I see more patients being prescribed methadone (Dolophine, Methadose, generics) for pain. How is methadone different from other opioids, and what special precautions should I be aware of? — Kerstin L. McSteen, BSN, MSN, ACHPN, CNS-BC, Minneapolis, MN

Use of methadone for cancer pain is becoming more common because of its low cost, availability in an oral formulation, and long duration of action. Methadone is a synthetic opioid that has activity at multiple receptors in addition to the opiate receptor. This provides some of methadone’s additional benefits, such as incomplete cross-tolerance with other opioids and benefit in neuropathic pain. The potency of methadone relative to other opioids varies significantly between patients and is affected by any previous opioid dose, so methadone should be prescribed by providers experienced in pain management.

Methadone metabolism is very extensive compared with other opioids, and this agent has a long and variable halflife: 12 to 100-plus hours compared with 2 to 4 hours for morphine). Because of extensive metabolism and accumulation in body tissue, methadone has a prolonged titration period compared with other opioids. A too-short titration period can result in toxicity when methadone accumulates. Respiratory depression, especially during the titration period, is a black box warning and may persist longer than analgesic effects.


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Methadone also has black box warnings for QT prolongation, so it should be used with caution in patients who take other QT-prolonging medications or who have electrolyte abnormalities. A baseline ECG should be considered in patients starting methadone, especially if they have other risk factors for torsade de pointes.

Because of its extensive metabolism, methadone has many drug interactions and should be avoided in patients with severe liver disease. Patients with an estimated creatinine clearance of less than 10 mL/min should receive lower doses. Patients may express concern about social stigma with methadone. The benefits of methadone in treatment of chronic pain—not its use in treatment of addiction—should be emphasized.