From the FDA Drug Label
5.3 Serotonin Syndrome The development of serotonin syndrome has been reported with 5-HT 3receptor antagonists alone. Most reports have been associated with concomitant use of serotonergic drugs (e.g., selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors, mirtazapine, fentanyl, lithium, tramadol, and intravenous methylene blue). Patients should be monitored for the emergence of serotonin syndrome, especially with concomitant use of ondansetron tablets and other serotonergic drugs. If symptoms of serotonin syndrome occur, discontinue ondansetron tablets and initiate supportive treatment
Amitriptyline is a tricyclic antidepressant that has serotonergic properties. The use of ondansetron with amitriptyline may increase the risk of serotonin syndrome.
- Key points to consider:
- Monitor patients for signs and symptoms of serotonin syndrome, such as mental status changes, autonomic instability, and neuromuscular symptoms.
- Discontinue ondansetron if symptoms of serotonin syndrome occur and initiate supportive treatment. It is not entirely safe to prescribe ondansetron to a patient taking amitriptyline without proper monitoring and caution due to the potential risk of serotonin syndrome 1.
From the Research
Prescribing ondansetron to a patient taking amitriptyline requires caution due to a potential drug interaction that may increase the risk of QT interval prolongation, and careful monitoring is recommended, especially in patients with pre-existing cardiac conditions or other risk factors for QT prolongation. This combination can be used if necessary, but it is crucial to consider the potential risks. Both medications individually can cause QT interval prolongation, and when used together, this effect may be additive 2, 3.
Key Considerations
- Before prescribing this combination, consider obtaining a baseline ECG, particularly in high-risk patients such as the elderly or those with heart disease, electrolyte abnormalities, or concomitant use of other QT-prolonging medications.
- If the combination is necessary for managing nausea, use the lowest effective doses of both medications, monitor for symptoms like palpitations, dizziness, or syncope, and consider periodic ECG monitoring during treatment 4.
- Alternative antiemetics that don't affect the QT interval, such as prochlorperazine or metoclopramide, might be preferable in patients with significant cardiac risk factors, though these have their own side effect profiles to consider.
Monitoring and Management
- The predictive models for QTc prolongation 1-hour post-ondansetron administration showed that a QTc0 = 375 msec indicated a QTc60 > 480 msec with a specificity of 97%, and a QTc0 of 400 msec had a sensitivity of 100% in predicting a QTc60 < 480 msec 2.
- The administration of ondansetron was associated with a statistically significant prevalence of QT prolongation in all age groups, particularly among patients older than 18 years of age 3.
- Pharmacodynamic drug-drug interactions involving ondansetron and other QT-prolonging medications, such as amiodarone or ciprofloxacin, increased the risk of QTc prolongation 4.