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

Understanding the Risk

Prochlorperazine belongs to the phenothiazine class of antiemetics that prolong cardiac repolarization through blockade of potassium channels (specifically the hERG/IKr current). 2, 3 While the evidence does not quantify the exact millisecond increase in QTc for prochlorperazine specifically, multiple cardiology and thoracic medicine guidelines classify it among antiemetics that carry QT-prolongation risk. 1

The European Society of Cardiology and American College of Cardiology explicitly recommend avoiding prochlorperazine in patients with prolonged QTc. 1

Clinical Decision Algorithm

Step 1: Assess Baseline Risk

Before prescribing prochlorperazine, obtain:

• Baseline 12-lead ECG to measure QTc interval 1, 4
• Serum electrolytes (potassium >4.5 mEq/L, normal magnesium) 1, 4
• Complete medication review for other QT-prolonging drugs 1, 5
• Cardiac history including family history of sudden death, syncope, or congenital long QT syndrome 4, 6

Step 2: Identify Absolute Contraindications

Do NOT use prochlorperazine if:

• QTc ≥500 ms 1, 4
• Congenital long QT syndrome 1
• Patient is already taking other QT-prolonging medications (the risk is exponential, not additive) 1, 4
• Uncorrected hypokalemia (K+ <4.0 mEq/L) or hypomagnesemia 1

Step 3: Stratify High-Risk Patients

Use extreme caution or choose alternatives if:

• Female gender (2-fold higher risk of torsades de pointes) 1, 5, 6
• Age >65 years 1, 4, 5
• Structural heart disease or heart failure 1, 4
• Bradycardia or recent conversion from atrial fibrillation 1, 5
• QTc 450-499 ms (men) or 460-499 ms (women) 4

Step 4: Choose Safer Alternatives When Possible

The evidence reveals important nuances about antiemetic selection:

• 5-HT3 antagonists (ondansetron, granisetron, dolasetron) also prolong QT and carry FDA warnings—they are NOT safer alternatives 1, 5
• Metoclopramide can prolong QT and should be used with extreme caution only 1
• Domperidone prolongs QTc and should be avoided 1
• Promethazine carries QT risk, particularly in women >65 years 1

If antiemetics with QT risk must be used: The guidelines suggest that when 5-HT3 antagonists must be avoided, phenothiazines (including prochlorperazine) or dopamine antagonists (metoclopramide, haloperidol) may be considered in cancer patients, but this represents choosing among imperfect options rather than identifying a truly safe alternative. 1

Monitoring Protocol If Prochlorperazine Is Used

• Repeat ECG at 7 days after starting therapy or after any dose change 1, 4

• Discontinue immediately if:

  • QTc exceeds 500 ms 1, 4
  • QTc increases >60 ms from baseline 1, 4
  • Patient develops palpitations, syncope, or dizziness 1, 7

• Maintain electrolyte surveillance throughout treatment, as vomiting itself causes potassium and magnesium loss that further prolongs QTc 1

Critical Pitfalls to Avoid

The most dangerous mistake is combining multiple QT-prolonging medications. 1, 4, 5 The risk increases exponentially rather than additively when prochlorperazine is combined with:

• Antipsychotics (haloperidol, quetiapine, ziprasidone) 4, 5
• Macrolide antibiotics (erythromycin, clarithromycin, azithromycin) 5
• Fluoroquinolones (moxifloxacin, levofloxacin) 5
• Antiarrhythmics (amiodarone, sotalol, quinidine) 5
• Antidepressants (citalopram, escitalopram, tricyclics) 4, 5
• Antimalarials (chloroquine, hydroxychloroquine) 5

Never assume that ECG monitoring alone makes these combinations safe—in high-risk patients, avoidance is the only truly safe approach. 1

Management of Prochlorperazine-Induced Torsades de Pointes

If torsades de pointes occurs:

• Immediate discontinuation of prochlorperazine 1, 4
• IV magnesium sulfate 2 g (effective even when serum magnesium is normal) 1, 4
• Potassium repletion to >4.5 mEq/L 1, 4
• Temporary cardiac pacing or isoproterenol for recurrent episodes 1, 4
• Non-synchronized defibrillation if hemodynamically unstable 1

Special Populations

In hyperemesis patients: The vomiting itself causes electrolyte depletion (potassium and magnesium loss) that dramatically amplifies QT-prolongation risk. 1 Correct electrolytes BEFORE administering prochlorperazine, not concurrently.

In cancer patients receiving chemotherapy: Many chemotherapeutic agents also prolong QT, creating additive risk. 1 Increase ECG monitoring frequency based on the specific chemotherapy regimen.