What is the recommended dosing for Benadryl (diphenhydramine)?

Diphenhydramine Dosing

The FDA-approved dosing for diphenhydramine is 25-50 mg every 4-6 hours for adults and children over 12 years, with a maximum of 6 doses in 24 hours; however, diphenhydramine should generally be avoided in favor of second-generation antihistamines due to significant anticholinergic side effects and limited clinical benefit. 1

Standard Dosing by Age

Adults and Children ≥12 Years

• Dose: 25-50 mg (10-20 mL of liquid formulation) every 4-6 hours 1
• Maximum: 6 doses in 24 hours (300 mg total daily) 1

Children 6 to <12 Years

• Dose: 25 mg (10 mL of liquid formulation) every 4-6 hours 1
• Maximum: 6 doses in 24 hours 1

Children <6 Years

• Do not use without physician direction 1

Special Clinical Applications

Acute Dystonic Reactions

• IV/IM: 1-2 mg/kg (maximum initial dose: 50 mg) 2
• May cause sedation, respiratory suppression, hypotension, and paradoxical excitement 2
• Rapid IV administration may precipitate seizures 2

Breakthrough Antiemetic (Chemotherapy-Induced)

• Dose: 25-50 mg PO or IV every 4-6 hours as needed for dystonic reactions from other antiemetics 2
• Alternative: Benztropine 1-2 mg IV/IM if allergic to diphenhydramine 2

Critical Warnings and Limitations

Not Recommended for Insomnia

The American Academy of Sleep Medicine explicitly recommends against using diphenhydramine for sleep onset or sleep maintenance insomnia. 2

• Mean sleep latency reduction of only 8 minutes versus placebo (not clinically significant) 2
• Total sleep time improvement of only 12 minutes versus placebo (not clinically significant) 2
• No improvement in quality of sleep compared to placebo 2

Elderly Patients Require Dose Reduction

• Patients over 85 years should receive reduced doses due to increased anticholinergic sensitivity 3
• Higher risk of cognitive impairment, delirium, and falls 3
• Consider alternative non-sedating antihistamines when sedation is a concern 3
• For insomnia in elderly, consider doxepin 3-6 mg instead 3

Toxicity Thresholds

• Children <6 years: Refer to emergency department if ingestion ≥7.5 mg/kg 4
• Patients ≥6 years: Refer to emergency department if ingestion ≥7.5 mg/kg OR ≥300 mg (whichever is less) 4
• Symptoms warranting immediate evaluation include agitation, hallucinations, seizures, QRS widening, or respiratory depression 4

Important Clinical Pitfalls

Anticholinergic Side Effects

• Confusion and delirium, especially in elderly 3
• Dry mouth, blurred vision, urinary retention, constipation 3
• Hypotension and tachycardia 3
• Impaired psychomotor performance 3

Cardiac Toxicity Risk

• QRS widening can occur with overdose 4
• Rapid IV administration increases risk of adverse cardiovascular effects 2, 5

Topical Application Risks

• Fatal toxicity has been reported from excessive topical application in children 6
• Systemic absorption can occur through skin 6

Preferred Alternatives

Second-generation antihistamines are strongly preferred over diphenhydramine for most indications due to fewer side effects, no sedation, and better safety profiles. 7

For Allergic Reactions

• Consider cetirizine, loratadine, or fexofenadine instead 7

For Pruritus in Elderly

• Topical treatments or non-sedating antihistamines preferred 3

Monitoring Requirements

• Monitor for changes in mental status or excessive sedation 3
• Assess falls risk, especially in elderly 3
• Watch for urinary retention and constipation 3