Which medication, Reglan (Metoclopramide) or Zofran (Ondansetron), is least likely to increase the QT interval?

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Last updated: March 13, 2025View editorial policy

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From the Guidelines

Reglan (Metoclopramide) is less likely to increase the QT interval compared to Zofran (Ondansetron). Metoclopramide has minimal effects on cardiac repolarization and is not significantly associated with QT prolongation at standard doses [ 1 ]. In contrast, ondansetron has been documented to cause dose-dependent QT interval prolongation, particularly at higher doses or with rapid intravenous administration [ 1 ]. This difference is important clinically because QT prolongation can lead to potentially dangerous heart rhythm disturbances such as Torsades de Pointes.

Some key points to consider when choosing between these medications include:

  • The patient's cardiac status and existing risk factors for arrhythmias
  • The presence of other QT-prolonging medications in the patient's regimen
  • The expected duration of treatment with the antiemetic
  • The potential for extrapyramidal symptoms and tardive dyskinesia with metoclopramide use [ 1 ]

For patients with existing QT prolongation, other risk factors for arrhythmias, or those taking multiple QT-prolonging medications, metoclopramide may be the safer choice when an antiemetic is needed [ 1 ]. However, metoclopramide carries its own risks, including extrapyramidal symptoms and tardive dyskinesia with prolonged use, so the selection between these medications should consider the patient's complete clinical picture [ 1 ].

It is also important to note that a baseline ECG should be obtained in all patients and electrolyte abnormalities corrected prior to starting treatment [ 1 ]. ECG should be repeated at 7 days after initiation of therapy, according to drug package inserts, and following any dosing changes [ 1 ]. Treatment should be stopped if the QTc is > 500 ms on monitoring [ 1 ].

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Medication Comparison

  • Reglan (Metoclopramide) and Zofran (Ondansetron) are both used to treat nausea and vomiting, but their effects on the QT interval differ.
  • There is no direct comparison between Reglan and Zofran in the provided studies, but the studies suggest that Ondansetron can cause QT interval prolongation 2, 3, 4, 5.
  • The studies on Ondansetron show that it can cause a mean prolongation of the QTc by 20 ms 2, and the maximum prolongation of the mean QT duration occurred at the fifth minute (7.9 ± 18.1 ms) 3.
  • However, the effect of Ondansetron administration on QT prolongation was found to be above the 'negligible' but below the 'significant' value, according to the ICH recommendations 3.
  • A study on the cardiac safety of Ondansetron suggests that the dose of 32 mg i.v. (or several doses that are equivalent to this) is the one that the FDA has concerns about, which is only used in preventing nausea and vomiting associated with cancer chemotherapy 4.
  • Another study evaluated the potential risk for selected cardiac adverse events associated with dolasetron, ondansetron, and granisetron use, and detected a potential signal for ventricular arrhythmias and cardiac arrest with dolasetron, but not with ondansetron or granisetron 6.
  • A prospective observational study found that single intravenous dose ondansetron induces QT prolongation in adult emergency department patients, and that 8 mg doses were associated with higher rates of QTc60 prolongation, while 4 mg doses favored maintaining QTc60 within normal limits 5.

QT Interval Prolongation

  • The QT interval prolongation associated with Ondansetron use is a concern, but the clinical impact is questionable 2.
  • The studies suggest that the QT interval prolongation caused by Ondansetron is generally not significant, but it can be a concern in certain patients, such as those with pre-existing heart conditions or those taking other medications that can affect the QT interval.
  • There is no information provided about the effect of Reglan (Metoclopramide) on the QT interval, so it is unclear which medication is least likely to increase the QT interval.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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