Methadone
Mechanism of action: mu-opioid agonist and may act as an antagonist at the NMDA receptor. Usually used as opioid substitution therapy for drug dependence. Methadone is a racemic mixture of two enantiomers: the R form is more potent with a 10-fold higher affinity for the mu opioid receptors, while the S form is the NMDA antagonist. The S enantiomer also inhibits reuptake of serotonin and norepinephrine.
Presentation: oral solution
Suggested dose: Determined by community addictions service. Continue usual dose while in hospital but can be given as two or three divided doses. [Withdrawal Prevention Algorithm]
Co-prescribe prn Naloxone
Oral absorption: Well absorbed. Bioavailability 40-100%
Protein binding: 60-90% bound to plasma proteins, mainly alpha1-acid glycoprotein
Metabolism: Hepatic and, to a lesser extent, intestinal. Metabolism involves cytochrome P450 enzymes, mainly CYP3A4, which has highly variable activity due to individual differences in its expression, but also CYP2D6, CYP2B6, CYP1A2 and CYP1B2.
Elimination: Up to 60% excreted in urine as unmodified drug and as 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) which is the metabolite identified in urine screening; and up to 40% excreted in faeces.
Half-life: 12-50 hours, but shorter analgesic action (4-8 hours)
Significant interactions (see the BNF for more interactions):
Methadone can cause prolongation of the QTc interval, which may predispose patients to the ventricular arrhythmia torsades de pointes. [See the Chou reference for more detail]
Risk increased by:
- hypokalaemia or hypomagnesaemia
- impaired liver function
- drugs with QT–prolonging properties, for example antibiotics and benzodiazepines
Further prescribing information (side effects, contraindications, interactions):