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ondansetron (Zuplenz / ondansetron OFDS)

✓ Approved

Galena Biopharma, Inc. · HTR3A · Small Molecule

What is ondansetron?

ondansetron is a small molecule developed by Galena Biopharma, Inc.. It is approved for therapeutic indications via oral (po).

Drug Profile

Brand NamesZuplenz, ondansetron OFDS
CompanyGalena Biopharma, Inc.
Drug ClassSmall Molecule
Molecular TargetHTR3A
RouteOral (PO)
StatusApproved
Sources: ClinicalTrials.gov, Galena Biopharma, Inc.

Mechanism of Action

Molecular Targets

ondansetron acts on 1 molecular target:

HTR3A5-hydroxytryptamine receptor 3A (5-HT3R, 5-HT-3)
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Related Research Articles

PubMedJournal of oncology pharmacy practice : official publication of the International Society of Oncology Pharmacy Practitioners2026-10-11

Add-on oral amisulpride for prevention of chemotherapy-induced nausea and vomiting during highly emetogenic chemotherapy: A randomized double-blind placebo-controlled group sequential trial.

Gr Gayathri G, Ramasubbu Mathan Kumar MK, Mishra Archana A, Hota Debasish D et al.

IntroductionGuideline-based prophylaxis prevents most vomiting during highly emetogenic chemotherapy (HEC), but nausea remains incompletely controlled, especially where NK1 receptor antagonists and olanzapine are inaccessible or ineffective. Amisulpride, a dopamine D2/D3 antagonist, may add benefit with less sedation than olanzapine.MethodsAdults receiving cisplatin-based or anthracycline-cyclophosphamide HEC were studied during a single cycle in this randomized, double-blind, placebo-controlled group sequential trial. All received intravenous ondansetron and dexamethasone on day 1 plus oral dexamethasone 8 mg twice daily on days 2-4, with oral amisulpride (25 mg before chemotherapy, then 12.5 mg nightly for 3 days) or placebo. The primary endpoint was the 4-day (0-96 h) no-nausea responder rate; the planned sample size of 94 targeted an 18 percentage-point improvement. Two interim and one final analysis used O'Brien-Fleming efficacy and futility boundaries.ResultsThe trial stopped for futility at the second interim analysis (70 participants; 35 per arm). No-nausea response was 65.7% with amisulpride versus 57.1% with placebo (risk difference 8.6 percentage points; 95% CI -14.2 to 31.3; p = 0.461). Complete response (no emesis or rescue medication) was 80.0% versus 68.6% (p = 0.274). VAS, FLIE, rescue medication use, and adverse-event frequency were similar, apart from more frequent constipation with amisulpride.ConclusionsThe 8.6 percentage-point difference favored amisulpride but fell short of the 18-point practice-changing MCID, in a well-controlled placebo arm. Without an olanzapine- or NK1-containing comparator, the trial cannot position amisulpride against those regimens, nor exclude a smaller benefit worth having where they are inaccessible.

PMID 42858047
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PubMedPloS one2026-10-08

Association of 5-hydroxytryptamine 3 receptor antagonists with prognosis in patients with advanced hepatocellular carcinoma: A propensity score-matched study.

Zhang Xiaoge X, Wang Xiaoyun X, Li Na N, Han Qunying Q et al.

