Diphenhydramine and Iloperidone interaction
Diphenhydramine and Iloperidone: 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 Iloperidone (FANAPT) label · effective 2026-05-06
Strenuous exercise, exposure to extreme heat, dehydration, and anticholinergic medications may contribute to an elevation in core body temperature; use FANAPT with caution in patients who may experience these conditions.
Table 7: Clinically Important Drug Interactions with FANAPT Strong CYP2D6 Inhibitors Clinical Impact Coadministration of fluoxetine with iloperidone increased exposure (area under curve, [AUC]) of iloperidone and its metabolite P88, by about 2- to 3- fold, and decreased the AUC of its metabolite P95 by one-half [see Clinical Pharmacology (12.3 , 12.5) ] .
Intervention Reduce the dose of FANAPT by one-half when administered with strong CYP2D6 inhibitors.
When a strong CYP2D6 inhibitor is withdrawn from the combination therapy, the iloperidone dose should be returned to the previous level [see Dosage and Administration (2.4) ] .
When the inhibitors of CYP2D6 and CYP3A4 are withdrawn from the combination therapy, the FANAPT dose should be returned to the previous level [see Dosage and Administration (2.4) ] .
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.