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Future Oncology (London, England) Aug 2016Granisetron transdermal delivery system (GTDS) is the first 5-HT3 drug to be transdermally delivered and represents a convenient alternative to oral and intravenous... (Review)
Review
Granisetron transdermal delivery system (GTDS) is the first 5-HT3 drug to be transdermally delivered and represents a convenient alternative to oral and intravenous antiemetics for the treatment of chemotherapy-induced nausea and vomiting. GTDS is effective and well tolerated in patients receiving multiple-day moderate-to-highly emetogenic chemotherapy. In this setting noninferiority studies showed similar efficacy when GTDS was compared with intravenous and oral granisetron and intravenous palonosetron. GTDS has shown good cardiovascular safety; however, special caution is needed in patients at risk for developing excessive QTc interval prolongation and arrhythmias. So far, GTDS has been investigated for intravenous prevention in comparison with granisetron and palonosetron; however, further prospects open the route to future clinical investigations.
Topics: Antiemetics; Antineoplastic Agents; Granisetron; Humans; Nausea; Transdermal Patch; Vomiting
PubMed: 27184113
DOI: 10.2217/fon-2016-0097 -
EClinicalMedicine Jul 2022Despite significant progress in the prevention of chemotherapy-induced nausea and vomiting (CINV) by using dexamethasone combined with palonosetron for patients who...
Aprepitant plus palonosetron versus dexamethasone plus palonosetron in preventing chemotherapy-induced nausea and vomiting in patients with moderate-emetogenic chemotherapy: A randomized, open-label, phase 3 trial.
BACKGROUND
Despite significant progress in the prevention of chemotherapy-induced nausea and vomiting (CINV) by using dexamethasone combined with palonosetron for patients who received moderate-emetogenic chemotherapy (MEC), some of these patients still suffer from CINV. We evaluated whether aprepitant combined with palonosetron can improve the efficacy in the prevention of CINV in patients receiving MEC.
METHODS
This was a single-centre, open-label, phase III, randomized controlled trial, which was done at the Sixth Affiliated Hospital of Sun Yat-sen University of China. The registered patients planned to receive mFOLFOX6 (oxaliplatin, leucovorin, and 5-fluorouracil) but had not received any chemotherapy previously. The patients were randomized in a 1:1 ratio to the aprepitant group (aprepitant 125 mg orally on day 1, 80 mg on day 2-3) and the dexamethasone group (dexamethasone 10 mg intravenously on day 1, 5 mg on days 2 and 3), both groups with palonosetron 0.25 mg intravenously on day 1. The primary endpoint was the proportion of patients who achieved a complete response (CR), defined as the absence of vomiting and no use of rescue medications in the overall phase (0-120 h). The primary outcome and safety were assessed in the modified intention-to-treat population, which excluded all patients who used estazolam within 24 h before registration and those who refused to keep a diary documenting the severity of nausea, frequency of vomiting, and the use of rescue therapy. This trial is registered with ClinicalTrials.gov, NCT02909478.
FINDINGS
Between Sep 1, 2017, and Oct 23, 2019, 320 patients were enrolled, and 315 patients were evaluated. The proportion of patients who achieved CR was significantly higher with aprepitant than that noted with dexamethasone in the overall phase (88.8% vs. 74.2%; = 0.0010; rate difference, RD 15%, 95% CI, 6% to 23%) and in the delayed phase (25-120 h), 90.6% vs. 75.5%, ( < 0.0001; RD 15%, 95%CI, 7% to 23%). No significant difference of CR rate was observed in the acute phase (0-24 h), 93.8% vs. 93.5%, ( = 0.94; RD 0%, 95% CI, -5% to 6%)). In the overall phase, the incidence of insomnia ( < 0.0010), dyspepsia ( = 0.038), and flushing ( = 0.0010) reported by the patients was significantly higher in the dexamethasone group than that in the aprepitant group.
INTERPRETATION
Aprepitant combined with palonosetron is superior to dexamethasone combined with palonosetron in patients who received the MEC regimen mFOLFOX6 in terms of preventing CINV.
FUNDING
The National Key R&D Program of China (2019YFC1316000) and the National Natural Science Foundation of China (81974369).
PubMed: 35747189
DOI: 10.1016/j.eclinm.2022.101480 -
Cancer Chemotherapy and Pharmacology Jul 2021Chemotherapy-induced nausea and vomiting (CINV) is considered one of the most serious adverse events affecting chemotherapy-receiving cancer patients. It dramatically... (Randomized Controlled Trial)
Randomized Controlled Trial
Evaluation of clinical outcomes and efficacy of palonosetron and granisetron in combination with dexamethasone in Egyptian patients receiving highly emetogenic chemotherapy.
