Promethazine and Zaleplon Interaction

Drug interaction information between Promethazine and Zaleplon.

Promethazine and Zaleplon have a documented minor interaction in FDA labeling.

FDA drug labeling documents a minor-severity interaction between Promethazine and Zaleplon. This page displays the available source-record category and label text. The category is not an individual risk estimate or medication-combination direction.

Drug A

Promethazine

Phenothiazine Antiemetic / Antihistamine

Drug B

Zaleplon

Non-Benzodiazepine Hypnotic (Z-Drug)

How They Interact

Promethazine slightly reduces the highest level of zaleplon in your blood, but the total amount in your body remains about the same.

FDA Label Information

Promethazine: Coadministration of a single dose of zaleplon and promethazine (10 and 25 mg, respectively) resulted in a 15% decrease in maximal plasma concentrations of zaleplon, but no change in the area under the plasma concentration-time curve. However, the pharmacodynamics of coadministration of zaleplon and promethazine have not been evaluated.

Frequently Asked Questions

What SPL severity band is on file for Promethazine + Zaleplon?

Compiled FDA labeling labels this pair minor. That is a source-record field, not an individual medication-combination decision.

Which drug in this pair has the larger labeled-interaction portfolio?

Zaleplon has 16 labeled pairs on file vs Promethazine's 3. In the minor band specifically: Promethazine has 3 (also Epinephrine, Famciclovir); Zaleplon has 16 (also Ibuprofen, Venlafaxine, Paroxetine, Warfarin).

What mechanism field is on file for Promethazine and Zaleplon?

Promethazine slightly reduces the highest level of zaleplon in your blood, but the total amount in your body remains about the same.

Zaleplon's labeled portfolio outnumbers Promethazine

SPL source-record counts only. This page's band is minor · classes on file: Promethazine (Phenothiazine Antiemetic / Antihistamine); Zaleplon (Non-Benzodiazepine Hypnotic (Z-Drug)).

Promethazine

0 major · 0 moderate · 3 minor · 3 total

Zaleplon

0 major · 0 moderate · 16 minor · 16 total

Sources: FDA Drug Labels (SPL) via openFDA (2026). This is for informational purposes only and is not medical advice. This registry does not provide individual medication-combination directions.