Showing papers on "Granisetron published in 2021"

Molecular mechanism of setron-mediated inhibition of full-length 5-HT3Areceptor.

Abstract: Serotonin receptor (5-HT3AR) is the most common therapeutic target to manage the nausea and vomiting during cancer therapies and in the treatment of irritable bowel syndrome. Setrons, a class of competitive antagonists, cause functional inhibition of 5-HT3AR in the gastrointestinal tract and brainstem, acting as effective anti-emetic agents. Despite their prevalent use, the molecular mechanisms underlying setron binding and inhibition of 5-HT3AR are not fully understood. Here, we present the structure of granisetron-bound full-length 5-HT3AR solved by single-particle cryo-electron microscopy to 2.92 A resolution. The reconstruction reveals the orientation of granisetron in the orthosteric site with unambiguous density for interacting sidechains. Molecular dynamics simulations and electrophysiology confirm the granisetron binding orientation and the residues central for ligand recognition. Comparison of granisetron-bound 5-HT3AR with the apo and serotonin-bound structures, reveals key insights into the mechanism underlying 5-HT3AR inhibition. Serotonin receptors (5-HT3R) belong to the pentameric ligand-gated ion channel superfamily and mediate excitatory postsynaptic signaling. Here the authors present the high-resolution cryo-EM structure of 5-HT3AR bound with the competitive antagonist granisetron and further validate the granisetron-binding mode with electrophysiology measurements and MD simulations.

Drugs for preventing postoperative nausea and vomiting in adults after general anaesthesia: an abridged Cochrane network meta-analysis

Abstract: Postoperative nausea and vomiting is a common adverse effect of anaesthesia. Although dozens of different anti-emetics are available for clinical practice, there is currently no comparative ranking of efficacy and safety of these drugs to inform clinical practice. We performed a systematic review with network meta-analyses to compare, and rank in terms of efficacy and safety, single anti-emetic drugs and their combinations, including 5-hydroxytryptamine3 , dopamine-2 and neurokinin-1 receptor antagonists; corticosteroids; antihistamines; and anticholinergics used to prevent postoperative nausea and vomiting in adults after general anaesthesia. We systematically searched for placebo-controlled and head-to-head randomised controlled trials up to November 2017 (updated in April 2020). We assessed how trustworthy the evidence was using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) and Confidence In Network Meta-Analysis (CINeMA) approaches for vomiting within 24 h postoperatively, serious adverse events, any adverse event and drug class-specific side-effects. We included 585 trials (97,516 participants, 83% women) testing 44 single drugs and 51 drug combinations. The studies' overall risk of bias was assessed as low in only 27% of the studies. In 282 trials, 29 out of 36 drug combinations and 10 out of 28 single drugs lowered the risk of vomiting at least 20% compared with placebo. In the ranking of treatments, combinations of drugs were generally more effective than single drugs. Single neurokinin-1 receptor antagonists were as effective as other drug combinations. Out of the 10 effective single drugs, certainty of evidence was high for aprepitant, with risk ratio (95%CI) 0.26 (0.18-0.38); ramosetron, 0.44 (0.32-0.59); granisetron, 0.45 (0.38-0.54); dexamethasone, 0.51 (0.44-0.57); and ondansetron, 0.55 (0.51-0.60). It was moderate for fosaprepitant, 0.06 (0.02-0.21) and droperidol, 0.61 (0.54-0.69). Granisetron and amisulpride are likely to have little or no increase in any adverse event compared with placebo, while dimenhydrinate and scopolamine may increase the number of patients with any adverse event compared with placebo. So far, there is no convincing evidence that other single drugs effect the incidence of serious, or any, adverse events when compared with placebo. Among drug class specific side-effects, evidence for single drugs is mostly not convincing. There is convincing evidence regarding the prophylactic effect of at least seven single drugs for postoperative vomiting such that future studies investigating these drugs will probably not change the estimated beneficial effect. However, there is still considerable lack of evidence regarding safety aspects that does warrant investigation.

