A Comparison of Opioid-Related Adverse Events with Fentanyl Iontophoretic Transdermal System Versus Morphine Intravenous Patient-Controlled Analgesia in Acute Postoperative Pain

Abstract

Objective: This analysis compared opioid-related adverse events (ORADEs) observed with fentanyl iontophoretic transdermal system (ITS) versus morphine intravenous (iv.) patient-controlled analgesia (PCA) in the management of postoperative pain. Methods: Safety data from four Phase IIIB randomized, active-comparator trials were pooled for this analysis (n = 1288 fentanyl ITS and 1313 morphine iv. PCA patients). Treatment-emergent adverse events were collected via spontaneous report. In this post hoc analysis, ORADEs were defined as apnea, confusion, constipation, dyspnea, hypotension, hypoventilation, hypoxia, ileus, nausea, pruritus, somnolence, tachycardia, urinary retention and vomiting. Odds ratios (OR) and 95% CI were calculated for all ORADEs and p-values were based on logistic regression with treatment as effect. Results: There were fewer patients in the fentanyl ITS group compared with the morphine iv. PCA group who experienced at least one ORADE (52.7 vs 59.1%, respectively; OR: 0.772: 95% CI: 0.661–0.901; p = 0.0011). The ORADEs that occurred less frequently in the fentanyl ITS group than in the morphine iv. PCA group included hypotension (3.7 vs 5.5%, respectively; OR: 0.667; 95% CI: 0.459–0.969; p = 0.0338), hypoventilation (0.9 vs 1.9%, respectively; OR: 0.444; 95% CI: 0.217–0.906; p = 0.0256), nausea (40.3 vs 44.5%, respectively; OR: 0.842; 95% CI: 0.721–0.984; p = 0.0310), pruritus (5.5 vs 9.4%, respectively; OR: 0.559; 95% CI: 0.413–0.757; p = 0.0002) and tachycardia (1.6 vs 2.8%, respectively; OR: 0.489; 95% CI: 0.277–0.863; p = 0.0136). No ORADEs occurred more frequently in the fentanyl ITS group compared with the morphine iv. PCA group. Conclusion: Fentanyl ITS, in the management of acute postoperative pain, offered safety advantages in terms of ORADEs compared with morphine iv. PCA.

KEYWORDS:

• fentanyl
• iontophoretic transdermal system
• morphine
• opioid-related adverse drug events
• patient-controlled analgesia
• postoperative pain

Financial & competing interests disclosure

The analyses and writing of this manuscript were supported financially by The Medicines Company. RS Sinatra is Acting Director of Pain Medicine at the West Haven VA Medical Center (CT, USA) and serves as a consultant to The Medicines Company (NJ, USA) and Pacira Pharmaceuticals (CA, USA). ER Viscusi is Professor of Anesthesiology and Director, Acute Pain Management at Thomas Jefferson University, Philadelphia, PA, USA. Funding research has been provided to the Thomas Jefferson University by: AcelRx, Pacira, Consulting: AcelRx, The Medicines Company, Mallinckrodt, Cubist, Trevena, Pacira, Speaking Honoraria: AstraZeneca, Mallinckrodt, Cubist, Salix, Pacira. S Grond is Director of the Clinic of Anesthesia and Intensive Care, Klinikum Lippe, Detmold, Germany and serves as a consultant to the Medicines Company and Jansen-Cilag. L Ding, H Danesi and JB Jones are employees of The Medicines Company (NJ, USA). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

The authors acknowledge writing assistance provided by Starr Grundy of SD Scientific, Inc, funded by The Medicines Company.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

The analyses and writing of this manuscript were supported financially by The Medicines Company. RS Sinatra is Acting Director of Pain Medicine at the West Haven VA Medical Center (CT, USA) and serves as a consultant to The Medicines Company (NJ, USA) and Pacira Pharmaceuticals (CA, USA). ER Viscusi is Professor of Anesthesiology and Director, Acute Pain Management at Thomas Jefferson University, Philadelphia, PA, USA. Funding research has been provided to the Thomas Jefferson University by: AcelRx, Pacira, Consulting: AcelRx, The Medicines Company, Mallinckrodt, Cubist, Trevena, Pacira, Speaking Honoraria: AstraZeneca, Mallinckrodt, Cubist, Salix, Pacira. S Grond is Director of the Clinic of Anesthesia and Intensive Care, Klinikum Lippe, Detmold, Germany and serves as a consultant to the Medicines Company and Jansen-Cilag. L Ding, H Danesi and JB Jones are employees of The Medicines Company (NJ, USA). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. The authors acknowledge writing assistance provided by Starr Grundy of SD Scientific, Inc, funded by The Medicines Company.