Stability indicating Rp-UPLC method development and validation for the simultaneous estimation of fosnetupitant and palonosetron in bulk and injection dosage form

Abstract A stability indicating UPLC method has been developed and validated for the simultaneous determination of fosnetupitant and palonosetron in bulk and in injection dosage form. This combination is used for the prevention of acute and delayed nausea and vomiting associated with initial and repeated courses of highly emetogenic chemotherapy for cancer. The chromatographic analysis was performed on an HSS, RP C18 column (2.1 x 100 mm, 1.8 µm) with an isocratic mobile phase composed of 0.25 M potassium dihydrogen orthophosphate buffer (pH 6.5), pH adjusted with dilute sodium hydroxide:acetonitrile (55:45 v/v), at a flow rate of 0.5 mL/min, and the eluents were monitored at an isosbestic point of 286 nm. The developed method was validated according to the ICH guidelines pertaining to specificity, precision, accuracy, linearity and robustness, and the stability indicating nature of the method was established by forced degradation studies. The retention times of fosnetupitant and palonosetron were observed at 1.390 and 2.404 min, respectively. The developed method proved to be accurate and precise. Linearity was established between 4.70 and 14.10 µg/mL for fosnetupitant and between 0.05 and 0.15 µg/mL for palonosetron. The LOD and LOQ were 0.115 and 0.385 µg/mL, respectively, for fosnetupitant, and 0.005 and 0.016 µg/mL, respectively, for palonosetron. Therefore, the proposed UPLC method was reliable, reproducible, precise and sensitive for the quantification of fosnetupitant and palonosetron.

Exploration of Risk Factors for Prevention Failure of Chemotherapy-related Nausea and Vomiting with Palonosetron Combined with Dexamethasone / 中国药房

OBJECTIVE：To explore t he risk factors that may lead to the ineff ectiveness of using palonosetron combined with dexamethasone to prevent chemotherapy-induced nausea and vomiting （CINV），and to provide a reference for the rational choice and use of antiemetic drugs. METHODS ：In a retrospective case-control study ，871 patients who used palonosetron combined with dexamethasone to prevent CINV in a tertiary cancer hospital from 2016 to 2020 were selected as the object. Totally 32 related data such as demographic data ，living habits ，medical history ，examination information and treatment information were counted as variables. Combined with single factor regression ，multi-factor regression， likelihood ratio forward or backward stepwise 163.com regression were used to comprehensively screen the factors for many times. The standard target factors screened by stepwise E-mail：kongtiandong@126.com regression were included in the multivariate Logistic regression analysis，and the regression model was evaluated by the ROC c urve. RESULTS ：The multivariate Logistic regression model fitted well（AUC in ROC was 0.83，but 0.82 after screening ）. The results showed that there were 15 statistically significant independent influential factors ，including 12 independent risk factors ，ie. poor nutritional status （OR＝2.11，95％CI（1.05，4.22），P＝0.036）， history of gastrointestinal disease （OR＝2.76，95％CI（1.87，4.07），P＜0.001），abnormal electrolyte level （OR＝2.54，95％CI （1.74，3.69），P＜0.001），nausea and vomiting 24 h before chemotherapy （OR＝8.47，95％CI（3.28，21.91），P＜0.001），history of chemotherapy-induced vomiting （OR＝3.20，95％ CI （2.18，4.71），P＜0.001），high risk level of vomiting caused by chemotherapy（OR＝3.16，95％CI（2.38，4.20），P＜0.001），application of opioid combined with non-steroidal analgesics （OR＝ 4.18，95％CI（2.06，8.49），P＜0.001），the use of other drugs that stimulate the intestine and stomach （OR＝2.49，95％CI（1.28， 4.83），P＝0.007），history of surgery （OR＝1.88，95％CI（1.34，2.63），P＜0.001），high level of albumin （OR＝1.05，95％CI （1.01，1.08），P＝0.015），multiple days of single chemotherapy （OR＝1.69，95％CI（1.11，2.56），P＝0.014），and opioid analgesia medicine （OR＝1.71，95％CI（1.15，2.53），P＝0.007）；and the following 3 independent protective factors included long time of diagnosis （OR＝0.65，95％CI（0.46，0.93），P＝0.019），non-first chemotherapy （OR＝0.52，95％CI（0.33，0.83），P＝ 0.006），and drugs combined chemotherapy （OR＝0.55，95％CI（0.34，0.90），P＝0.018）. CONCLUSIONS ：Patients with the following conditions are more likely to experience CINV prevention ineffectiveness ，ie. single long-term chemotherapy ，application of chemotherapy plan with a higher risk of emesis ，history of chemotherapy-induced vomiting ，history of gastrointestinal diseases ， nausea and vomiting 24 hours prior to chemotherapy ，history of surgery ，within 1 year of diagnosis ，chemotherapy for the first time，use of opioids ，use of 5-HT3 reuptake inhibitors ，malnutrition and electrolyte disorders.

