Analgesic efficacy and safety of a novel injectable formulation of diclofenac compared with intravenous ketorolac and placebo after orthopedic surgery: a multicenter, randomized, double-blinded, multiple-dose trial.

Objectives: A novel injectable formulation of diclofenac, Dyloject, utilizes hydroxypropyl-β-cyclodextrin (HPβCD) as a solubilizing agent, allowing dosing as a small-volume intravenous bolus for postoperative pain. In this test of the efficacy and safety of HPβCD diclofenac, we hypothesized that HPβCD diclofenac would relieve moderate and severe pain after orthopedic surgery.

Patients And Methods: Adults 18 to 85 years old with moderate and severe pain within 6 hours after surgery were randomized to HPβCD diclofenac, ketorolac tromethamine, or placebo, and stratified by risk cohort. The HPβCD diclofenac non-high-risk cohort dose was 37.5 mg, the high-risk cohort received 18.75 mg, and patients ≥95 kg received 50 mg. The ketorolac dose was 30 mg in the non-high-risk and high-weight cohorts and 15 mg in the high-risk cohort. Rescue intravenous morphine was given for pain as needed. Efficacy was measured by the sum of pain intensity differences (SPID).

Results: Mean SPID scores of 277 patients were significantly better with HPβCD diclofenac and ketorolac than with placebo (P<0.0001), across all risk cohorts (P<0.05). HPβCD diclofenac was associated with better SPID scores, faster onset of analgesia, and significantly lower opioid requirement (P<0.008) than ketorolac. In patients more than or equal to 65 years, HPβCD diclofenac was associated with significantly better analgesic efficacy (P=0.05), and lower opioid requirement versus ketorolac. The incidence of treatment-related adverse events was similar across groups.

Discussion: HPβCD diclofenac is safe and efficacious for acute moderate and severe pain after orthopedic surgery and significantly spares morphine use.