Petupitant and palonosetron


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Company: Helsinn
Approval Status: FDA/EMA Approved October 2014
Specific Treatments: chemotherapy-induced nausea and vomiting


Akynzeo is a fixed combination of netupitant, a substance P/neurokinin 1 (NK1) receptor antagonist, and palonosetron, a serotonin-3 (5-HT3) receptor antagonist. Oral palonosetron prevents nausea and vomiting during the acute phase and netupitant prevents nausea and vomiting during both the acute and delayed phase after cancer chemotherapy.

Akynzeo is specifically indicated for the prevention of acute and delayed nausea and vomiting associated with initial and repeat courses of cancer chemotherapy, including, but not limited to, highly emetogenic chemotherapy.

Akynzeo is supplied as a capsule for oral administration. Akynzeo should be administered approximately 1 hour prior to the start of chemotherapy, woth or without food.


FDA Approval

The FDA approval of Akynzeo was based on two trials.

Trial One

In a multicenter, randomized, parallel, double-blind, controlled clinical trial of 694 patients, the efficacy and safety of a single dose of oral netupitant in combination with oral palonosetron was compared with a single oral dose of palonosetron in cancer patients receiving a chemotherapy regimen that included cisplatin (median dose=75 mg/m2). The efficacy of Akynzeo was assessed in 135 patients who received Akynzeo (netupitant 300 mg and palonosetron 0.5 mg) and 136 patients who received oral palonosetron 0.5 mg. The efficacy endpoints were complete response (CR) (defined as no emetic episode and no use of rescue medication) for the 25-120 hour interval (delayed phase), CR for the 0-24 hour interval (acute phase), and CR within 120 hours (overall phase) after the start of the chemotherapy administration.

Complete Response- Delayed Phase: Akynzeo 90.4% and Palonosetron 80.1% (p-0.032)

Complete Response- Acute Phase: Akynzeo 98.5% and Palonosetron 89.7% (p- 0.002)

Complete Response- Overall Phase: Akynzeo 89.6% and Palonosetron 76.5% (p- 0.003)

Trial Two

In a multicenter, randomized, parallel, double-blind, active controlled, superiority trial, the efficacy and safety of a single oral dose of Akynzeo was compared with a single oral dose of palonosetron 0.5 mg in cancer patients scheduled to receive the first cycle of an anthracycline and cyclophosphamide (AC) regimen for the treatment of a solid malignant tumor. All patients received a single oral dose of dexamethasone. After completion of cycle 1, patients had the option to participate in a multiple-cycle extension, receiving the same treatment as assigned in cycle 1. There was no pre-specified limit of the number of repeat consecutive cycles for any patient. A total of 1455 patients were randomized to the Akynzeo arm or palonosetron arm. A total of 1450 patients (Akynzeo n=725; palonosetron n=725) received study medication: of these, 1438 patients (98.8%) completed cycle 1 and 1286 patients (88.4%) continued treatment in the multiple-cycle extension. A total of 907 patients (62.3%) completed the multiple-cycle extension up to a maximum of eight treatment cycles. The primary efficacy endpoint was the CR rate in the delayed phase, 25-120 hours after the start of chemotherapy administration. Complete response in the Delayed Phase was achieved by 76.9% of the subjects in the Akynzeo arm and 69.5% in the Palonosetron arm (p – 0.001).


Adverse effects associated with the use of Akynzeo may include, but are not limited to, the following:

  • headache
  • asthenia
  • dyspepsia
  • fatigue
  • constipation
  • erythema


Akynzeo is a fixed combination of netupitant and palonosetron. Netupitant is a selective antagonist of human substance P/neurokinin 1 (NK1) receptors. Delayed emesis has been largely associated with the activation of tachykinin family neurokinin 1 (NK1) receptors (broadly distributed in the central and peripheral nervous systems) by  substance P. In in vitro and in vivo studies, netupitant inhibits substance P mediated responses. Palonosetron is a 5-HT3 receptor antagonist with a strong binding affinity for this receptor and little or no affinity for other receptors. Cancer chemotherapy may be associated with a high incidence of nausea and vomiting, particularly when certain agents, such as cisplatin, are used. 5-HT3 receptors are located on the nerve terminals of the vagus in the periphery and centrally in the chemoreceptor trigger zone of the area postrema. Chemotherapeutic agents produce nausea and vomiting by stimulating the release of serotonin from the enterochromaffin cells of the small intestine. Serotonin then activates 5-HT3 receptors located on vagal afferents to initiate the vomiting reflex. The development of acute emesis is known to depend on serotonin and its 5-HT3 receptors have been demonstrated to selectively stimulate the emetic response. 


For additional information regarding Akynzeo or chemotherapy-induced nausea and vomiting, please visit

Source: centerwatch