Can oxycodone be administered concurrently with methadone (methadone hydrochloride)?

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Last updated: May 25, 2025View editorial policy

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From the Guidelines

Oxycodone and methadone should not be taken together without careful medical supervision, as this combination can significantly increase the risk of serious side effects, including respiratory depression, overdose, and death. According to the CDC clinical practice guideline for prescribing opioids for pain [ 1 ], clinicians should exercise caution when prescribing immediate-release opioids in combination with extended-release/long-acting (ER/LA) opioids, such as methadone, due to the potential for increased overdose risk.

Key Considerations

  • Methadone has a long and variable half-life, which can lead to accumulation in the body and increase the risk of overdose when combined with other opioids [ 1 ].
  • The combination of oxycodone and methadone can cause dangerous respiratory depression, potentially leading to overdose and death [ 1 ].
  • Clinicians should consider the potential for increased overdose risk and use caution when prescribing immediate-release opioids, such as oxycodone, in combination with ER/LA opioids, such as methadone [ 1 ].

Recommendations

  • If you are currently prescribed methadone, consult your healthcare provider immediately about appropriate pain management options, as they may adjust your methadone dose or recommend non-opioid pain relievers instead [ 1 ].
  • Never take oxycodone and methadone together without explicit medical direction and supervision from a healthcare provider who is aware of all medications you are taking [ 1 ].
  • Clinicians should use additional caution with ER/LA opioids, such as methadone, and consider a longer dosing interval when prescribing to patients with renal or hepatic dysfunction, as decreased clearance of medications can lead to accumulation of medications to toxic levels [ 1 ].

From the Research

Opioid Interactions

  • The provided studies do not directly address the interaction between oxycodone and methadone when given at the same time.
  • However, studies have shown that combining opioids with other central nervous system depressants can increase the risk of respiratory depression and other adverse events 2, 3.
  • The risk of respiratory depression is a significant concern when using opioids, and this risk can be increased when multiple opioids are used together 4.

Respiratory Depression

  • Respiratory depression is a potentially life-threatening condition that can occur when opioids are used, especially at high doses or in combination with other central nervous system depressants 5, 4.
  • The studies suggest that the risk of respiratory depression can vary depending on the specific opioids used, as well as the context in which they are used 2, 3.
  • For example, the use of opioids in a hospice setting may be associated with a lower risk of respiratory depression due to the careful monitoring and management of patients in this setting 2.

Opioid-Specific Interactions

  • There is limited information available on the specific interaction between oxycodone and methadone, and more research is needed to fully understand the risks and benefits of using these medications together.
  • However, the studies suggest that the use of multiple opioids can increase the risk of adverse events, including respiratory depression, and that careful monitoring and management are necessary to minimize these risks 3, 4.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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