Can buprenorphine be administered to patients on methadone (methadone hydrochloride)?

From the Guidelines

Buprenorphine should not be administered to patients currently on methadone without first allowing for a sufficient washout period, as it can precipitate acute opioid withdrawal due to its partial agonist properties and high receptor affinity. This is supported by the most recent and highest quality study, which emphasizes the importance of careful consideration when transitioning from methadone to buprenorphine 1.

Key Considerations for Transitioning from Methadone to Buprenorphine

• Patients should discontinue methadone and wait until they are experiencing moderate withdrawal symptoms (typically 24-36 hours after the last methadone dose) before initiating buprenorphine.
• The recommended approach is to taper the methadone dose to 30-40mg daily before considering the transition.
• When initiating buprenorphine, start with a low dose (2mg) and monitor for precipitated withdrawal.
• For patients on higher methadone doses, a more gradual transition with temporary use of short-acting opioids as an intermediate step may be necessary.
• The transition should always be medically supervised, as precipitated withdrawal can be severe and distressing for patients, potentially compromising their treatment adherence and recovery.

Rationale for Caution

The risk of precipitated withdrawal is a significant concern when transitioning from methadone to buprenorphine, as buprenorphine can displace methadone from opioid receptors without providing full activation, leading to sudden and severe withdrawal symptoms 1. Therefore, it is crucial to prioritize a medically supervised transition to minimize the risk of adverse outcomes and ensure the best possible quality of life for patients.

Clinical Implications

In clinical practice, healthcare providers should exercise caution when considering the transition from methadone to buprenorphine, taking into account the individual patient's needs and medical history. By prioritizing a careful and medically supervised transition, healthcare providers can help minimize the risk of precipitated withdrawal and ensure the best possible outcomes for patients.

From the FDA Drug Label

Patients Dependent on Methadone or Other Long-acting Opioid Products: Patients dependent upon methadone or other long-acting opioid products may be more susceptible to precipitated and prolonged withdrawal during induction than those on short-acting opioid products; therefore, the first dose of Buprenorphine Sublingual Tablets should only be administered when objective and clear signs of moderate opioid withdrawal appear, and generally not less than 24 hours after the patient last used a long-acting opioid product. There is little controlled experience with the transfer of methadone-maintained patients to buprenorphine. Available evidence suggests that withdrawal signs and symptoms are possible during induction onto buprenorphine Withdrawal appears more likely in patients maintained on higher doses of methadone (>30 mg) and when the first buprenorphine dose is administered shortly after the last methadone dose.

Buprenorphine administration to patients on methadone is possible, but it requires careful consideration of the timing and dose. The first dose of buprenorphine should be administered at least 24 hours after the last methadone dose, and only when signs of moderate opioid withdrawal appear. Patients on higher doses of methadone (>30 mg) may be more likely to experience withdrawal symptoms during induction onto buprenorphine. 2

From the Research

Administration of Buprenorphine to Patients on Methadone

• Buprenorphine can be administered to patients on methadone using a microdosing protocol, which involves giving low-dose buprenorphine concurrently with the patient's full dose of methadone and gradually titrating up the buprenorphine dose over 7 days 3.
• This approach can successfully transition patients from methadone to buprenorphine without the need for a period of opioid abstinence, with minimal symptoms of opioid withdrawal 3.
• However, there is a risk of precipitated opioid withdrawal when commencing patients on buprenorphine treatment, particularly when transferring from long-acting opioids like methadone 4.
• In cases where precipitated withdrawal occurs, rapid increases in buprenorphine dose can be used as an effective treatment, allowing the individual to continue on this highly effective treatment 4.

Transitioning from Methadone to Buprenorphine

• A short-acting agonist bridge can be used to transition patients from methadone to buprenorphine in the inpatient setting, using commonly available dosages and formulations of buprenorphine 5.
• Methadone can also be used under the "72-hour rule" to facilitate transitions of care and low-dose buprenorphine induction in an outpatient bridge clinic, enabling patients to successfully transition to buprenorphine without significant concomitant opioid use 6.
• The choice of treatment (methadone or buprenorphine) should be based on individual patient characteristics and preferences, with consideration given to factors such as treatment retention, safety, and risk of toxicity 7.