CriticalAntidepressant, irreversible non-selective monoamine oxidase inhibitor (MAO-A and MAO-B)×Other opioids
Updated · Methodology
Mechanism
Tramadol inhibits serotonin reuptake (secondary mechanism). Combined with phenelzine causes fatal serotonin syndrome – fatal cases reported. FDA boxed warning on tramadol.
Symptoms
Within 1–6 hours: hyperthermia above 39°C, myoclonus, agitation, seizures. High mortality without tramadol withdrawal.
Management
Combination contraindicated. Alternative analgesic: paracetamol or gabapentin (no serotonergic effect). If opioid is needed, morphine with caution.
Check the full regimen, not just this pair
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Sources
- FDA: Nardil (phenelzine sulfate) prescribing information (2009)– FDA Nardil label, Section 4 Contraindications; DailyMed setid 513a41d0-37d4-4355-8a6d-a2c643bce6fa