Switching Opioid-Dependent Patients From Methadone to Morphine: Safety, Tolerability, and Methadone Pharmacokinetics

Journal of Clinical Pharmacology
Paul GlueLawrence Friedhoff

Abstract

The aim of this study was to switch patients established on methadone opioid substitution therapy (OST) to morphine over 1 week. Subjects established on daily methadone OST (mean dose 60 mg/day) were switched to morphine slow-release capsules, dosed at 4× the previous total daily methadone dose, for 6 days, then given morphine syrup dosed q3h. All 27 subjects enrolled in this study completed the switch from methadone to morphine. Opioid withdrawal symptoms (OWS) peaked within 12-24 hours of starting morphine, and 24/27 subjects required higher daily morphine doses (mean 5.2× multiple). Pharmacokinetic evaluation showed that 91% of methadone was cleared during this time, with a mean elimination half-life of 59 hours. The most frequent treatment-emergent non-OWS adverse events were headache, nausea, constipation, and neck pain. The method described here appears to be a safe and acceptable approach to switch subjects from methadone to morphine.

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Citations

Nov 9, 2016·Annals of Emergency Medicine·Michael Gottlieb, Katarzyna Gore
Nov 22, 2016·Clinical Pharmacology in Drug Development·Paul GlueLawrence Friedhoff
Apr 4, 2017·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Avi A Weinbroum
May 30, 2019·Psychopharmacology·Fatemeh ChalabianlooOlav Spigset
Nov 16, 2019·Current Oncology Reports·Dylan FinnertyDonal J Buggy
Dec 22, 2019·Drug and Alcohol Dependence·Lindsey R HammerslagMichael T Bardo

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