From the Guidelines
No, Benadryl (diphenhydramine) and hydroxyzine do not carry the same degree of QT prolongation potential. Hydroxyzine has a higher risk of QT interval prolongation compared to diphenhydramine. According to the evidence from 1, hydroxyzine is listed as a QT-interval-prolonging medication, whereas diphenhydramine is also listed but with a less established risk. The difference in risk is significant because QT prolongation can lead to dangerous heart rhythm disturbances like torsades de pointes.
Key points to consider:
- Hydroxyzine carries a moderate risk of QT interval prolongation and has specific warnings about QT prolongation in its prescribing information.
- Diphenhydramine has a lower, less established risk of QT interval prolongation.
- Patients with existing risk factors, such as heart disease, electrolyte abnormalities, or those taking other QT-prolonging medications, should be particularly cautious with hydroxyzine.
- The mechanism behind this difference relates to how these antihistamines interact with cardiac ion channels, particularly potassium channels that regulate cardiac repolarization.
- When prescribing either medication, especially hydroxyzine, it's essential to consider a patient's complete cardiac risk profile and monitor appropriately if there are concerns about QT prolongation, as recommended by 1.
In clinical practice, it's crucial to weigh the benefits and risks of each medication and consider alternative treatments if necessary, as suggested by 1 and 1. By prioritizing patient safety and taking a cautious approach, healthcare providers can minimize the risk of QT prolongation and related complications.
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.
Caution is recommended during the concomitant use of drugs known to prolong the QT interval.
The FDA drug label does not answer the question about Benadryl. For hydroxyzine, QT prolongation is a potential risk, particularly in patients with other risk factors for QT prolongation/TdP.
- Key factors that increase the risk of QT prolongation with hydroxyzine include:
- Pre-existing heart disease
- Electrolyte imbalances
- Concomitant arrhythmogenic drug use
- Congenital long QT syndrome
- Family history of long QT syndrome
- Recent myocardial infarction
- Uncompensated heart failure
- Bradyarrhythmias However, without information on Benadryl, no comparison can be made between the two drugs regarding their potential for QT prolongation 2 2.
From the Research
QT Prolongation Potential of Benadryl and Hydroxyzine
- The studies provided do not directly compare the QT prolongation potential of Benadryl (diphenhydramine) and hydroxyzine.
- However, separate studies on each drug suggest that both can cause QT prolongation, but the degree of risk may vary.
- Hydroxyzine has been shown to inhibit several human cardiac ion channels, including the hERG potassium ion channels, which can lead to QT prolongation and torsade de pointes 3.
- Diphenhydramine, the active ingredient in Benadryl, has also been reported to cause QT prolongation, particularly at higher doses or in combination with other medications 4, 5.
- The risk of QT prolongation with diphenhydramine is dose-dependent, with a critical dose limit of 1.0 g 4, 5.
- In contrast, hydroxyzine's risk of QT prolongation is more closely tied to underlying medical conditions or concomitant medications that constitute additional risk factors 3.
- Another study compared the effects of cyproheptadine and hydroxyzine on ventricular repolarization, finding that hydroxyzine prolonged the QT interval, while cyproheptadine had little effect 6.
- A review of antihistamines' effects on cardiac ion channels noted that many antihistamines, including diphenhydramine, can block one or more cardiac ion currents, potentially leading to QT prolongation 7.