What the FDA labels say about taking them together
Clozapine and diphenhydramine
Clozapine's FDA label of June 6, 2025 names diphenhydramine in its drug interactions section; the diphenhydramine label PlainMeds reads does not name clozapine. The clozapine label: “Anticholinergic Drugs Concomitant treatment with clozapine and other drugs with anticholinergic activity can increase the risk for anticholinergic toxicity and severe gastrointestinal adverse reactions related to …”
Check it at the source: the clozapine FDA label on DailyMed (effective June 6, 2025, HLS Therapeutics (USA), Inc.); the diphenhydramine FDA label on DailyMed (effective November 18, 2025, Heritage Pharmaceuticals Inc. d/b/a Avet Pharmaceuticals Inc.).
What does the clozapine label say about diphenhydramine?
Clozapine label, drug interactionsAnticholinergic 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.
Source: FDA drug label (Clozaril), NDA019758 (Heritage Life), as published by HLS Therapeutics (USA), Inc., effective June 6, 2025 (SPL set 90876802-0e3a-44c9-9ff7-1754dfbe736a), via openFDA; the full label on DailyMed
What does the diphenhydramine label say about clozapine?
Diphenhydramine's label (effective November 18, 2025) does not name clozapine in these sections. A label lists what its studies and reports found; it is not a complete list.
Source: FDA drug label (Diphenhydramine Hydrochloride), Heritage Pharmaceuticals Inc. d/b/a Avet Pharmaceuticals Inc., effective November 18, 2025 (SPL set 6178d3a1-0741-49a4-be81-c4f7d29f8b2a), via openFDA; the full label on DailyMed
These are the labels' own sentences. PlainMeds does not grade interactions; a pharmacist or prescriber can say what they mean for one person's medicines.
Both medicines on the record
| Clozapine | Diphenhydramine | |
|---|---|---|
| Labeled for | Schizophrenia | Cough and cold, Allergies, Pain |
| Boxed warning | Yes | No |
| Pharmacy cost (NADAC) | $0.610 per tablet 100 mg tablet | $0.898 per mL 50 mg/mL vial |
| Shortage now | No current entry | No current entry |
Source: FDA NDC Directory, CMS NADAC of October 7, 2026 and the FDA Drug Shortage Database (FDA files October 8, 2026)
What next?
- Check more medicines together
- up to five at once