Aloxi® Onicit® Paloxi®

The active substance in Aloxi®, palonosetron, is a ‘5HT3 antagonist’. This means that it stops a chemical in the body called 5-hydroxytryptamine (5HT, also known as serotonin) from attaching to 5HT3 receptors in the gut. When 5HT attaches to these receptors, it normally causes nausea and vomiting. 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.

By blocking these receptors, Aloxi® prevents the nausea and vomiting that often happen after chemotherapy. 5-HT3 receptor 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) ¹. With Aloxi® long half-life and for certain chemotherapies, coverage with Aloxi® extends beyond 24 hours and into the delayed phase.

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.

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

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 corticosteroids. ⁵ 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 agents.^6,7

Postoperative nausea and vomiting (PONV) is a common complication following surgery under anesthesia. It is typically defined as any nausea, retching, or vomiting that occurs during the first 24 to 48 hours after surgery.¹

PONV can complicate recovery from surgery and, while it usually resolves or is treated without serious consequences, it may sometimes require unanticipated hospital admission and delay discharge from the recovery room¹. In some cases, vomiting or retching can lead to more severe complications such as wound dehiscence, esophageal rupture, aspiration, dehydration and increased intracranial pressure¹.

PONV refers to symptoms that occur in the post-anesthesia care unit or within the immediate 24/48 hours postoperatively. When similar symptoms occur after discharge from outpatient procedures, it is referred to as postdischarge nausea and vomiting (PDNV) ¹. The pathophysiology of PONV involves a variety of central and peripheral mechanisms, with the involvement of several neurotransmitter receptors being targets for PONV prevention or treatment².

References:

1. Management strategies for the treatment and prevention of postoperative/postdischarge nausea and vomiting: an updated review.Elvir-Lazo OL, White PF, Yumul R, Cruz Eng H.F1000Res. 2020 Aug 13;9:F1000 Faculty Rev-983. doi: 10.12688/f1000research.21832.1. eCollection 2020.


2. Tateosian VS, Champagne K, Gan TJ. What is new in the battle against postoperative nausea and vomiting? Best Pract Res Clin Anaesthesiol. 2018;32:137–48.

The currently available antiemetic drugs for the treatment and prevention of PONV include the 5-hydroxytryptamine (5-HT ₃) receptor antagonists, neurokinin-1 (NK-1) receptor antagonists, corticosteroids, butyrophenones, metoclopramide, phenothiazine, prochlorperazine, antihistamines, and anticholinergics.

A combination of prophylactic antiemetic drugs with different mechanisms of action should be administered to patients with moderate to high risk of developing PONV. In order to reduce the likelihood of patients developing PONV and PDNV after surgery strategies to reduce the baseline risk of PONV should be implemented in addition to utilize the adequate antiemetic prophylaxis¹.

Reference:

1. Management strategies for the treatment and prevention of postoperative/postdischarge nausea and vomiting: an updated review.Elvir-Lazo OL, White PF, Yumul R, Cruz Eng H.F1000Res. 2020 Aug 13;9:F1000 Faculty Rev-983. doi: 10.12688/f1000research.21832.1. eCollection 2020.