Pediatric Chemotherapy-Induced Nausea and Vomiting Medication

Updated: Aug 07, 2018
  • Author: Reuven J Schore, MD; Chief Editor: Max J Coppes, MD, PhD, MBA  more...
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Medication

Medication Summary

Various prevention and treatment options are available and contribute to the overall successful treatment of cancer. [2, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25] For guidance regarding selection of antiemetic regimen, see the table above. For treatment of anticipatory, breakthrough, or refractory emesis, see the recommendations above.

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Antiemetic, serotonin antagonists

Class Summary

These agents bind serotonin receptors to prevent chemotherapy-induced nausea and vomiting.

QT prolongation may occur with use of 5-HT3 antagonists (eg, ondansetron, dolasetron, granisetron). Avoid use in patients with long QT syndrome. Correct hypokalemia and hypomagnesemia before initiating. EKG monitoring may be warranted when coadministered with other drugs that may prolong QT interval, bradyarrhythmias, or congestive heart failure.

IV dolasetron is no longer indicated for CINV because of risk for QT prolongation. Palonosetron has been studied for its effect on QT interval, and results showed no significant effect at doses of as much as 2.25 mg. Although the increased QT interval warning with palonosetron use has been removed by the manufacturer, monitoring patients receiving other drugs known to cause QT interval prolongation may still be wise.

In June 2012, the 32 mg IV dose of ondansetron was removed from the prescribing information because of dose-related QT prolongation. The recommended dose for ondansetron IV for chemotherapy-induced nausea and vomiting is 3 doses of 0.15 mg/kg (not to exceed 16 mg/dose) IV 30 minutes before chemotherapy and repeated 4 and 8 hr after the first dose. [26]

In May 2014, palonosetron was approved by the US Food and Drug Administration (FDA) for prevention of CINV in children as young as 1 month. Approval was based on a randomized, double-blind, noninferiority, pivotal trial that compared single-dose IV palonosetron (20 mcg/kg given 30 min prior to chemotherapy) with the current standard of care, IV ondansetron regimen (0.15 mg/kg given 30 min prior to chemotherapy), followed by infusions 4 hours and 8 hours after the first dose of ondansetron. Within the first 24 hours after chemotherapy, complete response, defined as no vomiting, no retching, and no antiemesis rescue medication, was achieved in 59.4% of patients who received palonosetron compared with 58.6% of those who received the ondansetron regimen. [27, 28]

Dolasetron (Anzemet)

Prevents nausea and vomiting by binding to 5-HT3 receptors located on chemotherapy trigger zone (CTZ) and vagal neurons in GI tract. Prophylaxis with antiemetic agents prior to and following cancer treatment is often essential to ensure administration of the entire chemotherapy regimen.

Granisetron (Sancuso)

Used for prevention of chemotherapy-induced nausea and vomiting. At CTZ, peripherally and centrally blocks serotonin on vagal nerve terminals.

Ondansetron (Zofran, Zuplenz)

Selective 5-HT3 -receptor antagonist that blocks serotonin both peripherally and centrally. Prevents nausea and vomiting associated with emetogenic cancer chemotherapy (eg, high-dose cisplatin) and complete body radiotherapy.

Palonosetron (Aloxi)

Selective 5-HT3 -receptor antagonist with long half-life (40 h). Indicated for prevention and treatment of chemotherapy-induced nausea and vomiting. Peripherally and centrally blocks 5-HT3 receptors in CTZ.

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Corticosteroids

Class Summary

These agents are used to prevent nausea and vomiting caused by chemotherapy regimens with level 3 and level 4 agents. The antiemetic mechanism for corticosteroids is unknown, but inhibition of prostaglandin synthesis and cell membrane permeability are thought to be involved.

Dexamethasone

Antiemetic mechanism for corticosteroids is unknown. Used in combination with other agents as part of an antiemetic regimen.

Methylprednisolone (Depo-Medrol)

Antiemetic mechanism for corticosteroids is unknown. Used in combination with other agents as part of an antiemetic regimen.

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NK1 Receptor Antagonists

Class Summary

NK-1 receptors are highly concentrated in the vomiting center of the brain and bind a neurokinin termed substance P; Activation of NK-1 receptors by substance P plays a central role in eliciting chemotherapy-induced nausea and vomiting.

Aprepitant (Emend)

Neurokinin receptor (NK)-1 antagonist. NK-1 receptors are highly concentrated in the vomiting center of the brain and bind a neurokinin termed substance P. Blocking the interaction of substance P at the NK-1 receptor improve the management of nausea and vomiting.

It is approved in the United States for adults and children aged ≥6 months. It is indicated in combination with other antiemetic agents for prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy (including high-dose cisplatin). It is also indicated for nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.

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Benzodiazepines

Class Summary

These agents decrease anxiety associated with chemotherapy-induced nausea and vomiting.

Lorazepam (Ativan)

Sedative hypnotic with short onset of effects and relatively long half-life. By increasing the action of GABA, which is a major inhibitory neurotransmitter in the brain, may depress all levels of CNS, including limbic and reticular formation.

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Dopamine receptor antagonist

Class Summary

Consider adding these agents in patients with breakthrough or resistant nausea and vomiting.

Metoclopramide (Reglan, Metozolv ODT)

Dopamine antagonist that stimulates acetylcholine release in the myenteric plexus. Acts centrally on chemoreceptor triggers in the floor of the fourth ventricle, which provides important antiemetic activity.

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Phenothiazines

Class Summary

Consider adding these agents in patients with breakthrough or resistant nausea and vomiting.

Promethazine (Phenergan, Phenadoz, Promethegan)

For symptomatic treatment of nausea in vestibular dysfunction. Antidopaminergic agent effective in treating emesis. Blocks postsynaptic mesolimbic dopaminergic receptors in brain and reduces stimuli to brainstem reticular system.

Prochlorperazine (Compazine, Compro)

May relieve nausea and vomiting by blocking postsynaptic mesolimbic dopamine receptors through anticholinergic effects and depressing reticular activating system. In addition to antiemetic effects, has the advantage of augmenting hypoxic ventilatory response, acting as a respiratory stimulant at high altitude.

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Antiemetic, Cannabinoid

Class Summary

Consider adding these agents in patients with breakthrough or resistant nausea and vomiting.

Dronabinol (Marinol)

Synthetic cannabinoid for PO administration. Antiemetic effect attributed to action within cannabinoid receptor system (ie, CB1 receptor) located in neural tissues.

Indicated for nausea and vomiting associated with cancer chemotherapy in patients who have inadequate response to conventional antiemetic treatments. This restriction is required because a substantial proportion of patients treated with dronabinol experience disturbing psychotomimetic reactions not observed with other antiemetic agents.

Nabilone (Cesamet)

Synthetic cannabinoid for PO administration. Antiemetic effect thought to be due to action within cannabinoid receptor system (ie, CB1 receptor) located in neural tissues. Indicated for nausea and vomiting associated with cancer chemotherapy in patients who have inadequate response to conventional antiemetic treatments. This restriction is required because a substantial proportion of patients treated with nabilone will experience disturbing psychotomimetic reactions not observed with other antiemetic agents.

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