stopping naproxen sodium therapy. The clinical relevance of this interaction is not known. Treatment with naproxen, in patients with increased cardiovascular risk may limit the cardiovascular protection of acetylsalicylic acid (see “Special warnings and precautions for use”).
Healthcare professionals should advise consumers and patients regarding the appropriate concomitant use of NSAIDs (i.e. ibuprofen or naproxen) and ASA.
Interactions with food have not been established.
Interactions with herb have not been established.
Salicylates can produce changes in thyroid function tests.
Alcohol: Increased damage to gastrointestinal mucosa and prolonged bleeding time due to additive effects of acetylsalicylic acid and alcohol. Patients having 3 or more alcoholic drinks per day should consult their physician before use.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
