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

Abstract

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^®, 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.

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^® or a 30 min IV infusion of PG–BA diclofenac.

Results

The 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).

Conclusion

HPβCD, 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.