BACKGROUND
Chemotherapy-induced nausea and vomiting (CINV) is considered one of the most serious adverse events affecting chemotherapy-receiving cancer patients. It dramatically affects their food intake, nutritional status and more importantly their quality of life. We can observe CINV in highly emetogenic chemotherapy (HEC) such as adriamycin-cyclophosphamide combination (AC) in breast cancer patients and cisplatin-based regimens in other cancer types. This study aimed to evaluate the antiemetic efficacy of palonosetron (PALO) over granisetron (GRA) in combination with dexamethasone for multiple highly emetogenic chemotherapy drugs (HEC), especially in chemotherapy regimens in Egyptian breast cancer patients and cisplatin-based regimens in other diseases.
PATIENTS AND METHODS
An open-label randomized trial was carried out, including 115 patients receiving at least four cycles of highly emetogenic chemotherapy regimens. All patients received dexamethasone in combination with the 5-HT3 receptor antagonist. We recorded patients' clinical and biochemical characteristics and withdraw blood samples to monitor serum substance P and serotonin in correlation with chemotherapy-induced nausea and vomiting (CINV). We use the MASCC antiemetic tool in the acute phase (0-24 hr) and delayed phase (24-120 h) to evaluate patient outcomes in both stages after each chemotherapy cycle.
RESULTS
In (PALO) group, only 7.84% of patients showed acute vomiting, and 11.76% showed acute nausea, whereas 43.75% of patients showed acute vomiting and 89.06% showed acute nausea in (GRA) group (P < 0.0001). For delayed CINV, 23.53% of patients showed delayed vomiting, and 47.06% showed delayed nausea in the (PALO) group, while 82.81% of patients showed delayed emesis, and 92.19% showed delayed nausea in (GRA) group (P < 0.0001). The study showed that PALO is a cost-effective choice when compared to GRA in CINV prevention as 45.10% of patients in (PALO) required additional rescue medications (Domperidone 10 mg orally three times per day plus Trimebutine 200 mg orally three times per week both for 5 days), while 95.24% in the (GRA) group used the same medications. Adverse events of both antiemetic drugs (PALO and GRA) include headaches and constipation and QTc prolongation reports, mostly mild to moderate, with relatively low rates among the two groups.
CONCLUSION
Palonosetron, combined with dexamethasone, is more effective than granisetron and dexamethasone combination against both acute and delayed emesis induced by highly emetogenic chemotherapy (HEC) cisplatin-based protocols and the combination of cyclophosphamide and anthracyclines (AC). Medical team members should make more efforts, especially clinical pharmacy personnel, to monitor medications' effectiveness and help the medical team achieve a suitable and reliable care plan.
Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Cisplatin; Cyclophosphamide; Dexamethasone; Doxorubicin; Drug Therapy, Combination; Egypt; Female; Granisetron; Humans; Male; Middle Aged; Nausea; Palonosetron; Quality of Life; Vomiting
PubMed: 33835230
DOI: 10.1007/s00280-021-04257-7 -
Journal of Neurosurgical Anesthesiology Oct 2017Adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) polymorphisms may influence 5-hydroxytryptamine receptor antagonist efficacy by altering their... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) polymorphisms may influence 5-hydroxytryptamine receptor antagonist efficacy by altering their efflux transportation. We evaluated the influence of ABCB1 polymorphisms on the efficacy of ramosetron compared with palonosetron in managing postoperative nausea and vomiting (PONV) in patients who received intravenous patient-controlled analgesia after spinal surgery.
METHODS
Patients were randomly allocated to receive 2 boluses (20 min before the end of surgery and 24 h after surgery) of either ramosetron 0.3 mg (n=150) or palonosetron 0.075 mg (n=146). The incidence and severity of PONV, fentanyl consumption, and pain intensity were serially assessed for postoperative 48 hours. ABCB1 3435C>T and 2677G>T/A polymorphisms were assessed.
RESULTS
The incidences of nausea were similar between the 2 groups in patients with the 3435TT (50% vs. 56%, ramosetron and palonosetron group, respectively, P>0.999) or 2677TT (50% vs. 56%, ramosetron and palonosetron group, respectively, P>0.999). Mild PONV were more frequent in the ramosetron group than in the palonosetron group among patients with 3435TT (91% vs. 33%, P=0.034) and 2677TT (92% vs. 20%, P=0.002) genotypes. The intensity of nausea experienced by ramosetron-group TT genotype patients (1 [1 to 2], 3435TT; 1 [1 to 2.5], 2677TT) was lower than that experienced by ramosetron-group non-TT genotype patients (3 [1 to 6], 3435 non-TT, P=0.030; 3 [1 to 6], 2677 non-TT, P=0.038) and palonosetron-group TT genotype patients (6 [2 to 7], 3435TT, P=0.010; 6 [4 to 7], 2677TT, P=0.002).
