From the Guidelines
Antiemetics that do not cause prolonged QT syndrome include metoclopramide, prochlorperazine, promethazine, scopolamine, dexamethasone, and cannabinoids. These medications work through different mechanisms to control nausea and vomiting without significantly affecting cardiac repolarization.
Key Points
- Metoclopramide (10mg orally or IV every 6 hours) acts as a dopamine antagonist and promotes gastric emptying 1.
- Prochlorperazine (5-10mg orally or IV every 6-8 hours) is a phenothiazine that blocks dopamine receptors 1.
- Promethazine (12.5-25mg orally, IV, or IM every 4-6 hours) works as an antihistamine with antiemetic properties 1.
- Scopolamine (transdermal patch behind the ear, changed every 72 hours) is particularly useful for motion sickness.
- Dexamethasone (4-8mg IV or orally daily) is effective for chemotherapy-induced nausea 1. These alternatives are particularly important for patients with pre-existing cardiac conditions, those taking other QT-prolonging medications, or those with electrolyte abnormalities. In contrast, commonly used antiemetics like ondansetron, dolasetron, and droperidol can prolong the QT interval and should be used with caution in at-risk patients.
Mechanism of Action
The mechanism of action of these antiemetics varies, but they all work to control nausea and vomiting without affecting cardiac repolarization.
- Dopamine antagonists, such as metoclopramide, work by blocking dopamine receptors in the brain and promoting gastric emptying 1.
- Phenothiazines, such as prochlorperazine, work by blocking dopamine receptors in the brain and have antiemetic properties 1.
- Antihistamines, such as promethazine, work by blocking histamine receptors in the brain and have antiemetic properties 1.
- Corticosteroids, such as dexamethasone, work by reducing inflammation and have antiemetic properties 1.
From the Research
Antiemetics and QT Syndrome
- The risk of QTc prolongation with antiemetics is a concern in the palliative care setting 2.
- Certain antiemetic classes, such as serotonin and neurokinin antagonists, are effective in treating chemotherapy-induced nausea and vomiting, but some may prolong the QT interval 3.
- Ondansetron, a 5-HT3 receptor antagonist, is not associated with sedation or akathisia and may be used as a first-line agent for relief of nausea or vomiting in the emergency department 4.
Antiemetics that Do Not Cause Prolonged QT Syndrome
- Ondansetron is mentioned as a safe option that does not cause QT prolongation 4.
- Palonosetron, another 5-HT3 receptor antagonist, is also not associated with QT prolongation 5.
- Netupitant + palonosetron combination has little to no impact on complete control of vomiting during the overall treatment phase and does not cause QT prolongation 5.
Comparison of Antiemetic Combinations
- A network meta-analysis compared the efficacy of different antiemetic combinations, including those with NK1 and 5-HT3 inhibitors, and found that some combinations were more efficacious than others in preventing chemotherapy-induced nausea and vomiting 5.
- However, the analysis did not provide conclusive evidence on the superiority of one treatment over another in terms of preventing QT prolongation.