Methadone Inpatient and Discharge Prescribing Patterns for Pain at an Academic Health System Rabia S. Atayee, PharmD, BCPS, 1,2 Gene H. Hur, PhD, 1 Parisa Karimian, BS, 1 Kathy A. Hollenbach, PhD, MPH, 1 and Kyle P. Edmonds, MD 2 Abstract Background: Methadone is effective for the treatment of chronic pain, but its unique pharmacology requires additional considerations with dosing and monitoring. Objective: The study objective was to evaluate methadone prescribing for pain and subsequent monitoring. Methods: This retrospective chart review at a single center reviewed patients who received methadone over a two-year period. Results: Of the 100 patients, most were noncancer cases (60%) with unspecified pain (50%). The majority of methadone treatments were initiated by medicine service (37%), followed by burn service (27%), and trauma (10%). Forty-two percent of the patients were being followed by the palliative care team, primarily for the medicine patients (80%). Patients on the burn service had significantly higher oral morphine equivalent (v 2 = 10.6, p = 0.01) and longest length of stay (v 2 = 37.9, p = 0.0001). Patients on medicine service were significantly more likely to have an outpatient discharge plan for methadone starts in the hospital (odds ratio = 3.7, confidence interval: 1.4, 9.7). Only 45% of patients had an electrocardiogram (EKG) checked seven days before methadone start and 37% of those have a measured corrected QT (QTc) of greater than 450 milliseconds. Electrolytes (potassium and magnesium) were not consistently checked and, of those that were evaluated, 15–20% were abnormal. There was an average of 2.6 severe or major drug interactions per patient related to methadone, with the most common being related to concomitant sedatives and other medications that prolonged the QTc. Conclusions: Prescribing guidelines for methadone would provide a consistent approach for all practitioners involved in using methadone safely and effectively for chronic pain. Keywords: methadone; pain; chronic pain; mixture of nociceptive and neuropathic pain; burn Introduction M ethadone is a long-acting synthetic mu-opioid agonist used for pain 1 and maintenance treatment for heroin addiction. 2,3 Due to its low cost and unique pharmacokinetic (PK) and pharmacodynamic (PD) properties, methadone has gained popularity in the management of chronic pain. 2,4 It is an appealing option among patients unresponsive to other opioid analgesics, patients with end-stage renal failure, and those with true morphine allergy or morphine intolerance 4 at a low cost. Unlike most opioids, methadone’s structural profile en- ables it to act on two different receptors. Consisting of a racemic mixture, methadone’s l-isomer activates the mu- opioid receptor and the d-isomer inhibits the N-methyl-D- aspartate (NMDA) receptor, 4 which is involved in mediating neuropathic pain. 5 As a result of this dual mechanism of action, methadone provides a uniquely advantageous option as an analgesic for both neuropathic and nociceptive pain, especially in cancer. 6 Additionally, methadone’s analgesic use has been shown to be beneficial in the setting of non- cancer pain such as in burn patients. It has been reported that when methadone is initiated in early burn treatment, there is significant improvement in patient outcomes. 7 Despite its benefits, methadone’s PK and PD properties are also a cause for concern because of serious and potentially life- threatening side effects. Among the opioids, methadone is of- ten cited as causing a disproportionate number of unintentional deaths. 8,9 Whether this is true in populations with cancer- related pain has limited supporting data. 10 It has a variable elimination half-life of 12–150 hours. Its elimination pattern is biphasic with an alpha elimination pattern lasting 8–12 hours and a beta elimination lasting 30–60 hours. As a result, much of the drug remains in the system while repeated dosing oc- curs. 4,11 Consequently, patients may experience the target 1 Skaggs School of Pharmacy and Pharmaceutical Sciences, La Jolla, California. 2 Doris A. Howell Palliative Medicine Program, UC San Diego Health Sciences, La Jolla, California. Accepted August 12, 2016. JOURNAL OF PALLIATIVE MEDICINE Volume 20, Number 2, 2017 ª Mary Ann Liebert, Inc. DOI: 10.1089/jpm.2016.0267 184