CONCLUSIONS
Compared with palonosetron, ramosetron may be superior for reducing PONV severity, especially in patients with ABCB1 3435TT or 2677TT genotype.
Topics: ATP Binding Cassette Transporter, Subfamily B; Adult; Aged; Aged, 80 and over; Analgesia, Patient-Controlled; Analgesics, Opioid; Antiemetics; Benzimidazoles; Double-Blind Method; Female; Fentanyl; Genotype; Humans; Incidence; Isoquinolines; Male; Middle Aged; Pain, Postoperative; Palonosetron; Polymorphism, Genetic; Postoperative Nausea and Vomiting; Prospective Studies; Quinuclidines; Serotonin 5-HT3 Receptor Antagonists; Spine; Young Adult
PubMed: 27564555
DOI: 10.1097/ANA.0000000000000361 -
Cancer Treatment Reviews Dec 2015Many patients undergoing moderately or highly emetogenic chemotherapy experience chemotherapy-induced nausea/vomiting (CINV) and report reduced daily functioning,... (Review)
Review
Many patients undergoing moderately or highly emetogenic chemotherapy experience chemotherapy-induced nausea/vomiting (CINV) and report reduced daily functioning, despite prophylaxis with antiemetic drugs. While modern antiemetics have largely alleviated acute emesis, management of nausea and delayed emesis remains particularly challenging. We briefly review the pathophysiologic mechanisms of CINV and the clinical impact of current antiemetics, i.e., the serotonin subtype 3 (5-HT3) receptor antagonists (RAs) and neurokinin-1 (NK1)RAs, before summarizing recent data from clinical trials of new agents. The new antiemetics reviewed include the two most recently approved drugs, the NK1RA rolapitant and the fixed-dose combination product, NEPA, which is composed of the NK1RA netupitant and the 5-HT3RA palonosetron. Phase 3 studies demonstrate improved control of CINV in the delayed and overall phases when rolapitant is added to a standard 5-HT3RA regimen. Phase 2 and phase 3 clinical trials with NEPA demonstrate improved control of CINV in the acute, delayed, and overall phases vs. 5-HT3RA regimens. These data suggest that delayed emesis can be substantially reduced via combined 5-HT3 and NK1 receptor neurotransmitter pathway inhibition.
Topics: Antiemetics; Antineoplastic Agents; Drug Combinations; Humans; Isoquinolines; Nausea; Neurokinin-1 Receptor Antagonists; Pyridines; Quinuclidines; Spiro Compounds; Vomiting
PubMed: 26442475
DOI: 10.1016/j.ctrv.2015.09.005 -
Therapeutics and Clinical Risk... 2016As recommended by most recent antiemetic guidelines, the optimal prophylaxis of chemotherapy-induced nausea and vomiting (CINV) requires the combination of 5-HT3... (Review)
Review
As recommended by most recent antiemetic guidelines, the optimal prophylaxis of chemotherapy-induced nausea and vomiting (CINV) requires the combination of 5-HT3 receptor antagonist (RA) with an NK1-RA. Moreover, the major predictors of acute and delayed CINV include: young age, female sex, platinum- or anthracycline-based chemotherapy, nondrinker status, emesis in the earlier cycles of chemotherapy, and previous history of motion/morning sickness. Despite improved knowledge of the pathophysiology of CINV and advances in the availability of active antiemetics, an inconsistent compliance with their use has been reported, thereby resulting in suboptimal control of CINV in several cases. In this scenario, a new anti-emetic drug is now available, which seems to be able to guarantee better prophylaxis of CINV and improvement of adherence to guidelines. In fact, netupitant/palonosetron (NEPA) is a ready-to-use single oral capsule, combining an NK1-RA (netupitant) and a 5-HT3-RA (palonosetron), which is to be taken 1 hour before the administration of chemotherapy, ensuring the coverage from CINV for 5 days. We reviewed the role of NEPA in patients at high risk of CINV receiving highly emetogenic chemotherapy. In these patients, NEPA plus dexamethasone, as compared to standard treatments, achieved superior efficacy in all primary and secondary end points during the acute, delayed, and overall phases, including nausea assessment. Moreover, these results were also achieved in female patients receiving anthracycline plus cyclophosphamide-based chemotherapy. NEPA represents a real step forward in the prophylaxis of CINV.