5-Hydroxytryptamine and its receptor are involved in hepatocarcinogenesis. This study investigated the effects of 5-hydroxytryptamine 3 receptor antagonists (5-HT3RAs) on the prognosis of patients with advanced hepatocellular carcinoma (HCC). Patients with advanced HCC who received best supportive care were analyzed. Overall survival (OS) between 5-HT3RA users and nonusers was compared. Propensity score matching (PSM) was used to balance variables. Factors associated with prognosis were identified by Cox regression. A total of 1141 patients with advanced HCC were included and 102 of them received 5-HT3RAs. 5-HT3RA treatment was significantly associated with reduced mortality [hazard ratio (HR) = 0.690; 95% confidence interval (CI): 0.546-0.871; p = 0.002]. After 1:2 PSM (n = 89 and n = 161 in 5-HT3RA user and nonuser groups, respectively), 5-HT3RA treatment remained significantly associated with reduced mortality (HR = 0.615; 95% CI: 0.457-0.829; p = 0.001). Subgroup analysis of hepatitis B virus-associated HCC patients yielded similar findings. Subgroup analysis of 5-HT3RAs also yielded similar findings, showing that the 5-year OS was significantly higher in tropisetron users than nonusers (23.7% vs. 10.9%, p = 0.004) after PSM. The use of ondansetron (HR = 0.603; 95% CI: 0.365-0.995; p = 0.048) or tropisetron (HR = 0.477; 95% CI: 0.299-0.759; p = 0.002) was independent factor associated with improved prognosis after PSM. Taken together, this study shows that the use of 5-HT3RAs is associated with improved OS and the use of ondansetron or tropisetron was independently associated with a better prognosis in patients with advanced HCC, indicating a favorable effect of 5-HT3RAs on HCC patients.

PMID 42848747
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PubMedJAC-antimicrobial resistance2026-10-07

Promethazine use and QT prolongation risk during treatment with a shortened all-oral regimen for MDR/RR-TB.

Shen Edmund Q L EQL, Trevisi Letizia L, Mpinda Stephane S, Lahood Allison A et al.

Shortened all-oral regimens for multidrug- or rifampicin-resistant tuberculosis (MDR/RR-TB) combine multiple QTc prolonging agents, including bedaquiline and delamanid, which act partly through hERG potassium channel binding. Promethazine, a first-generation antihistamine used for nausea during TB therapy, shares this mechanism. Whether adjunctive promethazine further raises the risk of clinically relevant QTc prolongation in this setting is unclear. We conducted secondary analyses from a prospective observational cohort study of patients ≥15 years in Lesotho who received a 9- to 12-month all-oral regimen (bedaquiline, linezolid, levofloxacin, clofazimine, delamanid) for pulmonary MDR/RR-TB. We modelled time-varying promethazine exposure using the Andersen-Gill formulation of Cox regression, with time-to-first grade ≥3 (>500 ms) QTc event as the outcome of interest. We conducted comparator analyses with time-varying exposure to metoclopramide, ondansetron, and episodes of nausea, dizziness, and vomiting. Among 247 participants (median age 41, 63.2% living with HIV), 62 (25.1%) received promethazine. Grade ≥3 QTc prolongation occurred in 10 (4.0%). Incident clinically significant QTc prolongation was higher during promethazine-exposed than unexposed periods (7.4 versus 1.3 per 10 000 person-days; HR 7.0, 95% CI: 1.4-35.3). No comparable elevation was seen in analyses of exposure to metoclopramide (HR 1.0, 95% CI: 0.3-3.6), ondansetron, or episodes of nausea, dizziness, or vomiting (HR 1.5, 95% CI: 0.3-6.9). Promethazine use was associated with increased risk of clinically relevant QTc prolongation within a QTc-burdened all-oral MDR/RR-TB regimen. These findings provide preliminary evidence that clinicians may consider when selecting anti-emetics as part of MDR/RR-TB therapy with a shortened all-oral regimen and highlight the importance of evaluating adjunctive medications in DR-TB care.

PMID 42840306
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PubMedBMJ case reports2026-10-07

Emerging risks of health optimisation: refractory nausea associated with peptide injections reported to contain retatrutide.

Buzzi Raphael M RM, Huber Lars C LC

A woman in her mid-20s presented with 5 days of persistent nausea, repeated vomiting, loose stools and markedly reduced oral intake. Blood tests, urinalysis, abdominal ultrasonography and cerebral MRI identified no alternative cause. Symptoms persisted despite intravenous fluids, metoclopramide, ondansetron and domperidone. Repeated, non-judgemental exposure history revealed 4 once-weekly, dose-escalated subcutaneous injections of an unverified product reported to contain retatrutide, an investigational triple glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1 and glucagon receptor agonist, administered in a wellness setting by a self-described life coach without medical qualification. She did not consider the injections to be medication. Symptoms improved 2 days after admission and resolved within 1 week. The Naranjo score (7) indicated probable causality. This case illustrates how pharmacologically active substances supplied through the wellness industry may evade routine medication history. Clinicians should ask explicitly about injections, peptides, research chemicals, online products and substances recommended by non-medical wellness practitioners.

