Contraindicated Interactions: Methotrexate used at doses of 15 mg/week or more: Increased hematological 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 Contraindications).
Combinations requiring precautions for use: Methotrexate, used at doses of less than 15 mg/week: Increased hematological 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).
NSAIDs: The concurrent (same day) administration of some NSAIDs, such as ibuprofen and naproxen, may attenuate the irreversible platelet inhibition induced by Aspirin. The clinical relevance of these interactions is not known. Treatment with some NSAIDS, such as ibuprofen or naproxen, in patients with increased cardiovascular risk may limit the cardiovascular protection of Aspirin (see Precautions).
Anticoagulants, thrombolytics/other inhibitors of platelet aggregation/hemostasis: 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.
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 hypoglycemic effect by high doses of Aspirin via hypoglycemic action of Aspirin and displacement of sulfonylurea from its plasma protein binding.
Diuretics in combination with Aspirin at higher doses: 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 Aspirin at higher doses: 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 Aspirin and alcohol.
Uricosurics such as benzbromarone, probenecid: Decreased uricosuric effect (competition of renal tubular uric acid elimination).