PubMed: 27354807
DOI: 10.2147/TCRM.S89215 -
Current Therapeutic Research, Clinical... 2019Postoperative nausea and vomiting (PONV) are 2 of the most frequent adverse effects of anesthesia. PONV prolongs hospital stays and also delays the recovery of patients.
BACKGROUND
Postoperative nausea and vomiting (PONV) are 2 of the most frequent adverse effects of anesthesia. PONV prolongs hospital stays and also delays the recovery of patients.
OBJECTIVE
In this study, the effects of ondansetron, tropisetron, and palonosetron on PONV in patients who had undergone middle ear surgeries such as mastoidectomy or tympanoplasty were compared.
METHODS
The study included 165 American Society of Anesthesiologists grade 1 and 2 patients aged 18 to 65 years. Patients were randomized into 3 groups by a closed envelope method. Neither the patients nor the nurses administering the treatments knew which patient belonged to which group. The anesthetic technique was standardized for all groups. During skin closure, 0.075 mg palonosetron, 5 mg tropisetron, and 8 mg ondansetron were administered intravenously to the palonosetron, tropisetron, and ondansetron groups, respectively. After completion of the surgery, the patients were followed for 48 hours. Diclofenac sodium (100 mg IM) was administered to patients experiencing pain and metoclopramide chloride (10 mg IM) was administered to patients with nausea or vomiting. Potential side effects such as headache and constipation were recorded in the postanesthesia care unit and ear, nose, and throat clinic.
RESULTS
There was no significant difference in the effects of all 3 antiemetic agents on the severity of PONV ( = 0.081). At 48 hours postoperatively, the incidence of PONV was significantly lower in the palonosteron group (38.2%) than the ondansetron group (63.6%) and tropisetron group (61.8%) ( = 0.011). At 48 hours postoperatively, the incidence of postoperative nausea was significantly lower in the palonosetron group (32.7%) than in the ondansetron group (63.6%) and the tropisetron group (56.4%) ( = .003). The incidence of PONV between hours 12 and 24 postoperatively was significantly higher in the ondansetron group (27.3%) than in the palonosetron group (9.1%) ( = 0.013). The antiemetic requirement in the first hour after surgery was significantly higher in the tropisetron group (25.5%) than in the palonosetron group (7.3%) ( = .019).
CONCLUSIONS
The results of the current study support those of earlier studies that suggest that palonosetron was statistically more effective than the other 2 formulations in the prevention of PONV in patients who have undergone middle ear surgery. ( 2019; 80:XXXXXX).
PubMed: 31384338
DOI: 10.1016/j.curtheres.2019.06.002 -
Journal of Anesthesia Jun 2019Palonosetron is the most recent 5-hydroxytryptamine-3 receptor antagonist, and its fixed dose of 0.075 mg is indicated for the prevention of postoperative nausea and... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
Palonosetron is the most recent 5-hydroxytryptamine-3 receptor antagonist, and its fixed dose of 0.075 mg is indicated for the prevention of postoperative nausea and vomiting. This study aimed to examine whether fixed dosing is more appropriate than body size-based dosing through the development of a population pharmacokinetic model and model-based simulations.
METHODS
Fifty-one adult patients undergoing general anesthesia received single intravenous palonosetron administrations 30 min before the end of surgery. Palonosetron concentrations were measured in blood samples collected at various timepoints within 48 h. A population pharmacokinetic analysis was performed by non-linear mixed-effects modeling, and the area under the curves (AUCs) for fixed dosing and body size-based dosing were simulated.
RESULTS
The pharmacokinetics of palonosetron were best described by the three-compartment model, and lean body weight (LBW) was the most significant covariate for all pharmacokinetic parameters. In a patient with LBW of 40 kg, typical clearance and central volume of distribution were 0.102 L/min and 6.98 L, respectively. In simulations, the overall interindividual variability in AUC (0, 48 h) of fixed dosing was not much higher than that of body size-based dosing. In subgroup analysis, the AUCs (0, 48 h) of fixed dosing were considerably lower in the high-weight subgroup and higher in the low-weight subgroup than the median-weight subgroup. In contrast, LBW-based dosing showed similar AUC distributions among the three subgroups.
CONCLUSION
LBW-based dosing might be suitable for high-weight patients to avoid possible underdosing. Nevertheless, the current fixed dosing of palonosetron is acceptable for adult patients with normal weight.
