Drug combinations in syringe drivers: the compatibility and stability of diamorphine with cyclizine and haloperidol

Abstract

The compatibility and stability of 28 combinations of diamorphine hydrochloride (5-100 mg/ml) with cyclizine lactate (5-50 mg/ml), eight combinations of diamorphine (10-100 mg/ml) with haloperidol (2-4 mg/ml) and eight combinations of all three drugs was assessed after storage in 1 ml polypropylene syringes. Samples were stored for periods up to seven days in the light and at room temperature (22°C). Five combinations of diamorphine with cyclizine precipitated immediately upon preparation. After analysis and determination of t90% values (the time taken for 10% degradation), 16 of the remaining 23 combinations were judged to be compatible (no signs of crystallization or precipitation) and stable (less than 10% loss of potency of either drug) after storage for 24 h. After seven days storage only four remained compatible and stable. The results indicate that ratios of diamorphine to cyclizine of 1:1 are stable at concentrations up to 20 mg/ml. An increase in diamorphine concentration necessitates a reduction in cyclizine to 10 mg/ml, and an increase in cyclizine concentration necessitates a reduction in concentration of diamorphine to 15 mg/ml to maintain stability over 24 h. All the combinations of diamorphine with haloperidol remained compatible and stable for seven days. The addition of haloperidol (2 mg/ml) to the diamorphine and cyclizine combinations had no detrimental effect on their compatibility and stability. A stability curve is included as an easy way for palliative care personnel to avoid potential problems with incompatibilities and reduced stability when using these combinations. Furthermore, to reduce the possibility of precipitation with mixtures containing cyclizine, the use of 0.9% sodium chloride should be avoided.