Methadone Hydrochloride

METHADONE HYDROCHLORIDE- methadone hydrochloride solution
Precision Dose, Inc.

Addiction, Abuse, and Misuse

Methadone Hydrochloride Oral Solution exposes patients and other users to the risks of opioid addiction, abuse, and misuse, which can lead to overdose and death. Assess each patient’s risk prior to prescribing Methadone Hydrochloride Oral Solution, and monitor all patients regularly for the development of these behaviors or conditions [see Warnings and Precautions (5.2)].

Opioid Analgesic Risk Evaluation and Mitigation Strategy (REMS):

To ensure that the benefits of opioid analgesics outweigh the risks of addiction, abuse, and misuse, the Food and Drug Administration (FDA) has required a REMS for these products [see Warnings and Precautions (5.3)]. Under the requirements of the REMS, drug companies with approved opioid analgesic products must make REMS-compliant education programs available to healthcare providers.

Healthcare providers are strongly encouraged to

• complete a REMS-compliant education program,
• counsel patients and/or their caregivers, with every prescription, on safe use, serious risks, storage, and disposal of these products,
• emphasize to patients and their caregivers the importance of reading the Medication Guide every time it is provided by their pharmacist, and
• consider other tools to improve patient, household, and community safety.

Life-threatening Respiratory Depression

Serious, life-threatening, or fatal respiratory depression may occur with use of Methadone Hydrochloride Oral Solution. The peak respiratory depressant effect of methadone occurs later, and persists longer than the peak analgesic effect, especially during the initial dosing period. Monitor for respiratory depression, especially during initiation of Methadone Hydrochloride Oral Solution or following a dose increase [see Warnings and Precautions (5.4)].

Accidental Ingestion

Accidental ingestion of even one dose of Methadone Hydrochloride Oral Solution, especially by children, can result in a fatal overdose of methadone [see Warnings and Precautions (5.4)].

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 Hydrochloride Oral Solution [see Warnings and Precautions (5.5)].

Neonatal Opioid Withdrawal Syndrome

Neonatal opioid withdrawal syndrome (NOWS) is an expected and treatable outcome of use of Methadone Hydrochloride Oral Solution during pregnancy. NOWS may be life-threatening if not recognized and treated in the neonate. The balance between the risks of NOWS and the benefits of maternal Methadone Hydrochloride Oral Solution use may differ based on the risks associated with the mother’s underlying condition, pain or addiction. Advise the patient of the risk of NOWS so that appropriate planning for management of the neonate can occur [see Warnings and Precautions (5.6)].

Cytochrome P450 Interaction

The concomitant use of Methadone Hydrochloride Oral Solution 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 [see Warnings and Precautions (5.7), Drug interactions (7)].

Risks From Concomitant Use With Benzodiazepines Or Other CNS Depressants

Concomitant use of opioids with benzodiazepines or other central nervous system (CNS) depressants, including alcohol, may result in profound sedation, respiratory depression, coma, and death [see Warnings and Precautions (5.8), Drug Interactions (7)].

• Reserve concomitant prescribing of Methadone Hydrochloride Oral Solution and benzodiazepines or other CNS depressants for use in patients for whom alternatives to benzodiazepines or other CNS depressants are inadequate.
• Limit dosages and durations to the minimum required for patients being treated for pain.
• 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 the daily methadone dose.

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 [see Indications and Usage (1), Dosage and Administration (2.1)].

1 INDICATIONS AND USAGE

Methadone Hydrochloride Oral Solution is indicated for the:

• Management of pain severe enough to require daily, around-the-clock, long-term opioid treatment and for which alternative treatment options are inadequate.
  Limitations of Use:
  • Because of the risks of addiction, abuse, and misuse with opioids, even at recommended doses, and because of the greater risks of overdose and death with long-acting opioids [see Warnings and Precautions (5.2)] , reserve Methadone Hydrochloride Oral Solution for use in patients for whom alternative analgesic treatment options (e.g., non-opioid analgesics or immediate-release opioid analgesics) are ineffective, not tolerated, or would be otherwise inadequate to provide sufficient management of pain.
  • Methadone Hydrochloride Oral Solution is not indicated as an as-needed (prn) analgesic.
• Detoxification treatment of opioid addiction (heroin or other morphine-like drugs).
• Maintenance treatment of opioid addiction (heroin or other morphine-like drugs), in conjunction with appropriate social and medical services.Limitations of Use:
• Methadone products used for the treatment of opioid addiction in detoxification or maintenance programs are subject to the conditions for distribution and use required under 42 CFR 8.12 [see Dosage and Administration (2.1)].

2 DOSAGE AND ADMINISTRATION

2.1 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 21CFR 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 21CFR 1306.07(b)).