Methadone – demystifying an old pain killer

Abstract

Methadone is a µ-opioid receptor agonist and NMDA recep­tor antagonist which is often indicated for the management of severe refractory cancer or non-cancer pain, as well as for opioid addiction. This two-part article provides an overview of methadone use in pain management, and its use in opioid addiction will not be covered here. Metha­done has several advantages over other opioids. These ad­van­ta­ges include extended analgesic activity, multiple routes of administration, longer bioavailability, lack of ac­tive metabolites, predominantly intestinal excretion, and its relatively low cost compared to other opioids. This makes methadone an appealing option for patients with impaired creatinine clearance and for those facing finan­cial constraints in obtaining medications. On the other hand, there are notable concerns with this medication that make its use more complex than of other opioids. Metha­done has a variable individual plasma half-life that can lead to ac­cu­mu­lation and toxicity, and extensively utilizes cyto­chrome CYP450, therefore its metabolism can be affected when used in conjunction with inducers and especially in­hi­bi­tors of this cytochrome system. Methadone has also variable and quite complicated conversion formulas when transitioning from other opioids. Additionally, there is a risk for abuse that can lead to accidental overdose or even death. Finally, metha­done can cause QT interval pro­lon­ga­tion that may result in dangerous cardiac arrhythmias such as torsades de points and ventricular tachyarrhythmia. Des­pite its mul­­ti­­ple advantages in pain control, cautionary mes­sages from the European Association for Palliative Care (EAPC) and Na­­tio­­nal Comprehensive Cancer Network (NCCN) ad­vise for use of methadone only by experienced clinicians. It is highly re­­com­­mended that patients are counseled exten­sively on me­tha­­done safety use due to its numerous risks.