title: 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.
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.
authors.affiliation: Department of Anesthesiology, UPMC Presbyterian-Shadyside Hospital, Pittsburgh, Pennsylvania, USA.
authors.forename: Jacques E
authors.initials: JE
authors.lastname: Chelly
authors.forename: Sonia K
authors.initials: SK
authors.lastname: Singla
authors.forename: Timothy I
authors.initials: TI
authors.lastname: Melson
authors.forename: Peter G
authors.initials: PG
authors.lastname: Lacouture
authors.forename: Susan
authors.initials: S
authors.lastname: Paadre
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Carr
mesh_terms: D000005:Abdomen / Q000601:surgery; D000368:Aged; D000369:Aged, 80 and over; D000700:Analgesics / Q000008:administration & dosage; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage; D000925:Anticoagulants / Q000008:administration & dosage*; D002140:California / Q000453:epidemiology; D015897:Comorbidity; D004008:Diclofenac / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology*; D005260:Female; D006470:Hemorrhage / Q000453:epidemiology* / Q000517:prevention & control*; D006801:Humans; D007263:Infusions, Parenteral; D008297:Male; D008875:Middle Aged; D019637:Orthopedic Procedures / Q000706:statistics & numerical data; D010149:Postoperative Pain / Q000175:diagnosis / Q000517:prevention & control*; D010388:Pelvis / Q000601:surgery; D015995:Prevalence; D051437:Renal Insufficiency / Q000453:epidemiology*; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000925:Anticoagulants; D004008:Diclofenac