methadone

General Information

Methadone (brands include Methadose and Dolophine; generics) is a long-acting, full μ-opioid receptor agonist used for opioid use disorder (OUD) treatment (within regulated opioid treatment programs) and for analgesia (label).

In opioid use disorder care, methadone is associated with strong treatment retention and reduced illicit opioid use, but access is shaped by program requirements and early-treatment safety needs (guideline/clinical).

Methadone’s half-life is long and highly variable, creating accumulation risk early in treatment and after dose changes; cautious titration and close early monitoring are emphasized in label and guidance (label/clinical).

QTc prolongation is a key safety concern. Methadone has been associated with torsades de pointes, especially with higher doses or additive risk factors (label/clinical).

The compare view, methadone evidence feed, and methadone print page support counseling when opioid treatment decisions overlap with co-prescribed sedatives and psychiatric comorbidity.

Often used in opioid treatment programs when high opioid tolerance is present or when buprenorphine response is insufficient. QTc monitoring and careful coordination with sedating psychiatric medications are common safety considerations.

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Full μ-opioid receptor agonist producing opioid-agonist effects that suppress withdrawal and cravings in opioid use disorder (OUD) and provide analgesia in pain settings (label).

The long and variable pharmacokinetic profile increases accumulation risk and shapes cautious titration practices (label/clinical).

• Full μ-opioid receptor agonism (opioid agonist).

Metabolism and Pharmacokinetics

• Metabolized hepatically with contributions from CYP enzymes (including CYP2B6 and CYP3A4), with elimination via urine and feces; renal clearance is pH-dependent (label).
• Half-life variability is substantial and can be prolonged by interactions and patient factors, contributing to accumulation risk (label/clinical).
• Methadone can prolong QTc; risk rises with higher doses, other QT-active medications, and electrolyte abnormalities (label/clinical).

Dosing and Administration

• Opioid use disorder (OUD) dosing is typically managed within an opioid treatment program, with dose changes guided by withdrawal control, cravings, and safety (guideline/clinical).
• Because accumulation risk is highest early in treatment, many programs avoid rapid escalation and reassess frequently after dose changes (label/clinical).
• Co-occurring sedatives and interacting medications are commonly reviewed at each step in titration (label/clinical).

Monitoring & Labs

• Monitor sedation and respiratory status during initiation and after dose increases; reassess concurrent sedatives and polysubstance use risk (label/clinical).
• QTc planning: consider ECG monitoring when cardiac risk factors, high doses, or QT-active co-medications are present (label/clinical).
• Monitor for constipation and other opioid adverse effects that can affect adherence and quality of life (clinical).
• Reassess withdrawal control and cravings and adjust treatment supports (housing, therapy, peer support) when available (guideline/clinical).

Early treatment and medication changes are the highest-risk periods because of accumulation and interaction effects; structured follow-up is common in opioid treatment programs (label/clinical).

Adverse Effects

Interactions

• CNS depressants (alcohol, benzodiazepines, sedative-hypnotics, gabapentinoids) can increase sedation and respiratory depression risk (label/clinical).
• CYP inducers and inhibitors can change methadone exposure; regimen changes often prompt monitoring for withdrawal or over-sedation (label/clinical).
• QT-prolonging drugs and electrolyte disturbances can add risk; combined risk review is common in polypharmacy settings (label/clinical).

Other Useful Information

• Guidelines describe methadone as an effective medication for opioid use disorder with strong retention, while emphasizing the need for structured monitoring and program-based access in many jurisdictions (guideline/clinical).
• QTc risk is a frequent reason methadone is discussed alongside ECG planning and avoidance of additive QT-active medications when feasible (label/clinical).
• In psychiatric care, methadone may interact with antipsychotics and other sedating agents; coordination can reduce additive sedation and QT risk (clinical).

References

1. Methadone hydrochloride tablets prescribing information — DailyMed (2025)
2. The ASAM National Practice Guideline for the Treatment of Opioid Use Disorder: 2020 Focused Update — Journal of Addiction Medicine (2020)
3. TIP 63: Medications for Opioid Use Disorder — SAMHSA (2021)
4. Torsade DE Pointes Associated With Very High Dose Methadone — Annals of Internal Medicine (2002)