Might cause CNS depression. Might cause hypotension (use with caution in hypovolemia, cardiovascular disease (including acute MI), or drugs which may exaggerate hypotensive effects (including phenothiazines or general anesthetics)). Might prolong QTc interval and increase risk for torsade de pointes (use with caution in risk for QTc prolongation, with medications known to prolong the QTc interval, promote electrolyte depletion, or inhibit CYP3A4, or in history of conduction abnormalities). Severe respiratory depression occurred (use extreme caution during treatment initiation, dose titration and conversion from other opioid agonists to methadone). Might obscure diagnosis or clinical course of acute abdominal conditions. Use with caution in adrenal insufficiency, including Addison’s disease, in biliary tract dysfunction (acute pancreatitis may cause constriction of sphincter of Oddi), in CNS depression or coma, or in depression or suicidal tendencies. Potential for drug dependency. Tolerance, psychological and physical dependence might occur (with prolonged use). Use with extreme caution in head injury, intracranial lesions, or elevated intracranial pressure (exaggerated elevation of ICP may occur). Use with caution in severe hepatic or renal failure, in morbidly obese patients, in prostatic hyperplasia and/or urethral stricture, or in pre-existing respiratory compromise (hypoxia and/or hypercapnia), COPD or other obstructive pulmonary disease, and kyphoscoliosis or other skeletal disorder which may alter respiratory function (critical respiratory depression might occur). Use with caution in thyroid dysfunction. High potential for interactions (use with caution in patients receiving concurrent use of medications known to inhibit CYP3A4, prolong QTc interval, or promote hypokalemia, hypomagnesemia, or hypocalcemia). Effects may be potentiated when used with other sedative drugs or ethanol. Use with caution in debilitated patients (potential for critical respiratory depression), or in the elderly. Methadone is ineffective for relief of anxiety. Use caution in converting patients from other opioids to methadone. Concurrent use of agonist/antagonist analgesics may precipitate withdrawal symptoms and/or reduced analgesic efficacy in patients following prolonged therapy with μ-opioid agonists. Abrupt discontinuation following prolonged use may also lead to withdrawal symptoms.