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)).
Important General Information
Consider the following important factors that differentiate methadone from other opioids:
- The peak respiratory depressant effect of methadone occurs later and persists longer than its peak pharmacologic effect.
- A high degree of opioid tolerance does not eliminate the possibility of methadone overdose, iatrogenic or otherwise. Deaths have been reported during conversion to methadone from chronic, high-dose treatment with other opioid agonists and during initiation of methadone treatment of addiction in subjects previously abusing high doses of other opioid agonists.
- There is high interpatient variability in absorption, metabolism, and relative analgesic potency. Population-based conversion ratios between methadone and other opioids are not accurate when applied to individuals.
- With repeated dosing, methadone is retained in the liver and then slowly released, prolonging the duration of potential toxicity.
- Steady-state plasma concentrations are not attained until 3 to 5 days after initiation of dosing.
- Methadone Hydrochloride has a narrow therapeutic index, especially when combined with other drugs.
Patient Access to Naloxone for the Emergency Treatment of Opioid Overdose
Discuss the availability of naloxone for the emergency treatment of opioid overdose with the patient and caregiver. Because patients being treated for opioid use disorder have the potential for relapse, putting them at risk for opioid overdose, strongly consider prescribing naloxone for the emergency treatment of opioid overdose, both when initiating and renewing treatment with Methadone Hydrochloride. Also consider prescribing naloxone if the patient has household members (including children) or other close contacts at risk for accidental ingestion or opioid overdose (see WARNINGS and PRECAUTIONS, Life-Threatening Respiratory Depression).
Advise patients and caregivers that naloxone may also be administered for a known or suspected overdose with Methadone Hydrochloride itself (see OVERDOSAGE).
Inform patients and caregivers of their options for obtaining naloxone as permitted by individual state naloxone dispensing and prescribing regulations (e.g., by prescription, directly from a pharmacist, or as part of a community-based program) (see PRECAUTIONS, Information for Patients).
Induction/Initial Dosing for Detoxification and Maintenance Treatment of Opioid Addiction
|For detoxification and maintenance of opiate dependence, methadone should be administered in accordance with the treatment standards cited in 42 CFR Section 8.12, including limitations on unsupervised administration.|
The initial methadone dose should be administered, under supervision, when there are no signs of sedation or intoxication, and the patient shows symptoms of withdrawal. Initially, a single dose of 20 to 30 mg of methadone will often be sufficient to suppress withdrawal symptoms. The initial dose should not exceed 30 mg.
If same-day dosing adjustments are to be made, the patient should be asked to wait 2 to 4 hours for further evaluation, when peak levels have been reached. An additional 5 to 10 mg of methadone may be provided if withdrawal symptoms have not been suppressed or if symptoms reappear.
The total daily dose of methadone on the first day of treatment should not ordinarily exceed 40 mg. Dose adjustments should be made over the first week of treatment based on control of withdrawal symptoms at the time of expected peak activity (e.g., 2 to 4 hours after dosing). Dose adjustment should be cautious; deaths have occurred in early treatment due to the cumulative effects of the first several days’ dosing. Patients should be reminded that the dose will “hold” for a longer period of time as tissue stores of methadone accumulate.
Initial doses should be lower for patients whose tolerance is expected to be low at treatment entry. Loss of tolerance should be considered in any patient who has not taken opioids for more than 5 days. Initial doses should not be determined by previous treatment episodes or dollars spent per day on illicit drug use.
During the induction phase of methadone maintenance treatment, patients may show typical withdrawal symptoms, which should be differentiated from methadone-induced side effects. They may exhibit some or all of the following signs and symptoms associated with acute withdrawal from heroin or other opiates: lacrimation, rhinorrhea, sneezing, yawning, excessive perspiration, goose-flesh, fever, chilliness alternating with flushing, restlessness, irritability, weakness, anxiety, depression, dilated pupils, tremors, tachycardia, abdominal cramps, body aches, involuntary twitching and kicking movements, anorexia, nausea, vomiting, diarrhea, intestinal spasms, and weight loss.
For patients preferring a brief course of stabilization followed by a period of medically supervised withdrawal, it is generally recommended that the patient be titrated to a total daily dose of about 40 mg in divided doses to achieve an adequate stabilizing level. Stabilization can be continued for 2 to 3 days, after which the dose of methadone should be gradually decreased. The rate at which methadone is decreased should be determined separately for each patient. The dose of methadone can be decreased on a daily basis or at 2-day intervals, but the amount of intake should remain sufficient to keep withdrawal symptoms at a tolerable level. In hospitalized patients, a daily reduction of 20% of the total daily dose may be tolerated. In ambulatory patients, a somewhat slower schedule may be needed.
Titration and Maintenance Treatment of Opioid Dependence
Patients in maintenance treatment should be titrated to a dose at which opioid symptoms are prevented for 24 hours, drug hunger or craving is reduced, the euphoric effects of self-administered opioids are blocked or attenuated, and the patient is tolerant to the sedative effects of methadone. Most commonly, clinical stability is achieved at doses between 80 to 120 mg/day. During prolonged administration of methadone, monitor patients for persistent constipation and manage accordingly.
Medically Supervised Withdrawal After a Period of Maintenance Treatment
There is considerable variability in the appropriate rate of methadone taper in patients choosing medically supervised withdrawal from methadone treatment. It is generally suggested that dose reductions should be less than 10% of the established tolerance or maintenance dose, and that 10- to 14-day intervals should elapse between dose reductions. Apprise patients of the high risk of relapse to illicit drug use associated with discontinuation of methadone maintenance treatment.
Risk of Relapse in Patients on Methadone Maintenance Treatment of Opioid Addiction
Abrupt opioid discontinuation can lead to development of opioid withdrawal symptoms (see DRUG ABUSE AND DEPENDENCE). Opioid withdrawal symptoms have been associated with an increased risk of relapse to illicit drug use in susceptible patients.
Considerations for Management of Acute Pain During Methadone Maintenance Treatment
Patients in methadone maintenance treatment for opioid dependence who experience physical trauma, postoperative pain or other acute pain cannot be expected to derive analgesia from their existing dose of methadone. Such patients should be administered analgesics, including opioids, in doses that would otherwise be indicated for non-methadone-treated patients with similar painful conditions. When opioids are required for management of acute pain in methadone maintenance patients, somewhat higher and/or more frequent doses will often be required than would be the case for non-tolerant patients due to the opioid tolerance induced by methadone.
Dosage Adjustment During Pregnancy
Methadone clearance may be increased during pregnancy. During pregnancy, a woman’s methadone dose may need to be increased or the dosing interval decreased (see CLINICAL PHARMACOLOGY, Pharmacokinetics, Specific Populations, and PRECAUTIONS, Pregnancy).
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