Major
Established
Descripción
Diazepam and tramadol together produce additive CNS and respiratory depression with an FDA boxed warning for concomitant opioid-benzodiazepine use.
Mecanismo
GABA-A potentiation (diazepam) is additive to mu-opioid receptor activation and serotonin reuptake inhibition (tramadol), producing multi-receptor CNS depression.
Relevancia clínica
Real-world data show significantly increased overdose mortality with benzodiazepine-opioid analgesic combinations including tramadol.
Manejo clínico
Avoid combination; if pain management requires tramadol in a benzodiazepine user, prescribe naloxone and monitor closely.