What is the maximum recommended dose of Benadryl (diphenhydramine) in 24 hours?

Maximum Dose of Benadryl (Diphenhydramine) in 24 Hours

The maximum dose of diphenhydramine in 24 hours is 300 mg for adults and children over 12 years of age, administered as 25-50 mg every 4-6 hours, not exceeding 6 doses per day. 1

FDA-Approved Dosing Limits

• Adults and children ≥12 years: 25-50 mg per dose, every 4-6 hours, maximum 6 doses in 24 hours (total daily maximum: 300 mg) 1
• Children 6 to <12 years: 25 mg per dose, every 4-6 hours, maximum 6 doses in 24 hours (total daily maximum: 150 mg) 1
• Children <6 years: Do not use for routine indications 1

Weight-Based Dosing for Acute Medical Situations

For emergency department or hospital settings where weight-based dosing is used:

• Standard dose: 1 mg/kg per dose 2
• Maximum single dose: 50 mg regardless of weight 2
• Emergency situations (e.g., acute allergic reactions): 1-2 mg/kg IV/IM, not exceeding 50 mg per dose 3
• Frequency: May repeat every 4-6 hours as clinically indicated 1

The weight-based approach of 1-2 mg/kg is recommended by multiple pediatric emergency guidelines, but the absolute maximum single dose remains 50 mg 3, 2.

Critical Safety Thresholds

Toxicity concerns arise at significantly lower doses than many clinicians realize:

• Children <6 years: Referral to emergency department warranted at ≥7.5 mg/kg ingestion 4
• Patients ≥6 years: Emergency evaluation needed at ≥7.5 mg/kg OR 300 mg total, whichever is less 4
• Fatal overdose documented: Death has occurred with ingestions as low as 7.5 grams, though this represents a massive overdose 5

Important Clinical Caveats

Diphenhydramine should be avoided or used with extreme caution in several populations:

• Children under 6 years should not receive diphenhydramine for routine allergic symptoms, as 33 deaths were associated with its use in this age group between 1969-2006 6
• Second-generation antihistamines (cetirizine, loratadine) have superior safety profiles with equal efficacy and should be considered first-line 2, 6
• In anaphylaxis, diphenhydramine is only adjunctive therapy and never replaces epinephrine 2

Adverse effects to monitor include:

• Significant sedation and anticholinergic effects (dry mouth, urinary retention, confusion) 2
• Paradoxical agitation, particularly in young children 3
• Cardiac toxicity in overdose, including QRS widening and arrhythmias 4, 5
• Respiratory depression, especially when combined with other sedatives 3

Practical Dosing Algorithm

1. Determine indication: Is this for anaphylaxis, premedication, dystonic reaction, or routine allergic symptoms? 2

2. For anaphylaxis: Administer epinephrine first, then diphenhydramine 1-2 mg/kg IV slowly (max 50 mg) as adjunct only 2

3. For routine allergic symptoms: Consider second-generation antihistamines first (cetirizine, loratadine) due to better safety profile 2, 6

4. If diphenhydramine is chosen:

   • Adults/children ≥12 years: 25-50 mg every 4-6 hours, max 6 doses (300 mg/24 hours) 1
   • Children 6-12 years: 25 mg every 4-6 hours, max 6 doses (150 mg/24 hours) 1
   • Emergency weight-based dosing: 1-2 mg/kg (max 50 mg per dose) 3, 2

5. Monitor closely: Watch for excessive sedation, anticholinergic effects, and respiratory depression, particularly when combined with other sedatives 3, 2