Netupitant/Palonosetron: A Review in Chemotherapy-Induced Nausea and Vomiting

Abstract: Netupitant/palonosetron (NEPA; Akynzeo®), available in oral and intravenous (IV) formulations, is a fixed-dose combination of the neurokinin 1 (NK1) receptor antagonist netupitant (or the prodrug, fosnetupitant, in the IV formulation) and the second-generation serotonin 3 (5-HT3) receptor antagonist palonosetron. Administered as a single dose, (fos)netupitant/palonosetron (in combination with dexamethasone) is indicated for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) in adults. In clinical trials, (fos)netupitant/palonosetron plus dexamethasone was associated with high complete response rates (no emesis and no rescue medication) in the acute, delayed and overall phases in patients receiving highly or moderately emetogenic chemotherapy, with efficacy maintained over multiple cycles. Further, oral netupitant/palonosetron was found to be superior to palonosetron and non-inferior to aprepitant plus granisetron in preventing CINV in individual trials. Both the oral and IV formulations of the drug combination are well tolerated. The fixed-dose combination is concordant with guideline recommendations and provides a simple and convenient option for prophylaxis against acute and delayed CINV in patients receiving highly or moderately emetogenic chemotherapy. Chemotherapy-induced nausea and vomiting (CINV) is a common problem during cancer treatment. Netupitant/palonosetron (NEPA; Akynzeo®) is a fixed-dose combination of two drugs (netupitant, a neurokinin 1 receptor antagonist; and palonosetron, a serotonin 3 receptor antagonist) which target two different signalling pathways involved in the induction of vomiting. Approved for use in the prevention of acute and delayed CINV in adults, netupitant/palonosetron is given orally or via intravenous infusion as a single dose prior to chemotherapy. In clinical trials, high proportions of patients who received netupitant/palonosetron (used in combination with the corticosteroid dexamethasone) prior to chemotherapy reported no vomiting, no requirement for rescue medication, and no significant nausea in the 5 days post chemotherapy. Both the oral and intravenous formulations of the drug combination are well tolerated. In conclusion, netupitant/palonosetron is a simple, convenient and effective drug combination for the prevention of acute and delayed CINV in patients receiving chemotherapy that has a moderate to high potential to cause nausea and vomiting.

Effects of 5-HT₃ receptor antagonists on cisplatin-induced kidney injury.

Abstract: Nausea, vomiting, and renal injury are the common adverse effects associated with cisplatin. Cisplatin is excreted via the multidrug and toxin release (MATE) transporter, and the involvement of the MATE transporter in cisplatin-induced kidney injury has been reported. The MATE transporter is also involved in the excretion of ondansetron, but the effects of 5-HT3 receptor antagonists used clinically for cisplatin-induced renal injury have not been elucidated. Therefore, the aim of this study was to investigate the effects of 5-HT3 receptor antagonists in a mouse model of cisplatin-induced kidney injury and to validate the results using medical big data analysis of more than 1.4 million reports and a survey of 3000 hospital medical records. The concomitant use of a first-generation 5-HT3 receptor antagonist (ondansetron, granisetron, or ramosetron) significantly increased cisplatin accumulation in the kidneys and worsened renal damage. Conversely, the concomitant use of palonosetron had no effect on renal function compared with the use of cisplatin alone. Furthermore, an analysis of data from the US Food and Drug Administration Adverse Event Reporting System and retrospective medical records revealed that the combination treatment of cisplatin and a first-generation 5-HT3 receptor antagonist significantly increased the number of reported renal adverse events compared with the combination treatment of cisplatin and a second-generation 5-HT3 receptor antagonist. These results suggest that compared with the first-generation antagonists, second-generation 5-HT3 receptor antagonists do not worsen cisplatin-induced acute kidney injury. The findings should be validated in a prospective controlled trial before implementation in clinical practice.

