What is a toxic amount of hydroxyzine (antihistamine)?

Toxic Amounts of Hydroxyzine and Management of Overdose

There is no specific toxic threshold for hydroxyzine, but overdose can cause hypersedation, QT prolongation, seizures, and rarely death. Management includes supportive care, ECG monitoring, and addressing symptoms. 1

Clinical Manifestations of Hydroxyzine Toxicity

• Hypersedation is the most common manifestation of hydroxyzine overdose, with CNS depression ranging from mild drowsiness to coma 1, 2
• Other reported symptoms include:
  • Convulsions/seizures 1, 3
  • Stupor 1
  • Nausea and vomiting 1
  • QT prolongation and potential for Torsade de Pointes 1
  • Sinus tachycardia (particularly in pediatric cases) 3
• Hydroxyzine overdose is less likely to cause antimuscarinic effects (dry mouth, urinary retention, etc.) compared to other first-generation antihistamines like diphenhydramine 2

Severity and Mortality Risk

• Mortality from hydroxyzine overdose is rare, with reported rates of 0.02% to 0.8% in national datasets 2
• Severe outcomes are more common with:
  • Concomitant use of other CNS depressants 1, 4
  • Very high doses 1
  • Underlying cardiac conditions that predispose to QT prolongation 1
  • Pediatric patients may be more vulnerable to seizures 3

Management of Hydroxyzine Overdose

• Immediate interventions:

  • Induce vomiting if it hasn't occurred spontaneously 1
  • Consider gastric lavage 1
  • Provide supportive care with frequent monitoring of vital signs 1
  • ECG monitoring is recommended due to risk of QT prolongation 1

• For hypotension:

  • Administer intravenous fluids 1
  • If needed, use levarterenol or metaraminol 1
  • Do NOT use epinephrine, as hydroxyzine counteracts its pressor action 1

• For seizures:

  • Benzodiazepines are typically used 2
  • Physostigmine has been used successfully in pediatric cases 3

• There is no specific antidote for hydroxyzine overdose 1

• Hemodialysis is generally not effective for hydroxyzine removal but may be indicated if other substances were co-ingested 1

Special Considerations

• Older adults are more sensitive to hydroxyzine's psychomotor impairment and anticholinergic effects 5
• In moderate renal impairment, hydroxyzine doses should be halved 5
• Hydroxyzine should be avoided in severe liver disease 5
• Even therapeutic doses can impair driving ability and cognitive function 4
• Hydroxyzine has become increasingly common in impaired driving investigations, surpassing diphenhydramine in some regions 4

Prevention

• Second-generation antihistamines are generally preferred over first-generation antihistamines like hydroxyzine due to their better safety profile 6
• For older adults, fexofenadine, loratadine, or desloratadine are safer alternatives 5
• If hydroxyzine must be used in vulnerable populations, consider starting at lower doses (10-25 mg) 5

Hydroxyzine overdose typically presents with predominant CNS depression rather than the antimuscarinic toxidrome seen with other antihistamines, making it important to recognize its unique toxicity profile 2.