Rotation to Methadone
Methadone has proved to be very effective for relieving severe pain in selected patients when high dosages of other opioids are ineffective or result in unacceptable side effects. In addition to opioid agonist activity, methadone has been found to have antagonist effects on the N-methyl-D-aspartate receptor (NMDA) and may play a role in the treatment of neuropathic pain. Methadone is relatively lipophilic with rapid gastrointestinal absorption. The major route of metabolism is hepatic with primarily fecal excretion so no dosage adjustment is required for patients with renal failure. It has potentially significant drug interactions, particularly drugs metabolized by cytochrome P450 3A4 (CYP3A4).
Methadone can be administered orally, intravenously, rectally, or, with caution, subcutaneously. The process of converting from other opioids to methadone is complex because of its long and variable half-life (four to 150 hours), which is not aligned with the observed duration of analgesia (six to 12 hours). Conversion requires considerable attention, experience, and usually three to six days of observation in a setting in which a patient's highly variable reactions can be monitored closely. An increasing number of deaths has been attributed to the increased use of methadone for pain control, although it is unclear whether this is related to abuse of the drug, inappropriate titration schedules, or other causes such as cardiac arrhythmia. Recent reports have linked high-dose methadone to torsades de pointes, a potentially fatal result of ventricular arrhythmia caused by prolonged QT interval. EKGs may be considered for certain patients, depending on the goals of care.