Drugs for preventing postoperative nausea and vomiting in adults after general anesthesia: An abridged Cochrane network meta-analysis.

Abstract: Objective In this abridged version of the recently published Cochrane review on antiemetic drugs, we summarize its most important findings and discuss the challenges and the time needed to prepare what is now the largest Cochrane review with network meta-analysis in terms of the number of included studies and pages in its full printed form. Methods We conducted a systematic review with network meta-analyses to compare and rank single antiemetic drugs and their combinations belonging to 5HT₃-, D₂-, NK₁-receptor antagonists, corticosteroids, antihistamines, and anticholinergics used to prevent postoperative nausea and vomiting in adults after general anesthesia. Results 585 studies (97 516 participants) testing 44 single drugs and 51 drug combinations were included. The studies' overall risk of bias was assessed as low in only 27% of the studies. In 282 studies, 29 out of 36 drug combinations and 10 out of 28 single drugs lowered the risk of vomiting at least 20% compared to placebo. In the ranking of treatments, combinations of drugs were generally more effective than single drugs. Single NK1 receptor antagonists were as effective as other drug combinations. Of the 10 effective single drugs, certainty of evidence was high for aprepitant, ramosetron, granisetron, dexamethasone, and ondansetron, while moderate for fosaprepitant and droperidol. For serious adverse events (SAEs), any adverse event (AE), and drug-class specific side effects evidence for intervention effects was mostly not convincing. Conclusions There is high or moderate evidence for at least seven single drugs preventing postoperative vomiting. However, there is still considerable lack of evidence regarding safety aspects that does warrant investigation.

Influence of CYP2D6 metabolizer status on ondansetron efficacy in pediatric patients undergoing hematopoietic stem cell transplantation: A case series.

Abstract: Chemotherapy-induced nausea and vomiting (CINV) is commonly experienced by patients receiving antineoplastic agents prior to hemopoietic stem cell transplant (HSCT). Ondansetron, a 5-HT3 antagonist metabolized by CYP2D6, is an antiemetic prescribed to treat short-term CINV, but some patients still experience uncontrolled nausea and vomiting while taking ondansetron. Adult CYP2D6 ultrarapid metabolizers (UMs) are at higher risk for CINV due to rapid ondansetron clearance, but similar studies have not been performed in pediatric patients. We performed a retrospective chart review of 128 pediatric HSCT recipients who received ondansetron for CINV prevention and had CYP2D6 genotyping for 20 alleles and duplication detection. The number of emetic episodes for each patient was collected from the start of chemotherapy through 7 days after HSCT. The average age of the cohort was 6.6 years (range: 0.2-16.7) and included three UMs, 72 normal metabolizers, 47 intermediate metabolizers, and six poor metabolizers. Because UMs are the population at risk for inefficacy, we describe the course of treatment for these three patients, as well as the factors influencing emesis: chemotherapy emetogenicity, diagnosis, and duration of ondansetron administration. The cases described support guidelines recommending non-CYP2D6 metabolized antiemetics (e.g., granisetron) when a patient is a known CYP2D6 UM, but pediatric studies with a larger sample of CYP2D6 UMs are needed to validate our findings.

