“Methadone is a tricky drug to start, due to the narrow margin between therapeutic dose and fatal dose. Making it more difficult, people vary a great deal in the rate at which they metabolize methadone. Some people have a methadone half -life as short as 15 hours, while others have half- lives as long as 60 hours. The average is 22 hours. So even for people with a high tolerance to other opioids, increasing methadone too quickly can be deadly.
Methadone’s long half-life makes it good for a maintenance medication, since after stabilization, there’s not much fluctuation in the blood levels. However, the long half-life makes it more difficult to adjust the dose. The change I make in a patient’s dose today may not be fully experienced by the patient for five or more days.”
Source: Dr. Jana Burson – August 22, 2016