Comparison of palonosetron-dexamethasone and ondansetron-dexamethasone for prevention of postoperative nausea and vomiting in middle ear surgery: a randomized clinical trial / Comparação entre palonosetrona-dexametasona e ondansetrona-dexametasona na prevenção de náuseas e vômitos no pós-operatório de cirurgia do ouvido médio: estudo clínico randomizado

Abstract Background: Postoperative nausea and vomiting is the second most common complaint in the postoperative period after pain. The incidence of postoperative nausea and vomiting was 60-80% in middle ear surgeries in the absence of antiemetic prophylaxis. Because of this high incidence of postoperative nausea and vomiting, we aimed to assess the effect of palonosetron-dexamethasone and ondansetron-dexamethasone combination for the prevention of postoperative nausea and vomiting in patients of middle ear surgery. Methods: Sixty-four patients, scheduled for middle ear surgery, were randomized into two groups to receive the palonosetron-dexamethasone and ondansetron-dexamethasone combination intravenously before induction of anesthesia. Anesthesia technique was standardized in all patients. Postoperatively, the incidences and severity of nausea and vomiting, the requirement of rescue antiemetic, side effects and patient satisfaction score were recorded. Results: Demographics were similar in the study groups. The incidence difference of nausea was statistically significant between groups O and P at a time interval of 2-6 hours only (p = 0.026). The incidence and severity of vomiting were not statistically significant between groups O and P during the whole study period. The overall incidence of postoperative nausea and vomiting (0-24 hours postoperatively) was 37.5% in group O and 9.4% in group P (p = 0.016). Absolute risk reduction with palonosetron-dexamethasone was 28%, the relative risk reduction was 75%, and the number-needed-to-treat was 4. The patient's satisfaction score was higher in group P than group O (p = 0.016). The frequency of rescue medication was more common in group O than in group P patients (p = 0.026). Conclusion: The combination of palonosetron-dexamethasone is superior to ondansetron-dexamethasone for the prevention of postoperative nausea and vomiting after middle ear surgeries.

Resumo Justificativa: Náusea e vômito no pós-operatório é a segunda queixa pós-operatória mais frequente após a dor. Sem profilaxia antiemética, a incidência de náusea e vômito no pós-operatório foi de 60−80% após cirurgia do ouvido médio. Dada a alta incidência relatada de náusea e vômito no pós-operatório, nosso objetivo foi avaliar o efeito da combinação de palonosetrona-dexametasona e ondansetrona-dexametasona na prevenção de náusea e vômito no pós-operatório em pacientes submetidos a cirurgia do ouvido médio. Método: Sessenta e quatro pacientes programados para cirurgia de ouvido médio foram aleatoriamente divididos em dois grupos. Um recebeu a combinação de palonosetrona-dexametasona (grupo P) e o outro ondansetrona-dexametasona (grupo O) por via intravenosa antes da indução anestésica. A técnica anestésica foi padronizada em todos os pacientes. No pós-operatório, foram registradas incidência e gravidade das náuseas e vômitos, necessidade de antiemético de resgate, efeitos colaterais e índice de satisfação dos pacientes. Resultados: As características demográficas foram semelhantes nos grupos estudados. A diferença na incidência de náusea foi estatisticamente significante entre os grupos O e P apenas no intervalo de tempo entre 2 e 6 horas (p = 0,026). A incidência e gravidade de vômito não foram estatisticamente significantes entre os grupos O e P durante todo o período do estudo. A incidência geral de náusea e vômito no pós-operatório (0−24 horas de pós-operatório) foi de 37,5% no grupo O e de 9,4% no grupo P (p = 0,016). A combinação palonosetrona-dexametasona associou-se com redução do risco absoluto de 28%, redução do risco relativo de 75%, e o número necessário para tratar foi 4. O escore de satisfação do paciente foi maior no grupo P (p = 0,016). A frequência da medicação de resgate foi mais comum no grupo O (p = 0,026). Conclusão: A combinação de palonosetrona-dexametasona é superior à ondansetrona-dexametasona na prevenção da náusea e vômito no pós-operatório após cirurgia de ouvido médio.

A Comparison of Ondansetron, Palonosetron and Granisetron for Prevention of Post-Operative Nausea and Vomiting after Laparoscopic Surgeries.

Post-Operative Nausea and Vomiting (PONV) “the little big problem” after surgery/anaesthesia is a common side-effect which compromises the quality of care, delays discharge and thereby delays resumption of activities of daily living. A number of pharmacological agents (antihistamines, butyrophenones, dopamine receptor antagonists) have been used, and the 5‑hydroxytryptamine type 3 receptor antagonists have been found to be effective in prevention and treatment of PONV. Thus, we compared the prophylactic effects of intravenously administered ondansetron, palonosetron, and granisetron in prevention of postoperative nausea and vomiting in patients undergoing laparoscopic surgery under general anaesthesia. METHODSThis prospective, double blind study, comprising of 135 patients of ASA physical status I and II of either gender, was carried out after approval was obtained from the Institutional Ethical and Scientific Committee. Patients were randomized into three equal groups. Group P received inj. palonosetron (0.075 mg), group O received inj. ondansetron (8 mg), and group G received inj. granisetron (2.5 mg) intravenously five minutes before induction of anaesthesia. The episodes of postoperative nausea and vomiting, severity of nausea, need for rescue antiemetic, side effects and patient satisfaction were observed in the study groups for 24 hours in the post-operative period. At the end of study, results were compiled, and statistical analysis was done using ANOVA, chi‑square test, and Kruskal Wallis Test. Value of p < 0.05 was considered significant.RESULTSThe incidence of PONV was significantly less in the palonosetron group (95.6%) as compared to the ondansetron group (80%) and granisetron group (73.3%), with a lesser need for rescue antiemetic in the palonosetron group. All the three study groups did not have significant adverse effects reflecting that all the three drugs were well-tolerated. Patient satisfaction score was also more with palonosetron

