API

Methadone hydrochloride

Drug classification

Opioid analgesic (synthetic opioid).

Dosage form

Oral Solution

API strength per dosage

2mg/ml

Dose

Adults: For opioid dependence, initial dose 10–30 mg once daily, adjusted individually; usual maintenance 60–120 mg daily. For pain, 2.5–10 mg every 8–12 hours. Pediatrics: Not routinely recommended; specialist use only. Elderly or hepatic impairment: Start at lower doses with careful titration.

Mechanism of action

Binds primarily to μ-opioid receptors (MOR, OPRM1) as a full agonist, inhibiting adenylate cyclase, reducing cAMP, and decreasing neuronal excitability; also antagonizes N-methyl-D-aspartate (NMDA) receptors, modulating glutamatergic transmission and contributing to analgesic and anti-hyperalgesic effects.

Indications

Opioid dependence substitution therapy, severe pain unresponsive to alternative analgesics.

Side effects

Respiratory depression, sedation, constipation, nausea, vomiting, hypotension, QT interval prolongation, arrhythmias, sweating, miosis, confusion, dizziness, dependence, withdrawal symptoms, pruritus.

Pregnancy category

Precautions

Respiratory depression, risk of QT interval prolongation, hepatic or renal impairment, elderly or debilitated patients, concurrent CNS depressants, history of substance misuse, hypotension, head injury, pregnancy and breastfeeding, abrupt discontinuation, adrenal insufficiency, interactions with CYP3A4 inhibitors or inducers, risk of overdose, constipation.

Contraindications

Respiratory depression, acute asthma, paralytic ileus, concurrent monoamine oxidase inhibitor use or within 2 weeks of discontinuation, known hypersensitivity to methadone or excipients, acute alcoholism, head injury.