Antiemetic with the Least Impact on QT Interval
Lorazepam is the safest antiemetic option for patients at risk of QT prolongation as it does not cause QT interval prolongation and is considered safe from a cardiac arrhythmia perspective. 1
Comparison of Antiemetics and QT Prolongation Risk
5-HT3 Receptor Antagonists
- All 5-HT3 receptor antagonists except palonosetron carry warnings for QT interval prolongation 2
- The FDA required withdrawal of IV dolasetron and expanded warnings for ondansetron and granisetron due to cardiac safety concerns 2
- Palonosetron is the only 5-HT3 antagonist without a QT prolongation warning in its label 2
- Ondansetron has demonstrated QT prolongation in various studies, with higher doses carrying greater risk 3, 4
- Some pediatric studies suggest minimal QT effects with ondansetron, but these findings cannot be generalized to all populations 5, 6
Benzodiazepines (Lorazepam)
- Benzodiazepines, including lorazepam, have not been associated with QT interval prolongation in clinical practice 1
- Lorazepam is notably absent from comprehensive lists of QT-prolonging medications in major cardiology guidelines 1
- Lorazepam is classified as a "Class A" drug, considered to be without any risk of QT prolongation or Torsades de Pointes 1
- Lorazepam can be safely used as an antiemetic option for patients at risk of QT prolongation 1
Other Antiemetics
- Metoclopramide has been restricted by the EMA to short-term use (up to 5 days) primarily due to neurological side effects rather than QT concerns 2
- Dopaminergic antiemetics have shown efficacy but their use has been limited by safety concerns including QT prolongation 7
- Amisulpride at 10mg dose shows minimal QT prolongation (mean ΔΔQTcF of 5.2-8.0 milliseconds) 7
- Combination antiemetic regimens containing multiple QT-prolonging agents (like domperidone, ondansetron, and olanzapine) have shown significant QT prolongation, especially in female patients 4
Risk Factors for QT Prolongation
- Female gender increases susceptibility to drug-induced QT prolongation 1
- Electrolyte abnormalities, especially hypokalemia and hypomagnesemia, enhance risk 1, 2
- Bradycardia or recent conversion from atrial fibrillation 1
- Heart failure or structural heart disease 1
- Concomitant use of multiple QT-prolonging medications significantly increases risk 1, 4
Clinical Recommendations
- For patients at high risk of QT prolongation requiring antiemetic therapy, lorazepam should be the first choice 1
- If a 5-HT3 antagonist is necessary, palonosetron is preferred as it has no QT prolongation warning in its label 2
- Before administering any potentially QT-prolonging antiemetic, correct electrolyte abnormalities (particularly hypokalemia and hypomagnesemia) 2
- Obtain baseline ECG in patients receiving QT-prolonging antiemetics and repeat ECG at 7 days after initiation or following any dosing changes 2
- Stop treatment with QT-prolonging antiemetics if the QTc is > 500 ms on monitoring 2
- For patients requiring antiemetics for low emetogenic risk conditions, dexamethasone may be considered as an alternative with less QT concern than 5-HT3 antagonists 2
Monitoring Recommendations
- ECG monitoring is not specifically required when administering lorazepam alone 1
- For patients receiving QT-prolonging antiemetics, obtain baseline ECG and correct electrolyte abnormalities prior to starting treatment 2
- Monitor QTc interval according to CTCAE.4 guidelines: grade 1 (450-480 ms), grade 2 (481-500 ms), grade 3 (>501 ms) 2
- QTc >500 ms or >60 ms change from baseline are associated with increased risk for Torsades de Pointes 2