Safety and efficacy of palonosetron compared in prevention of postoperative nausea and vomiting in patients undergoing elective major surgery under general anaesthesia

Background: Post-operative nausea and vomiting continues to be a common side effect of surgery and anaesthesia, affecting the economics of medical care, as well as the degree of patients’ satisfaction, comfort and quality of life.The objective of the present study were to compare the efficacy and safety of palonosetron versus placebo for prophylaxis of early onset (within 24 hours post-surgery) and late onset (24-72 hours post-surgery) post-operative nausea or vomiting in patients undergoing elective major surgery under general anaesthesia.Methods: A prospective, randomized, parallel group, two arm, double blind placebo controlled trial was conducted on n=100 indoor patients undergoing elective major surgeries were enrolled into the present study.Results: The patients showing complete response were 32 (64%) in palonosetron group and 19 (38%) in the placebo group (p<0.05) in the 0-24 hour time interval. The patients receiving palonosetron showed higher complete response rates in the 0-24 hour and 0-72 hour time intervals. 42 patients (84%) on palonosetron and 30 (60%) on placebo showed complete control of vomiting in 0-24 hour period. Adverse events related to the drug were reported in 5 patients (10%) in palonosetron group as compared to 3 patients (6%) in placebo group.Conclusions: A single prophylactic 0.075 mg IV dose of palonosetron effectively reduced the occurrence and severity of nausea and vomiting and delayed the time to emesis and treatment failure in the early as well as the overall postoperative period of 72 hours.

Palonosetron for the prevention of chemotherapy induced nausea and vomiting: a comparative study in a tertiary care hospital from India

Background: Despite advances in symptom management, chemotherapy-induced nausea and vomiting (CINV) remains one of the most dreadful consequences of cancer therapy.Methods: The study was carried out at Medical Oncology Department, Vydehi Institute of Medical Sciences and Research Centre, Bangalore. Hundred and forty-four cancer patients of either sex, aged 18-65 years with adequate blood counts requiring moderately emetogenic chemotherapy (MEC) as per Hesketh classification were included. The patients were prospectively divided into two groups before the initial cycle of chemotherapy. Patients in Group A (n=71) received ondansetron, and dexamethasone along with aprepitant capsules, Whereas, Group B (n=73) received palonosetron, and dexamethasone along with placebo capsules, 30 minutes before chemotherapy. Thereafter the patients were administered with the drugs and observed for nausea and vomiting. The efficiency of both regimens was assessed by adopting validated functional living index emesis (FLIE) questionnaire. Analysis of the data was done using the SPSS 21.0 software.Results: The mean age of the patients was 40.5 years and the male to female ratio was 1:2.4. In all the patients, no changes were detected in the ECG readings after MEC. The nausea and vomiting score were comparable in both groups. No significant difference (p>0.05) was noticed between group A and group B in both mm and in FLIE points. No serious adverse events were found relating to antiemetic treatment.Conclusions: Palonosetron in combination with corticosteroids was non inferior to ondansetron in combination with aprepitant and corticosteroids in controlling acute and delayed stages of CINV in patients requiring MEC. Thus, it can be recommended as first-line therapy for patients treated with MEC.

Comparsion of Palonsteron, Ondansetron and Dexamethasone in Reduction of Post Operative Nausea and Vomiting Following Laparoscopic Cholecystectomy

The aim of the study is to compare efficacy of intravenous (i/v) Palonosetron (75mcg), i/v Ondansetron (4mg) and i/v Dexamethasone (5mg) as prophylactic agents for reducing post-operative nausea and vomiting that follows laparoscopic cholecystectomy. Methods: This prospective randomized double blind study was conducted in the Department of Anaesthesia and Critical Care, Tata Main Hospital, Jamshedpur. The study participants comprised of patients undergoing elective laparoscopic cholecystectomy surgeries under general anaesthesia. A total of 90 patients i.e. 30 in each of the three groups were enrolled for the study. Enrolled patients were randomly allocated to received with i/v Dexamethasone (5 mg) or i/v Ondansetron (4mg) or i/v Palonosetron (0.075 mg). The patients in the three groups were monitored and symptoms charted on basis of Post Operative Nausea and Vomiting (PONV) scale. Results: Palonosetron 0.075mg single intravenous dose given prior to induction of anaesthesia achieves 100% complete response with 3.33% reported side effect, and none needed rescue antiemetic. Dexamethasone 5mg single intravenous dose given prior to induction of anaesthesia achieves 93.33 % complete response with none reporting side effect and 6.67% needing rescue antiemetic. Ondansetron 4mg single intravenous dose given prior to reversal of neuromuscular blockade achieves 66.67 % complete response with 20% reporting side effect and 33.33 % needing rescue antiemetic. Conclusion: I.V. Palonosetron and Dexamethasone are equally potent and superior antiemetics than Ondansetron in the prevention of PONV in patients undergoing elective laproscopic cholecystectomy under general anaesthesia.

