IMPORTANT RISK INFORMATION
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.
Regulatory Exceptions to the General Requirement for Certification to Provide Opioid Agonist Treatment:
- During inpatient care, when the patient was admitted for any condition other than concurrent opioid addiction (pursuant to 21 CFR 1306.07(c)), to facilitate the treatment of the primary admitting diagnosis.
- During an emergency period of no longer than 3 days while definitive care for the addiction is being sought in an appropriately licensed facility (pursuant to 21 CFR 1306.07(b)).
- Methadose is contraindicated in patients with a known hypersensitivity to methadone hydrochloride or any other ingredient in Methadose.
- Methadose is contraindicated in any situation where opioids are contraindicated such as: patients with respiratory depression (in the absence of resuscitative equipment or in unmonitored settings), and in patients with acute bronchial asthma or hypercarbia.
- Methadone is contraindicated in any patient who has or is suspected of having a paralytic ileus.
WARNINGS AND PRECAUTIONS
- Methadose and Methadose Sugar-Free are for oral administration only. The preparation must not be injected. Methadose and Methadose Sugar-Free, if dispensed, should be packaged in child-resistant containers and kept out of reach of children to prevent accidental ingestion.
- Respiratory depression is the chief hazard associated with methadone hydrochloride administration.
- Cases of QT interval prolongation and serious arrhythmia (torsades de pointes) have been observed during treatment with methadone. Extreme caution is necessary when any drug known to have the potential to prolong the QT interval is prescribed in conjunction with methadone.
- Patients tolerant to other opioids may be incompletely tolerant to methadone.
- Methadone, a mu-agonist opioid with an abuse liability similar to other opioid agonists is a Schedule II controlled substance and like other opioids used in analgesia, can be abused and are subject to criminal diversion.
- Patients receiving other opioid analgesics, general anesthetics, phenothiazines, other tranquilizers, sedatives, benzodiazepines, hypnotics, or other CNS depressants (including alcohol) concomitantly with methadone may experience respiratory depression, hypotension, profound sedation, or coma.
- The respiratory depressant effects of opioids and their capacity to elevate cerebrospinal-fluid pressure may be markedly exaggerated in the presence of head injury, other intracranial lesions or a pre-existing increase in intracranial pressure.
- The administration of opioids may obscure the diagnosis or clinical course of patients with acute
- The administration of methadone may result in severe hypotension in patients whose ability to maintain normal blood pressure is compromised (e.g., severe volume depletion).abdominal conditions.
- Methadone should be given with caution, and the initial dose reduced, in certain patients such as the elderly and debilitated, and those with severe impairment of hepatic or renal function, hypothyroidism, Addison's disease, prostatic hypertrophy, or urethral stricture.
- Reproductive function in human males may be decreased by methadone treatment
- Serious adverse reactions from methadone may include respiratory depression and, to a lesser degree, systemic hypotension, respiratory arrest, shock, cardiac arrest, and death.
- The most common adverse reactions include lightheadedness, dizziness, sedation, nausea, vomiting, and sweating.
USE IN SPECIFIC POPULATIONS
- Women being treated with methadone for any indication who are already breastfeeding should be counseled to wean breastfeeding gradually in order to prevent the development of withdrawal symptoms in the infant. There have been rare cases of sedation and respiratory depression in infants exposed to methadone through breast milk.
- Safety and effectiveness in pediatric patients below the age of 18 years have not been established.
Dye-Free, Sugar-Free, Unflavored
Methadone Hydrochloride oral concentrate, USP
For additional information on Methadose™ Sugar-Free Oral Concentrate (Methadone Hydrochloride Oral Concentrate USP) 10 mg/mL, CII, call Customer Service at 1.800.325.8888 or Medical Information at 1.800.778.7898.