Is methadone a better alternative to oxycodone (Percocet) or hydrocodone (Norco) for patients on high-dose opioids?

From the Guidelines

Methadone can be a better alternative to Percocet or Norco for patients on high-dose opioids, particularly for chronic pain management, due to its longer duration of action and lower cost, but its use requires careful consideration of its complex pharmacokinetics and potential risks, such as QT prolongation and respiratory depression, as highlighted in the 2019 NCCN clinical practice guidelines 1. When transitioning from high-dose opioids to methadone, it is essential to start with a low dose, typically 5-10mg every 8-12 hours, and titrate slowly to avoid accumulation and adverse effects, as recommended by the NCCN panel members 1. Some key points to consider when using methadone include:

• Methadone has a long half-life, ranging from 8 to more than 120 hours, which makes its usage complex in patients with cancer 1
• Methadone should be started by or in consultation with an experienced pain or palliative care specialist due to its high potency and interindividual variations in pharmacokinetics 1
• Patients require close monitoring during initiation and dose adjustments, ideally every 5-7 days, as methadone's full effect may not be apparent for several days 1
• Methadone carries risks including QT prolongation, which necessitates ECG monitoring, and potentially dangerous drug interactions with medications that affect cytochrome P450 enzymes 1
• High doses of methadone (120 mg and above) may lead to QTc prolongation and torsades de pointes, which may lead to sudden cardiac death, as reported in studies 1 In contrast, oxycodone and hydrocodone have shorter half-lives and may require more frequent dosing, which can lead to peaks and valleys in analgesia, as discussed in the 2013 NCCN guidelines 1. However, the most recent and highest quality study, the 2019 NCCN clinical practice guidelines, suggests that methadone can be a viable alternative to oxycodone and hydrocodone for patients on high-dose opioids, when used carefully and with close monitoring 1.

From the FDA Drug Label

Methadone differs from many other opioid agonists in several important ways. Methadone's pharmacokinetic properties, coupled with high interpatient variability in its absorption, metabolism, and relative analgesic potency, necessitate a cautious and highly individualized approach to prescribing Particular vigilance is necessary during treatment initiation, during conversion from one opioid to another, and during dose titration. Deaths have been reported during conversion to methadone from chronic, high-dose treatment with other opioid agonists and during initiation of methadone treatment of addiction in subjects previously abusing high doses of other agonists. Incomplete cross-tolerance between m-opioid agonists makes determination of dosing during opioid conversion complex A high degree of "opioid tolerance" does not eliminate the possibility of methadone overdose, iatrogenic or otherwise

Methadone is not necessarily a better alternative to oxycodone (Percocet) or hydrocodone (Norco) for patients on high-dose opioids. Key considerations include:

• Complex pharmacokinetics: Methadone has unique properties that require cautious and individualized prescribing.
• Conversion risks: Deaths have been reported during conversion from high-dose treatment with other opioids to methadone.
• Incomplete cross-tolerance: Patients tolerant to other opioids may be incompletely tolerant to methadone, making dosing complex.
• Overdose risk: A high degree of opioid tolerance does not eliminate the possibility of methadone overdose.

Given these factors, methadone should be used with extreme caution in patients on high-dose opioids, and the decision to switch should be made on a case-by-case basis 2.

From the Research

Methadone as an Alternative to Oxycodone or Hydrocodone

• Methadone is a synthetic opioid analgesic that can be used as an alternative to oxycodone (Percocet) or hydrocodone (Norco) for patients on high-dose opioids 3.
• Methadone has a longer duration of action and higher efficacy compared to morphine, making it a suitable option for patients requiring high-dose opioids 3, 4.

Efficacy and Safety of Methadone

• Studies have shown that methadone is well-tolerated in patients with difficult pain syndromes who are receiving high-dose opioids 4.
• However, methadone can cause respiratory depression, and its use requires careful titration and monitoring 4, 5.
• The equianalgesic dose ratio of methadone to other opioids, such as morphine, can vary depending on the route of administration and individual patient factors 5.

Dose Conversion and Titration

• The dose ratio between oral methadone and oral morphine equivalent daily dose (MEDD) has been reported to be around 1:4.7, while the ratio for intravenous methadone to MEDD is around 1:13.5 5.
• A study found that patients rotated to methadone from high opioid doses had improved pain scale scores, but there was no correlation between high MED doses and methadone dose at stabilization 6.
• Caution should be exercised when converting patients to methadone, especially at high doses, due to the risk of adverse effects such as respiratory depression 4, 6.

Comparison to Other Opioids

• Methadone has been compared to other opioids, such as oxycodone and hydrocodone, in terms of its efficacy and safety profile 3, 7.
• A study found that high-dose methadone was more effective than moderate-dose methadone in reducing illicit opioid use in patients with opioid dependence 7.
• However, the choice of opioid should be individualized based on patient-specific factors, such as medical history, pain type, and tolerance to opioids 3, 7.