Which of the following antiemetics is contraindicated in patients with prolonged QT interval on baseline ECG?

Explanation

## Ondansetron and QT Prolongation Risk **Key Point:** Ondansetron (a 5-HT3 antagonist) carries an FDA safety communication (2011) and a dose-dependent risk of QT prolongation and torsades de pointes. It is **contraindicated** in patients with congenital long QT syndrome or pre-existing QT prolongation on baseline ECG. **High-Yield:** The FDA (2011) warned against the use of the 32 mg single IV dose of ondansetron due to QT prolongation risk, and it was withdrawn from the market. Ondansetron is the antiemetic most classically associated with QT prolongation contraindication in clinical practice and exam settings. ### Mechanism of QT Prolongation Ondansetron blocks cardiac hERG (IKr) potassium channels, delaying ventricular repolarization and prolonging the QT interval. Risk is: - **Dose-dependent** (higher IV doses carry greater risk) - Increased with hypokalemia, hypomagnesemia, or concurrent QT-prolonging drugs - Particularly dangerous in patients with baseline QT prolongation ### Safety Profile Comparison | Agent | QT Prolongation Risk | Regulatory Warning | Notes | |-------|----------------------|--------------------|-------| | Ondansetron | **HIGH** | FDA Safety Communication (2011) | Contraindicated in baseline QT prolongation | | Domperidone | Moderate | EMA restriction | Peripheral D2 antagonist; some cardiac risk at high doses | | Metoclopramide | Low–Moderate | Black box (tardive dyskinesia) | Primary warning is for tardive dyskinesia, NOT QT prolongation | | Aprepitant | None | No | NK1 antagonist; no significant cardiac effects | **Warning:** Ondansetron should be avoided in patients with congenital long QT syndrome, electrolyte abnormalities, or those on other QT-prolonging agents. ECG monitoring is recommended in high-risk patients. **Clinical Pearl:** While metoclopramide has some QT-prolonging potential at high IV doses, its primary FDA black box warning (2009) is for **tardive dyskinesia** with chronic use — not QT prolongation. Ondansetron is the antiemetic most specifically contraindicated in patients with a prolonged QT interval on baseline ECG, as per standard pharmacology references (KD Tripathi, 8th ed.; Harrison's Principles of Internal Medicine).