Evaluation of efficacy of palonosetron versus ramosetron in patients receiving emetogenic chemotherapy

Background: Chemotherapy induced nausea and vomiting is the most distressing side effect of cancer chemotherapy. It can seriously impact patient抯 quality of life, influence the adherence to chemotherapy and progression free survival causing a delay or refusal of potentially life-saving therapy. The objective of this study was to compare the efficacy of palonosetron with ramosetron in achieving complete response to the chemotherapy.Methods: This was a prospective randomized open-label study conducted on 130 patients admitted in Medical Oncology ward of a Tertiary Care Hospitals, Bangalore, India. Patients were randomized to receive either palonosetron 0.25 mg or ramosetron 0.3 mg I.V. along with aprepitant and dexamethasone 30 minutes prior to chemotherapy and were followed up for a period of 5 days post chemotherapy. The observations such as number and severity of vomiting and nausea, the outcome was assessed at the end of 5 days. Pearson抯 Chi-square test was used to demonstrate the difference between both the study groups with respect to various categorical data.Results: The complete response rate in delayed phase was more significant in patients who received palonosetron than patients who received ramosetron (72.3% vs 50.8%). Total control was achieved in 38.5% patients with palonosetron as compared to 15.4% patients with ramosetron.Conclusions: Palonosetron is more efficacious than ramosetron in controlling chemotherapy induced nausea and vomiting especially in delayed phase of emesis.

Aprepitant in combination with palonosetron for the prevention of postoperative nausea and vomiting in female patients using intravenous patient-controlled analgesia / 대한마취과학회지

BACKGROUND: The aim of this study was to evaluate aprepitant in combination with palonosetron as compared to palonosetron alone for the prevention of postoperative nausea and vomiting (PONV) in female patients receiving fentanyl- based intravenous patient-controlled analgesia (IV-PCA). METHODS: In this randomized single-blinded study, 100 female patients scheduled for elective surgery under general anesthesia were randomized to two groups: Group AP (80 mg aprepitant plus 0.075 mg palonosetron, n = 50) and Group P (0.075 mg palonosetron, n = 50). The patients in group AP received 80 mg aprepitant per oral 1–3 h before surgery, while all patients received 0.075 mg palonosetron after induction of standardized anesthesia. All patients had postoperative access to fentanyl-based IV-PCA. The incidence of nausea and vomiting, use of rescue medication, and severity of nausea were evaluated at 6 and 24 h after surgery. RESULTS: The incidence of nausea (54%) and vomiting (2%) in group AP did not differ significantly from that in group P (48% and 14%, respectively) during the first 24 h after surgery (P > 0.05). Patient requirements for rescue medication in group AP (29%) were similar to those in group P (32%) at 24 h after surgery (P > 0.05). There was no difference between the groups in severity of nausea during the first 24 h after surgery (P > 0.05). CONCLUSIONS: Aprepitant combined with palonosetron did not reduce the incidence of PONV as compared to palonosetron alone within 24 h of surgery in women receiving fentanyl-based IV-PCA.

Palonosetron combined with dexamethasone prevents nasopharyngeal carcinoma radiotherapy cisplatin-induced nausea and vomiting / 中国基层医药

Objective@#To investigate the efficacy and adverse reactions of palonosetron and dexamethasone in preventing cisplatin-induced nausea and vomiting.@*Methods@#From September 2015 to August 2017, a total of 217 nasopharyngeal carcinoma patients in the 163rd Hospital of PLA were randomly divided into two groups according to the digital table.The control group (n=108) was given palonosetron when used cisplatin treatment, the study group(n=109) was given palonosetron combined with dexamethasone.The clinical efficacy and adverse reactions in the two groups were observed.@*Results@#After treatment of 1-6 weeks, the incidence rates of headache, dizziness and fatigue in the study group were 7.2%, 2.9% and 3.4% respectively, which were significantly lower than those in the control group(12.7%, 6.0% and 6.3%), the differences between the two groups were statistically significant(χ2=10.902, 7.412, 6.207, all P<0.05). The prevention rate of nausea and vomiting in the control group was 75.5%, which in the study group was 80.9%, and at delay period, the prevention rate of nausea and vomiting in the control group was 85.5%, which in the study group was 91.0%, the differences between the two groups were statistically significant(χ2=5.615, 9.442, all P<0.05).@*Conclusion@#Palonosetron and dexamethasone are effective in the treatment of nasopharyngeal carcinoma with cisplatin-induced nausea and vomiting, and can reduce the side effects of palonosetron.