In Vitro Inhibition of Renal OCT2 and MATE1 Secretion by Antiemetic Drugs

Abstract: The organic cation transporter 2 (OCT2) and multidrug and toxin extrusion protein 1 (MATE1) mediate the renal secretion of drugs. Recent studies suggest that ondansetron, a 5-HT3 antagonist drug used to prevent nausea and vomiting, can inhibit OCT2- and MATE1-mediated transport. The purpose of this study was to test the ability of five 5-HT3 antagonist drugs to inhibit the OCT2 and MATE1 transporters. The transport of the OCT2/MATE1 probe substrate ASP+ was assessed using two models: (1) HEK293 kidney cells overexpressing human OCT2 or MATE1, and (2) MDCK cells transfected with human OCT2 and MATE1. In HEK293 cells, the inhibition of ASP+ uptake by OCT2 listed in order of potency was palonosetron (IC50: 2.6 μM) > ondansetron > granisetron > tropisetron > dolasetron (IC50: 85.4 μM) and the inhibition of ASP+ uptake by MATE1 in order of potency was ondansetron (IC50: 0.1 μM) > palonosetron = tropisetron > granisetron > dolasetron (IC50: 27.4 μM). Ondansetron (0.5-20 μM) inhibited the basolateral-to-apical transcellular transport of ASP+ up to 64%. Higher concentrations (10 and 20 μM) of palonosetron, tropisetron, and dolasetron similarly reduced the transcellular transport of ASP+. In double-transfected OCT2-MATE1 MDCK cells, ondansetron at concentrations of 0.5 and 2.5 μM caused significant intracellular accumulation of ASP+. Taken together, these data suggest that 5-HT3 antagonist drugs may inhibit the renal secretion of cationic drugs by interfering with OCT2 and/or MATE1 function.

Analysis of pharmacogenomic factors for chemotherapy-induced nausea and vomiting in patients with breast cancer receiving doxorubicin and cyclophosphamide chemotherapy.

Abstract: Chemotherapy-induced nausea and vomiting (CINV) can lead to a significant deterioration in the quality of life of cancer patients receiving chemotherapy. This study aimed to determine whether ABCB1 2677G > T/A was associated with complete response (CR; defined as no vomiting and no rescue medication) in acute phase (CR0–24), as well as to explore the genetic factors affecting delayed phase (CR24–120) CINV in cancer patients treated with a standard triple antiemetic regimen that included aprepitant. This prospective single-center study included a total of 166 chemotherapy-naive patients with breast cancer who received a standard dose of doxorubicin and cyclophosphamide combination chemotherapy; granisetron, dexamethasone, and aprepitant were administered prior to chemotherapy. CR0–24 was compared between minor allele homozygous (TT, AA, and TA) and major allele homozygous plus heterozygous (GG, GA, and GT) groups of ABCB1 2677G > T/A. In addition, 14 genetic polymorphisms were genotyped and their associations with CRs were investigated. The proportion of patients who achieved CR0–24, which was the primary endpoint of this study, was 59% in the minor allele homozygous and 61% in the major allele homozygous plus heterozygous groups of ABCB1 2677G > T/A. Although this difference was not statistically significant, multivariate logistic regression analysis adjusted for potential risk factors showed that TACR1 1323TT (OR, 2.57; P = 0.014) was a significant determinant of CR24–120. No significant association was found between ABCB1 2677G > T/A and CR0–24. However, it was observed that the polymorphism of TACR1, which encodes the neurokinin 1 receptor, might be a potential genetic risk factor for the development of delayed phase CINV.

Granisetron, a selective 5-HT3 antagonist, reduces L-3,4-dihydroxyphenylalanine-induced abnormal involuntary movements in the 6-hydroxydopamine-lesioned rat.

Abstract: Administration of L-3,4-dihydroxyphenylalanine (L-DOPA) provides Parkinson's disease patients with effective symptomatic relief. However, long-term L-DOPA therapy is often marred by complications such as dyskinesia. We have previously demonstrated that serotonin type 3 (5-HT3) receptor blockade with the clinically available and highly selective antagonist ondansetron alleviates dyskinesia in the 6-hydroxydopamine (6-OHDA)-lesioned rat. Here, we sought to explore the antidyskinetic efficacy of granisetron, another clinically available 5-HT3 receptor antagonist. Rats were rendered hemi-parkinsonian by 6-OHDA injection in the medial forebrain bundle. Following induction of stable abnormal involuntary movements (AIMs), granisetron (0.0001, 0.001, 0.01, 0.1 and 1 mg/kg) or vehicle was acutely administered in combination with L-DOPA and the severity of AIMs, both duration and amplitude, was determined. We also assessed the effect of granisetron on L-DOPA antiparkinsonian action by performing the cylinder test. Adding granisetron (0.0001, 0.001, 0.01, 0.1 and 1 mg/kg) to L-DOPA resulted in a significant reduction of AIMs duration and amplitude, with certain parameters being reduced by as much as 38 and 45% (P < 0.05 and P < 0.001, respectively). The antidyskinetic effect of granisetron was not accompanied by a reduction of L-DOPA antiparkinsonian action. These results suggest that 5-HT3 blockade may reduce L-DOPA-induced dyskinesia without impairing the therapeutic efficacy of L-DOPA. However, a U-shaped dose-response curve obtained with certain parameters may limit the therapeutic potential of this strategy and require further investigation.

