Does compazine (prochlorperazine) prolong the QT interval?

Does Compazine Prolong the QT Interval?

Yes, prochlorperazine (Compazine) can prolong the QT interval and is specifically contraindicated when combined with other QT-prolonging medications. 1

Evidence for QT Prolongation Risk

Multiple cardiology societies confirm that prochlorperazine belongs to the phenothiazine class of antiemetics that prolong the QTc interval:

• The Thorax journal explicitly states that prochlorperazine is contraindicated with other QT-prolonging medications, indicating recognized QT risk. 1
• The European Society of Cardiology recommends avoiding metoclopramide, domperidone, and prochlorperazine in patients with prolonged QTc, grouping prochlorperazine with other known QT-prolonging antiemetics. 1
• The American College of Cardiology identifies prochlorperazine among QT-prolonging medications that should be avoided in patients with congenital long QT syndrome. 1

Clinical Context: Relative Risk Among Antiemetics

When comparing antiemetic options, prochlorperazine falls into a moderate-risk category:

• 5-HT3 antagonists (ondansetron, granisetron, dolasetron) carry FDA warnings for QT prolongation and should be avoided in high-risk patients. 1
• Metoclopramide can prolong the QT interval and should be used with extreme caution only. 1
• Domperidone prolongs QTc and should be avoided entirely in at-risk patients. 1, 2
• Prochlorperazine is listed alongside these agents as requiring avoidance in QT-prolonged patients. 1

Mandatory Pre-Treatment Requirements

Before prescribing prochlorperazine, you must:

• Obtain a baseline ECG to document the current QTc interval before starting any antiemetic therapy in patients with known or suspected QT prolongation. 1
• Correct electrolyte abnormalities immediately, maintaining potassium levels above 4.5 mEq/L and normalizing magnesium levels, as hypokalemia and hypomagnesemia dramatically increase arrhythmia risk. 1, 2
• Review and discontinue all other QT-prolonging medications when possible, as concurrent use creates exponentially increased risk rather than simply additive effects. 1, 2

High-Risk Patient Factors Requiring Avoidance

Prochlorperazine should be avoided entirely in patients with:

• Baseline QTc > 500 ms (absolute contraindication). 1, 2
• Congenital long QT syndrome (any QT-prolonging medication is potentially harmful). 1
• Female sex and age > 65 years (two-fold higher incidence of torsades de pointes). 1
• Concurrent use of any other QT-prolonging medication (exponential risk increase). 1, 2
• Uncorrected hypokalemia (K⁺ < 4.0 mmol/L) or hypomagnesemia. 1
• Bradycardia, complete AV block, or recent conversion from atrial fibrillation. 1
• Decompensated heart failure or structural heart disease. 1

Monitoring Protocol If Prochlorperazine Is Used

When prochlorperazine cannot be avoided:

• Monitor ECG 7 days after starting therapy or after any dose change. 1
• Discontinue the antiemetic immediately if QTc exceeds 500 ms during treatment. 1, 2
• Stop treatment if QTc increases by more than 60 ms from baseline, regardless of absolute value. 1, 2
• Monitor continuously for symptoms of arrhythmia (palpitations, syncope, dizziness). 1, 3
• Maintain normal electrolyte levels throughout treatment, as vomiting-induced potassium and magnesium loss further prolongs QTc. 1

Safer Alternative Antiemetics

When QT prolongation is a concern, consider:

• First-line alternatives: Non-pharmacological approaches or antihistamines (if effective). 1
• If medication is absolutely necessary: Use the lowest effective dose with intensive monitoring. 1
• Benzodiazepines (lorazepam) do not prolong QTc and can be used for nausea-related agitation. 4

Common Pitfall to Avoid

The most dangerous error is combining prochlorperazine with other QT-prolonging drugs (antipsychotics, macrolide antibiotics, fluoroquinolones, antiarrhythmics, methadone, antimalarials). 1, 2 This combination creates exponentially—not additively—increased risk of torsades de pointes and sudden cardiac death. 1