Methadone for Pain
Methadone is an oral long acting synthetic opioid. It has a large volume of distribution in the body and its half life varies but is usually about 22 hours.
It is rapidly absorbed in the stomach. Once absorbed it’s distributed to the brain, liver, kidneys, liver and lungs. Tissue binding takes preference over binding to plasma proteins. Plasma concentration of Methadone is maintained by the tissue concentration.
Metabolized in the liver with no active metabolites. No need to adjust for renal impairment. Usually pain control can be achieved by q8h dosing (tid), but some patients manage even every 12 hours.
1. It’s a muopioid agonist. Mu-receptor affinity similar to Morphine but the longer it’s used, the more efficacious it is.
2. Inhibits the reuptake of mono-amines (serotonin, norepineophrine)
3. Inhibits NMDA (N-methyl-D-aspartate) receptors – provides additional analgesia (NMDA receptors are linked to central sensitization – therefore less chance of tolerance).
Slow onset & slow dose increments – probably prevent establishing reward behaviours. Recommended starting dose: 2.5mg every 8 hours. In the frail elderly, malnourished and chronically ill – 2.5mg daily or 1mg tid. Increase slowly every 5 to 7 days, by about 20%.
Dosing tables are not very reliable, but 10mg of Methadone daily is equal to about 15mg of Morphine. Titrate according to pain relief not previous level of Morphine.
Drug Interactions – (use with Benzodiazepines in Australia accounted for 74% deaths)
By drugs that change gastric pH: Verapamil; Quinidine
Drugs metabolized by CYP3A4 and CYP2D6: may need to adjust doses
Increase in Methadone levels:Cipro; diazepam; ethanol; fluconazole; urinary alkalinizers; Cimetidine; Fluoxetine; Omeprazole; Paroxetine; Quinidine; Delavirdine; grapefruit; ketoconazole; macrolides; troleandomycin; tricyclic antidepressants
Decrease in Methadone levels: Amprenavir; Efanvirenz; Nelfinavir; Nevirapine; Phenobarbital; Phenytoin; Rifampicin; Ritonavir; urinary acidifiers. Carbamazepine; Ethanol chronically
Side Effects (consider ECG for QT interval)
Itch; constipation; confusion; sedation; respiratory depression; excess sweating; flushing
British Columbia doctors please consider doing the course. www.methadone4pain.ca
And use www.raceconnect.ca for fast fantastic facilitation of opioid use in practice.