Drug reference

Methadone

Opioid Analgesic · null

Also known as Methadone Hydrochloride

Opioid Analgesicnull

CDSCO approvedSchedule X

Pharmacokineticsplasma · t hours

ONSET: 15min · Analgesia: 10-20 min (parenteral), 30-60 min (oral)
PEAK: 1.5h · Brain concentrations peak within 1-2 h (subcutaneous/intramuscular); Plasma concentrations peak ~4 h (oral)
t½: 1.1d · 15–40 h (long elimination half-life)
DURATION: 1d · Analgesia of single doses is similar to morphine, but cumulative effects lead to longer duration with repeated use; Miosis and respiratory depression can be detected for >24 h after a single dose

EXCRETION

—

not curated

INTERACTIONS

12 major

incl. contraindicated

PREGNANCY

Withdrawal symptoms in neonate; use lowest possible maintenance dose

FDA category + note

Top interactionssee all 12 →

AmisulprideContraindicatedDatabaseDDInter
AbarelixSevereDatabaseDDInter
AbirateroneSevereDatabaseDDInter
AdenosineSevereDatabaseDDInter

Mechanism

Methadone is a synthetic mu-opioid receptor agonist with two pharmacologically important properties that distinguish it from morphine: it has NMDA receptor antagonist activity, which may reduce opioid tolerance development and provide additional benefit in neuropathic pain; and an exceptionally long and variable plasma half-life (15-60 hours, mean ~22 hours) that enables once-daily dosing for opioid maintenance therapy. Its high oral bioavailability (80-90%) and slow onset reduce the euphoric peak, making it effective for treating opioid use disorder.

Indications

detoxification and maintenance therapy for opioid use disordermanagement of chronic painOpioid use disorder detoxificationOpioid maintenance therapyAnalgesicsubstitution therapy for opioid dependencemethadone maintenance therapy in opioid addictsanalgesic for the same conditions as morphineantitussive (occasionally)

Dosing

Adult: Severe pain: 5-10 mg every 6-8h, adjusted to response; on prolonged use not more than every 12h. Opioid dependence: initially 10-30 mg daily (low tolerance 10-20 mg), increased by 5-10 mg daily as needed. Max weekly increase 30 mg. Usual maintenance: 60-120 mg daily.
Pediatric: Oral: 0.1 mg/kg/12 h
Renal adjustment: Caution; reduce dose
Hepatic adjustment: Caution; reduce dose
Geriatric: Start with lower doses
Max dose: 60-120 mg daily maintenance (dependence); dose-titrated for pain

Pharmacokinetics

Onset

Analgesia: 10-20 min (parenteral), 30-60 min (oral)

Peak effect

Brain concentrations peak within 1-2 h (subcutaneous/intramuscular); Plasma concentrations peak ~4 h (oral)

Duration

Analgesia of single doses is similar to morphine, but cumulative effects lead to longer duration with repeated use; Miosis and respiratory depression can be detected for >24 h after a single dose

Half-life

15–40 h (long elimination half-life)

Bioavailability

Well absorbed from GI tract; can be absorbed from buccal mucosa

Protein binding

89 ± 2.9%

Metabolism

Extensive biotransformation in the liver; major metabolites are pyrrolidine and pyrroline derivatives from N-demethylation and cyclization

Excretion

In urine and bile along with small amounts of unchanged drug

Contraindications

Acute respiratory depression
Acute alcoholism
Raised intracranial pressure
labor

Side effects

Common

NauseaConstipationDrowsinessSweatingQT prolongationsedation (marked with repeated administration)vomitingSide effects similar to other opioidssedative (less intense than morphine)subjective effects (less intense than morphine)emetic actionsconstipation (less prominent than morphine)

Serious