Which medication has the most QT prolongation: Reglan (Metoclopramide), Compazine (Prochlorperazine), or Zofran (Ondansetron)?

QT Prolongation Risk: Reglan vs Compazine vs Zofran

Ondansetron (Zofran) carries the highest risk for clinically significant QT prolongation among these three antiemetics, followed by prochlorperazine (Compazine), with metoclopramide (Reglan) having the lowest risk.

Comparative QT Prolongation Data

Ondansetron (Zofran) is specifically identified as a medication that prolongs the QTc interval and requires careful monitoring in cancer patients and other vulnerable populations 1. The drug is classified among 5-HT3 receptor antagonists (including granisetron and dolasetron) that have synergistic effects on QT prolongation when combined with other QT-prolonging agents 2. Ondansetron is explicitly listed among important medications to consider for drug-drug interactions that prolong the QTc interval 1.

Prochlorperazine (Compazine) is identified as a QT-prolonging medication that should be avoided in patients receiving cancer therapies known to prolong QT 1. It is specifically contraindicated for concomitant use with dofetilide due to QT prolongation risk 1. Prochlorperazine is classified among antipsychotics that contribute to QT interval prolongation 1.

Metoclopramide (Reglan) is primarily recommended for treating nausea and improving gastric motility in migraine patients, with its main therapeutic role being adjunctive rather than as a primary antiemetic 1. Notably, metoclopramide is not specifically mentioned in the major guidelines addressing QT prolongation risk, suggesting a lower concern compared to the other two agents 1.

Clinical Risk Stratification

The risk hierarchy is particularly important in specific patient populations:

• Cancer patients receiving chemotherapy are at heightened risk due to electrolyte losses from nausea, vomiting, and diarrhea, which further prolongs the QT interval 1
• Female patients and those over 65 years have increased susceptibility to QT prolongation with these agents 3
• Patients with baseline QTc >500 ms should avoid all three medications if possible 3
• Concomitant use of multiple QT-prolonging drugs exponentially increases risk 1, 3

Evidence-Based Selection Algorithm

For patients without QT concerns: Ondansetron may be used as first-line therapy due to its lack of sedation and akathisia compared to dopamine antagonists 4.

For patients with QT prolongation risk factors:

1. First choice: Metoclopramide (Reglan) - lowest QT prolongation risk among the three options 1
2. Second choice: Prochlorperazine (Compazine) - moderate risk, but monitor closely 1
3. Avoid: Ondansetron (Zofran) - highest risk, particularly when combined with other QT-prolonging agents 1, 2

Monitoring Requirements

Before initiating any of these antiemetics in at-risk patients:

• Obtain baseline ECG to assess QTc interval 1, 3
• Correct hypokalemia and hypomagnesemia before treatment 1, 3
• Repeat ECG 7 days after initiation and after any dose changes 1
• Discontinue treatment if QTc exceeds 500 ms or increases by >60 ms from baseline 1, 3
• Monitor potassium and magnesium levels throughout treatment 1, 3

Critical Pitfalls to Avoid

Drug-drug interactions are the most common cause of clinically significant QT prolongation with these agents 1. Review all concomitant medications including antimicrobials, H2-blockers, proton pump inhibitors, and antipsychotics before prescribing 1.

Intravenous administration of ondansetron may carry higher risk than oral formulations, similar to the pattern seen with haloperidol 3, 5.

Underestimating cumulative risk when patients receive multiple antiemetics sequentially or in combination can lead to dangerous QT prolongation 2. The synergistic effects of combining ondansetron with chemotherapy agents or other QT-prolonging drugs are particularly concerning 2.