Diphenhydramine Dosing
The standard adult dose of diphenhydramine is 25-50 mg administered orally, intramuscularly, or intravenously every 4-6 hours, with a maximum of 6 doses in 24 hours, though specific clinical contexts require different dosing strategies. 1
Standard Adult Dosing
- Oral/Parenteral: 25-50 mg every 4-6 hours as needed 2, 1
- Maximum daily dose: Do not exceed 6 doses in 24 hours (300 mg total) 1
- Onset of action: Several minutes when given intravenously; duration of effect is 4-6 hours 2
Pediatric Dosing
- Children 6 to under 12 years: 10 mL (25 mg) orally every 4-6 hours 1
- Children under 6 years: Do not use oral formulation per FDA labeling 1
- Weight-based dosing (parenteral): 1-2 mg/kg per dose 2
Context-Specific Dosing
Anaphylaxis Management
- Parenteral dose: 1-2 mg/kg or 25-50 mg per dose administered intramuscularly or intravenously 2
- This is used as adjunctive therapy to epinephrine, not as primary treatment 2
- Combination with ranitidine (H2-blocker) is superior to diphenhydramine alone in anaphylaxis management 2
Procedural Sedation (Endoscopy)
- Intravenous dose: 25-50 mg administered 3 minutes before initiating sedation 2
- When used as adjunct, patients require less meperidine and midazolam 2
- Hypnotic effect is increased when combined with benzodiazepines or opioids 2
Acute Dystonic Reactions
- Initial dose: 1-2 mg/kg (maximum initial dose: 50 mg) IV/IM 3
- Alternative: 25-50 mg IV every 4-6 hours as needed for breakthrough dystonic reactions from antiemetics 3
Critical Dosing Warnings
Elderly Patients Require Dose Reduction
- Patients over 85 years: Use reduced doses due to increased anticholinergic sensitivity 3
- Higher risk of cognitive impairment, delirium, and falls in elderly populations 3
- Consider alternative non-sedating antihistamines when sedation is a concern 3
Rapid IV Administration Risks
- Rapid intravenous administration may precipitate seizures 3
- Increases risk of adverse cardiovascular effects including cardiac toxicity 3
- Administer slowly to minimize hypotension risk 2
Important Clinical Pitfalls
NOT Recommended for Insomnia
- The American Academy of Sleep Medicine explicitly recommends AGAINST using diphenhydramine for sleep onset or maintenance insomnia 2, 3
- Mean sleep latency reduction is only 8 minutes versus placebo 3
- Total sleep time improvement is only 12 minutes versus placebo 3
- No improvement in quality of sleep compared to placebo 3
Anticholinergic Side Effects
- Confusion and delirium, especially in elderly 3
- Dry mouth, blurred vision, urinary retention, constipation 2, 3
- Hypotension and tachycardia 2, 3
- Impaired psychomotor performance 3
Toxicity Threshold
- 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