Physical compatibility and in vivo evaluation of drug mixtures for subcutaneous infusion to cancer patients in palliative care

Abstract.

The objectives of this study were first to investigate the compatibility and physical stability of drug admixtures destined for s.c. administration through elastomeric infusion pumps to terminally ill cancer patients followed up at home by staff of the Palliative Care Unit (AECC), "La Paz" Hospital, Madrid and secondly, to evaluate the local side-effects related to the infusion of some of the drug mixtures to a population of 50 patients. The drug mixtures prepared included combinations of two, three, four and five of the following drugs: morphine hydrochloride, 60 mg/day; midazolam hydrochloride, 15 mg/day; haloperidol lactate, 7.5 mg/day; hyoscine-N-butyl-bromide, 60 mg/day; dexamethasone sodium phosphate, 16 mg/day; metoclopramide hydrochloride, 40 mg/day, and tramadol, 400 mg/day. Out of 86 mixtures evaluated in vitro, 52 were found to be physically compatible. Precipitation was always obtained when dexamethasone sodium phosphate at the concentrations assayed was combined with haloperidol lactate and/or midazolam hydrochloride. However, no precipitation occurred when morphine hydrochloride, the opioid most frequently used in patients of this type, and dexamethasone sodium phosphate were combined. Of the drug mixtures that were physically compatible, 18 were administered to the patient population evaluated. Very good symptom control was obtained with all of them, and especially with the mixture of morphine + midazolam + haloperidol + hyoscine, which is the one most frequently administered to cancer patients for palliative care in the final stages of life in our Unit.