ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Drugs Outcomes Research and Policies
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1579634
Association of morphine vs fentanyl prescription dispensation with adverse clinical outcomes
Provisionally accepted
Carlen Reyes1,2*
Maria Antonia Pou2,3
Cesar Diaz-Torne2,4Cristina Carbonell-Abella2,3,5
Carlos Brotons1Daniel Martinez-Laguna2,3- 1Sardenya Primary Health Care Center, EAP Sardenya- Research Institute Sant Pau (IR- Sant Pau), Barcelona, Spain
- 2Sistema d’Informació per al Desenvolupament de la Investigació en Atenció Primària, Fundació Institut Universitari per a la recerca a l'Atenció Primària de Salut Jordi Gol i Gurina (IDIAPJGol), Mataró, Spain
- 3Catalan Health Institute (ICS), Barcelona, Catalonia, Spain
- 4Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Barcelona, Catalonia, Spain
- 5Autonomous University of Barcelona, Barcelona, Catalonia, Spain
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The aim was to assess the associations between morphine, fentanyl and adverse events in primary care patients. Methods: A retrospective, propensity-score-weighted cohort study using a primary-care database covering >75% population of Catalonia, Spain was conducted.Patients aged ≥18 years with ≥1 year of available data and incident exposure period of morphine or fentanyl, were included from 1 st January 2007 to 31 st December 2017. Patients could contribute to >1 exposure period during the study period. Outcomes were all-cause mortality, cardiac arrhythmias, fractures (hip, pelvis, vertebra, wrist, humerus), constipation, delirium, falls, opioid abuse/dependence, and sleep disorders while on treatment. risk ratios (RRs) and hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using cause-specific Cox models. Results: A total of 12,632 patients (3,040 with morphine and 9,695 with fentanyl) were included (median [IQR] age, 78.4 [63.8; 86.1] years; 63.6% female). Compared with morphine, fentanyl dispensation was associated with a higher risk of fractures (incidence, 6.92 vs 4.13 per 1,000 dispensations-month; HR, 1.63 [95% CI, 1.15 to 2.32]; RR, 1.78 [95% CI, 1.25 to 2.53]), especially in men and in those <65 and >80 years old. No difference was observed for the rest of outcomes. Conclusions: Among outpatients, a new prescription dispensation of fentanyl, compared with morphine, was associated with a higher risk of fractures. The findings should be interpreted cautiously given the potential for residual confounding.
Keywords: Cr, CCA, MPA, CBC and CDT have nothing to declare. DML has receiving personal fees from Amgen, UCB, Novartis, Rubió, Gedeon Ritcher
Received: 19 Feb 2025; Accepted: 23 May 2025.
Copyright: © 2025 Reyes, Pou, Diaz-Torne, Carbonell-Abella, Brotons and Martinez-Laguna. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Carlen Reyes, Sardenya Primary Health Care Center, EAP Sardenya- Research Institute Sant Pau (IR- Sant Pau), Barcelona, Spain
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