BACKGROUND: Injectable formulations of diclofenac have long been available in Europe and other countries. These formulations use a default dose of 75 mg of diclofenac delivered IV over 30 to 120 minutes or as an IM injection. A novel formulation of injectable diclofenac sodium, Dyloject (R), is solubilized with hydroxypropyl beta-cyclodextrin (HP beta CD) so that it can be given IV or IM in a small volume bolus. In this multicenter, multiple-dose, multiple-day, randomized, double-blind, parallel-group phase 3 study, we investigated whether lower doses of HP beta CD diclofenac delivered as a small volume bolus would be effective for the management of acute pain after abdominal or pelvic surgery. METHODS: Adults with moderate and severe pain, defined as >= 50 mm on a 0 to 100 mm visual analog scale, within 6 hours after surgery were randomly assigned (1:1:1:1 ratio) to receive HP beta CD diclofenac, 18.75 mg or 37.5 mg; ketorolac tromethamine 30 mg; or placebo. Patients in all treatment arms received a bolus IV injection every 6 hours until discharged. They were observed for at least 48 h, and for up to 5 days. Rescue IV morphine was available any time, up to a total of 7.5 mg over a 3-hour period. The primary efficacy measure was the sum of pain intensity differences from 0 to 48 hours after study drug initiation. RESULTS: Three hundred thirty-one patients received >= 1 dose of study drug. Over the first 48 hours, both IV HP beta CD diclofenac doses, as well as ketorolac, produced significant reductions in pain intensity over placebo (all P < 0.05), as well as significant reductions in the need for rescue morphine administration. Both doses of HP beta CD diclofenac, as well as ketorolac, significantly reduced rescue morphine dosages, as compared to placebo (P <= 0.0001), and time to rescue morphine administration was significantly increased by treatment with 18.75 mg diclofenac and ketorolac. The overall incidence of treatment-related adverse events was 20.2%. No treatment-related serious adverse events were reported in either diclofenac dose group, whereas only 1 was reported in the ketorolac group. CONCLUSIONS: For patients with acute moderate and severe pain after abdominal or pelvic surgery, repeated 18.75 mg and 37.5 mg doses of HP beta CD diclofenac provided significant analgesic efficacy, as compared to placebo. Significant analgesic efficacy was also provided by the active comparator ketorolac. Both HP beta CD diclofenac and ketorolac significantly reduced the need for opioids. (Anesth Analg 2012;115:1212-20)
