Methadone for Pain

Methadone is used for both chronic pain and Opioid Use Disorder (OUD). A CPSA approval is required only for Opioid Agonist Treatment (OAT) when treating patients with OUD. This is no longer required when prescribing methadone for chronic pain. For analgesia, methadone is generally dosed three times daily; for OUD, methadone is generally dosed once daily with witnessed ingestion.

• Mu-opioid receptor agonist, serotonin and norepinephrine reuptake inhibitor, NMDA-receptor antagonist.
• Long half-life (average 24 hours); however duration of analgesia is typically 6-8 hours.
• Methadone blood levels continue to rise for approximately 5 days after a dose increase. Accumulated toxicity may result from increasing a dose before the full effect of the current dose is known.

• Patients will be discharged from the Chronic Pain Centre on a stable dose of methadone.
• For vomited doses:
  • Less than 15 minutes after ingestion, replace 50% of the dose.
  • 15 minutes or more after ingestion, no replacement.
• For missed doses:
  • Loss of tolerance can occur as early as 3 days. After 3 days of missed dosing, the total daily dose should be reduced by 50%, and the dose can be increased over a period of days to the previous dose.
• For acute-on-chronic pain:
  • If short-acting opioids are required for the management of acute pain in methadone patients, generally higher doses and more frequent intervals are required compared to opioid-naïve individuals.

• Methadone is metabolized by a number of cytochrome P450 enzymes – mainly CYP3A4 and, to a lesser extent, 1A2 and 2D6. Medications or natural health products that are enzyme inducers and inhibitors may result in decreases or increases, respectively, of methadone serum levels.
  • Inducers of CYP3A4 may decrease methadone levels
    • Examples: phenytoin, carbamazepine
  • Inhibitors of CYP3A4 may increase methadone levels
    • Examples: ciprofloxacin, clarithromycin, erythromycin, fluconazole, fluvoxamine, verapamil, diltiazem, grapefruit juice. When methadone patients start a CYP3A4 inhibitor, careful monitoring is required, and in some cases, the methadone dose may need to be reduced.
• Methadone may cause QT prolongation. Other drugs that have been associated with QT prolongation include:
  • Antidepressants: citalopram, escitalopram, amitriptyline, nortriptyline
  • Antiemetics: domperidone, ondansetron
  • Antibiotics: azithromycin, clarithromycin, erythromycin, ciprofloxacin
• Drug interactions can be checked online. Select the Professional tab for detailed information.

• Similar to all other opioids, safe prescribing practices including routine monitoring must be in place. Refer to the 2017 Canadian Guideline for Opioids for Chronic Non-Cancer Pain.
• Methadone may cause QT prolongation, and an ECG is recommended annually and when clinically indicated.

• Teleconsult Service
  • Book a 15-minute telephone conversation to discuss your patient’s chronic pain management. Use the Path to Care Referral Form. Refer to Chronic Pain Centre; Fax to (403) 209-2954; and Requested Action “Telephone consultation”.
• Specialist Link Advice
  • Call a chronic pain nurse practitioner at 403-910-2551 (toll-free 1-844-962-5465). Your call will be returned within one hour; available Monday - Friday 8:00am – 4:00pm.
• eReferral Advice 
  • Available via your Alberta Netcare login. Add eReferral to your Alberta Netcare homepage, search for your patient, and click on the Create Referral icon in the menu bar. You will receive advice within five calendar days.

• The 2017 Canadian Guideline for Opioids for Chronic Non-Cancer Pain
• Lynch ME et al. A review of the use of methadone for the treatment of chronic noncancer pain. Pain Res Manage 2005;10(3):133-44.