Background Methadone is a drug infrequently used in palliative care with complex pharmacokinetics and a risk of adverse effects (AEs) on switching. There is a paucity of evidence-based guidelines for methadone use within palliative care.
Aims This systematic review evaluated the evidence for the different methods used to switch to methadone and the need for ECG monitoring as part of this. Guidelines for switching were formulated on the basis of this.
Methods Two systematic reviews were carried out by searching EMBASE, MEDLINE, Cochrane and DARE databases; journals and reference lists identifying randomised controlled trials (RCT) or prospective studies comparing different methods of switching to oral methadone and the need for ECG monitoring as part of this process. SIGN methodology was used to develop guidelines.
Results Twelve studies met the inclusion criteria. Of these, only one compared two methods of switching. The remainder were low-quality studies with no comparison group. The ‘3-day switch’ method, where morphine is tapered and replaced over 3 days, had an inadequately powered RCT to support its use. The ‘Stop-and-Go’ method, where morphine is switched to methadone immediately, had inconsistent results on benefits and incidence of AE and serious adverse effects (SAE). Two poor-quality studies that lacked clarity on the incidence of AE and SAE were found on the Ad Libitum method, where methadone is given as required up to 3-hourly after stopping morphine, and then converted to a stable daily dose. A high quality prospective cohort study showed the incidence of clinically significant QT-prolongation to be low and no episodes of ventricular arrhythmia or death were seen on switching to methadone doses less than 100 mg.
Conclusions The Ad libitum method of switching is recommended based on expert opinion. ECG monitoring is not required when switching patients to less than 100 mg methadone for treatment of cancer pain.
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