Can Benadryl (Diphenhydramine) Prolong the QT Interval?
Yes, diphenhydramine (Benadryl) can prolong the QT interval, particularly in overdose situations, though this effect is generally moderate at therapeutic doses. 1, 2
Mechanism and Risk
- Diphenhydramine inhibits fast sodium channels and, at higher concentrations, also inhibits potassium channels, which can result in QT interval prolongation 1
- The QT prolongation effect is dose-dependent, with more significant prolongation observed at doses exceeding 500 mg 2
- In clinical studies, diphenhydramine overdose has been associated with a significant but moderate QTc prolongation (453 ± 43 ms vs 416 ± 35 ms in controls) 2
Risk Factors for QT Prolongation with Diphenhydramine
- Concurrent use of other QT-prolonging medications 3
- Pre-existing cardiac conditions, especially those with prolonged QT intervals 3
- Electrolyte abnormalities, particularly hypokalemia or hypomagnesemia 3
- Advanced age 3
- Renal impairment (reduced drug clearance) 4
- Overdose situations (doses >500 mg) 2, 5
Clinical Presentation of QT Prolongation
- Most cases of significant QT prolongation occur in overdose situations 1, 2
- May present with abnormal T-wave morphology in addition to QT prolongation 1
- Despite QT prolongation, torsades de pointes is rarely reported with diphenhydramine, possibly due to the protective effect of diphenhydramine-induced tachycardia 1, 2
Monitoring Recommendations
- For patients requiring diphenhydramine who have risk factors for QT prolongation, consider baseline ECG assessment 3
- Monitor QTc in the same lead over time if following a patient for drug-induced QT prolongation 3
- For patients with diphenhydramine overdose, ECG monitoring is recommended until drug levels decrease and QT interval normalizes 3
Management of Diphenhydramine-Induced QT Prolongation
- Discontinue diphenhydramine if marked QT prolongation occurs (QTc >500 ms or increase >60 ms from baseline) 3
- Correct any electrolyte abnormalities, particularly hypokalemia and hypomagnesemia 3
- Avoid concurrent use of other QT-prolonging medications 3
- In overdose situations, maintain heart rate to potentially protect against torsades de pointes, as the tachycardia caused by diphenhydramine may have a protective effect 1
Clinical Implications
- Use diphenhydramine with caution in patients with known cardiac disease or risk factors for QT prolongation 3
- Consider alternative H1-antihistamines in patients with pre-existing QT prolongation or those on multiple QT-prolonging medications 3
- Be particularly cautious in patients with end-stage renal disease who may receive diphenhydramine for dialysis-associated pruritus 4
While diphenhydramine can prolong the QT interval, the risk of serious cardiac arrhythmias like torsades de pointes appears to be low with therapeutic doses in patients without additional risk factors 2.