Does Compazine (prochlorperazine) prolong the QT interval?

Does Compazine (Prochlorperazine) Prolong QT Interval?

Yes, prochlorperazine (Compazine) does prolong the QT interval and is specifically listed as a medication that can cause QT prolongation in multiple clinical guidelines.

Evidence for QT Prolongation

The evidence clearly demonstrates that prochlorperazine has QT-prolonging effects:

• Prochlorperazine is explicitly listed as contraindicated with dofetilide due to the risk of QT interval prolongation according to the American Heart Association and American College of Cardiology guidelines 1.

• In the British Thoracic Society guidelines, prochlorperazine is specifically identified among antipsychotics that pose a "risk of prolonged QT interval" 2.

• The ACC/AHA/HRS guidelines for management of adult patients with supraventricular tachycardia also list prochlorperazine as a medication that can cause QT prolongation and is contraindicated with dofetilide 2.

Mechanism and Risk Assessment

Prochlorperazine belongs to the phenothiazine class of antipsychotics, which are known to block potassium channels (particularly IKr) involved in cardiac repolarization. This blockade leads to prolongation of the QT interval, which can increase the risk of torsades de pointes (TdP), a potentially fatal ventricular arrhythmia.

Risk Factors That Increase Danger of QT Prolongation

The risk of clinically significant QT prolongation with prochlorperazine is higher in patients with:

• Pre-existing QT prolongation or history of torsades de pointes
• Concomitant use of other QT-prolonging medications
• Electrolyte abnormalities (particularly hypokalemia, hypomagnesemia)
• Advanced age
• Female gender
• Structural heart disease or heart failure
• Bradycardia
• Renal or hepatic dysfunction

Clinical Recommendations

When considering the use of prochlorperazine:

1. Avoid combination with other QT-prolonging drugs whenever possible 2

   • Particularly avoid combination with dofetilide, which is specifically contraindicated 2, 1

2. Perform baseline ECG assessment before initiating treatment, especially in high-risk patients 2

3. Monitor electrolytes and correct any abnormalities before and during treatment 2

4. Consider alternative antiemetics with less QT-prolonging potential in high-risk patients

5. Discontinue or reduce dose if QT interval reaches >500 ms or increases by >60 ms from baseline 2

Comparative QT Risk Among Antiemetics

Recent research suggests that prochlorperazine has a lesser QT-prolonging potential compared to ondansetron. A 2024 study found that ondansetron initiation versus initiation of antiemetics with lesser QT-prolonging potential (including prochlorperazine) was associated with higher 10-day sudden cardiac death risk in hemodialysis patients 3.

Conclusion

Prochlorperazine does prolong the QT interval, as confirmed by multiple authoritative guidelines. While it may have less QT-prolonging potential than some other medications, caution is still warranted, particularly in patients with additional risk factors for QT prolongation or torsades de pointes.