Is it safe to take cyclobenzaprine (muscle relaxant) and methadone (opioid analgesic) together?

Cyclobenzaprine and Methadone Combination: Safety Concerns

Combining cyclobenzaprine with methadone is not recommended due to increased risk of respiratory depression, sedation, and potentially fatal outcomes. 1

Risks of This Combination

• Methadone may increase the likelihood of toxicity when combined with other medications that increase serotonergic and/or noradrenergic activity, such as cyclobenzaprine (which is structurally related to tricyclic antidepressants) 1
• Cyclobenzaprine causes significant sedation through its noncompetitive antagonism of histamine H1 receptors, which would compound the central nervous system depressant effects of methadone 2
• The combination increases risk of respiratory depression, which is the primary mechanism of opioid-related deaths 1
• Methadone has unique pharmacokinetic properties including a long and variable half-life with peak respiratory depressant effects occurring later and lasting longer than peak analgesic effects, making this combination particularly dangerous 1

Pharmacological Considerations

• Cyclobenzaprine is a centrally acting skeletal muscle relaxant structurally related to tricyclic antidepressants, primarily indicated for relief of muscle spasm associated with acute, painful musculoskeletal conditions 3
• Methadone should be administered only by clinicians experienced in its use because of risk of accumulation and complex pharmacokinetics 1
• Methadone has complicated pharmacokinetics and pharmacodynamics, including QT interval prolongation risk, making safe prescribing especially challenging 1
• The sedative effects of cyclobenzaprine are significant - more than 30% of patients experience drowsiness and sedative-hypnotic effects 2

Clinical Decision-Making

• For patients requiring both muscle relaxation and pain management:
  • Consider alternative muscle relaxants with less sedative properties if opioid therapy is necessary 3
  • Consider non-opioid analgesics such as NSAIDs as an alternative to methadone when muscle relaxants are needed 4
  • If pain management is required for patients on methadone maintenance therapy, non-opioid analgesics should be first-line 1

Monitoring if Combination Cannot Be Avoided

• If the combination must be used in exceptional circumstances (which should be rare):
  • Use the lowest effective dosage of cyclobenzaprine (2.5mg instead of 5mg or 10mg) 5
  • Implement more frequent monitoring for signs of excessive sedation and respiratory depression 1
  • Consider offering naloxone to patients and their caregivers to reverse potential overdose 1
  • Educate patients about the increased risks of sedation, respiratory depression, and the importance of not taking more than prescribed 1

Alternative Approaches

• For muscle spasm management:
  • NSAIDs alone may be sufficient for many cases of acute musculoskeletal pain with spasm 6, 4
  • Physical therapy and non-pharmacological approaches should be considered 1
• For patients on methadone for opioid use disorder:
  • Coordinate care with the prescriber managing the methadone therapy before adding any potentially interacting medications 1

Important Caveats

• The CDC guidelines specifically caution against concurrent use of opioids with other central nervous system depressants 1
• Methadone's unique risk profile requires clinicians to be familiar with its properties before prescribing 1
• The combination of these medications could potentially be fatal due to additive central nervous system and respiratory depression effects 1