Dyloject is a novel formulation of diclofenac intended for intravenous (IV) administration. This formulation employs the solubilizing agent hydroxypropyl-β-cyclodextrin to permit bolus IV administration. The efficacy and safety of 5 dose levels of IV diclofenac were compared with IV ketorolac and placebo following third molar extraction. This was a single-dose, randomized, double-blind, placebo- and comparator-controlled, parallel-group study. A total of 353 subjects with moderate to severe pain received placebo; ketorolac 30 mg; or IV diclofenac 3.75, 9.4, 18.75, 37.5, or 75 mg (N = 51 for all groups, except N = 47 for ketorolac). The primary endpoint was total pain relief over 6 hours (TOTPAR6) as measured by the visual analog scale (VAS). Secondary endpoints included multiple measures of pain intensity and relief; patient global evaluation; and times to pain relief and rescue medication. Dropouts and adverse effects (AEs) were also monitored. IV diclofenac was superior to placebo as measured by TOTPAR6 (P < .0001 for all doses except 3.75 mg, for which P = .0341). IV diclofenac 3.75 mg was statistically superior to placebo for TOTPAR2 and TOTPAR4. IV diclofenac at both 37.5 and 75 mg was superior to placebo (P < .05) at the earliest (5 minute) assessments of pain intensity and pain relief, but ketorolac was not. The proportion of patients reporting 30% or greater pain relief at 5 minutes was significantly greater after IV diclofenac 37.5 and 75 mg than after ketorolac 30 mg or placebo. Secondary endpoints confirmed the primary findings. Treatment-related AEs were generally mild to moderate and were typical for nonsteroidal anti-inflammatory drugs (NSAIDs). The more rapid onset of action of IV diclofenac compared with the reference injectable NSAID ketorolac suggests additional clinical benefit. If confirmed in larger series, these findings may improve the safety and efficacy of postoperative NSAID analgesia.Abstract
Mean pain relief (on a 0–100 mm visual analog scale) versus time after administration of single, graded doses intravenous (IV) diclofenac (“DIC-075V”), placebo, or the positive comparator ketorolac 30 mg. Confidence intervals surrounding each point are omitted for legibility. If these were depicted, their overlap at 6 hours and later for the 3 highest doses of IV diclofenac and ketorolac indicates that the apparently prolonged analgesic effect of ketorolac relative to IV diclofenac was not statistically significant.
Mean sum of pain intensity differences (on a 0–100 mm visual analog scale) from 0–6 hours following administration of single, graded doses of IV diclofenac. A significant dose response with a plateau above 37.5 mg was evident according to linear, quadratic, and cubic models.
Cumulative proportions of patients requiring rescue medication during the 8 hours after single, graded doses of IV diclofenac (“DIC075V”), ketorolac 30 mg, or placebo.
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