Efficacy of palonosetron plus dexamethasone in preventing chemotherapy-induced nausea and emesis in patients receiving carboplatin-based chemotherapy for gynecologic cancers: a phase II study by the West Japan Gynecologic Oncology Group (WJGOG 131) / 부인종양

OBJECTIVE: Palonosetron is effective for the management of acute and delayed chemotherapy-induced nausea and vomiting (CINV). While emetogenic carboplatin-based chemotherapy is widely used to treat gynecologic cancers, few studies have evaluated the antiemetic effectiveness of palonosetron in this setting. METHODS: A multicenter, single-arm, open-label phase II trial was conducted to evaluate the safety and effectiveness of palonosetron in controlling CINV in patients with gynecologic cancer. Chemotherapy-naïve patients received intravenous palonosetron (0.75 mg/body) and dexamethasone before the infusion of carboplatin-based chemotherapy on day 1. Dexamethasone was administered (orally or intravenously) on days 2–3. The incidence and severity of CINV were evaluated using the patient-completed Multinational Association of Supportive Care in Cancer Antiemesis Tool and treatment diaries. The primary endpoint was the proportion of patients experiencing complete control (CC) of vomiting, with “no rescue antiemetic medication” and “no clinically significant nausea” or “only mild nausea” in the delayed phase (24–120 hours post-chemotherapy). Secondary endpoints were the proportion of patients with a complete response (CR: “no vomiting” and “no rescue antiemetic medication”) in the acute (0–24 hours), delayed (24–120 hours), and overall (0–120 hours) phases, and CC in the acute and overall phases. RESULTS: Efficacy was assessable in 77 of 80 patients recruited. In the acute and delayed phases, the CR rates the primary endpoint, were 71.4% and 59.7% and the CC rates, the secondary endpoint, were 97.4% and 96.1%, respectively. CONCLUSION: While palonosetron effectively controls acute CINV, additional antiemetic management is warranted in the delayed phase after carboplatin-based chemotherapy in gynecologic cancer patients (Trial registry at UMIN Clinical Trials Registry, UMIN000012806).

The effect of palonosetron on rocuronium-induced withdrawal movement / O efeito de palonosetron sobre o movimento de retração induzido por rocurônio

Abstract Background: Rocuronium causes pain and withdrawal movement during induction of anesthesia. In this study, palonosetron was investigated to have analgesic effect on the reduction of rocuronium-induced withdrawal movement. Methods: 120 patients were randomly assigned to one of three groups to receive either saline, lidocaine 20 mg, or palonosetron 0.075 mg with a tourniquet applied two minutes before thiopental sodium (5 mg.kg-1) was given intravenously. After loss of consciousness, rocuronium (0.6 mg.kg-1) was injected and the withdrawal movement was estimated by 4-point scale in a double-blind manner. Results: The overall incidence of rocuronium withdrawal movement was 50% with lidocaine (p = 0.038), 38% with palonosetron (p = 0.006) compared with 75% for saline. The incidence of no pain to mild pain was significantly lower in the lidocaine and palonosetron groups (85% and 92% respectively) than in the saline group (58%). However, there was no significant difference in withdrawal movement between the lidocaine and palonosetron groups. There was no severe movement with palonosetron. Conclusion: Pretreatment of palonosetron with venous occlusion may attenuate rocuronium-induced withdrawal movement as effective as the use of lidocaine. It suggested that peripheral action of palonosetron was effective to reduce rocuronium-induced withdrawal movement.

Resumo Justificativa: Rocurônio provoca dor e reflexo de retirada durante a indução da anestesia. Neste estudo, avaliamos se palonosetron tem efeito analgésico para reduzir esse movimento induzido por rocurónio. Métodos: Cento e vinte pacientes foram randomicamente designados para um de três grupos para receber solução salina, lidocaína (20 mg) ou palonosetron (0.075 mg), com aplicação de torniquete dois minutos antes da administração intravenosa de tiopental sódico (5 mg.kg-1). Após a perda de consciência, rocurônio (0.6 mg.kg-1) foi injetado e o reflexo de retirada foi avaliado com o uso de uma escala de quatro pontos, de modo duplo-cego. Resultados: A incidência global do reflexo de retirada induzido por rocurônio foi de 50% para lidocaína (p = 0,038), 38% para palonosetron (p = 0,006), em comparação com 75% para solução salina. A incidência de dor ausente ou leve foi significativamente menor nos grupos lidocaína e palonosetron (85% e 92%, respectivamente) que no grupo solução salina (58%). Porém, não houve diferença significativa no reflexo de retirada entre os grupos lidocaína e palonosetron. Não houve movimento grave com palonosetron. Conclusão: O pré-tratamento com palonosetron com oclusão venosa pode atenuar o reflexo de retirada induzido por rocurônio de modo tão eficaz como o uso de lidocaína. Sugeriu-se que a ação periférica de palonosetron foi eficaz para reduzir o reflexo de retirada induzido por rocurônio.

