Aspirin should be avoided by those known to be allergic to ibuprofen or naproxen, or to have salicylate intolerance or a more generalized drug intolerance to NSAIDs, and caution should be exercised in those with asthma or NSAID-precipitated bronchospasm. Due to its effect on the stomach lining, manufacturers recommend that patients with kidney disease, peptic ulcers, mild diabetes, gout or gastritis talk to their doctors before using aspirin. Even if none of these conditions are present, there is still an increased risk of stomach bleeding when aspirin is taken with alcohol or warfarin. Patients with hemophilia or other bleeding tendencies should not take aspirin or other salicylates.
Aspirin is known to cause hemolytic anemia in people who have the genetic disease glucose-6-phosphate dehydrogenase deficiency (G6PD), particularly in large doses and depending on the severity of the disease. Aspirin should not be given to children or adolescents to control cold or influenza symptoms as this has been linked with Reye’s syndrome. Use of aspirin during Dengue Fever is not recommended due to increased bleeding tendency. For some people, aspirin does not have as strong an effect on platelets as for others, an effect known as aspirin “resistance” or insensitivity. One study has suggested that women are more likely to be resistant than men and a different, aggregate study of 2,930 patients found 28% to be resistant.
Aspirin use has been shown to increase the risk of gastrointestinal bleeding. Although some enteric coated formulations of aspirin are advertised as being “gentle to the stomach”, in one study enteric coating did not seem to reduce this risk. Combining aspirin with other NSAIDs has also been shown to further increase this risk. Using aspirin in combination with clopidogrel or warfarin also increases the risk of upper GI bleeding.
Large doses of salicylate, a metabolite of aspirin, have been proposed to cause tinnitis, based on the experiments in rats, via the action on arachidonic acid and NMDA receptors cascade.
Reye’s syndrome can occur when children or pediatric patients are given aspirin for a fever or other illnesses or infections. In one study, 213 patients under the age of 18 were reported for Reye’s syndrome from the nationwide Reye’s syndrome surveillance system. Out of 213 patients 211 had known that had another antecedent illness: 89% reported being ill (severe vomiting, mental strain, respiratory illness, vericella or gastrointestinal illness) two weeks before onset of Reye’s syndrome. Salicylate levels, the active acid in aspirin, were present in 162 of the 213 patients.
Reye’s syndrome is due to fatty deterioration of liver cells. In another study, 12 livers were obtained from children who had died from Reye’s syndrome, and another liver from a child who died of accidental causes was used as a control. The autopsy stated in seven of the 12 livers, micro vesicular fatty change was present.
Aspirin can cause prolonged bleeding after operations for up to 10 days. In one study, thirty patients were observed after their various surgeries. Twenty of the thirty patients had to have an additional unplanned operation because of postoperative bleeding. This diffuse bleeding was associated with aspirin alone or in combination with another NSAID in 19 out of the 20 who had to have another operation due to bleeding after their operation. The average recovery time for the second operation was 11 days.
Aspirin can induce angioedema in some people. In one study, angioedema appeared 1-6 hours after ingesting aspirin in some of the patients participating in the study. However, when the aspirin was taken alone it did not cause angioedema in these patients; the aspirin was either taken in combination with another NSAID-induced drug when angioedema appeared.
Aspirin is known to interact with other drugs. For example, acetazolamide and ammonium chloride have been known to enhance the intoxicating effect of salicyclates, and alcohol also enhances the gastrointestinal bleeding associated with these types of drugs as well.
Aspirin is known to displace a number of drugs from protein binding sites in the blood, including the anti-diabetic drugs tolbutamide and chlorpropamide, the immunosuppressant methotrexate, phenytoin, probenecid, valproic acid (as well as interfering with beta oxidation, an important part of valproate metabolism) and any nonsteroidal anti-inflammatory drug. Corticosteroids may also reduce the concentration of aspirin. The pharmacological activity of spironolactone may be reduced by taking aspirin, and aspirin is known to compete with Penicillin G for renal tubular secretion. Aspirin may also inhibit the absorption of vitamin C.
For adults doses are generally taken four times a day for fever or arthritis, with doses near the maximal daily dose used historically for the treatment of rheumatic fever. For the prevention of myocardial infarction in someone with documented or suspected coronary artery disease, much lower doses are taken once daily.
For those under 12 years of age, the dose previously varied with the age, but aspirin is no longer routinely used in children due to the association with Reye’s syndrome; paracetamol (known as acetaminophen in North America) or other NSAIDs, such as ibuprofen, are now used instead. Kawasaki disease remains one of the few indications for aspirin use in children, with aspirin taken at dosages based on body weight, initially four times a day for up to two weeks and then at a lower dose once daily for a further six to eight weeks.
Aspirin overdose can be acute or chronic. In acute poisoning, a single large dose is taken; in chronic poisoning, supratherapeutic doses are taken over a period of time. Acute overdose has a mortality rate of 2%. Chronic overdose is more commonly lethal with a mortality rate of 25%; chronic overdose may be especially severe in children.
Aspirin overdose has potentially serious consequences, sometimes leading to significant morbidity and mortality. Patients with mild intoxication frequently have nausea and vomiting, abdominal pain, lethargy, tinnitus, and dizziness. More significant symptoms occur in more severe poisonings and include hyperthermia, tachypnea, respiratory alkalosis, metabolic acidosis, hyperkalemia, hypoglycemia, hallucinations, confusion, seizure, cerebral edema, and coma. The most common cause of death following an aspirin overdose is cardiopulmonary arrest usually due to pulmonary edema.
The toxic dose of aspirin is generally considered greater than 150 mg per kg of body mass. Moderate toxicity occurs at doses up to 300 mg/kg, severe toxicity occurs between 300 to 500 mg/kg, and a potentially lethal dose is greater than 500 mg/kg. This is the equivalent of many dozens of the common 325 mg tablets, depending on body weight. However children cannot tolerate as much aspirin per unit body weight as adults can.