Stability and compatibility of morphine

Morphine is a widely used analgesic for the treatment of severe cancer pain . For a large number of terminally ill patients oral administration is no l onger possible and morphine is administered parenterally using portable pum ps allowing comfortable treatment of the patient at home. In this situation the storage of pre-filled reservoirs and/or the administration over a long er period of time are daily practices and require data on the stability of morphine solutions. As most of these patients suffer from several other sym ptoms, the administration of admixtures with other drugs is common and requ ires information on the compatibility of morphine. Morphine degrades in aqu eous solutions with the formation of mainly pseudomorphine, to a lesser ext ent morphine-N-oxide and probably apomorphine. From the study of the kineti cs of morphine degradation it was concluded that the degradation of morphin e is accelerated in the presence of oxygen and at higher pH of the solution , whereas temperature and light have only a minor influence on the degradat ion rate. The data reported on the stability of morphine infusion solutions kept under ambient conditions indicated that oxygen, light, the type of re servoir, the type of diluent, the salt form and the concentration of morphi ne do not affect the stability of morphine solutions stored for up to 3 mon ths. Morphine solutions should preferably be stored at room temperature in order to avoid precipitation at low temperatures and water evaporation at h igher temperatures causing increase in morphine concentration when stored i n polymer reservoirs. Analyzing the data available on the compatibility of morphine infusion solutions revealed that differences in the formulation of the drug solutions (drug concentration, salt form, type and concentration of additives) and diluent, as well as temperature and order and ratio of mi xing might affect the compatibility. Only few reports provide all necessary information, limiting the information useful for daily practice. Moreover, the majority of the compatibility studies are performed in intensive care units, where other drugs and other concentrations of morphine are required than in palliative care settings, limiting its merit for this sector. (C) 1 999 Elsevier Science B.V. All rights reserved.