Obtain baseline ECG in at-risk patient populations, along with monitoring sodium, potassium, calcium, and magnesium.

Arrhythmia

5-HT3 receptor antagonist use correlates with many dose-dependent increases in ECG intervals (PR, QRS, QT/QTc, JT), usually occurring 1 to 2 hours after intravenous (IV) administration. When used in conjunction with other interval prolonging agents, there is the risk of arrhythmia development. Healthcare providers should observe caution with patients with a history of congenital long QT syndrome, ventricular arrhythmias, cardiac disease, electrolyte abnormalities, or with those who are receiving concomitant cardiotoxic chemotherapy.

Serotonin Syndrome

There are cases of fatal serotonin syndrome reported with 5-HT3 receptor antagonists, most often in the post-anesthesia setting or an infusion center. This condition appears to be from the concomitant use of serotonergic medications, such as SSRIs, selective norepinephrine serotonin reuptake inhibitors (SNRIs), lithium, fentanyl, and mirtazapine. Patients require monitoring for signs of serotonin syndrome, including mental status changes, autonomic instability, tachycardia, labile blood pressure, diaphoresis, flushing, neuromuscular changes, GI symptoms, and/or seizures. If serotonin syndrome occurs, discontinue 5-HT3 receptor antagonists, and initiate supportive management.

Constipation

Constipation is a commonly reported adverse effect with all formulations of 5-HT3 receptor antagonists, especially the use of tablets or extended-release subcutaneous injection; this can be compounded during pregnancy or for patient populations at risk for constipation. There is concern regarding the masking of symptoms of bowel obstruction with 5-HT3 receptor antagonist use and should not be a substitute for nasogastric suctioning. Exercise caution in patients with recent abdominal surgery.

Other

Some dosage forms of 5-HT3 receptor antagonists may contain sodium benzoate/benzoic acid, which is a metabolite of benzyl alcohol. Large amounts of benzyl alcohol (greater than 99 mg/kg per day) have correlated with fatal neonatal “gasping syndrome,” which consists of metabolic acidosis, respiratory distress, gasping respirations, central nervous system (CNS) depression, renal failure, and hypotension. Caution should be taken in patients with phenylketonuria, as orally disintegrating tablets contain phenylalanine. Clinicians should decrease the dosing of 5-HT3 receptor antagonists in patients with hepatic impairment, due to the altered hepatic clearance and prolonged drug half-life.

Overdose is rare, and there is no fatal dose yet established. 5-HT3 receptor antagonists have a broad therapeutic index with mild side effects that occur infrequently. Treatment is mostly supportive. Monitor for the rare cases of ECG changes, ventricular arrhythmias, serotonin syndrome, and masked bowel ileus or bowel obstruction. Due to the unknown fatal dose and extremely rare documented cases of overdose causing significant morbidity or mortality, there is little commercial motivation or clinical need for antidote development. Additionally, there are a few notable drug interactions notable with 5-HT3 antagonists of Amiodarone, Amisulpride, Apomorphine, and Bosentan.

Clinicians frequently manage nausea and vomiting with the use of selective serotonin receptor (5-HT3) antagonists. Because these two symptoms are very common patients, all healthcare workers need to be familiar with these agents. Consequently, an interprofessional team approach is the most effective means to use these agents.

The clinician (MD, DO, NP, PA) will order or prescribe these agents. It would be advantageous to include a pharmacist in the decision, as they can perform medication reconciliation, verify dosing, and even suggest the optimal agent in class. Nursing will administer these drugs to inpatients and can provide counsel on home administration to outpatients, and monitor treatment effectiveness over time. These examples if interprofessional teamwork demonstrate how this approach leads to better outcomes for patients [Level 5]

Currently, there are four 5-HT3 receptor antagonists on the market, which are FDA-approved for the prevention of nausea and vomiting in children and adults related to chemotherapy use, radiation therapy, and the effects of postoperative anesthesia. Dolasetron is also FDA-approved for the treatment of postoperative nausea and vomiting in adults and children. The 5-HT3 receptor antagonists are effective drugs and are relatively safe. Rarely, 5-HT3 receptor antagonists can cause QT prolongation if administered concomitantly with other QT-prolonging medications or in patients with a history of congenital long-QT syndrome. There is also the concern for masking symptoms of bowel obstruction in the elderly or postoperative patient. An overdose of 5-HT3 receptor antagonists is rare, and there has not been the establishment of a fatal dose. Treatment is mainly supportive in these cases. Overall, select serotonin receptor antagonists are an effective antiemetic class with a broad therapeutic index and mild side effect profile.[7][4]