Efficacy and safety of multiple-dose 5-HT3 receptor antagonists in preventing multi-day-based and highly emetogenic chemotherapy-induced nausea and vomiting / 中国肿瘤临床

Objective:To evaluate efficacy and safety of multiple-dose tropisetron plus dexamethasone (DXM) versus palonosetron plus DXM for chemotherapy-induced nausea and vomiting. (CINV) in patients received multiple day-based highly emetogenic chemotherapy. Methods:Cancer patients who were receiving multiday-based highly emetogenic chemotherapy were randomly assigned to AB or BA groups. A randomized, cross self-control ed method was applied. Patients in AB group received palonosetron (0.25 mg) 30 min before chemotherapy on day 1 and 3 or additional day 5 in the first cycle;and with tropisetron (5 mg) 30 min before chemotherapy on day 1, 2, and 3, or sup-plementary days (day 4 and 5) in the second cycle. Patients in BA group were treated with tropisetron in the first cycle and with palonosetron in the second cycle. Tropisetron and palonosetron were administered with DXM (10 mg) on day 1, followed by additional doses (5 mg) on days 2 to 5. Palonosetron group comprised patients in the AB group in the first cycle and BA group in the second cycle, whereas tropisetron group included patients in the AB group in the second cycle and BA group in the first cycle. Efficacy and safety of tropisetron versus palonosetron in preventing CINV were evaluated. Results:Ninety-one patients were included in analyses. At day 3, 4, and 5, incidence rates of nausea in the palonosetron group reached 28.6%, 30.8%, and 24.2%, respectively, and those of the tropisetron group totaled 42.8%, 47.3%, and 39.6%, respectively (P<0.05). At day 4, 5, and 6, incidence rates of vomiting in the palonosetron group measured 28.6%, 18.7%, and 5.5%, respectively, and those of the tropisetron group reached 42.9%, 34.1%, and 14.3%, respectively (P<0.05). From day 4 to day 5, day 6 to day 7, and day 1 to day 7, the palonosetron group yielded significantly lower incidence rates of nausea and vomiting than tropisetron group (P<0.05). Rate of rescue treatment in the palonosetron group was lower than that in tropisetron group (13.2%vs. 24.2%, P=0.057). No statistical difference in toxicities was observed between the two groups. Conclusion:Palonosetron plus DXM features better efficacy than that of tropisetron plus DXM against delayed CINV induced by multiple day-based highly emetogenic chemotherapy, which was well tolerated in the two treatments.

Aprepitant therapy for prevention of moderately chemotherapy-induced nausea and vomiting in patients with gastrointestinal cancer / 上海交通大学学报（医学版）

Objective · To investigate antiemetic effect of aprepitant for moderately chemotherapy-induced nausea and vomiting in patients with gastrointestinal cancer. Methods · From 2014 July to 2015 August, 130 cases of gastrointestinal cancer patients were collected in Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, who received moderate emetogenic risk of chemotherapy for at least four courses. One hundred and nine patients were treated with aprepitant, palonosetron and dexamethasone on day 1, and aprepitant and dexamethasone on day 2 and 3. Twenty-one patients only received aprepitant and dexamethasone on day 1 and dexamethasone on day 2 and 3 in the first course of chemotherapy. During subsequent courses of chemotherapy they received aprepitant and treated in the same way as 109 patients. MASCC antiemetic tool (MAT) was used to evaluate the intensity of nausea. The primary endpoint was complete response (CR, no emesis and use of no rescue antiemetics) during the overall study phase (0-120 h after chemotherapy) at the second course. The secondary endpoint was complete protection (CP, CR plus no significant nausea) during the overall, acute (0-24 h), and delayed (24-120 h) phases at the second course. Results · The CR rates were 90.0%, 94.6% and 90.8% of patients in the overall, acute and delayed phases, respectively. The corresponding CP rates were 83.8%, 87.8% and 84.6 %, respectively. The CR rate increased from 42.9% to 57.1% during acute phase and increased from 9.5% to 90.5% during delayed phase for 21 patients after treatment with aprepitant. The main adverse reactions include constipation, anorexia and hiccups. Conclusion · Aprepitant combined with palonosetron and dexamethasone can effectively prevent moderately chemotherapy-induced nausea and vomiting in patients with gastrointestinal cancer. Aprepitant therapy can effectively maintain antiemetic effect in patients with many chemotherapy courses.

