Should a patient who overdosed on hydroxyzine (an antihistamine) go to the Emergency Room (ER)?

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Last updated: November 6, 2025View editorial policy

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Should a Patient Who Overdosed on Hydroxyzine Go to the Emergency Room?

Yes, any patient with a hydroxyzine overdose should be evaluated in the Emergency Room immediately, as overdose can cause serious complications including hypersedation, seizures, QT prolongation with risk of Torsade de Pointes, and rarely death, requiring monitoring and supportive care. 1

Rationale for Emergency Department Evaluation

Primary Manifestations of Hydroxyzine Overdose

The FDA drug label clearly states that the most common manifestation of hydroxyzine overdosage is hypersedation, with other reported signs including convulsions, stupor, nausea, and vomiting 1. Critically, hydroxyzine overdose may cause QT prolongation and Torsade de Pointes, and ECG monitoring is recommended in cases of hydroxyzine overdose 1.

Severity and Mortality Data

  • While mortality from hydroxyzine overdose is rare (0.02% in the National Poison Data System and 0.8% in the Toxicologic Investigators Consortium), serious complications do occur 2
  • Hydroxyzine-poisoned patients can develop coma/CNS depression, respiratory depression, seizures, ventricular dysrhythmias, and may require intubation 2
  • Historical case reports document severe toxicity including generalized seizures and sinus tachycardia requiring seizure control with physostigmine 3

Critical Differences from Other Antihistamines

Hydroxyzine produces a different toxidrome than diphenhydramine - patients are more likely to have mild CNS depression and sedation rather than classic antimuscarinic findings 2. This means:

  • Clinicians should not generalize the illness script of diphenhydramine exposures to hydroxyzine exposures 2
  • Hydroxyzine-poisoned patients were less likely to develop antimuscarinic findings (dry mouth, urinary retention, mydriasis) than diphenhydramine-poisoned patients 2

Emergency Department Management

Immediate Interventions Required

The FDA label specifies that management should include 1:

  • Immediate gastric lavage if vomiting has not occurred spontaneously
  • General supportive care with frequent monitoring of vital signs and close observation
  • ECG monitoring to detect QT prolongation and Torsade de Pointes
  • Hypotension control with IV fluids and levarterenol or metaraminol (NOT epinephrine, as hydroxyzine counteracts its pressor action)

Cardiac Risk Considerations

Hydroxyzine may produce abnormal ventricular repolarization when given in substantial doses or to susceptible individuals 4. This risk is augmented by concurrent use of:

  • Phenothiazines (e.g., thioridazine)
  • Tricyclic antidepressants
  • Antiparkinson drugs
  • Atropine, quinidine, or procainamide 4

These EKG abnormalities may increase the likelihood of dysrhythmias and sudden death 4.

Observation Period

After return of spontaneous breathing and stabilization, patients should be observed in a healthcare setting until the risk of recurrent toxicity is low and the patient's level of consciousness and vital signs have normalized 5. This is particularly important because:

  • Hydroxyzine has a prolonged half-life (7-10 days recommended discontinuation before oral food challenge testing) 5
  • The dose should be halved in moderate renal impairment, which may prolong effects 6

Common Pitfalls to Avoid

  • Do not use epinephrine for hypotension - hydroxyzine counteracts its pressor action 1
  • Do not assume antimuscarinic toxidrome - hydroxyzine presents differently than diphenhydramine with more sedation and less anticholinergic effects 2
  • Do not discharge without adequate observation - recurrent CNS depression can occur given the long half-life 5, 6
  • Do not forget ECG monitoring - QT prolongation and Torsade de Pointes are specific risks 1

When to Activate Emergency Services

Per American Heart Association guidelines, if the patient exhibits any signs or symptoms of a life-threatening condition (e.g., sleepiness, seizures, difficulty breathing, vomiting) after exposure to a poison, activate the EMS immediately 5. The Poison Help hotline (800-222-1222) is an excellent resource for additional guidance 5.

References

Research

Hydroxyzine hydrochloride: possible adverse cardiac interactions.

Psychopharmacology communications, 1975

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Hydroxyzine Clinical Applications and Safety Considerations

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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