Major
Established
Description
Diazepam and morphine together produce additive CNS and respiratory depression, carrying an FDA boxed warning for fatal outcomes.
Mechanism
Diazepam enhances GABA-A inhibitory neurotransmission; morphine binds mu-opioid receptors and suppresses respiratory centers in the brainstem, with synergistic depression of the CNS.
Clinical Significance
The benzodiazepine-opioid combination is implicated in a large proportion of opioid overdose deaths in the United States.
Management
Avoid combination; if co-prescribing is necessary, use the lowest doses, monitor closely, and prescribe naloxone.