Ginger Relief Chemotherapy Induced Nausea and Vomiting (CINV) in Children: A Randomized Clinical Trial

Abstract: Background One of the major adverse effects of chemotherapy is chemotherapy induced nausea and vomiting (CINV) which can obviously reduce patients’ quality of life. Ginger (Zingiber officinale), an herbal supplement, has been used for centuries for gastrointestinal complaints. Although many surveys have been conducted to find the efficiency of ginger on CINV, its benefit has not been proven yet. We aimed to find ginger’s efficiency on pediatric patients throughout their chemotherapy cycles. Materials and Methods: This was a double-blinded, randomized, single institutional, placebo-controlled trial conducted at oncology ward in Aliasghar children’s hospital, Tehran, Iran. The study took place between October 2017 and October 2018. We included 49 chemotherapy cycles, 25 cycles for treatment group and 24 cycles for placebo groups. Intervention group took encapsulated ginger which contained 240mg of powdered ginger (Nausophar), and control group took placebo. All patients took the study medication four times per day (every 6h), starting on the first day of chemotherapy until 24h after completion of chemotherapy. Frequency and severity of nausea and vomiting were measured by Edmonton’s Symptom Assessment Scale (ESAS) from the first day of chemotherapy until 24h after completion of chemotherapy. Results: The median age of all participants was 13 (IQR=8-14 year-old). Fourteen patients were male (28.6%), and 35 patients were female (71.4%). There were no significant differences in distribution of patients’ characteristics in two groups. The frequency and severity of nausea and vomiting were significantly lower in ginger group (p <0.05). Conclusion According to our findings, ginger acts as an efficient antiemetic for pediatric patients. We recommend that ginger be prescribed as well as other antiemetics like Granisetron, with no loss of function.

Low-Dose Olanzapine Plus Granisetron and Dexamethasone for Carboplatin-Induced Nausea and Vomiting in Patients with Thoracic Malignancies: A Prospective Multicenter Phase II Trial.

Abstract: Background Olanzapine is an inexpensive and durable agent for the treatment of chemotherapy-induced nausea and vomiting and is also superior to neurokinin-1 receptor antagonists in the control of nausea. This study aimed to investigate the efficacy and safety of a low dose of 5 mg olanzapine plus granisetron and dexamethasone for treatment of carboplatin (CBDCA)-induced nausea and vomiting in patients with thoracic malignancies. Materials and methods We conducted a prospective, open-label, single-arm, multicenter, phase II trial in four centers in Japan. Registered patients were scheduled to receive area under the curve (AUC) ≥5 mg/mL per minute of CBDCA and had never received moderately to highly emetogenic chemotherapy. Patients received olanzapine 5 mg/day orally after supper for 4 days, in combination with granisetron and dexamethasone. Primary endpoint was complete response (CR; no emesis and no use of rescue medication) rate during the overall phase (0-120 hours). Results Between February 2018 and June 2020, 51 patients were enrolled, and 50 patients were evaluated. The CR rates in the overall (0-120 hours), acute (0-24 hours), and delayed phases (24-120 hours) were 94.0%, 100%, and 94.0%, respectively. No grade 3 or higher adverse effects of olanzapine were observed. Conclusions Prophylactic antiemetic therapy with a low dose of 5 mg olanzapine plus granisetron and dexamethasone showed durable efficacy with an acceptable safety profile. This three-drug combination appears to be a reasonable treatment approach in patients with thoracic malignancies receiving an AUC ≥5 mg/mL per minute of CBDCA-based regimen. Clinical trial identification number. UMIN000031267. Implications for practice The results of this phase II trial indicated that the prophylactic administration of low-dose olanzapine (5 mg) combined with granisetron and dexamethasone has promising activity with acceptable safety profile in patients with thoracic malignancy receiving high-dose carboplatin chemotherapy.

