Haloperidol and Diphenhydramine Injection: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Haloperidol
No brand names on recordDiphenhydramine Injection
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
What happens
Increased haloperidol exposure, an increased risk of haloperidol-related adverse events, including QTc interval prolongation and an increased risk of CNS depression
Interaction Deep Dive
Haloperidol may be capable of potentiating CNS depressants. Hence concomitant use of haloperidol and CNS depressants, such as diphenhydrAMINE may increase the risk of CNS depression12. Coadminister of haloperidol and diphenhydrAMINE (CYP2D6 inhibitor) may increase haloperidol exposure, which may increase haloperidol-related adverse events, including QTc interval prolongation. It is recommended that patients who take haloperidol concomitantly with diphenhydrAMINE be monitored for signs or symptoms of increased or prolonged pharmacologic effects of haloperidol, and haloperidol dose be reduced as deemed necessary 1.
Why it happens (mechanism)
Inhibition of CYP2D6-mediated metabolism of haloperidol; an increased risk of CNS depression
Literature reports
1 report — tap to read
a) Increases in QTc have been observed when haloperidol was given with a combination of the metabolic inhibitors ketoconazole (CYP3A4 inhibitor) (400 mg/day) and PARoxetine (CYP2D6 inhibitor) (20 mg/day) 1.
Common questions
Can I take Haloperidol and Diphenhydramine Injection together?
Increased haloperidol exposure, an increased risk of haloperidol-related adverse events, including QTc interval prolongation and an increased risk of CNS depression Always confirm with your pharmacist or prescriber before making any change.
How serious is the Haloperidol and Diphenhydramine Injection interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
Questions for your pharmacist
- Does my dose of Haloperidol or Diphenhydramine Injection need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (2)
- Product Information: HALDOL(R) Decanoate 100 intramuscular injection, haloperidol decanoate intramuscular injection. Janssen Pharmaceuticals Inc (per FDA), Titusville, NJ, 2025.
- Product Information: Haloperidol oral solution, haloperidol oral solution. Advagen Pharma Ltd. (per DailyMed), East Windsor, NJ, 2024. DailyMed
Keep reading about Haloperidol
Keep reading about Diphenhydramine Injection
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