Diphenhydramine and Lofexidine interaction
Diphenhydramine and Lofexidine: both prescribing labels describe an interaction that usually calls for monitoring, a dose change, or spacing the doses.
Usually manageable with monitoring or a dose change. Tell your pharmacist you take both.
What the FDA labels say
From the Diphenhydramine label · effective 2026-03-05
Drug Interactions Diphenhydramine hydrochloride has additive effects with alcohol and other CNS depressants (hypnotics, sedatives, tranquilizers, etc).
From the Lofexidine label · effective 2026-07-22
Increased Risk of CNS Depression with Concomitant use of CNS Depressant Drugs : Lofexidine tablets potentiates the CNS depressant effects of benzodiazepines and may potentiate the CNS depressant effects of alcohol, barbiturates, and other sedating drugs.
Increased Risk of Central Nervous System Depression with Concomitant use of CNS Depressant Drugs Lofexidine tablets potentiates the CNS depressive effects of benzodiazepines and can also be expected to potentiate the CNS depressive effects of alcohol, barbiturates, and other sedating drugs.
CYP2D6 Inhibitors : Concomitant use of paroxetine resulted in increased plasma levels of Lofexidine tablets.
Monitor for symptoms of orthostasis and bradycardia with concomitant use of a CYP2D6 inhibitor.
CNS Depressant Drugs Lofexidine tablets potentiates the CNS depressant effects of benzodiazepines and may potentiate the CNS depressant effects of alcohol, barbiturates, and other sedating drugs.
Taking more than these two? Interactions stack. Check your whole list at once; it stays in your browser.
Open in the checkerNot medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.