Should hydroxyzine be used in patients with a history of arrhythmia or congenital long‑QT syndrome, and what precautions are recommended?

Hydroxyzine and Arrhythmia: Contraindications and Management

Hydroxyzine is contraindicated in patients with congenital long-QT syndrome and should be avoided in patients with a history of arrhythmias, particularly ventricular arrhythmias or torsades de pointes. 1, 2

Absolute Contraindications to Hydroxyzine

Do not use hydroxyzine in the following situations:

• Congenital long-QT syndrome or family history of long-QT syndrome 1, 2
• Baseline QTc ≥500 ms 3, 1
• History of torsades de pointes or ventricular arrhythmias 1
• Recent myocardial infarction, uncompensated heart failure, or bradyarrhythmias 2

The FDA label explicitly states that hydroxyzine should be used with caution in patients with congenital long-QT syndrome, and multiple case reports document torsades de pointes occurring even at low doses (12.5-75 mg) in susceptible patients. 2, 4, 5, 6 One particularly striking case involved a 34-year-old woman with an undiagnosed HERG mutation who developed repetitive syncope after taking 75 mg of hydroxyzine, with her QTc prolonging to 630 ms. 4

High-Risk Factors Requiring Extreme Caution or Avoidance

If hydroxyzine must be considered despite arrhythmia history, all of the following high-risk factors exponentially increase the likelihood of torsades de pointes:

• Female sex and age >65 years 1, 2
• Uncorrected hypokalemia (K+ <4.5 mEq/L) or hypomagnesemia 3, 1
• Bradycardia or complete atrioventricular block 2, 6
• Heart failure or structural heart disease 2
• Concurrent use of other QT-prolonging medications (Class IA/III antiarrhythmics, certain antipsychotics, antidepressants, antibiotics including azithromycin, ondansetron, methadone) 3, 2

A pharmacovigilance review of 59 cases of QT prolongation/torsades de pointes associated with hydroxyzine found that the combination of cardiovascular disorders plus concomitant QT-prolonging drugs represented the greatest combined risk factor. 7 The risk is not simply additive but exponential when multiple factors are present. 1

Mandatory Pre-Treatment Assessment if Hydroxyzine is Being Considered

Before prescribing hydroxyzine to any patient, complete the following steps:

• Obtain a baseline 12-lead ECG to measure QTc using Fridericia's formula 1
• Check serum potassium and magnesium; correct potassium to ≥4.5 mEq/L and normalize magnesium before initiating therapy 3, 1
• Review all current medications and discontinue other QT-prolonging drugs whenever possible 1, 2
• Document absence of personal or family history of long-QT syndrome, unexplained syncope, or sudden cardiac death 8

Safer Alternatives to Hydroxyzine

For anxiety management in patients with arrhythmia history:

• Benzodiazepines (e.g., lorazepam) do not prolong the QT interval and represent the safest alternative 1

For antihistamine needs:

• Cetirizine and loratadine carry minimal risk of QT prolongation compared to hydroxyzine 9
• However, cetirizine is a metabolite of hydroxyzine and rare cases of QT prolongation have been reported, so caution is still warranted in patients with renal failure 9

Monitoring Protocol if Hydroxyzine Cannot Be Avoided

If no alternative exists and hydroxyzine must be used:

• Start with the lowest effective dose 5
• Obtain repeat ECG 7 days after initiation or after any dose change 8
• Monitor continuously for arrhythmia symptoms (palpitations, syncope, dizziness) 8
• Maintain normal electrolyte concentrations throughout treatment; vomiting-induced electrolyte losses must be promptly corrected 8

Discontinue hydroxyzine immediately if:

• QTc exceeds 500 ms on any serial ECG 3, 8
• QTc increases by >60 ms from baseline 8
• Development of ventricular ectopy or any arrhythmia symptoms 8

Emergency Management of Hydroxyzine-Induced Torsades de Pointes

If torsades de pointes occurs:

• Administer 2g IV magnesium sulfate immediately, regardless of serum magnesium level 3, 1
• Perform immediate non-synchronized defibrillation if hemodynamically unstable 1
• Correct potassium urgently to >4.5 mEq/L 3, 1
• Consider temporary overdrive pacing or isoproterenol (titrated to heart rate >90 bpm) for recurrent episodes after electrolyte repletion 3, 1

Critical Clinical Pitfall

A dangerous misconception is that ECG monitoring alone makes hydroxyzine safe in high-risk patients. 8 In patients with congenital long-QT syndrome or significant arrhythmia history, avoidance is the only truly safe approach. 8, 1 Case reports demonstrate that torsades de pointes can occur even with small doses (12.5 mg) in susceptible individuals, particularly those with bradycardia or complete heart block. 6 The elderly are particularly vulnerable due to decreased renal excretion and higher likelihood of polypharmacy with other QT-prolonging agents. 2