title: A Pooled Analysis Evaluating Renal Safety in Placebo- and Active Comparator-Controlled Phase III Trials of Multiple-Dose Injectable HPβCD-Diclofenac in Subjects with Acute Postoperative Pain.
abstract: OBJECTIVE : While injectable nonsteroidal anti-inflammatory drugs (NSAIDs) are a key component of postoperative multimodal analgesia, renal safety concerns may limit use in some patients. This study examined the renal safety of injectable HPβCD-diclofenac when given for ≤ 5 days following orthopedic or abdominal/pelvic surgery. METHODS : Pooled analysis of data from two randomized, placebo- and active comparator-controlled phase III trials in 608 total patients was conducted. Renal safety was assessed by examining treatment-emergent adverse events (AEs) and postoperative blood urea nitrogen (BUN) and serum creatinine shifts. RESULTS : There were three renal AEs each in the HPβCD-diclofenac (n = 318 patients) and placebo (n = 148 patients) groups, and two renal AEs in the ketorolac group (n = 142 patients). No significant difference in renal AE risk was detected for patients receiving HPβCD-diclofenac (RR: 1.40 [0.15,13.3]; P = 0.75) or ketorolac (RR: 2.08 [0.19,22.7]; P = 0.56) versus placebo. All renal AEs were mild or moderate in severity, and a single renal AE (acute renal failure in a patient receiving HPβCD-diclofenac) was treatment-related. One incidence of postoperative shift to high (> upper limit of normal) serum creatinine occurred in the HPβCD-diclofenac group (n = 2 in the ketorolac group). Mean changes in serum creatinine or BUN did not differ significantly between patients receiving HPβCD-diclofenac and placebo. CONCLUSIONS : While this analysis examined relatively brief exposure typical for parenterally administered analgesics in the postoperative setting in patients with largely normal renal function, the results suggest that HPβCD-diclofenac use for acute postoperative pain may not be associated with added renal safety risks over placebo in this patient population.
authors.affiliation: *Premier Research, Austin, Texas.
authors.forename: Stephen E
authors.initials: SE
authors.lastname: Daniels
authors.affiliation: Department of Anesthesiology, Stony Brook University, Stony Brook, New York.
authors.forename: Tong J Tj
authors.initials: TJ
authors.lastname: Gan
authors.affiliation: Javelin Pharmaceuticals, Inc. (now Hospira), a Pfizer Company, Lake Forest, Illinois.|New Biology Ventures LLC, San Mateo, California.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Hamilton
authors.affiliation: Lotus Clinical Research, LLC, Pasadena, California.
authors.forename: Neil
authors.initials: N
authors.lastname: Singla
authors.affiliation: Magidom Discovery, LLC, St. Augustine, Florida.|Brown University School of Medicine, Providence, Rhode Island.
authors.forename: Peter G
authors.initials: PG
authors.lastname: Lacouture
authors.affiliation: **Hospira, a Pfizer Company, Lake Forest, Illinois.
authors.forename: Olufunmibi
authors.initials: O
authors.lastname: Johnson
authors.affiliation: **Hospira, a Pfizer Company, Lake Forest, Illinois.
authors.forename: Lauren H
authors.initials: LH
authors.lastname: Min
authors.affiliation: **Hospira, a Pfizer Company, Lake Forest, Illinois.
authors.forename: Christian R D
authors.initials: CR
authors.lastname: Reyes
authors.affiliation: Javelin Pharmaceuticals, Inc. (now Hospira), a Pfizer Company, Lake Forest, Illinois daniel.carr@tufts.edu.|Department of Anesthesiology, Tufts Medical Center, Boston, Massachusetts, USA.
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Carr
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D000293:Adolescent; D000328:Adult; D000368:Aged; D000700:Analgesics / Q000008:administration & dosage / Q000009:adverse effects; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects*; D004008:Diclofenac / Q000008:administration & dosage* / Q000009:adverse effects*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007668:Kidney / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D010149:Postoperative Pain / Q000188:drug therapy*; D055815:Young Adult; D047392:beta-Cyclodextrins / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D047392:beta-Cyclodextrins; D004008:Diclofenac; D000073738:2-Hydroxypropyl-beta-cyclodextrin
keywords: Acute Pain; Diclofenac; NSAID; Pain Management; Renal; Safety