Stability of vincristine sulfate, doxorubicin hydrochloride and etoposide phosphate admixtures in polyisoprene elastomeric pump supporting transition of the EPOCH regimen to outpatient care

Abstract

Background The EPOCH regimen, consisting of vincristine sulfate, doxorubicin hydrochloride, and etoposide phosphate, is typically administered by continuous infusion over four days to oncology inpatients. If the EPOCH regimen was available to be administered through portable elastomeric pumps, chemotherapy could be transitioned to an outpatient setting, reducing inpatient bed days and overall healthcare costs. However, a lack of stability data for the admixtures in the elastomeric infusion devices currently prevents the transition of the regime to an outpatient setting. The purpose of this study is to determine the physical and chemical stability of the admixture in polyisoprene elastomeric pumps under different storage conditions to support the transition of the EPOCH regime to an outpatient setting. Methods The physico-chemical stability of three admixtures at a range of clinically relevant concentrations compounded in polyisoprene elastomeric infusors was determined when refrigerated at 2-6℃ over a 14-day period followed by 35℃ up to 7 days in the dark, and under standardized fluorescent light to simulate scenarios in clinical practice. Results All tested admixtures were compatible and the drugs were stable in the elastomeric infusors for up to 14 days when stored at 2-6℃ followed by 7 days at 35℃ in the dark, with nominal losses of <5%. The major degradant of etoposide phosphate was its active form etoposide. There was no degradation (<1% loss) found when the admixture was exposed to a standardized fluorescent light dose of 80 klux-h (25℃) for 10 h. The temperature and light conditions the infusors were exposed to during the stability study were more severe than the conditions determine during clinical administration. Conclusion The extended stability of the three infusional admixtures compounded in elastomeric infusion pumps demonstrated herein permits advance preparation and storage of these drugs, reducing pharmacy compounding resources. The demonstrated stability at 35℃ and under light exposure, conditions more severe than those experienced during clinical practice, support continuous infusions for up to seven days from the elastomeric infusors without a loss of potency. The proven stability of the EPOCH regimens in the tested elastomeric infusion device supports the transition of treatment to an outpatient setting which will reduce inpatient bed days and overall healthcare costs.

Continuous-infusion and outpatient setting: A chance for patients, a challenge for hospital pharmacists

“…8 Recently, to confirm these data Svirskis et al demonstrated the stability of the admixture of these three drugs for up to seven days stored in elastomeric infusion pump at 35 C and under light exposure, which are more severe than those experienced during clinical practice. 1 Despite the available data, today we have to prepare a daily fresh-admixture because of the impossibility to find etoposide phosphate on the national territory. The infusion must be carried out in inpatient setting.…”

“…At the present time different chemotherapy protocols administered as continuous-infusion could foresee the passage from inpatient to outpatient setting. Indeed, EPOCH, 1,2 ifosfamide þ mesna 3,4 and many others contemplate the possibility to infuse different drugs in continuous way, allowing patient to receive chemotherapy in outpatient setting even directly at home.…”

“…5 The estimate made by Svirskis et al highlights the important difference in terms of total time consumed for the EPOCH regimen in inpatient or outpatient setting: 144 h per patient and 54 h per patient, respectively. 1 These aspects could provide health related cost savings besides improved patient acceptability. 6 However patient's safety is still a topic of debate.…”

“…Differently from other chemotherapy regimens (e.g. EPOCH or IFO þ Mesna) for which data stability have been the subject of further investigations, 1,[7][8][9][10][11][12] in these specific cases data stability and data compatibility with different materials and/or infusion devices are provided into the Summary of product characteristics (SPC). 13,14 This makes the choice about the way and the time of infusion easier: in the usual approach to drug administration in outpatient setting, a number of infusionpump reservoirs could be filled, dispensed to the patient and refrigerated until use; alternatively and preferably a portable infusion pump designed to administer the total dosage over several days is used (a single container is filled and dispensed to the patient for short-term storage and prolonged use).…”

Stability

“…In that aim, a stability study demonstrates a 7-day stability at 35 °C and a 14-day stability when refrigerated at 2-6 °C. The transition of this treatment to an outpatient setting reduces important bed days and health costs [113].…”