Clozapine and Diphenhydramine Interaction
Drug interaction information between Clozapine and Diphenhydramine.
Clozapine and Diphenhydramine have a documented moderate interaction in FDA labeling.
FDA drug labeling documents a moderate-severity interaction between Clozapine and Diphenhydramine. This page displays the available source-record category and label text. The category is not an individual risk estimate or medication-combination direction.
How They Interact
These two drugs both block certain signals in the body, which can lead to a 'double dose' of side effects like extreme sleepiness and severe constipation. This happens because both medications have similar drying and slowing effects on the body.
FDA Label Information
Anticholinergic Drugs Concomitant treatment with clozapine and other drugs with anticholinergic activity (e.g., benztropine, cyclobenzaprine, diphenhydramine) can increase the risk for anticholinergic toxicity and severe gastrointestinal adverse reactions related to hypomotility.
Clozapine Also Interacts With
- Cyclobenzaprine moderate
- Fluoxetine moderate
- Sertraline minor
- Escitalopram minor
- Bupropion minor
Frequently Asked Questions
What SPL severity band is on file for Clozapine + Diphenhydramine?
Compiled FDA labeling labels this pair moderate. That is a source-record field, not an individual medication-combination decision.
Which drug in this pair has the larger labeled-interaction portfolio?
Clozapine has 42 labeled pairs on file vs Diphenhydramine's 2. In the moderate band specifically: Clozapine has 3 (also Cyclobenzaprine, Fluoxetine); Diphenhydramine has 1.
What mechanism field is on file for Clozapine and Diphenhydramine?
These two drugs both block certain signals in the body, which can lead to a 'double dose' of side effects like extreme sleepiness and severe constipation. This happens because both medications have similar drying and slowing effects on the body.
Clozapine's labeled portfolio outnumbers Diphenhydramine
SPL source-record counts only. This page's band is moderate · classes on file: Clozapine (Atypical Antipsychotic); Diphenhydramine (First-Generation Antihistamine).
0 major · 3 moderate · 39 minor · 42 total
- Other moderate peers for Clozapine
- Cyclobenzaprine
- Fluoxetine
0 major · 1 moderate · 1 minor · 2 total
Diphenhydramine has no other moderate-band peer in this dataset besides Clozapine.
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.
Read our methodology - how this data is sourced, computed, and verified.