Drug Interaction Report

ADJUST DOSE: Use of high maintenance dosages of aspirin may decrease the effectiveness of ticagrelor in preventing thrombotic events in patients with acute coronary syndromes. The underlying biological mechanism has not been established. Data from PLATO, a large, randomized, double-blind efficacy and safety comparison study with clopidogrel, suggest that the efficacy of ticagrelor is associated with aspirin dosage during maintenance therapy. Patients who received a low maintenance dosage (75 to 150 mg daily) of aspirin benefited more than those who received a high maintenance dosage (above 300 mg daily). Because data for the high maintenance dosages of aspirin do not provide conclusive evidence of efficacy of ticagrelor relative to clopidogrel, the dosage of aspirin should be limited during maintenance dual antiplatelet therapy with ticagrelor. In drug interaction studies, coadministration of ticagrelor with aspirin did not have any effect on the plasma levels of ticagrelor or its active metabolite.

MANAGEMENT: Following the initial loading dose (usually 325 mg) of aspirin, a daily maintenance dose of 75 to 100 mg is recommended by the manufacturer to be used with ticagrelor.

GENERALLY AVOID: The concurrent use of aspirin or nonsteroidal anti-inflammatory drugs (NSAIDs) and ethanol may lead to gastrointestinal (GI) blood loss. The mechanism may be due to a combined local effect as well as inhibition of prostaglandins leading to decreased integrity of the GI lining.

MANAGEMENT: Patients should be counseled on this potential interaction and advised to refrain from alcohol consumption while taking aspirin or NSAIDs.

MONITOR: Coadministration of two or more sympathomimetic agents may increase the risk of adverse effects such as nervousness, irritability, and increased heart rate. Central nervous system (CNS) stimulants, particularly amphetamines, can potentiate the adrenergic response to vasopressors and other sympathomimetic agents. Additive increases in blood pressure and heart rate may occur due to enhanced peripheral sympathetic activity.

MANAGEMENT: Caution is advised if two or more sympathomimetic agents are coadministered. Pulse and blood pressure should be closely monitored.

One study has reported that coadministration of caffeine and aspirin lead to a 25% increase in the rate of appearance and 17% increase in maximum concentration of salicylate in the plasma. A significantly higher area under the plasma concentration time curve of salicylate was also reported when both drugs were administered together. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that coadministration of aspirin and caffeine may lead to higher salicylate levels faster.