Drug Interactions between Axotal 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.

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GENERALLY AVOID: Coadministration with inducers of CYP450 3A4 may decrease the plasma concentrations of ticagrelor, which is primarily metabolized by the isoenzyme. In 14 healthy volunteers, administration of a single 180 mg oral dose of ticagrelor on day 12 of treatment with the potent CYP450 3A4 inducer rifampin (600 mg once daily for 14 days) decreased mean ticagrelor peak plasma concentration (Cmax), systemic exposure (AUC) and plasma half-life by 73%, 86% and 67%, respectively, compared to administration of ticagrelor alone. Mean Cmax of the major active metabolite was unchanged in the presence of rifampin, but mean AUC decreased by 46% and plasma half-life by 50%. Inhibition of platelet aggregation (IPA) was also assessed in the study. Mean IPA at 12 hours was 87% with ticagrelor alone versus 63% in combination with rifampin; corresponding values at 24 hours were 70% and 15%, respectively. It is not known to what extent ticagrelor may interact with weak and moderate CYP450 3A4 inducers.

MANAGEMENT: Concomitant use of ticagrelor with CYP450 3A4 inducers should generally be avoided. Otherwise, caution is advised, and patients should be closely monitored for diminished clinical response to ticagrelor therapy. Alternative treatment may be required if an interaction is suspected.

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