Alcohol, other opioids/sedatives (benzodiazepines, sleep medicines), SSRIs/SNRIs/TCAs/MAOIs (serotonin syndrome, seizures), anticoagulants/antiplatelets (warfarin, aspirin, clopidogrel—bleeding risk), other NSAIDs/steroids (GI bleed), antihypertensives/diuretics (reduced effect, kidney risk), lithium, methotrexate, anticonvulsants (carbamazepine, phenytoin), CYP inhibitors/inducers affecting tramadol (e.g., fluoxetine, paroxetine)