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.

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--cyclodextrin (HPCD) 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 HPCD 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. HPCD 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 HPCD 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.