Literature DB >> 23566212

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.

Jacques E Chelly1, Sonia K Singla, Timothy I Melson, Peter G Lacouture, Susan Paadre, Daniel B Carr.   

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. Wiley Periodicals, Inc.

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Year:  2013        PMID: 23566212     DOI: 10.1111/pme.12076

Source DB:  PubMed          Journal:  Pain Med        ISSN: 1526-2375            Impact factor:   3.750


  10 in total

Review 1.  Diclofenac Sodium Bolus Injection (Dyloject(TM)): A Review in Acute Pain Management.

Authors:  Sheridan M Hoy
Journal:  Drugs       Date:  2016-08       Impact factor: 9.546

Review 2.  Single-dose intravenous diclofenac for acute postoperative pain in adults.

Authors:  Ewan D McNicol; McKenzie C Ferguson; Roman Schumann
Journal:  Cochrane Database Syst Rev       Date:  2018-08-28

3.  Systematic Review and Meta-Analysis of the Association Between Non-Steroidal Anti-Inflammatory Drugs and Operative Bleeding in the Perioperative Period.

Authors:  Tasce Bongiovanni; Elizabeth Lancaster; Yeranuí Ledesma; Evans Whitaker; Michael A Steinman; Isabel Elaine Allen; Andrew Auerbach; Elizabeth Wick
Journal:  J Am Coll Surg       Date:  2021-01-27       Impact factor: 6.532

4.  A Phase I study evaluating the effect of age and weight on the pharmacokinetics of an injectable formulation of diclofenac solubilized with hydroxypropyl-β-cyclodextrin.

Authors:  Ronald Goldwater; William G Kramer; Douglas A Hamilton; Eric Lang; Jianyuan Wang; Donna E Madden; Peter G Lacouture; Atulkumar Ramaiya; Daniel B Carr
Journal:  Clin Pharmacol       Date:  2016-12-15

5.  Postoperative opioid sparing with injectable hydroxypropyl-β-cyclodextrin-diclofenac: pooled analysis of data from two Phase III clinical trials.

Authors:  Tong J Gan; Neil Singla; Stephen E Daniels; Douglas A Hamilton; Peter G Lacouture; Christian Rd Reyes; Daniel B Carr
Journal:  J Pain Res       Date:  2016-12-20       Impact factor: 3.133

6.  Safety of Injectable HPβCD-Diclofenac in Older Patients with Acute Moderate-to-Severe Postoperative Pain: A Pooled Analysis of Three Phase III Trials.

Authors:  Jacques E Chelly; Peter G Lacouture; Christian Russel D Reyes
Journal:  Drugs Aging       Date:  2018-03       Impact factor: 3.923

Review 7.  Efficacy and Safety Profile of Diclofenac/Cyclodextrin and Progesterone/Cyclodextrin Formulations: A Review of the Literature Data.

Authors:  Cristina Scavone; Angela Colomba Bonagura; Sonia Fiorentino; Daniela Cimmaruta; Rosina Cenami; Marco Torella; Tiziano Fossati; Francesco Rossi
Journal:  Drugs R D       Date:  2016-06

8.  The Drug Excipient Cyclodextrin Interacts With d-Luciferin and Interferes With Bioluminescence Imaging.

Authors:  Jeyan S Kumar; Lisa M Miller Jenkins; Michael M Gottesman; Matthew D Hall
Journal:  Mol Imaging       Date:  2016-01-27       Impact factor: 4.488

9.  Pharmacokinetics of Diclofenac and Hydroxypropyl-β-Cyclodextrin (HPβCD) Following Administration of Injectable HPβCD-Diclofenac in Subjects With Mild to Moderate Renal Insufficiency or Mild Hepatic Impairment.

Authors:  Douglas A Hamilton; Cynthia C Ernst; William G Kramer; Donna Madden; Eric Lang; Edward Liao; Peter G Lacouture; Atulkumar Ramaiya; Daniel B Carr
Journal:  Clin Pharmacol Drug Dev       Date:  2017-12-02

Review 10.  Safety of Non-Steroidal Anti-Inflammatory Drugs in the Elderly: An Analysis of Published Literature and Reports Sent to the Portuguese Pharmacovigilance System.

Authors:  Cristina Monteiro; Samuel Silvestre; Ana Paula Duarte; Gilberto Alves
Journal:  Int J Environ Res Public Health       Date:  2022-03-16       Impact factor: 3.390

  10 in total

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