What are the contraindications for using diphenhydramine in patients, particularly those with a history of glaucoma, urinary retention, gastrointestinal obstruction, asthma, chronic obstructive pulmonary disease (COPD), seizure disorders, or impaired renal function, and in geriatric patients or those with dementia?

Diphenhydramine Contraindications

Diphenhydramine should be used with extreme caution—or avoided entirely—in older adults, patients with glaucoma, benign prostatic hypertrophy/urinary retention, ischemic heart disease, uncontrolled hypertension, chronic obstructive pulmonary disease, and those with dementia or cognitive impairment. 1, 2

Absolute and Relative Contraindications

Respiratory Conditions

• Chronic bronchitis and COPD are explicit contraindications per FDA labeling, as diphenhydramine's anticholinergic effects can worsen bronchospasm and impair respiratory function 2
• Asthma patients should avoid diphenhydramine due to potential bronchospasm exacerbation from anticholinergic properties 2

Urologic Conditions

• Benign prostatic hypertrophy and urinary retention are major contraindications because diphenhydramine's anticholinergic effects impair bladder contraction and can precipitate acute urinary retention 1, 3, 2
• The FDA explicitly warns against use in patients with "trouble urinating due to enlarged prostate gland" 2

Ophthalmologic Conditions

• Glaucoma is a contraindication as diphenhydramine causes pupillary dilation and can precipitate acute angle-closure glaucoma 1, 4, 2
• The anticholinergic effects interfere with accommodation and increase intraocular pressure 4

Cardiovascular Conditions

• Ischemic heart disease and uncontrolled hypertension warrant extreme caution per AGA guidelines 1
• Diphenhydramine can cause hypotension, particularly when combined with other CNS depressants, requiring careful hemodynamic monitoring 5
• Cardiac toxicity risk exists in overdose situations 6

Neurologic and Psychiatric Conditions

• Dementia and cognitive impairment are strong relative contraindications given the high risk of delirium and cognitive decline 1
• Seizure disorders require caution, though this applies more to other antihistamines like prochlorperazine 1

Special Population Considerations

Geriatric Patients

• Older adults are at dramatically increased risk for adverse effects, including delirium, cognitive decline, confusion, and falls 1, 5, 7
• Hospitalized elderly patients receiving diphenhydramine had 1.7 times increased risk of delirium symptoms, 3.0 times increased risk of inattention, and 5.5 times increased risk of disorganized speech 7
• A dose-response relationship exists for cognitive decline and other adverse outcomes in elderly patients 7
• The American Academy of Sleep Medicine recommends avoiding diphenhydramine in older adults due to increased sensitivity and anticholinergic burden 5

Pediatric Patients

• Paradoxical reactions occur unpredictably in children and adolescents, including increased rage, agitation, and excitability 5, 2
• These reactions cannot be predicted unless previously documented in that specific patient 5

Pregnancy and Lactation

• Pregnant or breastfeeding women should consult healthcare professionals before use per FDA labeling 2

Drug Interactions and Combination Therapy

CNS Depressants

• Avoid combining with alcohol, sedatives, benzodiazepines, or opioid narcotics as diphenhydramine's hypnotic effect is significantly increased 5, 2
• When used intentionally in combination (e.g., procedural sedation), continuous monitoring by trained personnel is mandatory until the patient is awake and ambulatory 5

Anticholinergic Medications

• Do not use with any other product containing diphenhydramine, including topical formulations 2
• Avoid combining with other anticholinergic agents due to additive effects 1

Clinical Pitfalls and Practical Considerations

Common Prescribing Errors

• Approximately 24% of diphenhydramine doses in hospitalized elderly patients are administered inappropriately 7
• Diphenhydramine is frequently used when newer, safer second-generation antihistamines are available and more appropriate 6, 8

Duration of Effects

• The 4-6 hour duration often exceeds the time needed for symptom control, potentially extending recovery time and delaying discharge 5
• Anticholinergic effects on pupils and other organs may persist even as systemic drug levels decline 5

Monitoring Requirements When Use is Unavoidable

• Continuous vital sign monitoring including blood pressure (for hypotension) and respiratory rate (for respiratory depression) 5
• Watch for allergic reactions, paradoxical reactions, and anticholinergic crisis 5
• Evaluate for urinary retention, constipation, dry mouth, blurred vision, and delirium 1, 5

Renal Considerations

• While not a primary contraindication, diphenhydramine can have adverse renal effects in some patients, warranting extra precautions especially in elderly patients 9

Alternative Approaches

• Second-generation antihistamines are preferred as they have similar efficacy with significantly fewer adverse effects and no anticholinergic burden 6, 8
• For insomnia, cognitive-behavioral therapy for insomnia (CBT-I) is first-line treatment before any medication 3
• When pharmacological sleep aids are necessary, non-benzodiazepine receptor agonists may be preferable to antihistamines in appropriate patients 3