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

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.

Ascending Single‐Dose, Double‐Blind, Placebo‐Controlled Safety Study of Noribogaine in Opioid‐Dependent Patients

“…Twenty subjects were white, 5 were Maori, and 2 were other. Comorbid diagnoses and concomitant medications are listed elsewhere …”

“…In the week before noribogaine/placebo dosing, methadone was replaced by oral controlled‐release morphine capsules (M‐Eslon) for 6 days, followed by 1 day of oral immediate‐release morphine (this is described in more detail elsewhere). After an overnight fast of at least 10 hours, the last morphine dose was given at 6 am on day 1, and at ∼8 am blinded noribogaine or placebo capsules were administered with 240 mL of water.…”

Changes in fentanyl demand following naltrexone, morphine, and buprenorphine in male rats

“…The persistent effects we observed suggest that individuals continuing to misuse opioids during MAT may still experience a beneficial decrease in economic demand for illicit opioids, which may persist beyond the half-life of the treatment medication. Notably, the therapeutic formulations of MAT compounds used in humans have half-lives of 20 to 177 h (Dunbar et al, 2006;Elkader and Sproule, 2005;Glue et al, 2016) and therefore may have large windows of effectiveness, even after discontinuation of treatment. The FDA is currently interested in validating preclinical endpoints that reflect clinical outcomes like "harm-reduction" as alternatives to the standard metric of "sustained total abstinence".…”