methadone

Introduction

an opioid agonist which is well absorbed orally with a long half-life allowing once daily dosing
developed in Germany during world war II as a synthetic alternative to morphine as morphine was hard to obtain
introduced in Australia for Rx of heroin dependence in 1964
pts attend a clinic or pharmacy each day to be given a supervised dose
detoxification is not required for pts starting methadone
psychosocial interventions are an important adjunct
as many as 85% will stay on methadone for 12mths & most require Rx for at least 2 yrs
pts retained in Rx on a larger dose & for a longer duration generally achieve better results
optimal dose is 60-100mg/day
important Rx factors include optimal dosing & the morale of clinic staff
programs are not available in the NT

mu opioid receptor agonist
NMDA receptor antagonist actions thought to decrease tolerance
large Vd 4L/kg as widely distributed to tissues which prolongs its half life as it gets secondarily re-distributed
eliminated mainly by widespread metabolism to metabolites which, along with some methadone, is excreted in urine
- CYP3A4 inducers increase metabolism
  - eg carbamazepine and phenytoin
- CYP3A4 inhibitors reduce metabolism and increase clinical effect
  - eg. fluconazole, macrolides, antiretrovirals
half life is extremely variable:
- opiate naive patients have much longer half lives of up to 59hrs
- most patients have half lives of around 30hrs

constipation
sedation
diaphoresis
methadone overdose - resp. depression, coma, non-cardiogenic pulmonary oedema, etc
prolonged QTc and increased frequency of syncope related to the hERG K+ channel ¹⁾
- patients with significantly prolonged QTc should probably be switched to buprenorphine

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