Methadone

• Opioid Use Disorder
• Chronic Pain Management
• Opioid Withdrawal

Methadone is a long-acting synthetic opioid used for opioid use disorder (OUD) treatment and chronic pain management. As one of the most effective medications for opioid addiction treatment, methadone has been used for over 50 years in medication-assisted treatment (MAT) programs.

Mechanism of Action

Methadone exerts its effects through multiple mechanisms:

• Mu-opioid receptor agonist: Primary mechanism for analgesia and preventing withdrawal
• NMDA receptor antagonist: May contribute to analgesic efficacy and reduced tolerance development
• Inhibition of serotonin and norepinephrine reuptake: May provide additional analgesic benefits

Its long half-life (24-36 hours) allows once-daily dosing, providing stable blood levels that prevent withdrawal symptoms and reduce cravings without producing the euphoria associated with shorter-acting opioids.

Available Formulations

For Opioid Use Disorder (dispensed through certified OTPs only):

• Oral solution: 5 mg/5 mL, 10 mg/5 mL
• Oral concentrate: 10 mg/mL
• Dispersible tablets: 40 mg

For Pain Management:

• Tablets: 5 mg, 10 mg
• Oral solution: 5 mg/5 mL, 10 mg/5 mL
• Injectable: 10 mg/mL (rarely used)

Medical Uses

FDA-Approved Indications:

• Treatment of opioid use disorder (detoxification and maintenance)
• Management of pain severe enough to require daily, around-the-clock opioid treatment

Methadone for OUD can only be dispensed through SAMHSA-certified opioid treatment programs (OTPs), unlike buprenorphine which can be prescribed in office settings.

Dosing Guidelines

Opioid Use Disorder:

• Initial dose: 20-30 mg on day 1
• Titration: Increase by 5-10 mg every 3-7 days as needed
• Maintenance: Typically 80-120 mg daily, though doses vary widely
• Maximum: No absolute maximum; doses >120 mg require additional documentation

Chronic Pain:

• Opioid-naive: 2.5 mg every 8-12 hours
• Titrate slowly due to unpredictable accumulation
• Exercise extreme caution in dose adjustments

Important Safety Information

Black Box Warnings:

• Life-threatening respiratory depression
• QT prolongation and serious arrhythmias (Torsades de pointes)
• Accidental ingestion can cause fatal overdose
• Neonatal opioid withdrawal syndrome
• CYP450 drug interactions
• Conditions for distribution for OUD treatment

Contraindications:

• Significant respiratory depression
• Acute or severe bronchial asthma without monitoring
• Known or suspected paralytic ileus
• Hypersensitivity to methadone

Warnings:

• Long elimination half-life increases overdose risk during titration
• Cardiac conduction effects (obtain baseline ECG)
• Risk of QT prolongation increases with higher doses

Drug Interactions

• CYP3A4 inducers (rifampin, phenytoin, carbamazepine): May decrease methadone levels, precipitating withdrawal
• CYP3A4 inhibitors (ketoconazole, erythromycin): May increase methadone levels
• QT-prolonging drugs: Increased risk of arrhythmias
• Benzodiazepines and CNS depressants: Potentially fatal respiratory depression
• MAOIs: Severe reactions possible

Special Populations

• Pregnancy: Methadone is the standard of care for pregnant women with OUD
• Hepatic Impairment: Use with caution; consider dose reduction
• Renal Impairment: Use with caution
• Elderly: Start with lower doses; increased sensitivity