Morphine Interaction with Aspirin: a Double-Blind, Crossover Trial in Healthy Volunteers

Abstract

Aspirin is a cornerstone in the antiplatelet therapy for acute coronary syndromes. Coadministration of morphine may potentially influence the intestinal absorption, pharmacokinetics, and pharmacodynamics, as seen with P2Y inhibitors. In this trial, healthy volunteers were randomized to receive morphine (5 mg, i.v. bolus injection) at one of seven different time points before, after, or with aspirin (162 mg, p.o.) in a double-blind, placebo-controlled fashion. After a 14-day washout, subjects received placebo instead of morphine. Pharmacokinetics were determined by liquid chromatography, and aspirin's effects were measured by platelet function tests (whole-blood platelet aggregation: multiplate, platelet plug formation: PFA-100). Morphine increased the total acetylsalicylic acid exposure by 20% compared with placebo when given simultaneously with aspirin, whereas and were not altered. Morphine had no significant effect on aspirin-induced platelet inhibition. In contrast to coadministration with P2Y inhibitors, morphine appears to have negligible interaction with aspirin.

Clinical pharmacology of morphine in infants and children

“…Morphine significantly decreases the peak plasma concentration of prasugrel [26]. Morphine co-administered with acetylsalicylic acid increase the acetylsalicylic acid exposure by 20% [27]. Co-administration of morphine with prasugrel or ticagrelor, inhibitors of P2Y12, decreases their efficacy in platelet inhibition [28].…”

ANalgesic Efficacy and safety of MOrphiNe versus methoxyflurane in patients with acute myocardial infarction: the rationale and design of the ANEMON-SIRIO 3 study: a multicentre, open-label, phase II, randomised clinical trial

“…[11][12][13][14][15][16] Similar effect was observed for clopidogrel 17 18 and prasugrel, 17 19 20 but not for aspirin. 9 Unfortunately, different tested strategies failed to overcome the 'morphine effect'. [21][22][23] Therefore, replacing morphine with another highly effective non-opioid analgesic that does not weaken and does not delay the effect of antiplatelet agents may improve the clinical efficacy of treatment of patients with AMI.…”

“…These side effects affect the intestinal absorption of oral drugs co-administered with morphine. 9 10 Previously performed randomised studies revealed unfavourable influence of morphine on the pharmacokinetics of ticagrelor resulting in weaker and retarded antiplatelet effect. 11–16 Similar effect was observed for clopidogrel 17 18 and prasugrel, 17 19 20 but not for aspirin.…”

Does morphine remain a standard of care in acute myocardial infarction?

“…In modern ACS therapy the ESC guidelines clearly recommend the use of more potent antiplatelet agents like ticagrelor and prasugrel over clopidogrel [6]. In a double-blind cross-over trial in healthy volunteers, morphine had no significant effect on aspirin-induced platelet inhibition [7]. The first reports suggesting possible drug-drug interaction between morphine and clopidogrel come from the CRUSADE registry [8].…”