Ondansetron

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Continuing Education Activity

Ondansetron is one of the medications most commonly used for empiric treatment of nausea and vomiting. Ondansetron has extreme utility as an antiemetic drug, and it is effective against nausea and vomiting of various etiologies. Common uses of ondansetron include the prevention of chemotherapy-induced and radiation-induced nausea and vomiting, the prevention of postoperative nausea and vomiting, and off-label use for the prevention of nausea and vomiting associated with pregnancy. However, it is not effective for motion sickness-induced nausea. This activity will cover the mechanism of action, pharmacology, adverse event profiles, eligible patient populations, contraindications, monitoring, and highlights the role of the interprofessional team in the management of ondansetron therapy.

Objectives:

  • Identify the antiemetic mechanism of action of ondansetron.
  • Outline the approved and off-label indications for using ondansetron.
  • Summarize the adverse event profile of ondansetron.
  • Review the importance of improving care coordination among the interprofessional team to enhance the delivery of care for patients who can benefit from therapy with onsadnsetron.

Indications

Nausea and vomiting are two of the most common presenting complaints seen by emergency department physicians and primary care physicians daily.[1] Ondansetron is one of the medications most commonly used for empiric treatment. It appears on the World Health Organization’s (WHO) List of Essential Medicines, a list of medications considered effective and safe regarding meeting the essential needs in a health system. Other antiemetics that appear on this list with ondansetron include dexamethasone and metoclopramide. In 2006 (the last year of its patent), the brand-name version of ondansetron was the 20th highest-selling brand-name drug in the United States, and its popularity continues today. Ondansetron has extreme utility as an antiemetic drug, and it is effective against nausea and vomiting of various etiologies.

Typical uses of ondansetron include the prevention of chemotherapy-induced and radiation-induced nausea and vomiting, the prevention of postoperative nausea and vomiting (PONV), and off-label use for the prevention of nausea and vomiting associated with pregnancy. It is considered first-line therapy for the treatment of chemotherapy-induced and radiation-induced nausea and vomiting. Although the drug works particularly well for these indications, it has minimal effect on nausea and vomiting caused by motion sickness, mediated by different control centers and pathophysiologic mechanisms. There are limited data available from pediatric populations. Ondansetron is used in pediatric populations for the acute treatment of cyclic vomiting syndrome; however, there is little information available on the efficacy of this disease.[2][3][4][5]

Mechanism of Action

Ondansetron is a selective 5-HT3 serotonin-receptor antagonist used for its antiemetic properties. It is one of the four FDA-approved 5-HT3 serotonin-receptor antagonists used to combat nausea and vomiting, with the others including granisetron, dolasetron, and the second-generation drug, palonosetron.[6]

Ondansetron acts both centrally and peripherally to prevent and treat nausea and vomiting. Central effects are mediated by the antagonism of 5HT-3 serotonin receptors in the area postrema. The area postrema, located on the fourth ventricle floor, contains the “chemoreceptor trigger zone.” This zone senses neurotransmitters like serotonin, toxins, and other signals and plays a role in mediating the sensation of nausea and subsequent vomiting. Ondansetron also has effects peripherally by acting on the vagus nerve. It works on the 5-HT3 receptors that can be found at the vagus nerve terminals. The vagus nerve can sense nausea and vomiting triggers within the GI tract, such as stomach irritants. It forms synapses within the nucleus tractus solitarius of the brainstem, another region important in vomiting. The peripheral actions of ondansetron are thought to be the predominant mechanism for its antiemetic effects. It is metabolized primarily by the cytochrome P450 system of the liver.[7][8][9][10]

Administration

Routes of administration include oral, intramuscular (IM), and intravenous (IV). Oral formulations are available in dissolving tablet and soluble film forms. When administered orally, ondansetron tablets should be administered 1 to 2 hours before radiotherapy, 30 minutes before chemotherapy, and an hour before anesthesia induction.  Oral and IV formulations have been shown to have similar efficacy for the treatment of emetogenic chemotherapy.

