Major
duloxetine × Tramadol
SNRI×Other opioids
Mechanism
Dual risk. Duloxetine (SNRI) raises synaptic serotonin and norepinephrine. Tramadol blocks serotonin and norepinephrine reuptake and lowers seizure threshold. Combined action amplifies serotonergic activity.
Symptoms
Serotonin syndrome: agitation, confusion, tremor, myoclonus, hyperreflexia. Autonomic features: sweating, tachycardia, hypertension, fever. First signs appear within hours of co-administration.
Management
Avoid the combination. For analgesia on duloxetine, use paracetamol, an NSAID, or morphine/oxycodone. For neuropathic pain, gabapentin or pregabalin.
Check the full regimen, not just this pair
Opens the checker with these two drugs prefilled. Add the rest of the regimen and recompute additive risks.