AKYNZEO

What it is

AKYNZEO IV is a concentrated injection containing 235 mg fosnetupitant (as chloride hydrochloride) and 250 micrograms palonosetron (as hydrochloride) per vial. Fosnetupitant is a phosphorylated pro-drug of netupitant that is converted rapidly to netupitant when administered intravenously. AKYNZEO IV is an anti-emetic and anti-nauseant containing serotonin (5-HT3) and neurokinin-1 (NK1) receptor antagonists.

Approved indications —

Prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly emetogenic cancer chemotherapy in adult patients. — Prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy in adult patients.

Dosing overview

One vial of AKYNZEO IV (235 mg fosnetupitant/250 micrograms palonosetron) should be administered as an intravenous infusion over 30 minutes, initiated approximately 30 minutes prior to the start of each chemotherapy cycle. The recommended oral dexamethasone dose should be reduced by approximately 50% when co-administered with AKYNZEO IV.

Key safety warnings

Patients with a history of constipation or signs of subacute intestinal obstruction should be monitored following administration, as palonosetron may increase large bowel transit time. Since AKYNZEO IV contains a 5-HT3 receptor antagonist, caution should be exercised in patients with a personal or family history of QT prolongation, electrolyte abnormalities, congestive heart failure, bradyarrhythmia, conduction disturbances, or in patients taking anti-arrhythmic agents or other medicines that lead to QT prolongation or electrolyte abnormalities. Hypokalaemia and hypomagnesemia should be corrected prior to AKYNZEO IV administration. Netupitant is a moderate inhibitor of CYP3A4 with a half-life of 88 hours, so its inhibitory effect can last for over 4 days. Systemic exposure to chemotherapy agents and other medicines metabolised by CYP3A4 may increase when administered with or after AKYNZEO IV, and patients should be closely monitored for adverse reactions. There have been reports of serotonin syndrome with the use of 5-HT3 antagonists either alone or in combination with other serotonergic drugs including selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenaline reuptake inhibitors (SNRIs).

Contraindications

AKYNZEO IV is contraindicated in patients with hypersensitivity to palonosetron, fosnetupitant or netupitant, or to any of the excipients. AKYNZEO IV is contraindicated during pregnancy.

PBS listing

In March 2023, PBAC recommended AKYNZEO IV for prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly and moderately emetogenic cancer chemotherapy, and for patients receiving highly or moderately emetogenic chemotherapy who are unable to swallow or are contraindicated to an oral anti-emetic regimen. Further details regarding strength, item count, restriction type and ex-manufacturer price are not provided in the available sources.

Regulatory history

AKYNZEO IV (fosnetupitant/palonosetron 235 mg/250 microgram concentrated injection) was first listed on the ARTG on 28 January 2022. In March 2023, PBAC recommended the product for prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of highly and moderately emetogenic cancer chemotherapy. The medicinal product is subject to additional monitoring in Australia.