Clinical Pearls

Methadone Safety Guidelines for Hospice and Palliative Care

Mary Lynn McPherson, PharmD MA BCPS

Methadone is a synthetic mu-opioid agonist and N-methyl-D-aspartate receptor antagonist prescribed for approximately 1 million individuals at any given time in the United States to treat pain or aid in substance abuse recovery.¹ Methadone has several pharmacokinetic and pharmacodynamic characteristics that make it a desirable opioid for pain relief in advanced illness including long duration of action, lack of pharmacologically active metabolites, low cost, high oral bioavailability (approximately 70%–80%), and perceived effectiveness in difficult pain syndromes. Unfortunately the methadone-overdose death rate has increased in recent years and is disproportionately more likely to cause fatality from overdose compared to other opioids.² In response to this growing trend, the American Pain Society (APS) and College on Problems of Drug Dependence, in collaboration with the Heart Rhythm Society, issued guidelines on the use of methadone, recommending best practices to maximize methadone safety.³ Subsequent to this publication, a group of hospice and palliative care (HPC) experts convened to develop recommendations to maximize benefit and minimize risks of methadone therapy in patients with advanced illness. A white paper is being finalized for publication, but a summary of recommendations are provided in this update.

Appropriate and Inappropriate Candidates for Methadone

The HPC consensus group addressed criteria for appropriate and inappropriate candidates for methadone therapy in the face of advanced illness. Potentially appropriate patients include those with moderate-severe pain (especially as a second line agent) who have true phenanthrene (e.g., morphine) allergy, significant renal impairment, need for a long-acting opioid (particularly as an oral concentrate solution), high opioid tolerance, and poorly controlled opioidinduced adverse effects from other opioids. Potentially inappropriate methadone candidates include patients who live alone without a responsible caregiver or those with a history of opioid or medication nonadherence. Patients with multiple risk factors for methadoneinduced adverse effects should be evaluated carefully prior to starting therapy (i.e., clinical instability, multiple transitions in care, history of transplant, QTc prolongation or at risk for such, etc.). Similarly, patients who are likely to die before reaching methadone steadystate may not be appropriate for complete rotation to methadone, although some evidence suggests methadone may be useful in an adjunctive role.^{4, 5}