“…Specifically, the lack of reliable equianalgesic conversion ratios, increased potency associated with methadone in patients previously exposed to high-dose opioids, large interindividual variability in methadone pharmacokinetics, and the potential for pharmacological interaction with other drugs have made the clinical use of methadone difficult. Systematic reviews on switching to methadone have shown a large heterogeneity in terms of opioid ratios, outcomes, and modality of switching utilized [4,5,10,15,16]. The dose of methadone cannot be easily predicted as it will depend on a series of factors, including individual response, pharmacodynamics, pain mechanism, pharmacogenetics, and degree of cross-tolerance [4].…”