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

SummaryBackgroundThrombophlebitis 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®, a novel injectable diclofenac solubilised with hydroxypropyl-β-cyclodextrin (HPβCD), suggested that this complication occurred less frequently and with lower severity with the newer formulation.MethodsWe conducted a safety analysis of seven single-dose clinical trials that enrolled 531 patients receiving either a rapid intravenous (IV) bolus of Dyloject® or a 30 min IV infusion of PG–BA diclofenac.ResultsThe incidence of thrombophlebitis observed as an adverse event following Dyloject® 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® 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® (0% incidence).ConclusionHPβCD, the solubilising agent in Dyloject®, may be less irritating and result in less clinical thrombophlebitis than the cosolvents propylene glycol and benzyl alcohol used in PG–BA diclofenac.