Dosing varies depending on the route of administration and the cause of the symptoms. However, 16 mg per dose IV is the maximum recommended single dose due to the risk for QTc prolongation and arrhythmias. Standard dosing to prevent postoperative nausea and vomiting includes 8 mg every 12 hours orally or 4 mg given intravenously. No dosage adjustments are necessary for IV or oral administration in patients with renal impairment. The same holds for patients with mild to moderate hepatic impairment, but the maximum daily dosing is reduced to 8 mg IV or 8 mg orally in patients with severe hepatic impairment. Pediatric dosing is weight-based at 0.15 mg/kg per dose with a maximum of 16 mg per dose.[11]

Adverse Effects

The most commonly reported side effects (occurring in more than 10% of adults) include headaches, fatigue, dry mouth, malaise, and constipation. Some less common effects range from central nervous systems (CNS) manifestations, such as drowsiness and sedation, to local injection site reactions and pruritus. A transient increase in liver function tests has been reported as well. Serotonin syndrome is another reported risk that may occur when taking ondansetron, although the greatest risk exists when taken in conjunction with other serotonergic medications.[12][13][14]

Although typically clinically insignificant, ECG interval changes such as QTc elongation can be seen. These changes typically occur within 1 to 2 hours after administration, returning to baseline within 24 hours. As with any medication that causes QTc elongation, there is a concern for Torsade de Pointes and other arrhythmias. IV administration is where the greatest risk lies. Because of this risk, single doses greater than 16 mg IV are not recommended per the FDA.[9]

Contraindications

Ondansetron is contraindicated in patients with hypersensitivity to the drug or any components of it. It is also contraindicated in patients currently taking apomorphine. Concomitant use of ondansetron and apomorphine can lead to profound hypotension and loss of consciousness, with ondansetron enhancing the hypotensive effects of apomorphine. Patients with phenylketonuria (PKU) should be cautious, as the dissolving tablet formulation can contain phenylalanine.[15]

It is considered pregnancy risk-factor category B and should only be used when other medications have been trialed and failed to treat pregnancy-associated nausea and vomiting and hyperemesis gravidarum.[8] Antihistamines, like diphenhydramine and meclizine, and dopamine antagonists, like metoclopramide and promethazine, should be considered in this patient population before using ondansetron. Pregnancy category B drugs are medications that have failed to demonstrate a risk to the fetus in animal reproductive studies, and no adequate trials in human pregnant women exist, or drugs that have shown adverse effects in animal trials but adequate studies in pregnant women have failed to show a risk to the fetus in any trimester.[15][16]

Monitoring

Due to the potential for dose-dependent QTc interval elongation, the FDA recommends ECG monitoring along with potassium and magnesium monitoring in particularly susceptible populations, such as the elderly or other at-risk groups. These at-risk groups include patients with electrolyte abnormalities such as hypokalemia, hypomagnesemia, heart failure, bradyarrhythmias, or patients on other medications that may prolong the QTc interval. For patients without any of the above risk factors, current evidence does not demonstrate a need to pre-screen this population prior to the administration of ondansetron.[17][9][18][19]

Toxicity

There is no known antidote to ondansetron, and supportive measures are used for overdose.

Enhancing Healthcare Team Outcomes

Ondansetron is a widely prescribed medication for nausea and vomiting from a variety of causes. The drug is relatively safe, but prescribers, including nurse practitioners, primary care providers, internists, surgeons, and emergency department physicians, need to monitor the drug in specific populations. Due to the potential for dose-dependent QTc interval prolongation, clinicians should monitor ECG and potassium and magnesium levels in a susceptible population. It includes elderly or patients with electrolyte abnormalities such as hypokalemia, hypomagnesemia, heart failure, bradyarrhythmias, or patients on other medications that may prolong the QTc interval. For patients without any of the above risk factors, current evidence does not demonstrate a need to pre-screen this population before administering ondansetron.

A multidisciplinary team is critical for diagnosing, managing symptoms, treating patients with nausea and vomiting, and managing the adverse effects of the treatments. Pharmacists should ensure proper dose, perform medication reconciliation and consult prescribers of any concerns. Nursing staff should monitor patients administering medicine and inform clinicians of any side effects observed. An interprofessional team approach would maximize the efficacy and minimize potential adverse drug reactions for the patients requiring ondansetron, resulting in better patient outcomes. [level 5]


Article Details

Article Author

Alexandria Griddine

Article Editor:

Jeffrey S. Bush

Updated:

9/29/2021 7:42:02 AM

PubMed Link:

Ondansetron

References

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