Palonosetron-Induced Anaphylaxis During General Anesthesia: A Case Report

Palonosetron is a 5-hydroxytryptamine-3 (5-HT-3) receptor antagonist used for preventing postoperative nausea and vomiting. Compared with ondansetron and granisetron, it is a better drug because of prolonged action and minimal side effects. Some adverse effects of palonosetron have been reported. In this report, we describe a 37-year-old male who developed severe hypersensitivity reactions to palonosetron during surgery for kidney donation. His medical history was unremarkable, except for inguinal hernia with herniorrhaphy 8 years ago. The surgery was uneventful until 2 hours 20 minutes. After palonosetron injection, his blood pressure dropped to 80/50 mm Hg, and facial edema, rash, conjunctival swelling, and wheezing developed. The patient was resuscitated by administration of ephedrine, hydrocortisone, and peniramine. Following the surgery, the patient was monitored for 3 days, and there were no subsequent anaphylactic reactions or other complications. The skin test on postoperative day 54 was positive for hypersensitivity to palonosetron. Although palonosetron is known for its safety, other hypersensitivity events have been reported. Ondansetron is another widely used 5-HT-3 antagonist, which has been reported to cause anaphylaxis. Therefore, clinicians should be aware of the possibility of patients experiencing severe adverse reactions to palonosetron.

Morphologic changes in the spinal cord following intrathecal palonosetron-HCl injection in rats

BACKGROUND: Intravenous palonosetron-HCl, a second-generation antagonist of selective serotonin type 3 (5-HT3) receptors, can prevent chemotherapy-induced nausea and vomiting (CINV) and postoperative nausea and vomiting (PONV). 5-HT3 receptors are abundant in the lower brainstem and the substantia gelatinosa of the spinal cord, which provides a theoretical rationale for neuraxial administration of 5-HT3 receptor antagonists for CINV, PONV, and opioid-induced nausea and vomiting. However, there are no reports of neuraxial administration of palonosetron-HCl. Before neuraxial administration of a drug is accepted for clinical use, its safety must be proven. This study was conducted to determine whether neuraxial administration of palonosetron-HCl produces neurologic injury. METHODS: Male Sprague-Dawley rats under general anesthesia were catheterized intrathecally and the catheter tip was advanced caudally to the L1 vertebra. After 7 days, 20 µl of normal saline (N group, n = 6) or 20 µl (1 µg) of palonosetron-HCl (P group, n = 6) were injected intrathecally once per day for 2 weeks. Neurotoxic changes were evaluated by light microscopy (LM) and electron microscopy (EM) of the spinal cord. Behavioral changes were also evaluated in both groups. RESULTS: One of the N group rats and three of the P group rats demonstrated abnormal behavior during intrathecal drug injection, but otherwise their behavior was normal. The spinal cords of the N group did not have any abnormal findings by LM or EM. The spinal cords of the P group had multiple vacuoles in the white matter by LM, especially in the dorsal funiculus, and EM revealed myelin, axonal, and mitochondrial swelling. CONCLUSIONS: Results suggest that chronic intrathecal administration of palonosetron-HCl produced microscopic morphologic changes in the spinal cords of rats.

Efficacy of Palonosetron vs. Ramosetron for the Prevention of Postoperative Nausea and Vomiting: A Meta-Analysis of Randomized Controlled Trials

PURPOSE: This study was designed as a meta-analysis of randomized controlled trials (RCTs) that included the comparison of palonosetron and ramosetron for postoperative nausea and vomiting (PONV) prophylaxis. MATERIALS AND METHODS: A systematic search was conducted for the PubMed, EMBASE, Web of Science, CENTRAL, KoreaMed, and Google Scholar databases (PROSPERO protocol number CRD42015026009). Primary outcomes were the incidences of postoperative nausea (PON) and postoperative vomiting (POV) during the first 48 hrs after surgery. The total 48-hr period was further analyzed in time epochs of 0–6 hrs (early), 6–24 hrs (late), and 24–48 hrs (delayed). Subgroup analyses according to number of risk factors, sex, and type of surgery were also performed. RESULTS: Eleven studies including 1373 patients were analyzed. There was no difference in PON or POV between the two drugs for the total 48-hr period after surgery. However, palonosetron was more effective in preventing POV during the delayed period overall [relative risk (RR), 0.59; 95% confidence interval (CI), 0.39 to 0.89; p=0.013], as well as after subgroup analyses for females and laparoscopies (RR, 0.56; 95% CI, 0.36 to 0.86; p=0.009 and RR, 0.46; 95% CI, 0.23 to 0.94; p=0.033). Subgroup analysis for spine surgery showed that ramosetron was more effective in reducing POV during the total 48-hr (RR, 3.34; 95% CI, 1.46 to 7.63; p=0.004) and early periods (RR, 8.47; 95% CI, 1.57 to 45.72; p=0.013). CONCLUSION: This meta-analysis discovered no definite difference in PONV prevention between the two drugs. The significant findings that were seen in different time epochs and subgroup analyses should be confirmed in future RCTs.

