Major
Probable
Description
Diphenhydramine potentiates morphine-induced CNS and respiratory depression and may increase the risk of fatal overdose.
Mechanism
H1 receptor blockade and anticholinergic effects of diphenhydramine are additive to mu-opioid receptor-mediated CNS and respiratory depression.
Clinical Significance
The combination carries significant risk of profound sedation, respiratory compromise, and death, particularly at higher doses.
Management
Use non-sedating antihistamines; if diphenhydramine is needed, monitor closely for excessive sedation and reduce opioid dose.