Deaths have been reported during initiation of methadone treatment for opioid dependence. In some cases, drug interactions with other drugs, both licit and illicit, have been suspected. However, in other cases, deaths appear to have occurred due to the respiratory or cardiac effects of methadone and too-rapid titration without appreciation for the accumulation of methadone over time. It is critical to understand the pharmacokinetics of methadone and to exercise vigilance during treatment initiation and dose titration. Patients must also be strongly cautioned against self-medicating with CNS depressants during initiation of methadone treatment.
Respiratory depression is the chief hazard associated with methadone hydrochloride administration. Methadone's peak respiratory depressant effects typically occur later, and persist longer than its peak analgesic effects, particularly in the early dosing period. These characteristics can contribute to cases of iatrogenic overdose, particularly during treatment initiation and dose titration.
Cases of QT interval prolongation and serious arrhythmia (torsades de pointes) have been observed during treatment with methadone. Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction.
Conditions for Distribution and Use of Methadone Products for the Treatment of Opioid Addiction
Code of Federal Regulations, Title 42, Sec 8
METHADONE PRODUCTS WHEN USED FOR THE TREATMENT OF OPIOID ADDICTION IN DETOXIFICATION OR MAINTENANCE PROGRAMS, SHALL BE DISPENSED ONLY BY OPIOID TREATMENT PROGRAMS (AND AGENCIES, PRACTITIONERS OR INSTITUTIONS BY FORMAL AGREEMENT WITH THE PROGRAM SPONSOR) CERTIFIED BY THE SUBSTANCE ABUSE AND MENTAL HEALTH SERVICES ADMINISTRATION AND APPROVED BY THE DESIGNATED STATE AUTHORITY. CERTIFIED TREATMENT PROGRAMS SHALL DISPENSE AND USE METHADONE IN ORAL FORM ONLY AND ACCORDING TO THE TREATMENT REQUIREMENTS STIPULATED IN THE FEDERAL OPIOID TREATMENT STANDARDS (42 CFR 8.12). See below for important regulatory exceptions to the general requirement for certification to provide opioid agonist treatment.
FAILURE TO ABIDE BY THE REQUIREMENTS IN THESE REGULATIONS MAY RESULT IN CRIMINAL PROSECUTION, SEIZURE OF THE DRUG SUPPLY, REVOCATION OF THE PROGRAM APPROVAL, AND INJUNCTION PRECLUDING OPERATION OF THE PROGRAM.