Dyloject, a novel injectable diclofenac formulation, offers greater safety and efficacy than voltarol for postoperative dental pain

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 beta-cyclodextrin (HP beta CD) to solubilize diclofenac in a small volume. We compared the efficacy and safety of an IV HP beta CD 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 HP beta CD diclofenac sodium 75 mg, PG-BA diclofenac sodium 75 mg, or placebo. Primary endpoints were superiority of HP beta CD diclofenac sodium to placebo and noninferiority of HP beta CD 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: HP beta CD diclofenac sodium had efficacy superior to both placebo and PG-BA diclofenac sodium. At 15 minutes, more patients given HP beta CD 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 HP beta CD diclofenac sodium were high, superior to placebo, and similar to PG-BA diclofenac sodium. The adverse event (AE) incidence was similar for HP beta CD 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 HP beta CD 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 HP beta CD diclofenac sodium than with PG-BA diclofenac sodium.