Akynzeo is the first and only fixed combination antiemetic, composed of a NK1 receptor antagonist (RA) [either netupitant (oral) or fosnetupitant (intravenous)] and the 5-HT3 RA, palonosetron8. Akynzeo, together with dexamethasone, constitutes a triple antiemetic combination recommended by all major antiemetic guidelines6,7 and approved for the prevention of chemotherapy-induced nausea and vomiting (CINV) for patients receiving highly and moderately emetogenic chemotherapy8. The simultaneous targeting of two critical antiemetic pathways, in unison with the single-dose administration, offers a simpler convenient antiemetic with long-lasting protection from CINV. The convenience of Akynzeo may also enhance patient compliance and improve adherence to antiemetic guidelines1,2.

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How does Akynzeo work?

5-HTreceptor antagonists are considered to be one of the most effective classes of antiemetic drugs in the prevention of CINV during the first 24 hours after chemotherapy (also known as the acute phase) 5. These drugs work by blocking the binding of serotonin to its receptor, which in turn stops the transmission of signals to the vomiting center in the brain. Neurokinin-1 receptor antagonists block the binding of substance P to the NK1 receptor; substance P has been shown to play a predominant role in CINV in the period from 24 hours up to 5 days post-chemotherapy (also known as the delayed phase)5. As a combination agent of both an NK1 RA and a 5-HT3 RA, Akynzeo simultaneously inhibits the two key CINV pathways, thereby preventing nausea and vomiting during both the acute phase and delayed phase following chemotherapy.

CINV (Chemotherapy-induced nausea and vomiting)

Chemotherapy-induced nausea and vomiting (known as “CINV”) are common unpleasant and debilitating side effects of many cancer treatments5. CINV is one of the most feared side effects of chemotherapy for both patients and caregivers and, without adequate antiemetic prophylaxis, can occur in >90% of patients. The pathophysiology of CINV is a complex process that involves several molecules, such as neurotransmitters [serotonin (5-hydroxytryptamine or 5-HT3), substance P (neurokinin-1), and dopamine] and their respective receptors in the central nervous system and the gastrointestinal tract, following activation by certain chemotherapy5. Consequences of uncontrolled CINV include dehydration and electrolyte imbalance, malnutrition, impaired daily functioning and quality of life, postponement or dose reduction of chemotherapy, and increased resource use and costs7. Patients tend to experience nausea more often than vomiting, and antiemetic medications (those intended to prevent, lessen or relieve CINV) are generally less effective in controlling nausea5.

Who is at risk of CINV?

Factors leading to the development of CINV can be related to the chemotherapy itself or to characteristics specific to the patient taking the anticancer drug. Historically, the risk of CINV was determined only by considering the emetogenic potential of the chemotherapy agent. A classification system details the emetogenicity of different chemotherapeutic agents and this has formed the basis for antiemetic treatment.4 Highly emetogenic agents can cause CINV in >90% of patients without antiemetic prophylaxis; moderately emetogenic agents can cause CINV in 30–90% of patients; low emetogenic agents in 10–30% of patients; and minimally emetogenic agents have <10% risk of causing CINV without antiemetic prophylaxis. More recently, individual patient-related risk factors that may increase the chance of experiencing CINV have been identified. These include younger age, female gender, having had CINV previously, little or no previous alcohol use, being susceptible to motion sickness, having experienced morning sickness with pregnancy, anxiety/high pre-treatment expectation of nausea.7

Can CINV be prevented?

Significant advances in this field have made the complete prevention of nausea and vomiting the goal of clinical management. A range of drugs are available for the management of CINV, with the choice of drugs guided by the type of chemotherapy agent(s) used and its ability to induce vomiting, along with patient-specific risk factors. The three key families of drugs used to prevent CINV are serotonin receptor antagonists (5-HT3 RAs), which block the serotonin receptor, neurokinin-1 (NK-1) RAs, which block the NK-1 receptor, and corticosteroids5. Olanzapine, a potent antipsychotic that inhibits multiple receptors, is also a recent effective option. Antiemetic guidelines are available that advise prescribing clinicians on the optimal combinations of antiemetic agents6,7.


  1. Aapro M, Jordan K, Scotté F, et al. Netupitant-palonosetron (NEPA) for Preventing Chemotherapy-induced Nausea and Vomiting: From Clinical Trials to Daily Practice. Curr Cancer Drug Targets 2022;22(10):806-824.
  2. Aapro M, Molassiotis A, Dicato M, et al. The effect of guideline-consistent antiemetic therapy on chemotherapy-induced nausea and vomiting (CINV): the Pan European Emesis Registry (PEER). Ann Oncol. 2012 Aug;23(8):1986-1992.
  3. Feyer P, Jordan K. Update and new trends in antiemetic therapy: the continuing need for novel therapies. Ann Oncol. 2011; 22(1):30-38.
  4. Hesketh PJ, Kris MG, Grunberg SM, et al. Proposal for classifying the acute emetogenicity of cancer chemotherapy. J Clin Oncol. 1997 Jan;15(1):103-9.
  5. Navari RM, Aapro M. Antiemetic prophylaxis for chemotherapy-induced nausea and vomiting. N. Engl. J. Med., 2016, 374(14), 1356-1367.
  6. Multinational Association of Supportive Care in Cancer. MASCC/ESMO antiemetic guidelines. 2019.
  7. National Comprehensive Cancer Network. NCCN Clinical practice guidelines in oncology (NCCN Guidelines).1. 2023.
  8. Akynzeo 300 mg/0.50 mg hard capsules; Akynzeo 235 mg/0.25 mg powder for concentrate for solution for infusion, Akynzeo 235 mg/0.25 mg concentrate for solution for infusion [Summary of Product Characteristics] Dublin, Ireland: Helsinn Birex Pharmaceuticals Ltd; 2024.