Diphenhydramine and Pitolisant interaction
Diphenhydramine and Pitolisant: the Pitolisant prescribing label flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.
Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.
What the FDA labels say
From the Pitolisant (Wakix) label · effective 2026-02-13
Prevention or Management: Avoid centrally acting H1 receptor antagonists.
Strong CYP2D6 Inhibitors: Increased exposure of WAKIX; reduce the maximum recommended dose of WAKIX by half ( 2.6 , 7.1 )
Drugs Having Clinically Important Interactions with WAKIX Table 2: Clinically Significant Drug Interactions with WAKIX Effect of Other Drugs on WAKIX Strong CYP2D6 Inhibitors Clinical Implication: Concomitant administration of WAKIX with strong CYP2D6 inhibitors increases pitolisant exposure by 2.2-fold.
Histamine-1 (H1) Receptor Antagonists Clinical Implication: WAKIX increases the levels of histamine in the brain; therefore, H1 receptor antagonists that cross the blood-brain barrier may reduce the effectiveness of WAKIX.
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.