What are the cardiac effects of Hydroxyzine (Atarax)?

From the Guidelines

Hydroxyzine can affect the heart by potentially causing QT interval prolongation, which may increase the risk of dangerous heart rhythm disturbances, and its use should be cautious in patients with pre-existing risk factors, such as existing heart conditions, electrolyte abnormalities, or concurrent use of other QT-prolonging medications 1.

Key Considerations

• The risk of QT interval prolongation is generally rare but more likely at higher doses or in patients with pre-existing risk factors.
• Common risk factors include older age, heart disease, low potassium or magnesium levels, and concurrent use of certain medications like antiarrhythmics, antipsychotics, or some antibiotics.
• Symptoms of heart rhythm problems may include palpitations, dizziness, fainting, or shortness of breath, and patients should seek medical attention immediately if they experience these symptoms.

Patient Guidance

• Patients taking hydroxyzine should inform their healthcare provider about all medications they're taking and any history of heart problems before starting hydroxyzine.
• Healthcare providers should monitor patients who receive hydroxyzine, especially those with pre-existing risk factors, and consider alternative treatments if necessary.
• The use of hydroxyzine should be approached with caution in older adults, who are more sensitive to the psychomotor impairment promoted by first-generation antihistamines and are at increased risk for complications such as fractures and subdural hematomas caused by falls 1.

Clinical Recommendations

• A baseline 12-lead ECG should be acquired before initiating hydroxyzine, especially in patients with pre-existing risk factors.
• Patients should be stratified into low-risk or high-risk groups based on their QTc interval, and monitoring should be adjusted accordingly.
• Healthcare providers should be aware of the potential for QT interval prolongation and proarrhythmia associated with hydroxyzine and take steps to minimize these risks, such as correcting modifiable predisposing factors and avoiding the use of other QT-prolonging medications whenever possible 1.

From the FDA Drug Label

QT Prolongation/Torsade de Pointes (TdP): Cases of QT prolongation and Torsade de Pointes have been reported during post-marketing use of hydroxyzine. The majority of reports occurred in patients with other risk factors for QT prolongation/TdP (pre-existing heart disease, electrolyte imbalances or concomitant arrhythmogenic drug use) Therefore, hydroxyzine should be used with caution in patients with risk factors for QT prolongation, congenital long QT syndrome, a family history of long QT syndrome, other conditions that predispose to QT prolongation and ventricular arrhythmia, as well as recent myocardial infarction, uncompensated heart failure, and bradyarrhythmias Caution is recommended during the concomitant use of drugs known to prolong the QT interval. Hydroxyzine overdose may cause QT prolongation and Torsade de Pointes ECG monitoring is recommended in cases of hydroxyzine overdose.

Hydroxyzine may have heart effects, including QT prolongation and Torsade de Pointes, especially in patients with pre-existing heart conditions or risk factors.

• The drug should be used with caution in patients with risk factors for QT prolongation.
• ECG monitoring is recommended in cases of hydroxyzine overdose.
• Concomitant use of drugs known to prolong the QT interval should be done with caution 2.

From the Research

Hydroxyzine Heart Effects

• Hydroxyzine, an H1-receptor antagonist, has been associated with QT prolongation and torsade de pointes (TdP) 3, 4, 5, 6.
• The risk of TdP with hydroxyzine use is increased in patients with underlying medical conditions or concomitant medications that constitute at least one additional risk factor for such events 4.
• Healthcare providers should conduct personalized risk assessments, monitor electrolyte levels, and perform regular electrocardiograms to minimize the risk of TdP associated with hydroxyzine therapy 3.
• Administering the lowest effective dose, avoiding drug interactions, and exercising caution in patients with underlying repolarization abnormalities or a history of TdP are crucial 3.

Mechanism of Action

• Hydroxyzine has been shown to inhibit human ether-a-go-go-related gene (HERG) current, which can lead to QT prolongation and TdP 5.
• The combination of genetic mutation and intake of hydroxyzine can lead to a severe phenotype, probably syncope due to TdP 5.

Clinical Implications

• Hydroxyzine should be used with caution in patients with complete atrioventricular block or other underlying heart conditions 6.
• The drug's potential to prolong the QT interval and cause TdP should be considered when administering hydroxyzine for sedation during surgery 6.
• While hydroxyzine may be effective in treating generalized anxiety disorder, its use is not recommended as a reliable first-line treatment due to the high risk of bias in included studies and the small number of studies 7.