What are the contraindications for Benadryl (diphenhydramine) in patients with various medical conditions, such as glaucoma, urinary retention, asthma, seizure disorders, and impaired renal function, especially in the elderly?

Benadryl (Diphenhydramine) Contraindications

Diphenhydramine should be avoided entirely—or used with extreme caution—in older adults, patients with glaucoma, benign prostatic hypertrophy/urinary retention, ischemic heart disease, uncontrolled hypertension, chronic obstructive pulmonary disease, dementia, cognitive impairment, and seizure disorders. 1

Absolute Contraindications

Glaucoma

• Diphenhydramine causes pupillary dilation through its anticholinergic effects and can precipitate acute angle-closure glaucoma. 1
• The FDA drug label explicitly warns against use in patients with glaucoma. 2

Benign Prostatic Hypertrophy and Urinary Retention

• Diphenhydramine's anticholinergic effects impair bladder contraction and can precipitate acute urinary retention, making this a major contraindication. 1
• The FDA label specifically warns against use in patients with "trouble urinating due to enlarged prostate gland." 2
• Up to 10% of acute urinary retention episodes may be attributable to anticholinergic medications like diphenhydramine. 3

Chronic Obstructive Pulmonary Disease and Asthma

• The FDA label warns against use in patients with "a breathing problem such as chronic bronchitis." 2
• Diphenhydramine can cause wheezing and respiratory complications. 1

Strong Relative Contraindications (Use with Extreme Caution)

Elderly Patients

• Older adults are at dramatically increased risk for delirium, cognitive decline, confusion, and falls when exposed to diphenhydramine. 1
• Hospitalized elderly patients receiving diphenhydramine have a 1.7-fold increased risk of any delirium symptoms (95% CI 1.3-2.3), with specific risks including inattention (RR 3.0), disorganized speech (RR 5.5), and altered consciousness (RR 3.1). 4
• A dose-response relationship exists for adverse cognitive outcomes in elderly patients. 4
• The American Geriatrics Society recommends avoiding diphenhydramine in older adults to prevent postoperative delirium. 5

Ischemic Heart Disease and Uncontrolled Hypertension

• The American Gastroenterological Association guidelines recommend extreme caution or avoidance in patients with ischemic heart disease or uncontrolled hypertension. 1
• Diphenhydramine can cause cardiac toxicity in overdose, including wide-complex tachycardia and QRS prolongation. 6

Dementia and Cognitive Impairment

• Dementia and cognitive impairment are strong relative contraindications given the high risk of delirium and further cognitive decline. 1
• Diphenhydramine is associated with increased risk of cognitive decline in hospitalized older patients. 4

Seizure Disorders

• The American Gastroenterological Association notes caution is warranted in patients with seizure disorders. 5
• Status epilepticus, though rare, has been reported following diphenhydramine overdose. 6

Important Drug Interactions

Avoid Combination With:

• Other anticholinergic agents (cyclobenzaprine, oxybutynin, prochlorperazine, promethazine, tricyclic antidepressants, paroxetine) due to additive anticholinergic effects. 5, 1
• Alcohol, sedatives, benzodiazepines, and opioid narcotics, as diphenhydramine's hypnotic and sedative effects are significantly increased with these combinations. 1, 2
• The FDA label explicitly warns that "alcohol, sedatives, and tranquilizers may increase drowsiness." 2

Critical Monitoring Parameters When Use Cannot Be Avoided

Anticholinergic Toxicity Assessment

• Monitor for urinary retention, constipation, dry mouth, blurred vision, and delirium. 1
• Watch for paradoxical reactions including increased agitation and rage, particularly in children and adolescents. 1
• Assess for hypotension, especially when given intravenously or with other CNS depressants. 1

Cardiovascular Monitoring

• Monitor blood pressure for hypotension and heart rate for tachycardia. 1
• In overdose situations, obtain ECG to assess for QRS widening and consider sodium bicarbonate therapy if wide-complex tachycardia develops. 6

Special Population Considerations

Pregnancy and Breastfeeding

• The FDA label advises asking a healthcare professional before use if pregnant or breastfeeding. 2

Renal Impairment

• While not an absolute contraindication, elderly patients with renal insufficiency may have prolonged effects and increased sensitivity to anticholinergic adverse effects. 1

Common Clinical Pitfalls

• Inappropriate prescribing: Studies show 24% of diphenhydramine doses in hospitalized elderly patients are administered inappropriately. 4
• Polypharmacy concerns: Avoid prescribing diphenhydramine with other anticholinergic medications, as additive effects dramatically increase risk. 1
• Duration of effect: The 4-6 hour duration often exceeds the time needed for symptom control, potentially extending recovery time and adverse effects. 1
• Availability of safer alternatives: Second-generation antihistamines are widely available, affordable, and have fewer adverse effects, making diphenhydramine increasingly obsolete for most indications. 7