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®, is solubilized with hydroxypropyl β-cyclodextrin (HPβCD) 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 HPβCD diclofenac delivered as a small volume bolus would be effective for the management of acute pain after abdominal or pelvic surgery.
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
HPβCD 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.
Three hundred thirty-one patients received ≥1 dose of study drug. Over the first 48 hours, both IV HPβCD 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 HPβCD 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.