Background and Objectives: Voltarol for injection (a diclofenac sodium formulation employing polyethylene glycol and benzyl alcohol [PG-BA] as excipients) is marketed in Europe but not in North America. A suspension, PG-BA diclofenac sodium, requires preparation for each patient and slow IV infusion to minimize venous irritation. Dyloject, a novel diclofenac formulation, employs hydroxypropyl β-cyclodextrin (HPβCD) to solubilize diclofenac in a small volume. We compared the efficacy and safety of an IV HPβCD diclofenac sodium bolus, a 30-minute PG-BA diclofenac sodium infusion, and placebo in post–molar extraction pain.
Methods: A total of 155 adult patients were randomized to receive HPβCD diclofenac sodium 75 mg, PG-BA diclofenac sodium 75 mg, or placebo. Primary endpoints were superiority of HPβCD diclofenac sodium to placebo and noninferiority of HPβCD diclofenac sodium to PG-BA diclofenac sodium with respect to total pain relief over 4 hours (TOTPAR4) on a 0 to 100-mm visual analog scale (VAS). Secondary endpoints included categorical TOTPAR4, VAS and categorical TOTPAR up to 8 hours, other measures of pain intensity and relief, patient global evaluation, and time to rescue medication.
Results: HPβCD diclofenac sodium had efficacy superior to both placebo and PG-BA diclofenac sodium. At 15 minutes, more patients given HPβCD diclofenac sodium than PG-BA diclofenac sodium reported 30% reduction in pain intensity (52% vs. 21%, P = .0022). Both diclofenac products had a 6-hour duration of effect and were well tolerated. Patient global evaluations of HPβCD diclofenac sodium were high, superior to placebo, and similar to PG-BA diclofenac sodium. The adverse event (AE) incidence was similar for HPβCD diclofenac sodium and PG-BA diclofenac sodium, except that in the current trial and in integrated safety results from the present and prior studies, phlebitis was more common with PG-BA diclofenac sodium. No cardiac or renal AEs or gastrointestinal bleeding were reported or observed.
Conclusions: IV bolus HPβCD diclofenac sodium produced analgesia more quickly than, and with equal duration as, the 30-minute PG-BA diclofenac sodium infusion. Pooled data on thrombophlebitis from the present investigation and our prior studies of the novel formulation indicate this adverse effect is less frequent and less severe with HPβCD diclofenac sodium than with PG-BA diclofenac sodium.
- Dental surgery
- Multimodal analgesia
- Postoperative pain
- Randomized controlled trial
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This experimental protocol was supported financially by Javelin Pharmaceuticals, Inc.
All coauthors contributed to the design, conduct, and/or interpretation of this study and/or manuscript preparation.
The findings presented in this manuscript were reported in preliminary form as a podium presentation (Abstract #216) at the 24th Annual Meeting of the European Society of Regional Anaesthesia and Pain Therapy, Berlin, Germany, September 16, 2005.