What is the toxic dose of Benadryl (diphenhydramine)?

Toxic Dose of Benadryl (Diphenhydramine)

The toxic dose of diphenhydramine requiring emergency department evaluation is 7.5 mg/kg or 300 mg (whichever is less) in patients 6 years and older, and 7.5 mg/kg in children under 6 years of age. 1

Threshold for Toxicity

Emergency department referral is warranted at the following doses:

• Children <6 years: ≥7.5 mg/kg 1
• Patients ≥6 years: ≥7.5 mg/kg OR 300 mg, whichever is less 1

This represents the consensus threshold where significant toxicity becomes likely and medical evaluation is necessary, even in asymptomatic patients 1.

Clinical Manifestations of Toxicity

Moderate to severe symptoms requiring immediate emergency department referral include: 1

• Agitation, staring spells, or hallucinations 1
• Abnormal muscle movements or seizures 1, 2
• Loss of consciousness or respiratory depression 1
• Inconsolable crying (in children) 1

The most common severe outcome is seizures, occurring in 11.6% of all toxic ingestions. 2

Critical Laboratory and Clinical Markers

Signs most strongly associated with severe outcomes include: 2

• QRS prolongation (>120 ms) - indicates cardiac sodium channel blockade 2
• Acidemia (pH <7.2) - marker of severe toxicity 2
• Elevated anion gap (>20) - associated with worse outcomes 2

These findings predict increased risk of seizures, ventricular dysrhythmias, and need for intubation 2.

Lethal Dose Range

Fatal diphenhydramine toxicity has been documented with postmortem blood concentrations around 49,658 ng/mL, representing massive overdose scenarios 3. While therapeutic blood levels are typically <100 ng/mL, lethal concentrations are several hundred-fold higher, though exact lethal doses vary significantly based on individual factors 3.

Time-Based Observation Guidelines

For patients who remain asymptomatic after ingestion below toxic thresholds: 1

• Diphenhydramine: If >4 hours post-ingestion with no symptoms, emergency department referral is not needed 1
• Dimenhydrinate (related compound): If >6 hours post-ingestion with no symptoms, emergency department referral is not needed 1

Management Principles

Do not induce emesis or administer activated charcoal at home due to risk of rapid onset of altered mental status or seizures 1.

For ingestions above toxic thresholds or symptomatic patients: 1

• Transport to emergency department, consider ambulance based on patient condition 1
• Benzodiazepines for seizures or severe agitation (if authorized by EMS medical direction) 1
• Sodium bicarbonate for QRS widening >0.10 msec (if authorized by EMS medical direction) 1
• Physostigmine reserved for hospital administration only 1

Common Pitfalls

Intentional self-harm ingestions and male patients have higher rates of severe outcomes, particularly requiring intubation 2. The recreational misuse trend, including social media "challenges," has resulted in fatal outcomes in adolescents 3. Healthcare providers must recognize that diphenhydramine's over-the-counter availability does not equate to safety in overdose - it carries significant cardiac toxicity risk including ventricular dysrhythmias 2, 4.