FDA BLACK BOX WARNING
WARNING: LIFE-THREATENING RESPIRATORY DEPRESSION, LIFE-THREATENING QT PROLONGATION, ACCIDENTAL INGESTION, ABUSE POTENTIAL, INTERACTIONS WITH DRUGS AFFECTING CYTOCHROME P450 ISOENZYMES and TREATMENT FOR OPIOID ADDICTION
Life-Threatening Respiratory Depression
Respiratory depression, including fatal cases, have been reported during initiation and conversion of patients to methadone, and even when the drug has been used as recommended and not misused or abused. Proper dosing and titration are essential and methadone Dispersible Tablets should only be prescribed by healthcare professionals who are knowledgeable in the use of methadone for detoxification and maintenance treatment of opioid addiction. Monitor for respiratory depression, especially during initiation of methadone Dispersible Tablets or following a dose increase. The peak respiratory depressant effect of methadone occurs later, and persists longer than the peak pharmacologic effect, especially during the initial dosing period.
Risks From Concomitant Use With Benzodiazepines or Other CNS Depressants
Concomitant use with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, is a risk factor for respiratory depression and death.
Reserve concomitant prescribing of benzodiazepines or other CNS depressants in patients in methadone treatment to those for whom alternatives to benzodiazepines or other CNS depressants are inadequate.
Follow patients for signs and symptoms of respiratory depression and sedation. If the patient is visibly sedated, evaluate the cause of sedation and consider delaying or omitting daily methadone dosing.
Life-Threatening QT Prolongation
QT interval prolongation and serious 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, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction. Closely monitor patients with risk factors for development of prolonged QT interval, a history of cardiac conduction abnormalities, and those taking medications affecting cardiac conduction for changes in cardiac rhythm during initiation and titration of methadone Dispersible Tablets.
Accidental ingestion of methadone Dispersible Tablets, especially by children, can result in fatal overdose of methadone.
Misuse, Abuse, and Diversion of Opioids
Methadone is 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 use of methadone with all cytochrome P450 3A4, 2B6, 2C19, 2C9 or 2D6 inhibitors may result in an increase in methadone plasma concentrations, which could cause potentially fatal respiratory depression. In addition, discontinuation of concomitantly used cytochrome P450 3A4, 2B6, 2C19, or 2C9 inducers may also result in an increase in methadone plasma concentration. Follow patients closely for respiratory depression and sedation, and consider dosage reduction with any changes of concomitant medications that can result in an increase in 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 in accordance with the treatment standards cited in 42 CFR Section 8, including limitations on unsupervised administration.
Public Citizen Warning on New Methadone Dose
The FDA recommended dosages for patients starting methadone treatment for pain have been radically reduced.
The new approved starting dose is 2.5 milligrams to 10 milligrams every 8 to 12 hours – up to 30 milligrams per day.
The dangerous old starting dose for methadone was 2.5 milligrams to 10 milligrams every 3 to 4 hours as necessary – up to 80 milligrams per day.
No patient should ever receive more than 30 milligrams on day one for pain management, and, thereafter, dosage increases should be no more than 10 milligrams twice per week. Exceeding these limits can lead to death.