Topics: Administration, Intravenous; Aged; Anesthesia, General; Area Under Curve; Body Weight; Female; Humans; Male; Middle Aged; Palonosetron; Postoperative Nausea and Vomiting
PubMed: 30976908
DOI: 10.1007/s00540-019-02641-5 -
Brazilian Journal of Anesthesiology... 2024End-stage renal diseases patients have a high risk of postoperative nausea and vomiting (PONV), which is multifactorial and need acute attention after renal... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
End-stage renal diseases patients have a high risk of postoperative nausea and vomiting (PONV), which is multifactorial and need acute attention after renal transplantation for a successful outcome in term of an uneventful postoperative period. The study was done to compare the efficacy of palonosetron and ondansetron in preventing early and late-onset PONV in live donor renal transplantation recipients (LDRT).
METHODS
The prospective randomized double-blinded study was done on 112 consecutive patients planned for live donor renal transplantation. Patients of both sexes in the age group of 18...60 years were randomly divided into two groups: Group O (Ondansetron) and Group P (Palonosetron) with 56 patients in each group by computer-generated randomization. The study drug was administered intravenously (IV) slowly over 30.ßseconds, one hour before extubation. Postoperatively, the patients were accessed for PONV at 6, 24, and 72.ßhours using the Visual Analogue Scale (VAS) nausea score and PONV intensity scale.
RESULTS
The incidence of PONV in the study was found to be 30.35%. There was significant difference in incidence of PONV between Group P and Group O at 6.ßhours (12.5% vs. 32.1%, p.ß=.ß0.013) and 72.ßhours (1.8% vs. 33.9%, p.ß<.ß0.001), but insignificant difference at 24.ßhours (1.8% vs. 10.7%, p.ß=.ß0.113). VAS-nausea score was significantly lower in Group P as compared to Group O at a time point of 24.ßhours (45.54.ß...ß12.64 vs. 51.96.ß...ß14.70, p.ß=.ß0.015) and 72.ßhours (39.11.ß...ß10.32 vs. 45.7.ß...ß15.12, p.ß=.ß0.015).
CONCLUSION
Palonosetron is clinically superior to ondansetron in preventing early and delayed onset postoperative nausea and vomiting in live-related renal transplant recipients.
Topics: Male; Female; Humans; Adolescent; Palonosetron; Ondansetron; Postoperative Nausea and Vomiting; Antiemetics; Kidney Transplantation; Prospective Studies; Double-Blind Method
PubMed: 34411635
DOI: 10.1016/j.bjane.2021.07.027 -
Supportive Care in Cancer : Official... Nov 2022The aim of this study was to assess the cost-effectiveness of NEPA, a fixed-dose combination of oral netupitant (300 mg) and palonosetron (0.5 mg), compared to...
Cost-effectiveness analysis of NEPA, a fixed-dose combination of netupitant and palonosetron, for the prevention of highly emetogenic chemotherapy-induced nausea and vomiting: an international perspective.
PURPOSE
The aim of this study was to assess the cost-effectiveness of NEPA, a fixed-dose combination of oral netupitant (300 mg) and palonosetron (0.5 mg), compared to available treatments in Spain after aprepitant generic introduction in the market, and to discuss results in previously performed analyses in different wordwide settings.
METHODS
A Markov model including three health states, complete protection, complete response at best and incomplete response, was used to evaluate the cost-effectiveness of NEPA versus common treatment options in Spain during 5 days after chemotherapy. Incremental costs including treatment costs and treatment failure management cost as well as incremental effects including quality adjusted life days (QALDs) and emesis-free days were compared between NEPA and the comparator arms. The primary outcomes were cost per avoided emetic event and cost per QALDs gained.
RESULTS
NEPA was dominant (more effective and less costly) against aprepitant combined with palonosetron, and fosaprepitant combined with granisetron, while, compared to generic aprepitant plus ondansetron, NEPA showed an incremental cost per avoided emetic event of €33 and cost per QALD gained of €125.
CONCLUSION
By most evaluations, NEPA is a dominant or cost-effective treatment alternative to current antiemetic standards of care in Spain during the first 5 days of chemotherapy treatment in cancer patients, despite the introduction of generics. These results are in line with previously reported analyses throughout different international settings.
Topics: Humans; Palonosetron; Cost-Benefit Analysis; Aprepitant; Emetics; Vomiting; Antineoplastic Agents; Nausea; Antiemetics; Internationality; Quinuclidines
PubMed: 36074186
DOI: 10.1007/s00520-022-07339-1