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Objective: Diclofenac is an effective and well-tolerated nonsteroidal anti-inflammatory drug (NSAID) frequently used in the treatment of acute pain. Marketed formulations for parenteral administration usually contain 75 mg/3 mL of diclofenac sodium, which provide limited dosing flexibility, and are usually given intramuscularly., Methods: We present a randomized, double-blind, active comparator- and placebo-controlled, parallel-group phase III multicenter study, investigating efficacy and tolerability of a new 1 mL-volume formulation of diclofenac sodium (25, 50 or 75 mg) containing hydroxypropyl-β-cyclodextrin (HPβCD) as a solubility enhancer. This low-volume formulation allows subcutaneous (SC), in addition to intramuscular (IM) administration. Patients developing moderate-to-severe pain (≥ 50 mm on Visual Analogue Scale) after third molar extraction under local anesthesia were randomized to one of the 4 SC injections: 25 mg diclofenac HPβCD (n = 77), 50 mg diclofenac HPβCD (n = 76), 75 mg diclofenac HPβCD (n = 78), or placebo (n = 75)., Results: Mean pain intensity difference at 1.5 hours postdose (primary endpoint) was higher in all diclofenac-treated groups than placebo group. The adjusted means (95% CI) were 36.5 (31.7 to 41.2) in diclofenac 25 mg group, 37.3 (32.6 to 42.1) in diclofenac 50 mg group, 37.7 (33.0 to 42.4) in diclofenac 75 mg group, and 12.3 (7.44 to 17.1) in placebo group. Both 25 and 50 mg doses of diclofenac produced significantly greater pain relief than placebo (P < 0.001 in both comparisons)., Conclusion: Single SC doses of diclofenac HPβCD of 25 and 50 mg are effective and well tolerated for relieving pain compared with placebo., (© 2013 World Institute of 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 (HPbetaCD) to solubilize diclofenac in a small volume. We compared the efficacy and safety of an IV HPbetaCD 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 HPbetaCD diclofenac sodium 75 mg, PG-BA diclofenac sodium 75 mg, or placebo. Primary endpoints were superiority of HPbetaCD diclofenac sodium to placebo and noninferiority of HPbetaCD 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: HPbetaCD diclofenac sodium had efficacy superior to both placebo and PG-BA diclofenac sodium. At 15 minutes, more patients given HPbetaCD 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 HPbetaCD diclofenac sodium were high, superior to placebo, and similar to PG-BA diclofenac sodium. The adverse event (AE) incidence was similar for HPbetaCD 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 HPbetaCD 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 HPbetaCD diclofenac sodium than with PG-BA diclofenac sodium.