Drug Interactions between aspirin / caffeine / dihydrocodeine and ticagrelor

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.

MONITOR: Coadministration with opioid agonists may delay and reduce the absorption of orally administered P2Y12 inhibitors (e.g., clopidogrel, prasugrel, ticagrelor). The proposed mechanism may involve opioid-mediated slowed gastric emptying. In one study, IV morphine (5 mg) given immediately prior to a loading dose of clopidogrel (600 mg) decreased the systemic exposure (AUC) and maximum concentration (Cmax) of the active metabolite of clopidogrel by 34% and increased the time to peak concentration (Tmax) of clopidogrel when compared with placebo (105 minutes vs 83 minutes, respectively). In addition, morphine reduced the pharmacodynamic (antiplatelet) effects of clopidogrel. In another study, IV morphine (5 mg) given immediately prior to a loading dose of ticagrelor (180 mg) decreased the AUC of ticagrelor and its active metabolite by approximately 36%, doubled the Tmax of ticagrelor, and reduced the antiplatelet effects of ticagrelor. The clinical relevance of this interaction is unknown. The risks associated with other opioid agonists are also unknown.

MANAGEMENT: Although data are limited, caution is recommended when orally administered P2Y12 inhibitors are given concomitantly with opioid agonists. In acute coronary syndrome patients who require an opioid agonist, the use of a parenteral antiplatelet agent, such as cangrelor, should be considered.

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.