Oncology Overview: Akynzeo for Chemotherapy-Induced Nausea and Vomiting

The combination netupitant and palonosetron capsules/fosnetupitant and palonosetron for injection (Akynzeo) combines a selective serotonin (5-HT3) receptor antagonist and neurokinin 1 (NK1) receptor antagonist with dexamethasone to prevent acute and delayed nausea and vomiting associated with highly emetogenic chemotherapy.¹ Akynzeo prevents emesis during the first 24 hours and up to 120 hours after chemotherapy.²

Akynzeo was approved by the FDA in 2014 to treat chemotherapy-related nausea. In 2 clinical trials that evaluated 1720 participants receiving chemotherapy, patients were randomly assigned to receive either Akynzeo or oral palonosetron to measure whether the drugs were able to prevent vomiting episodes during the acute, delayed, and overall phase following the beginning of chemotherapy.

The researchers found that 98.5%, 90.4%, and 89.6% of patients treated with Akynzeo did not experience vomiting or the need for nausea medication during the acute, delayed, and overall phases, respectively. In comparison, among patients who received treatment with oral palonosetron, 89.7%, 80.1%, and 76.5% did not experience vomiting or the need for nausea medication during the acute, delayed, and overall phases, respectively.³

Mechanism of Action^1,4

Palonosetron selectively blocks serotonin on vagal nerve terminals in the peripheral and central chemoreceptor trigger zone responsible for the immediate phase of nausea. Netupitant selectively inhibits substance P/neurokinin 1 receptors to inhibit both acute and delayed chemotherapy-induced emesis. Fosnetupitant is a prodrug converted to netupitant by in vivo metabolic hydrolysis.

Dosage and Administration

Netupitant 300 mg/palonosetron 0.5 mg capsules: Take 1 capsule by mouth 1 hour prior to the start of chemotherapy, with or without food.

Fosnetupitant 235 mg/palonosetron 0.25 mg for injection off-white lyophilized powder in single-dose vial for reconstitution: One vial diluted and administered as a 30-minute infusion starting 30 minutes prior to the start of chemotherapy.

Fosnetupitant 235 mg/palonosetron 0.25 mg per 20 mL injection clear solution in a single-dose vial: One vial administered as a 30-minute infusion starting 30 minutes prior to the start of chemotherapy.

Adverse Events (AEs)

The most common AEs are headache, weakness, fatigue, dyspepsia, constipation, and erythema.⁵

Warning and Precautions

Hypersensitivity reactions have been reported with administration of palonosetron in patients with or without known hypersensitivity to other 5-HT3 receptor antagonists.

The risk of serotonin syndrome increases with concomitant use of Akynzeo and other serotonergic drugs. Patients should monitor for signs indicating the development of serotonin syndrome, such as mental status changes, tachycardia, dizziness, flushing, and tremor.

Pregnancy and Lactation

Avoid use if pregnant because limited data are available to assess whether Akynzeo causes fetal harm.⁴ It is not known whether palonosetron or netupitant are present in breast milk. According to the manufacturer, clinicians should consider the mother’s clinical need for antiemesis and any potential AE on the child.¹

About the Author

Gabriela Scala is a 2023 PharmD candidate at the University of Connecticut.

References

1. AKYNZEO prescribing information. June 2021. Accessed October 31, 2021. https://www.akynzeo.com/assets/pdf/Akynzeo-USPI.pdf

2. Drug Trials Snapshots: AKYNZEO. U.S. Food and Drug Administration. Accessed October 31, 2021. https://www.fda.gov/drugs/drug-approvals-and-databases/drug-trials-snapshots-akynzeo.

3. Chemotherapy-Related Nausea Treatment Gets FDA Nod. Pharmacy Times. Accessed February 22, 2022. https://www.pharmacytimes.com/view/chemotherapy-related-nausea-treatment-gets-fda-nod

4. AKYNZEO. European Medicines Agency. Accessed Octpber 31, 2021. https://www.ema.europa.eu/en/medicines/human/EPAR/akynzeo

5. AKYNZEO (lealthcare Professionals). Helsinn. Accessed Octpber 31, 2021. https://www.akynzeo.com/hcp/