A comparison of palonosetron and dexamethasone for postoperative nausea and vomiting in orthopedic patients receiving patient-controlled epidural analgesia / 대한마취과학회지

BACKGROUND: Postoperative nausea and vomiting (PONV) is one of the major concerns after anesthesia and surgery, and it may be more frequent in orthopedic patients receiving patient-controlled epidural analgesia (PCEA). The purpose of this study was to compare the effect of palonosetron and dexamethasone on the prevention of PONV in patients undergoing total joint arthroplasty and receiving PCEA. METHODS: Patients scheduled for total hip or knee arthroplasty under spinal anesthesia/PCEA were randomly allocated to receive either intravenous palonosetron (0.075 mg, n = 50) or dexamethasone (5 mg, n = 50). Treatments were administered intravenously to the patients 30 min before the beginning of surgery. The total incidence of PONV and incidence in each time period, severity of nausea, need for rescue anti-emetics, pain score, and adverse effects during the first 48 h postoperatively were evaluated. RESULTS: The total incidence of PONV was lower in the palonosetron group compared with the dexamethasone group (18.4% vs. 36.7%, P = 0.042), but there were no statistically significant differences in incidence between the groups at all time points. No significant intergroup differences were observed in the severity of nausea, use of rescue anti-emetics, pain score, and adverse effects. CONCLUSIONS: Although there were no significant differences in the incidence of PONV between the treatment groups at all time points, intravenous palonosetron reduced the total incidence of PONV in orthopedic patients receiving PCEA compared with dexamethasone.

Comparative Study Of Efficacy Of Palonosetron With Dexamethasone Versus Granisetron With Dexamethosone In Laproscopic Abdominal Surgeries For Control Of Post Operative Nausea And Vomiting.

Background & Aim: This study was carried out to demonstrate the efficacy and compare a dose of Granisetron with Dexamethasone and Palonosetron with Dexamethasone for prophylaxis against postoperative nausea and vomiting. Aim is to study the effectiveness of palonosetron and granisetron with aims of evaluating the efficacy of palonosetron and granisetron with dexamethasone in prevention of postoperative nausea and vomiting and to study associated adverse effects. The study was carried out in Civil Hospital, Ahmedabad with prior permission of ethical committee of the hospital. Methodology: This study was designed to evaluate the efficacy and compare a dose of study drugs in 60 patients of either sex and age ranging from 18 to 60 years and physical status ASA risk I or II undergoing general anaesthesia for various laparoscopic surgical procedures. Patients were divided into 2 groups(n=30), assigned to receive granisetron 1mg plus dexamethasone 8mg i.v and palonosetron 0.075mg plus dexamethasone 8mg i.v. A standard general anaesthesia technique and post operative analgesia were used throughout our study. The groups were compared with regards to the incidence of complete response, mean PONV score, mean nausea VDS scores and requirement of rescue anti emetics drug at various intervals (0-6,6-24,24-72hrs). Differences in continuous variables (age and duration of anaesthesia) across two dosage groups were compared using analysis of variance (ANOVA) test which is a parametric statistical test. Differences in categorical variables (gender, presence of complete response, use of rescue anti-emetics) across two dosage groups were compared using chi square test. Differences in ordinal variables (PONV scores and 4-point verbal descriptive nausea scores) across two dosage groups were compared using non-parametric Kruskal Wallis one-way analysis of variance. Mann Whitney U test was used to conduct sub-group analyses for comparing PONV scores and 4-point verbal descriptive nausea scale scores between two given groups. McNemar's test was done to compare differences in rates of complete response in a given dosage group across different time periods of assessment. Results: Our study results shows clear superiority of palonosetron with dexamethasone as a prophylactic drug for the prevention of PONV than that of granisetron with dexamethasone. Conclusions: Due to its longer duration of action, a single dose of palonosetron with dexamethasone before induction is effective in preventing PONV for upto 72 hours and hence can be termed as a prophylactic drug for PDNV also. It’s optimal and effective dose is 0.075mg i.v. with minimal side effects.

Randomized controlled trial of palonosetron in preventing postoperative nausea and vomiting in gyneco-logical surgeries / 临床麻醉学杂志

Objective To compare the effects of a single injection of palonosetron and tropise-tron to prevent postoperative nausea and vomiting (PONV ) in gynecological surgeries. Methods Sixty patients undergoing elective major gynecological surgeries with general anesthesia (Apfel score ≥ 3 ) were included and randomized to group P (palonosetron ) and group T (tropisetron),30 patients in each group.All patients received general anesthesia with tracheal intuba-tion,and palonosetron 0.25 mg or tropisetron 5 mg were injected before anesthesia respectively in two groups.Intravenous hydromorphine was delivered for postoperative analgesia in all patients. PONV were evaluated and followed up for 72 hours.The degree of PONV was recorded and the com-plete response rate (CR)and complete control rate (CC)were calculated.Results The degree of PONV in 0-24 h and 24-48 h was milder in group P than in group T (P <0.05),while in 48-72 h the degree of PONV was similar between the two groups.In group P,5 patients had vomiting postopera-tively with the failure period of treatment of (1 9.6±9.4)h,and no patients needed rescue treatments. While in group T,1 9 patients suffered from vomiting with the failure period of treatment of (20.6± 4.5)h,and rescue treatments were delivered 3 times in total.The CR and CC of preventing PONV in 0-24 h,24-48 h and 0-72 h were significantly higher in group P than in group T (P <0.05).The CR and CC of the two groups were comparable in 48-72 h postoperatively.Conclusion A preoperative single dose of palonosetron 0.25 mg is better than tropisetron 5 mg in preventing PONV within 48hours after gynecological surgery.