Safety of a Novel Parenteral Formulation of Diclofenac after Major Orthopedic or Abdominal/Pelvic Surgery in a Population Including Anticoagulated, Elderly or Renally Insufficient Patients: An Open-Label, Multiday, Repeated Dose Clinical Trial

Authors


  • Disclosures and Conflicts of Interest: Financial support for the study was provided by Javelin Pharmaceuticals, Inc., Cambridge, MA (Hospira, Inc., Lake Forest, IL, following acquisition in 2010). DB Carr was the full-time Chief Medical Officer for the study sponsor during this trial. JE Chelly, SK Singla, and TI Melson received compensation for participation in the trial in large part to defray the costs associated with patient recruitment, participation, and assessment. PG Lacouture serves as Medical Director, Pain Management for Hospira, Inc. S Paadre serves as Biostatistics Manager at Veristat, Inc.

Reprint requests to: Daniel B. Carr, MD, Department of Anesthesiology, Tufts Medical Center, #298, 800 Washington Street, Boston, MA 02111, USA. Tel: 617-636-9710; Fax: 617-636-9709; E-mail: daniel.carr@tufts.edu.

Abstract

Objective

Decisions to use or avoid nonsteroidal anti-inflammatory drugs (NSAIDs) for postsurgical pain are often influenced by concerns about bleeding and renal adverse effects. The objective of this study was to evaluate the safety of a novel parenteral NSAID, hydroxypropyl-β-cyclodextrin (HPβCD) diclofenac, in a large postsurgical patient population, with particular focus on bleeding and renal effects.

Methods

This was a large open-label study in adult patients with acute moderate-to-severe pain following major surgery. Patients received ≥2 days of continuous treatment with HPβCD diclofenac, administered as a small-volume bolus injection every 6 hours. Few exclusion criteria were applied in order to reflect surgical patient populations commonly managed in clinical practice. Adverse events (AEs) were recorded throughout the study. The incidences of bleeding- and renal-related AEs were examined in patient subpopulations with known risk factors for NSAID-induced complications: advanced age, pre-existing renal insufficiency, concomitant anticoagulant use, prolonged exposure, elevated dosage, and major surgeries.

Results

Of the total 971 patients studied, 38% were ≥65 years old (12% >75 years), 62% received concomitant anticoagulants, and 6% had pre-existing renal insufficiency. HPβCD diclofenac was well tolerated by the patient population. AE rates are presented by risk factor to enable clinicians to better describe renal- or bleeding-related AEs.

Conclusions

In addition to its previously demonstrated efficacy, this study provides evidence of HPβCD diclofenac's safety in a large postsurgical population including anticoagulated, elderly or renally insufficient patients. Because study exclusion criteria were minimal, these findings may be broadly generalizable to populations commonly treated in clinical practice.

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