What are the side effects of Diphenhydramine (Benadryl) to counsel a patient?

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From the Guidelines

When counseling patients about Benadryl (diphenhydramine) side effects, it is crucial to inform them that drowsiness, confusion, and delirium are significant concerns, particularly in older adults, making it generally not recommended for elderly patients, as highlighted in a recent study 1. The most common side effects of Benadryl include:

  • Drowsiness, which makes it unsafe to drive or operate machinery after taking it
  • Dry mouth
  • Blurred vision
  • Constipation
  • Difficulty urinating
  • Dizziness Patients should be aware that Benadryl can cause confusion or delirium, particularly in older adults, due to its anticholinergic effects, as noted in a study on the diagnosis and management of rhinitis 1. Some people may experience paradoxical excitation, especially in children. Benadryl can interact with other medications that cause drowsiness, including alcohol, sleep aids, and certain antidepressants, potentially increasing sedation, as discussed in a study on polypharmacy management in older patients 1. Long-term use is not recommended as tolerance to its effects can develop. These side effects occur because Benadryl blocks histamine receptors but also affects cholinergic pathways in the brain and peripheral nervous system. Patients should contact their healthcare provider if they experience severe side effects or allergic reactions such as rash, itching, or swelling. It is essential to consider the potential risks and benefits of Benadryl, particularly in older adults, and to explore alternative treatment options with fewer side effects, as suggested in a study on the management of allergic rhinitis 1.

From the FDA Drug Label

Warnings Do not use • to make a child sleepy • with any other product containing diphenhydramine, even one used on skin Ask a doctor before use if you have • a breathing problem such as chronic bronchitis • glaucoma • trouble urinating due to enlarged prostate gland Ask a doctor or pharmacist before use if you are taking sedatives or tranquilizers When using this product • marked drowsiness may occur • avoid alcoholic drinks • alcohol, sedatives, and traquilizers may increase drowsiness • be careful when driving a motor vehicle or operating machinery • excitability may occur, especially in children If pregnant or breast-feeding, ask a healthcare professional before use Keep out of reach of children. In case of accidental overdose, get medical help or contact a Poison Control Center right away (1-800-222-1222)

Key Side Effects to Counsel the Patient:

  • Drowsiness: marked drowsiness may occur
  • Increased drowsiness with other substances: alcohol, sedatives, and tranquilizers may increase drowsiness
  • Excitability: especially in children
  • Impaired driving or machinery operation: be careful when driving a motor vehicle or operating machinery 2

From the Research

Benadryl Side Effects

Benadryl, also known as diphenhydramine, is a first-generation antihistamine that can cause several side effects, including:

  • Sedation
  • Impaired psychomotor performance
  • Excessive mucosal drying
  • Anticholinergic side effects

Comparison with Other Antihistamines

In comparison to newer, second-generation antihistamines, Benadryl has a higher risk of side effects due to its ability to cross the blood-brain barrier 3. Some second-generation antihistamines, such as cetirizine, loratadine, and desloratadine, have been shown to be effective in treating urticaria and rhinitis with fewer side effects 4, 5, 6, 7.

Counseling Patients

When counseling patients about Benadryl side effects, it is essential to discuss the potential risks and benefits of treatment. Patients should be informed about the possible side effects, including sedation and impaired psychomotor performance, and advised to use caution when operating heavy machinery or driving. Additionally, patients should be encouraged to report any adverse effects to their healthcare provider.

Alternative Treatment Options

For patients who experience significant side effects from Benadryl, alternative treatment options may be considered. Second-generation antihistamines, such as cetirizine and loratadine, may be a better option for some patients due to their lower risk of side effects 4, 5, 6, 7. However, the choice of treatment should be individualized based on the patient's specific needs and medical history.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Pharmacology of antihistamines.

The Journal of allergy and clinical immunology, 1990

Research

H1-antihistamines for chronic spontaneous urticaria.

The Cochrane database of systematic reviews, 2014

Research

Comparative inhibition profiles of three non-sedating antihistamines assessed by an extended Lewis model.

Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 1992

Research

Treatment of urticaria and angioedema: low-sedating H1-type antihistamines.

Journal of the American Academy of Dermatology, 1991

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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