Ondansetron: Side effect
Generic Clinical Sciences
Numerous conditions (i.e., infection, pregnancy, vestibular dysfunction, increased intracranial pressure) and exposures to various pharmaceuticals agents – including inhalational anesthetics – can cause nausea and vomiting.
Several sources of afferent input are known to stimulate the vomiting center, including the chemoreceptor trigger zone (CTZ), located near the area postrema on the floor of the fourth ventricle, where the blood brain barrier is not as developed, making it readily accessible to emetogenic stimuli in the blood and cerebrospinal fluid (CSF). This area is rich in a number of different receptor classes, including: dopamine D2, serotonin 5-HT3, and opioid receptors. Other afferent fibers are activated by the vestibular system (important in motion sickness) through CN VIII, which is rich in muscarinic and histamine H1 receptors; vagal and enteric afferent fibers in the mucosa of the GI tract are also rich in 5-HT3 receptors. (2)
The first of this class of drugs (-setrons) to be developed was ondansetron (Zofran), a carbazole derivative developed by Glaxo in 1984. Its efficacy was first established in 1987 and it was approved by the United States Food and Drug Administration in 1991. (3,4)
Side Effects : While the 5-HT3 receptor antagonists are well-tolerated, commonly reported side effects include: fever, headache, dizziness, and constipation. On 15 September 2011, the U.S. Food and Drug Administration (FDA) informed the public of an ongoing safety review of the anti-nausea drug Zofran (ondansetron, ondansetron hydrochloride and their generics): Ondansetron may increase the risk of developing abnormal changes in the electrical activity of the heart, which can result in a potentially fatal abnormal heart rhythm, specifically, torsades de pointes.
Over the past two decades, the single most common cause of withdrawal or restriction of a medication that has already entered the market has been prolongation of the QT interval associated with polymorphic ventricular tachycardia or torsades de pointes. (10) While case reports have been published documenting the proarrhythmic potential of -setrons in both adults and children, overall electrocardiographic data have been conflicting. (11,12)
As per the Center for Education and Research at the University of Arizona: Ondansetron is a member of the risk category of “possible drugs” that could prolong the QTc interval, leading to torsades de pointes.
In patients admitted for either heart failure or acute coronary syndromes with at least one additional risk factor for torsades de pointes, we found that this effect could be seen at least 120 minutes following drug exposure. When considering using ondansetron for long-term administration in the inpatient setting, patients with cardiovascular disease who are at high risk for drug-induced torsades de pointes should at least be monitored via telemetry. From a patient safety perspective, ondansetron should be added to the clinician’s list of drugs that can possibly prolong the QTc interval. (15)