PMID 42843917
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PubMedMolecular metabolism2026-10-06

Parabrachial CGRP neurons mediate incretin-induced aversion and anti-aversion, but not anorexia or weight loss.

Province Haley S HS, Leong Nathan A NA, Conley Nicholas J NJ, Hayes Nikolas W NW et al.

Incretin mimetics such as the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide cause decreased food intake, weight loss, and aversion. Here, we examined the extent to which parabrachial calcitonin gene-related peptide (CGRP) neurons contribute to these effects. Further, we assessed whether glucose-dependent insulinotropic polypeptide receptor (GIPR) agonism alters liraglutide-induced behavior and CGRP neuron activity. We found that liraglutide activates parabrachial CGRP neurons and that this is required for liraglutide-induced aversion, but not anorexia or weight loss. Additionally, treatment with a GIPR agonist (GIPRA) or the well-established anti-emetic drug ondansetron ameliorated liraglutide-induced conditioned taste avoidance (CTA) and CGRP neuron activation without affecting acute liraglutide-induced feeding suppression. Taken together, our findings demonstrate that the aversive and anorexigenic effects of liraglutide are mediated by distinct neural mechanisms that can be separably manipulated. Our findings also highlight GIPR agonism as an emerging anti-aversive approach to GLP-1RA-induced malaise while maintaining the beneficial metabolic effects.

PMID 42838450
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PubMedCurrent medical research and opinion2026-10-04

Comparative efficacy and safety of antiemetics for pediatric gastroenteritis-related vomiting in emergency departments: a network meta-analysis.

Alsabri Mohammed M, Abouelmagd Khaled K, Bostamy Elsnhory Ahmed A, Kamal Ibrahim I et al.

Vomiting is a leading cause of emergency department (ED) visits among children with acute gastroenteritis (AGE). Although antiemetics are commonly used, uncertainty persists regarding the comparative efficacy and safety of individual agents across clinically relevant timeframes. To compare the efficacy and safety of commonly used antiemetics for pediatric AGE-related vomiting in ED settings using a network meta-analysis (NMA) of randomized controlled trials (RCTs). A systematic search of major databases was conducted through 2025. Eligible studies were RCTs enrolling children ≤21 years presenting to the ED with AGE. Interventions included ondansetron (all routes), dimenhydrinate, domperidone, metoclopramide, bromopride, and placebo. Outcomes included vomiting frequency (short-, intermediate-, and long-term), cessation of vomiting, need for intravenous (IV) rehydration, ED length of stay, hospitalization, and adverse events. A random-effects frequentist NMA was performed. Risk of bias was assessed using ROB-2, and certainty of evidence was evaluated with GRADE. Thirty-three RCTs were included. In the short term, all ondansetron formulations reduced vomiting compared with placebo, with the strongest effect seen with IV administration (MD -1.86, 95% CI -3.25 to -0.47). For intermediate-term outcomes, IV ondansetron was the only agent consistently superior to placebo and active comparators. For long-term vomiting, dimenhydrinate (oral and rectal) demonstrated significant benefit (rectal: MD -0.72, 95% CI -1.14 to -0.30). Vomiting cessation within 24 h favored IV ondansetron (RR 1.56, 95% CI 1.29-1.89), with additional benefit from rectal dimenhydrinate (RR 1.48, 95% CI 1.08-2.04). Ondansetron reduced the need for IV rehydration (RR 0.62, 95% CI 0.44-0.88) and modestly shortened ED stay. Safety comparisons were imprecise, though ondansetron showed fewer adverse events than metoclopramide. Ondansetron provides the most consistent benefit for acute vomiting control and reducing IV fluid use in pediatric AGE, while dimenhydrinate may support longer-term symptom control.

PMID 42829926
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