What are the concerns regarding QT interval prolongation with Diphenhydramine (Benadryl)?

From the Guidelines

Benadryl (diphenhydramine) can potentially contribute to QT prolongation, especially at high doses or in vulnerable individuals, and its use should be cautious in patients with heart problems or those taking other QT-prolonging medications. According to the study published in Pediatrics 1, diphenhydramine is listed as a medication that can prolong the QT interval. Another study published in the European Heart Journal 1 provides recommendations for the clinical management of QT prolongation induced by psychotropic medications, including avoiding concomitant treatment with more than one drug that can prolong the QT interval and assessing cardiac risk before initiation of treatment.

Key Considerations

• The standard recommended dose for adults is 25-50 mg every 4-6 hours, not exceeding 300 mg in 24 hours.
• Patients with existing QT prolongation, heart disease, electrolyte abnormalities (especially low potassium or magnesium), or those taking other QT-prolonging medications should consult their healthcare provider before using Benadryl.
• The risk of QT prolongation increases with higher doses, which is why overdoses can be particularly dangerous.
• Benadryl works by blocking histamine receptors but also has anticholinergic effects that can influence cardiac conduction.

Monitoring and Precautions

• If you experience palpitations, irregular heartbeat, dizziness, or fainting while taking Benadryl, seek medical attention immediately as these could be signs of cardiac rhythm disturbances.
• Close clinical observation, cardiorespiratory monitoring, pulse oximetry, and/or an electrocardiogram may be necessary when administering Benadryl, especially in patients with pre-existing heart conditions or those taking other QT-prolonging medications 1.
• The QT interval should be evaluated before initiation of treatment and during titration of dose, and hypokalaemia should be avoided during treatment with drugs capable of prolonging the QT interval 1.

From the Research

Benadryl and QT Prolongation Concerns

• Benadryl, also known as diphenhydramine, has been associated with QT interval prolongation, a rare but potentially serious cardiac side effect 2, 3.
• The mechanism of QT prolongation is thought to be due to the inhibition of the fast sodium channels and the repolarizing potassium channels, leading to a prolongation of the action potential and the QT interval 2.
• Studies have shown that diphenhydramine overdose is associated with a significant increase in heart rate and a moderate QTc prolongation, although none of the studied patients experienced torsades de pointes ventricular tachycardia 3.
• Other antihistamines, such as terfenadine and astemizole, have also been associated with QT interval prolongation and ventricular arrhythmias, particularly torsades de pointes 4, 5.
• The risk of QT prolongation and ventricular arrhythmias is thought to be dose-dependent, with higher doses of antihistamines increasing the risk of these adverse events 2, 6.
• Certain populations, such as those with liver disease or congenital long QT syndrome, may be at increased risk of QT prolongation and ventricular arrhythmias when taking antihistamines 4, 6.
• Clinicians should be aware of the potential for QT prolongation and ventricular arrhythmias when prescribing antihistamines, particularly in high-risk populations, and monitor patients closely for signs of these adverse events 2, 6.