Does Atarax (hydroxyzine) prolong the QTc interval?

Hydroxyzine (Atarax) and QTc Prolongation

Yes, hydroxyzine (Atarax) does cause QTc prolongation and should be used with caution in patients with risk factors for QT prolongation or torsade de pointes.

Evidence of QTc Prolongation

• The FDA drug label explicitly states that cases of QT prolongation and Torsade de Pointes have been reported during post-marketing use of hydroxyzine 1
• Hydroxyzine is listed in clinical guidelines as a medication that can prolong the QT interval 2
• Hydroxyzine is contraindicated in patients with a prolonged QT interval according to the FDA label 1
• Patch-clamp studies have demonstrated that hydroxyzine causes concentration-dependent inhibition of human cardiac ion channels, including the hERG potassium channels that are critical for cardiac repolarization 3

Risk Factors for QTc Prolongation with Hydroxyzine

• Pre-existing heart disease increases the risk of QTc prolongation with hydroxyzine 1
• Electrolyte imbalances, particularly hypokalemia and hypomagnesemia, enhance the QTc-prolonging effect 1
• Concomitant use of other QTc-prolonging medications significantly increases the risk 1, 3
• Genetic predisposition, such as congenital long QT syndrome or family history of long QT syndrome, increases susceptibility 1
• Recent myocardial infarction, uncompensated heart failure, and bradyarrhythmias are additional risk factors 1
• Renal failure may increase the risk of QTc prolongation with hydroxyzine 4, 5

Drug Interactions That Increase Risk

Hydroxyzine should be used with caution when combined with:

• Class 1A antiarrhythmics (e.g., quinidine, procainamide) 1
• Class III antiarrhythmics (e.g., amiodarone, sotalol) 1
• Certain antipsychotics (e.g., chlorpromazine, haloperidol) 1
• Certain antidepressants (e.g., citalopram, fluoxetine) 1
• Certain antibiotics (e.g., azithromycin, erythromycin) 1
• Other medications known to prolong QT interval (e.g., ondansetron, methadone) 1

Clinical Significance and Reported Cases

• A case report documented a patient who experienced repetitive syncope after taking 75 mg of hydroxyzine for several days, with QTc interval of 630 ms that shortened to 464 ms after discontinuation 6
• Another case report described a patient who developed torsade de pointes after receiving hydroxyzine 50 mg for anxiety during opioid withdrawal 7
• A pharmacovigilance review identified 59 reports of QT prolongation and/or torsade de pointes potentially linked to hydroxyzine use between 1955 and 2016 3

Recommendations for Clinical Practice

• Avoid hydroxyzine in patients with known QT prolongation, congenital long QT syndrome, or history of torsade de pointes 1
• Perform baseline ECG before initiating hydroxyzine in patients with cardiovascular risk factors 1
• Monitor electrolytes, particularly potassium and magnesium, in patients taking hydroxyzine 1
• Use the lowest effective dose, especially in elderly patients who are more susceptible to adverse effects 1
• Consider alternative non-sedating antihistamines with minimal QT prolongation risk (such as cetirizine or loratadine) in patients with risk factors for QT prolongation 4
• Be particularly cautious in patients with renal dysfunction, as hydroxyzine has been associated with QT prolongation in patients with chronic kidney disease 5

Monitoring Recommendations

• Obtain baseline ECG in patients with cardiovascular risk factors before starting hydroxyzine 1
• Consider follow-up ECG monitoring in high-risk patients, especially when using higher doses or when combining with other QT-prolonging medications 1
• Monitor for symptoms such as palpitations, dizziness, or syncope that may indicate arrhythmias 6, 7
• Discontinue hydroxyzine if QTc interval exceeds 500 ms or increases by >60 ms from baseline 1

Hydroxyzine should be considered a medication with "conditional risk of torsade de pointes" and used with appropriate caution, especially in patients with underlying risk factors for QT prolongation 3.