Methadone

Generic Name: Methadone Hydrochloride

Brand Names: Dolophine, Methadose

Methadone is a long-acting opioid used for opioid use disorder treatment and severe chronic pain.

Addiction MedicinePainOpioid

Drug Class

Opioid Agonist (Synthetic Diphenylheptane Derivative)

DEA Schedule

Schedule Schedule II

Pregnancy

Category C; prolonged use during pregnancy can cause neonatal opioid withdrawal syndrome (NOWS). However, for pregnant patients with opioid use disorder, methadone maintenance is considered standard of care because the benefits of treatment outweigh the risks of untreated addiction. The newborn should be monitored for withdrawal symptoms.

Available Forms

5 mg oral tablet, 10 mg oral tablet, 40 mg dispersible oral tablet (for opioid treatment programs only), 5 mg/5 mL oral solution, 10 mg/5 mL oral concentrate, 10 mg/mL injectable solution

What It's Used For

Dosage Quick Reference

These are general dosage guidelines. Your doctor will determine the appropriate dose for your specific situation.

Condition	Starting Dose	Maintenance Dose
Opioid Use Disorder (OTP setting)	20-30 mg orally on day 1; may give additional 5-10 mg if withdrawal symptoms not suppressed after 2-4 hours (max 40 mg day 1)	60-120 mg once daily orally; individualized titration over weeks
Chronic Pain (opioid-tolerant patients)	2.5 mg orally every 8-12 hours; slow titration due to long half-life	Individualized; titrate no more frequently than every 3-5 days due to delayed peak effect; typical range 5-20 mg every 8-12 hours
Chronic Pain (conversion from other opioids)	Reduce calculated equianalgesic dose by 50-75% due to incomplete cross-tolerance	Individualize based on response; monitor for 5-7 days after each dose change

Side Effects

Common Side Effects:

Constipation
Sweating
Drowsiness
Nausea and vomiting
Dry mouth
Sexual dysfunction

Serious Side Effects:

Respiratory depression (potentially fatal)
QT prolongation and Torsades de pointes
Severe hypotension
Adrenal insufficiency
Seizures

Drug Interactions

Benzodiazepines (diazepam, alprazolam, lorazepam) and other CNS depressants: FDA black box warning — concurrent use causes profound sedation, respiratory depression, coma, and death. If combined, use lowest effective doses and shortest duration.
CYP3A4 inducers (rifampin, phenytoin, carbamazepine, St. John's Wort): These reduce methadone levels, potentially precipitating withdrawal. Rifampin can reduce methadone levels by over 50%. Dose adjustments are necessary.
CYP3A4 inhibitors (fluconazole, erythromycin, grapefruit juice): Increase methadone levels, potentially causing sedation and respiratory depression. Monitor closely and consider dose reduction.
QT-prolonging medications (amiodarone, sotalol, fluoroquinolones, ondansetron, antipsychotics): Methadone prolongs the QTc interval in a dose-dependent manner. Combination with other QT-prolonging agents significantly increases the risk of torsades de pointes and sudden cardiac death.
Serotonergic drugs (SSRIs, SNRIs, tramadol, triptans, MAOIs): Concurrent use can precipitate serotonin syndrome. Monitor for agitation, hyperthermia, tachycardia, and muscle rigidity.
Naltrexone and naloxone: Opioid antagonists will block methadone's effects and can precipitate severe acute withdrawal in methadone-maintained patients.

Additional Information

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

Frequently Asked Questions

Pharmacologically, it is the same medication. However, when used for opioid use disorder, methadone can only be dispensed through a certified Opioid Treatment Program (OTP) and is given once daily under supervision. For pain management, methadone can be prescribed by any appropriately licensed physician and is usually dosed every 8-12 hours. The dosing strategies, regulatory requirements, and clinical monitoring differ substantially.

Methadone can prolong the QTc interval on an electrocardiogram (EKG), which is a risk factor for a dangerous heart rhythm called torsades de pointes. The risk increases at higher doses and when combined with other QT-prolonging medications. A baseline EKG is recommended before starting methadone, and follow-up EKGs should be considered at 30 days, annually, and after significant dose increases.

Methadone has a uniquely long and variable half-life (8 to 59 hours, with an average around 22 hours). This means the drug accumulates in the body over several days. The analgesic effect lasts only 4-8 hours (shorter than the drug stays in the body), which can lead patients or providers to increase the dose too quickly, risking fatal respiratory depression as the drug accumulates. Dose increases should occur no more frequently than every 3 to 7 days.

Methadone can cause drowsiness, impaired coordination, and slowed reaction times, especially during dose initiation or increases. Patients stabilized on a consistent dose for several weeks may be able to drive safely, but you should know how the medication affects you before operating a vehicle. Follow your doctor's guidance and your state's laws regarding driving on prescription medications.

Related Health Conditions

This medication is commonly used to treat or manage the following conditions:

Attention Deficit Hyperactivity Disorder (ADHD)

ADHD is a neurodevelopmental disorder marked by inattention, hyperactivity, and/or impulsivity, stemming from complex interactions between genetics, brain differences, and environmental factors, not poor parenting.

Learn More

Medical Disclaimer: This information is for educational purposes only and should not be considered medical advice. Always consult with your healthcare provider before starting, stopping, or changing any medication. Your doctor can provide personalized recommendations based on your specific health condition and medical history.