Does Benadryl Lower Your White Blood Cell Count?
No, diphenhydramine (Benadryl) does not lower white blood cell count and is not associated with hematologic toxicity in clinical practice.
Evidence from Clinical Guidelines and Research
Hematologic Safety Profile
Diphenhydramine is not listed among medications that require white blood cell monitoring or that carry risk of blood count suppression. Multiple clinical guidelines addressing drug-induced hematologic toxicity specifically identify medications requiring WBC monitoring—such as clozapine, azathioprine, cyclophosphamide, and rifabutin—but diphenhydramine is notably absent from these lists 1.
Documented Adverse Effects of Diphenhydramine
The established side effect profile of diphenhydramine includes 1, 2:
- Anticholinergic effects: dry mouth, blurred vision, urinary retention, constipation
- Central nervous system effects: sedation, dizziness, paradoxical agitation (particularly in children and elderly)
- Cardiovascular effects: hypotension (especially when given IV or with other CNS depressants)
- Other effects: epigastric discomfort, wheezing
Notably, hematologic toxicity including leukopenia, neutropenia, or agranulocytosis is not documented as an adverse effect of diphenhydramine 1, 2.
Clinical Context: Medications That DO Lower WBC
For comparison, medications that genuinely require WBC monitoring due to risk of blood count suppression include 1:
- Clozapine: Requires weekly WBC monitoring for 6 months, then biweekly, with discontinuation if WBC falls below 3,000/mm³ or absolute neutrophil count below 1,500/mm³
- Azathioprine and cyclophosphamide: Require dose reduction or discontinuation if WBC drops below 4,000/mm³
- Rifabutin: Commonly causes WBC reduction below 5,000/mm³, though severe leukopenia is unusual
Transfusion Medicine Evidence
Research examining diphenhydramine as premedication for blood transfusions provides additional reassurance. Studies evaluating thousands of transfusions with diphenhydramine premedication found no association with hematologic complications or changes in blood counts 3, 4. If diphenhydramine affected WBC counts, this would have been detected in these large-scale transfusion studies.
Clinical Implications
Diphenhydramine can be used without concern for white blood cell suppression 1, 2. No baseline or monitoring blood counts are required when prescribing diphenhydramine, unlike the extensive hematologic monitoring protocols mandated for medications with genuine bone marrow toxicity 1.
The primary safety concerns with diphenhydramine relate to its anticholinergic and sedative properties, not hematologic effects 1, 2.