Dyloject庐, a novel injectable diclofenac solubilised with cyclodextrin: Reduced incidence of thrombophlebitis compared to injectable diclofenac solubilised with polyethylene glycol and benzyl alcohol

摘要

Background; Thrombophlebitis is a common complication of a widely used formulation of injectable diclofenac that employs propylene glycol and benzyl alcohol (PG-BA) as solvents. Initial studies of Dyloject庐, a novel injectable diclofenac solubilised with hydroxypropyl-p-cyclodextrin (HPpCD), suggested that this complication occurred less frequently and with lower severity with the newer formulation. Methods: We conducted a safety analysis of seven single-dose clinical trials that enrolled 531 patients receiving either a rapid intravenous (IV) bolus of Dyloject庐 or a 30 min IV infusion of PG-BA diclofenac. Results: The incidence of thrombophlebitis observed as an adverse event following Dyloject庐 treatment was 1.2% (5 of 423) versus 6.5% (7 of 108) following PG-BA diclofenac (p< 0.01). In a subset of clinical studies that included an observer-rated thrombophlebitis assessment, the incidence of mild irritation was similar for both products (5.4% for Dyloject庐 and 4.9% for PG-BA diclofenac). Differences between the formulations were most evident in the higher incidence of moderate to severe thrombophlebitis after PG-BA diclofenac (2.4% incidence) compared to Dyloject庐 (0% incidence). Conclusion: HPbetaCD, the solubilising agent in Dyloject庐, may be less irritating and result in less clinical thrombophlebitis than the cosolvents propylene glycol and benzyl alcohol used in PG-BA diclofenac.