What are the risks and management strategies for a patient with a history of cardiac arrhythmias taking hydroxyzine due to its potential to prolong the QT interval?

Hydroxyzine and QT Prolongation: Risks and Management

Direct Recommendation

Hydroxyzine is contraindicated in patients with a history of cardiac arrhythmias or prolonged QT interval (QTc ≥500 ms) due to documented risk of Torsades de Pointes and sudden cardiac death. 1, 2

Understanding the Risk

Hydroxyzine causes QT prolongation through blockade of the HERG (human ether-a-go-go-related gene) potassium channel, the same mechanism responsible for drug-induced Torsades de Pointes. 3 The FDA label explicitly warns that post-marketing surveillance has documented cases of QT prolongation and Torsades de Pointes with hydroxyzine use, particularly in patients with pre-existing risk factors. 2

Critical context: A case report documented a patient with an underlying HERG mutation (A614V) who developed recurrent syncope after taking 75 mg of hydroxyzine, with QTc prolonging to 630 ms—the combination of genetic susceptibility and drug exposure created a life-threatening scenario. 3

Absolute Contraindications to Hydroxyzine

Do not prescribe hydroxyzine if any of the following are present:

• QTc ≥500 ms (universally considered high-risk) 1
• Congenital long QT syndrome or family history of long QT syndrome 1, 2
• Recent myocardial infarction 2
• Uncompensated heart failure 2
• Bradyarrhythmias 2
• History of ventricular arrhythmias including Torsades de Pointes 4

High-Risk Factors Requiring Extreme Caution

If hydroxyzine must be considered despite cardiac history, the following factors exponentially increase risk:

• Female sex (women have higher incidence of drug-induced Torsades de Pointes) 4, 5
• Age >65 years 5
• Uncorrected hypokalemia or hypomagnesemia 4, 2
• Concurrent use of other QT-prolonging medications 4, 2
• Impaired left ventricular function 4
• Concurrent digoxin therapy 4
• Bradycardia 4

Common pitfall: The FDA label emphasizes that the majority of reported cases occurred in patients with "other risk factors"—this does not make hydroxyzine safe in their absence, but rather highlights that multiple risk factors create compounding danger. 2

Safer Alternatives to Hydroxyzine

For Anxiety Management:

• Lorazepam or other benzodiazepines do not prolong the QT interval and are safe alternatives in patients with cardiac arrhythmias 1, 6
• Cetirizine and loratadine carry minimal risk of QT prolongation compared to hydroxyzine 6

Important caveat: Cetirizine is a metabolite of hydroxyzine, and cross-sensitivity reactions have been reported. Avoid cetirizine in patients who have experienced adverse reactions to hydroxyzine. 2

For Antiemetic Needs:

• Metoclopramide can be used as first-line, though it requires caution and monitoring 7
• Avoid all 5-HT3 antagonists (ondansetron, granisetron, dolasetron) as they also prolong QT 7
• Non-pharmacologic approaches should be prioritized when possible 7

Mandatory Pre-Treatment Assessment (If Hydroxyzine Cannot Be Avoided)

Before initiating hydroxyzine in any patient, the following must be completed:

1. Obtain baseline ECG to measure QTc using Fridericia's formula (more accurate than Bazett's, especially with abnormal heart rates) 4, 8
2. Check electrolytes: Maintain potassium >4.5 mEq/L and normalize magnesium 4, 8
3. Review all medications and discontinue other QT-prolonging drugs including:
   • Class IA antiarrhythmics (quinidine, procainamide, disopyramide) 4, 8, 2
   • Class III antiarrhythmics (amiodarone, sotalol, dofetilide) 4, 8, 2
   • Certain antipsychotics (ziprasidone, iloperidone, clozapine, quetiapine, chlorpromazine) 2
   • Certain antibiotics (azithromycin, erythromycin, clarithromycin, moxifloxacin) 2
   • Methadone, ondansetron, droperidol 2
4. Obtain cardiology consultation if QTc >500 ms or if multiple risk factors present 4, 8

Monitoring Protocol During Treatment

If hydroxyzine is prescribed despite cardiac history:

• Repeat ECG at 7 days after initiation or any dose change 8, 7
• Immediately discontinue hydroxyzine if QTc exceeds 500 ms or increases >60 ms from baseline 4, 8
• Monitor electrolytes regularly to avoid hypokalemia during treatment 4
• Educate patient to report palpitations, syncope, or dizziness immediately 8

Management of Hydroxyzine Overdose

Hydroxyzine overdose may cause QT prolongation and Torsades de Pointes—ECG monitoring is mandatory in all overdose cases. 2

If Torsades de Pointes occurs:

• Administer 2g IV magnesium sulfate immediately, regardless of serum magnesium level 4, 8, 7
• Perform immediate defibrillation if hemodynamically unstable 8
• Temporary pacing is highly effective for recurrent episodes after electrolyte repletion 4, 8
• Do not use epinephrine (hydroxyzine counteracts its pressor action) 2

Critical Clinical Pitfalls to Avoid

1. Never combine multiple QT-prolonging medications without expert consultation—the risk is exponential, not additive 8, 7
2. Do not rely on monitoring alone to make hydroxyzine safe in high-risk patients—avoidance is the only truly safe approach in congenital long QT syndrome 7
3. Correct electrolyte abnormalities before attributing QT prolongation solely to medications—hypokalemia and hypomagnesemia are independent risk factors 8
4. Avoid using Bazett's formula at high heart rates as it overcorrects and may lead to inappropriate clinical decisions 8
5. Remember that elderly patients have greater frequency of decreased cardiac function—start at low doses and observe closely 2

Special Population Considerations

Geriatric patients: Sedating drugs like hydroxyzine may cause confusion and oversedation in the elderly. Start at the low end of dosing range and monitor closely for both sedation and cardiac effects. 2

Patients with renal impairment: The extent of renal excretion of hydroxyzine has not been fully determined, but caution is warranted in dose selection for patients with decreased renal function. 2