Can fentanyl be given with rasagiline?

Fentanyl and Rasagiline: Potential Interaction and Management

Fentanyl should not be administered with rasagiline due to the risk of serotonin syndrome, as fentanyl has serotonin reuptake inhibitory activity that can interact with monoamine oxidase inhibitors like rasagiline. 1

Understanding the Interaction

• Fentanyl has serotonin reuptake inhibitory activity, which increases the risk of serotonin syndrome when given with medications that affect serotonin levels, including monoamine oxidase inhibitors (MAOIs) like rasagiline 1
• Rasagiline is a selective irreversible inhibitor of monoamine oxidase B (MAO-B) used in Parkinson's disease treatment 2
• While rasagiline is selective for MAO-B at recommended doses, this selectivity may not be absolute, creating potential for interaction with serotonergic drugs 3

Clinical Implications

• Serotonin syndrome is a potentially fatal condition characterized by neuroexcitatory symptoms, autonomic dysfunction, and neuromuscular abnormalities 1
• Unlike with meperidine (which has a documented life-threatening interaction with MAOIs), the specific interaction between fentanyl and rasagiline is less well-documented but still concerning 1
• The Mayo Clinic Proceedings specifically warns about perioperative risk of serotonin syndrome when using serotonergic opioids (including fentanyl) with MAOIs 1

Alternative Approaches

• Consider hydromorphone as an alternative opioid analgesic, which does not have significant serotonergic activity 1
• If opioid analgesia is necessary in a patient taking rasagiline:
  • Use non-serotonergic opioids 1
  • Ensure close monitoring for signs of serotonin syndrome 4
  • Have naloxone readily available for reversal of opioid effects if needed 5

Special Considerations

• Rasagiline has shown better MAO-B selectivity than older MAOIs like selegiline, which may reduce but not eliminate interaction risk 3
• A study of rasagiline with the SSRI escitalopram showed good tolerability in healthy volunteers, but this doesn't guarantee safety with fentanyl, which has different pharmacologic properties 6
• Rasagiline undergoes extensive hepatic metabolism primarily by CYP1A2, which is a different metabolic pathway than fentanyl, potentially reducing but not eliminating interaction risk 2

Monitoring and Management

• If fentanyl must be used in a patient on rasagiline (which is not recommended):
  • Use the lowest effective dose 1
  • Monitor closely for signs of serotonin syndrome including agitation, hyperthermia, hyperreflexia, and autonomic instability 1
  • Consider temporary discontinuation of rasagiline if possible before fentanyl administration 2
  • Have benzodiazepines available for management of agitation if serotonin syndrome develops 1

Conclusion

Given the potential risk of serotonin syndrome and the availability of safer alternatives, fentanyl should be avoided in patients taking rasagiline. When analgesia is required, non-serotonergic opioids should be selected instead 1.