Table of Contents
Life-threatening Respiratory Depression
Respiratory depression, including lethal cases, has been reported during the initiation and conversion of patients to Methadose. Even when the drug has been utilized as recommended and not misused or abused, Methadose can still cause addiction. Appropriate dosing and titration are essential, and Methadose prescriptions should only be made by healthcare professionals who are knowledgeable in the use of methadone for detox and maintenance treatment of opioid addiction.
Monitor for respiratory depression, especially during initiation of a Methadose prescription or following a dose increase. The peak respiratory depressant effect of methadone occurs later and persists more extended than the peak pharmacologic effect, especially during the initial dosing period.
Life-Threatening QT Prolongation
QT interval prolongation and severe arrhythmia (torsades de pointes) have occurred during treatment with methadone. Most cases involve patients being treated for pain with large, multiple daily doses of methadone. However, cases have been reported in patients receiving doses commonly used to maintain opioid addiction.
Closely monitor patients with risk factors for the development of prolonged QT interval, a history of cardiac conduction abnormalities, and those taking medications affecting cardiac conduction for cardiac rhythm changes during initiation and titration of Methadose.
Accidental Ingestion
Accidental ingestion of Methadose, especially by children, can result in a fatal overdose of methadone.
Misuse, Abuse, and Diversion of Opioids
Methadose contains methadone, an opioid agonist and Schedule II controlled substance with an abuse liability similar to other opioid agonists, legal or illicit.
Interactions with Drugs Affecting Cytochrome P450 Isoenzymes
The concomitant Methadose use with all cytochrome P450 3A4, 2B6, 2C19, 2C9, or 2D6 inhibitors may increase methadone plasma concentrations, which could cause potentially fatal respiratory depression. Besides, discontinuation of concomitantly used cytochrome P450 3A4 2B6, 2C19, or 2C9 inducers may also increase methadone plasma concentration. Follow patients closely for respiratory depression and sedation, and consider dosage reduction with any changes in concomitant medications that can increase methadone levels.
Conditions For Distribution And Use Of Methadone Products For The Treatment of Opioid Addiction
For detoxification and maintenance of opioid dependence, methadone should be administered following the treatment standards cited in 42 CFR Section 8, including limitations on unsupervised administration.
Mechanism of Action
Uses for Methadose are usually as a mu-agonist. It is a synthetic opioid analgesic with multiple actions qualitatively similar to morphine, the most prominent of which involves the central nervous system and organs composed of smooth muscle. The principal therapeutic uses for Methadose are analgesia and detoxification or maintenance treatment in opioid addiction.
The methadone abstinence syndrome, although qualitatively similar to that of morphine, differs in that the onset is slower, the course is more prolonged, and the symptoms are less severe. Some data also indicate that methadone acts as an antagonist at the N-methyl-D-Aspartate (NMDA) receptor. The contribution of NMDA receptor antagonism to methadone’s efficacy is unknown.
Effects on the Central Nervous System
Methadone produces respiratory depression by direct action on brain stem respiratory centers. The respiratory depression involves a reduction in the brainstem respiratory centers’ responsiveness to both increases in carbon dioxide tension and electrical stimulation.
Methadone causes miosis, even in total darkness. Pinpoint pupils are a sign of opioid overdose but are not pathognomonic (e.g., pontine lesions of hemorrhagic or ischemic origins may produce similar findings). Marked mydriasis rather than mitosis may be seen due to hypoxia in overdose situations.
Some NMDA receptor antagonists have been shown to produce neurotoxic effects in animals.
