Least QT Prolonging Antiemetic Drugs
Aripiprazole is the least QT prolonging antiemetic drug with 0 ms QT prolongation, followed by olanzapine with only 2 ms prolongation. 1
QT Prolongation Risk by Antiemetic Class
Low QT Risk Antiemetics
- Aripiprazole: 0 ms QT prolongation 1
- Olanzapine: 2 ms QT prolongation 1
- Scopolamine: No significant QT prolongation reported 2
- Diphenhydramine/Dimenhydrinate: Not listed among high-risk QT prolonging medications 2
- Ginger: Natural antiemetic with no known QT effects 2
Moderate QT Risk Antiemetics
- Quetiapine: 6 ms QT prolongation 1
- Haloperidol: 7 ms QT prolongation 1
- Clozapine: 8-10 ms QT prolongation 1
- Granisetron: Less QT prolongation than ondansetron but still carries risk 2
High QT Risk Antiemetics
- Ondansetron and other 5-HT3 antagonists: Significant QT prolongation (except palonosetron) 2
- Domperidone: High risk of QT prolongation, doses above 10 mg TID not recommended 2, 1
- Metoclopramide: Associated with QT prolongation 2
- Pimozide: 13 ms QT prolongation 1
- Ziprasidone: 5-22 ms QT prolongation 1
- Thioridazine: 25-30 ms QT prolongation 1
Antiemetic Selection Algorithm Based on QT Risk
Step 1: Assess Patient's QT Risk Factors
- Pre-existing QT prolongation
- Electrolyte abnormalities (especially hypokalemia, hypomagnesemia)
- Concurrent QT-prolonging medications
- Female gender, advanced age (>65 years)
- Cardiac disease, heart failure, bradycardia
- Hepatic or renal dysfunction
Step 2: Select Antiemetic Based on Risk Profile
- No QT risk factors: Any antiemetic appropriate for the clinical situation
- Moderate QT risk factors: Choose low QT risk options (aripiprazole, olanzapine)
- High QT risk factors: Use only the lowest QT risk options (aripiprazole, ginger)
Special Considerations
For Chemotherapy-Induced Nausea and Vomiting
- Palonosetron is the only 5-HT3 antagonist without QT prolongation warnings in its label 2
- NEPA (netupitant/palonosetron) combination has shown no cardiac safety concerns in studies 2
For Pregnancy-Related Nausea
- Antihistamines (diphenhydramine, dimenhydrinate) have lower QT risk profiles 3
For Palliative Care
- Consider anticholinergics (scopolamine) or antihistamines which have lower QT prolongation risk 4
Monitoring Recommendations
- Obtain baseline ECG before initiating high-risk antiemetics
- Correct electrolyte abnormalities (maintain potassium 4.5-5 mmol/L)
- Monitor ECG when:
- Steady-state levels are achieved
- Dose adjustments are made
- New potentially interacting medications are started
Important Caveats
- QT prolongation risk is dose-dependent for most antiemetics
- Combination of multiple QT-prolonging antiemetics (e.g., ondansetron with domperidone and olanzapine) significantly increases risk, especially in females 5
- Palonosetron appears to have the most favorable cardiac safety profile among 5-HT3 antagonists 2
- Amisulpride at 10 mg IV does not have clinically significant QT effects even when combined with ondansetron 6
- Using Fridericia's formula (QT/RR^1/3) for QTc calculation is more accurate than Bazett's formula, especially with heart rates >80 bpm 1
By selecting antiemetics with minimal QT prolongation effects like aripiprazole or olanzapine, clinicians can effectively manage nausea and vomiting while minimizing the risk of potentially dangerous cardiac arrhythmias.