Rotation from buprenorphine/naloxone to methadone or SROM is relatively uncomplicated, as methadone and SROM are full agonists, while buprenorphine is a partial agonist. Thus, there is no risk of precipitated withdrawal during this switch.

Generally, the first dose of methadone or SROM can be administered within 24 hours of the last dose of buprenorphine/naloxone, using established protocols for starting methadone treatment in opioid tolerant patients. An example protocol follows.

Table 20. Example Protocol for Transition from Buprenorphine/naloxone to Methadone

There is a potential for precipitated withdrawal when transitioning from methadone to buprenorphine-containing products. This is due to buprenorphine’s high affinity and lower intrinsic activity at the mu-opioid receptor, which displaces methadone and replaces the full agonist with a partial agonist.144 Historically, it has been challenging to transition from methadone to buprenorphine/naloxone, as the terminal elimination half-life of methadone ranges from 8 to 59 hours, requiring a wait before buprenorphine/naloxone induction, to prevent precipitated withdrawal.144,486 The requirement to be in moderate withdrawal before initiating buprenorphine/naloxone has, thus, presented a significant challenge for individuals wanting to transition to buprenorphine.

Low-dose induction is the preferred method for transitioning from methadone to buprenorphine/naloxone, as it reduces the risk of precipitated withdrawal and does not require a wash-out period. This method maintains the patient’s dose of methadone while gradually increasing the buprenorphine/naloxone dose, allowing it to slowly accumulate at the mu-opioid receptors over time, gradually displacing methadone. Methadone is then abruptly stopped once the target buprenorphine/naloxone dose is reached.144,487,488 Patients should be seen frequently to assess the titration, with speed of transition modified as needed based on symptoms. 
 

Table 21. Sample Low-dose Induction Protocol

Both methadone and SROM are full agonists at the mu receptor, which means that no wash out period is required. There is a lack of published research on strategies to transition between methadone and slow-release oral morphine for individuals with opioid use disorder. 

When transitioning from methadone to SROM, use a 1:6 to 1:8 ratio of methadone to SROM. For patients who are currently using unregulated opioids to supplement their current methadone dose, a 1:8 ratio and a more rapid transition schedule is preferable to address their higher opioid tolerance, while a 1:6 ratio or a more gradual titration schedule may be more suitable for patients who are not using unregulated opioids. 
 

Table 22. Rapid Transition from 100mg to SROM Using a 1:8 Ration of Methadone to SROM

Table 23. Gradual Transition from 150mg Methadone to SROM Using a 1:6 Ratio of Methadone to SROM

Table 24. Gradual Transition from 150mg Methadone to SROM Using a 1:8 Ratio of Methadone to SROM

Transitioning from SROM to methadone is challenging due to the different pharmacokinetics of these two long-acting opioid agonists. When transitioning from SROM to methadone, a conservative ratio of 12:1 or 10:1 SROM to methadone is appropriate in order to avoid inadvertent methadone toxicity. An even more conservative ratio should be used if the tolerance of the patient is unknown, if the patient does not have experience with methadone, or if they have medical comorbidities that may impact tolerance or safety. Patients should be monitored closely during transition. Example protocols follow.
 

Table 25. Rapid Transition from 1000mg SROM Using a 12:1 Ratio of SROM to Methadone (Not Suitable for Methadone-naïve Patients)

Table 26. Gradual Cross-titration from 1000mg SROM Using a 12:1 Ratio of SROM to Methadone

Table 27. Gradual Cross-titration from 1000mg SROM Using a 10:1 Ratio of SROM to Methadone