title: A new method to obtain and present complete information on the compatibility: study of its validity for eight binary mixtures of morphine with drugs frequently used in palliative care.
abstract: Parenteral administration of mixtures of morphine with other drugs has become common practice in palliative care. Such mixtures are sometimes found to be incompatible but compatibility data are scarce. An attempt was made to develop a quick and simple investigation strategy to obtain complete information on the compatibility of two drugs. This strategy was then used to study the physical and chemical compatibility of morphine HCl with alizapride HCl, atropine sulphate, dexamethasone sodium phosphate, hyoscine butylbromide, metoclopramide HCl, octreotide lactate, ranitidine HCl and hyoscine hydrobromide. These compatibility data are presented in such a way that they are easy to use in clinical practice. The investigation strategy outlined here allows the collection of complete information on the compatibility of morphine with another drug by studying a limited number of carefully selected mixtures per combination. The mixtures to be studied are selected using a scheme in which all possible mixtures prepared by mixing morphine solutions of varying concentrations with a drug solution in different volume ratios can be visualized. Applying this strategy to the eight combinations revealed, except for ranitidine HCl, no physical (visual) or chemical (HPLC; >90%) incompatibility in any of the mixtures studied for seven days at 22 and 32 degrees C. This indicates that all possible mixtures of these drug solutions with morphine HCl are compatible. For the combination with ranitidine incompatibility was observed only when using morphine HCl solutions containing >40 mg/ml and at certain ratios (drug/morphine HCl [D/M]: 4/42, 10/6 and 8/8, v/v), but all physically compatible mixtures were chemically stable (>90%). Studying extra mixtures in addition to those required to be studied according to the strategy revealed no discrepancies for any of the eight combinations studied. Adaptation of the layout of the scheme and the design of a decision tree resulted in an easy tool to check compatibility in daily practice. The scheme designed in this study is a useful tool for research and for daily practice. It simplifies and thereby encourages investigation of the compatibility of drugs. The availability of data on the physical as well as chemical compatibility in daily practice will contribute to a better quality of the mixtures used in palliative care and help to avoid complications and inadequate symptom control.
authors.affiliation: Laboratory of Pharmaceutical Technology, Faculty of Pharmaceutical Sciences, Ghent University, Belgium.
authors.forename: An
authors.initials: A
authors.lastname: Vermeire
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Remon
authors.forename: Dirk
authors.initials: D
authors.lastname: Schrijvers
authors.forename: Peter
authors.initials: P
authors.lastname: Demeulenaere
mesh_terms: D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000737:chemistry*; D000930:Antidiarrheals / Q000008:administration & dosage / Q000737:chemistry; D000932:Antiemetics / Q000008:administration & dosage / Q000737:chemistry; D004338:Drug Combinations; D004344:Drug Incompatibility; D004355:Drug Stability; D006635:Histamine H2 Antagonists / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D007263:Infusions, Parenteral / Q000379:methods; D009020:Morphine / Q000008:administration & dosage / Q000737:chemistry*; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000737:chemistry; D010166:Palliative Care / Q000379:methods; D012985:Software Design
chemical_list: D000701:Analgesics, Opioid; D000930:Antidiarrheals; D000932:Antiemetics; D004338:Drug Combinations; D006635:Histamine H2 Antagonists; D018727:Muscarinic Antagonists; D009020:Morphine