What are the side effects of Benadryl (diphenhydramine)?

Side Effects of Benadryl (Diphenhydramine)

Benadryl (diphenhydramine) has significant side effects including sedation, anticholinergic effects, and risk of toxicity in overdose, making it less desirable than second-generation antihistamines for most uses. 1

Common Side Effects

Diphenhydramine causes several common side effects due to its anticholinergic properties:

• Sedation/Drowsiness: Marked drowsiness is the most common side effect 2
• Dizziness 3
• Dry mouth 3
• Blurred vision 3
• Urinary retention 3
• Epigastric discomfort 3
• Wheezing 3

Cardiovascular Effects

• Hypotension: Can occur particularly with intravenous administration 3
• Tachycardia: Common with therapeutic doses 4
• ECG disturbances: Can occur with moderate overdoses 4
• Cardiac arrhythmias: Possible in severe overdoses 5

Central Nervous System Effects

• Excitability: Particularly in children 2
• Impaired coordination and performance: Makes driving and operating machinery dangerous 2
• Cognitive impairment: Especially concerning in elderly patients 6

Dose-Dependent Toxicity

The severity of side effects increases with dose:

• Moderate symptoms (isolated agitation, confusion, hallucinations) occur at doses above 300 mg 4
• Severe symptoms (delirium/psychosis, seizures, coma) occur at doses above 1000 mg 4

Special Populations at Risk

Elderly

• More susceptible to anticholinergic side effects
• Higher risk of cognitive impairment and falls 6

Children

• Risk of paradoxical excitability 2
• Should not be used to make children sleepy 2

Pregnant Women

• Has been associated with development of cleft palate 3
• Should consult healthcare provider before use 2

Drug Interactions

Diphenhydramine has important interactions:

• Alcohol: Increases drowsiness and impairment 2
• Sedatives and tranquilizers: Enhance sedative effects 2
• Other diphenhydramine-containing products: Risk of overdose when combined 2

Overdose Risks

Diphenhydramine overdose can cause:

• Toxic psychosis: Hallucinations and bizarre behavior 7
• Anticholinergic crisis: Hyperthermia, dry skin, urinary retention
• Status epilepticus: Seizures that don't resolve without intervention 5
• Coma: In severe cases 5
• Cardiac arrhythmias: Potentially life-threatening 5

Important Precautions

Do not use diphenhydramine if you have:

• Breathing problems like chronic bronchitis
• Glaucoma
• Urinary problems due to enlarged prostate 2

Modern Perspective

Despite its long history of use, many experts now recommend avoiding diphenhydramine when possible:

• Second-generation antihistamines provide similar efficacy with fewer side effects 1
• Some countries have restricted access to first-generation antihistamines like diphenhydramine 6
• The therapeutic ratio (benefit vs. risk) is particularly problematic in children and older adults 6

In case of accidental overdose, seek immediate medical help or contact a Poison Control Center (1-800-222-1222) 2.