What is the recommended dosage of diphenhydramine for an allergic reaction?

Diphenhydramine Dosing for Allergic Reactions

For acute allergic reactions, administer diphenhydramine 1-2 mg/kg (maximum 50 mg) orally or intravenously, with oral liquid formulations absorbed more rapidly than tablets. 1

Dosing by Clinical Setting and Severity

Outpatient/Emergency Setting

• Standard dose: 1-2 mg/kg per dose, maximum 50 mg 1
• Route: IV or oral (oral liquid preferred over tablets for faster absorption) 1
• Timing: Administer as adjunctive therapy after epinephrine in anaphylaxis 1

Hospital-Based Setting

• Same dosing: 1-2 mg/kg per dose, maximum 50 mg IV or oral 1
• Alternative: Consider less-sedating second-generation antihistamines as an alternative 1
• Combination therapy: May add H2-antihistamine (ranitidine 1-2 mg/kg, max 75-150 mg) for enhanced effect 1

Discharge Therapy

• Continuation: Diphenhydramine every 6 hours for 2-3 days 1
• Alternative: Non-sedating second-generation antihistamine may be substituted 1

Critical Clinical Considerations

Route-Specific Warnings

• IV administration carries significant risk: Rapid IV diphenhydramine can cause cardiac arrest, particularly in vulnerable populations 2, 3
• Infuse slowly: When giving IV, administer over several minutes, never as rapid push 1
• IM alternative: Consider 25-50 mg IM for endoscopic or procedural contexts 1

Epinephrine Remains First-Line

• Diphenhydramine is adjunctive only: Never delay or substitute for epinephrine in anaphylaxis 1
• Epinephrine dosing: 0.01 mg/kg IM (1:1,000 solution), max 0.5 mg, or use auto-injector (0.15 mg for 10-25 kg; 0.3 mg for >25 kg) 1
• Repeat epinephrine: May need every 5-15 minutes; diphenhydramine does not replace this 1

Comparative Effectiveness Data

Onset of Action

• Oral diphenhydramine: Works within several minutes, duration 4-6 hours 1
• No significant advantage over fexofenadine: Despite perception of faster onset, oral fexofenadine (180 mg) shows comparable time to 50% flare reduction with better safety profile 4
• Risk-benefit consideration: Marginal onset advantage may not justify sedation and adverse effects of diphenhydramine 4

Symptom-Specific Efficacy

• For pruritus alone: Diphenhydramine 50 mg IV superior to cimetidine; combination offers no additional benefit 5
• For urticaria: Combination of diphenhydramine plus cimetidine (H1 + H2 blockade) significantly more effective than diphenhydramine alone (92% vs 46% relief) 5

Common Pitfalls and Adverse Effects

Dystonic Reactions

• Paradoxical effect: Diphenhydramine itself can cause acute dystonia (trismus, dysarthria, tremors, altered consciousness) 1, 6
• Treatment: Benztropine 1-2 mg IV/IM if patient allergic to diphenhydramine; otherwise use diphenhydramine 25-50 mg for dystonic reactions from other medications 1
• Timing: Can occur after single dose or long-term use 6

Cardiovascular Risks

• Hypotension: Common adverse effect, particularly with IV administration 1
• Cardiac arrest: Reported with 1.25 mg/kg IV dose in infant with congenital heart disease 2
• High-risk populations: Exercise extreme caution in infants, patients with cardiac disease, or when using IV route 2, 3

Other Adverse Effects

• Sedation: Significant CNS depression, avoid in situations requiring alertness 1
• Anticholinergic effects: Dry mouth, blurred vision, urinary retention, wheezing 1
• Respiratory: Paradoxically has modest stimulatory effect on ventilation and may counteract opioid-induced hypoventilation 1

Alternative Antihistamine Considerations

When diphenhydramine is contraindicated or poorly tolerated, chlorpheniramine provides an alternative first-generation H1-antihistamine option with established dosing for anaphylaxis management 7:

• Adults/children >12 years: 10 mg IM or IV slowly 7
• Children 6-12 years: 5 mg IM or IV slowly 7
• Children 6 months-6 years: 2.5 mg IM or IV slowly 7