Special Topics in Pain: Opioids
Methadone Safety: A Clinical Practice Guideline From the American Pain Society and College on Problems of Drug Dependence, in Collaboration With the Heart Rhythm Society.
Author(s): Chou R, et al.
Journal: The Journal of Pain. 2014; 15(4):321-337. 111 references.
Reprint: Roger Chou, MD, 3181 SW Sam Jackson Park Road, Mail code BICC, Portland, or 97239. Email: firstname.lastname@example.org
Faculty Disclosure: Abstracted by N Walea, who has nothing to disclose. Please see original article for disclosures.
Objective: Review and evaluate the latest advances and newest information in the area of Opioids
Editor’s Note: Methadone is a potentially useful drug but its use comes with risks including serious cardiac complications. This report recognizes current deficiencies in research while offering useful dosing instructions and cardiac precautions.
Class: Pharmacology: Methadone Safety
The American Pain Society and the College on Problems of Drug Dependence, in collaboration with the Heart Rhythm Society, commissioned an interdisciplinary expert panel to develop a clinical practice guideline on safer prescribing of methadone for treatment of opioid addiction and chronic pain. As part of the guideline development process, a systematic review of various aspects related to safety of methadone was performed. Some of the specific recommendations are summarized below.
When considering initiation of methadone, the panel recommended that clinicians perform an individualized medical and behavioral risk evaluation to assess risk and benefits of methadone, given methadone's specific pharmacologic properties and adverse effect profile.
The panel recommends that clinicians educate and counsel patients prior to the first prescription of methadone about the indications for treatment and goals of therapy, availability of alternative therapies, and specific plans for monitoring therapy, adjusting doses, potential adverse effects associated with methadone and methods for reducing the risk of potential adverse effects and managing them.
The panel recommends that clinicians obtain an ECG prior to initiation of methadone in patients with risk factors for QTc interval prolongation or a history suggestive of prior ventricular arrhythmia. Clinicians should consider obtaining and ECG prior to initiation of methadone in patients not known to be at higher risk for QTc interval prolongation. Risk factors for QTC prolongation include electrolyte abnormalities such as hypokalemia or hypomagnesemia; impaired liver function; structural heart disease; genetic predisposition such as congenital prolonged QT syndrome or familial history of prolonged QT syndrome; and use of drugs with QTc-prolonging properties.
Torsades de pointes is a polymorphic ventricular arrhythmia usually preceded by QTc interval prolongation that can lead to ventricular fibrillation and result in sudden death or cardiac arrest. Methadone use appears to be associated with risk of prolongation of the QTc interval and case reports describe torsade de pointes in patients prescribed methadone.
The panel recommends that clinicians initiate methadone at low doses individualized based on the indication for treatment and prior opioid exposure status, titrate doses slowly, and monitor patients for sedation.
The panel recommends that for patients prescribed methadone, clinicians perform follow-up ECGs based on baseline ECG findings, methadone dose changes, and other risk factors for QTc interval prolongation. The panel recommends the use of alternative opioids in patients at high risk of complications related to QTc interval prolongation.
The panel recommends that patients receiving methadone be monitored for common opioid adverse effects and toxicities and that adverse effects management be considered part of routine therapy. It is recommended for face-to-face or phone assessment with patients for adverse events within three to five days after initiating methadone, and within three to five days after each dose increase.
The panel recommends that clinicians obtain urine drug screens prior to initiating methadone and at regular interval in patients prescribed methadone for opioid addiction. Patients prescribed methadone for chronic pain who have risk factors for drug abuse should undergo urine drug testing prior to initiating methadone and at regular intervals thereafter. The panel recommends that clinicians consider urine drug testing in all patients regardless of assessed risk status.
The panel recommends that clinicians use methadone with care in patients using concomitant medications with potentially additive side effects or pharmacokinetic or pharmacodynamic interactions with methadone.
The panel recommends monitoring of neonates born to mothers receiving methadone for neonate abstinence syndrome and treatment for neonate abstinence syndrome when present.
These guidelines are based on a systematic review of the evidence on methadone safety. There were numerous research gaps identified during the review. Nonetheless, the panel of experts came to near-unanimous consensus on almost all of its recommendations, including the need to educate and counsel patients on methadone safety, use of ECG to identify persons at greater risk for methadone-associated arrhythmia, use of alternative opioids in patients at high risk of complications related to QTc interval prolongation, careful dose initiation and titration of methadone, and diligent monitoring and follow-up.