Evaluation of clinical outcomes and efficacy of palonosetron and granisetron in combination with dexamethasone in Egyptian patients receiving highly emetogenic chemotherapy

Abstract: 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 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 In (PALO) group, only 784% of patients showed acute vomiting, and 1176% showed acute nausea, whereas 4375% of patients showed acute vomiting and 8906% showed acute nausea in (GRA) group (P < 00001) For delayed CINV, 2353% of patients showed delayed vomiting, and 4706% showed delayed nausea in the (PALO) group, while 8281% of patients showed delayed emesis, and 9219% showed delayed nausea in (GRA) group (P < 00001) The study showed that PALO is a cost-effective choice when compared to GRA in CINV prevention as 4510% 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 9524% 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 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

Effectiveness of palonosetron versus granisetron in preventing chemotherapy-induced nausea and vomiting: a systematic review and meta-analysis

Abstract: Chemotherapy-induced nausea and vomiting (CINV) commonly occurs after chemotherapy, adversely affecting patients’ quality of life. Recently, studies have shown inconsistent antiemetic effects of two common 5-hydroxytryptamine 3 receptor antagonists, namely, palonosetron and granisetron. Therefore, we conducted a meta-analysis to evaluate the effectiveness of palonosetron versus granisetron in preventing CINV. Relevant studies were obtained from PubMed, Embase, and Cochrane databases. The primary outcome was the complete response (CR) rate. Secondary outcomes were headache and constipation events. In total, 12 randomized controlled trials and five retrospective studies were reviewed. Palonosetron was consistently statistically superior to granisetron in all phases in terms of the CR rate (acute phases: odds ratio [OR] = 1.28, 95% confidence interval [CI] = 1.06–1.54; delayed phases: OR = 1.38, 95% CI = 1.13–1.69; and overall phases: OR = 1.37, 95% CI = 1.17–1.60). Moreover, a non-significant difference was found between the two groups in terms of the headache event, but the occurrence of the constipation event was lower in the granisetron group than in the palonosetron group. Palonosetron showed a higher protective efficacy in all phases of CINV prevention, especially in delayed phases, and no relatively severe adverse effects were observed.

Effects of Palonosetron on Nausea and Vomiting Induced by Multiple-Day Chemotherapy: A Retrospective Study.

Abstract: Patients who undergo multiple-day chemotherapy sessions experience hard-to-treat nausea and vomiting. Currently, there is no effective standard treatment for this condition. This study compared the preventive effect of first-generation 5-hydroxytryptamine 3 receptor antagonists (5-HT3 RAs) and second-generation 5-HT3 RAs palonosetron in multiple-day chemotherapy-induced nausea and vomiting. The design of this study was a retrospective case-control study of patients who received a five-day cisplatin-based chemotherapy and were treated with aprepitant, dexamethasone, granisetron, and ramosetron or palonosetron. The patients were divided into two groups: patients given granisetron and ramosetron (the first-generation group), and those given palonosetron (palonosetron group). The percentage of patients with a complete response or total control was assessed. They were divided into three phases: 0-216 h (overall phase), 0-120 h (remedial phase), and 120-216 h (after phase). The remedial phase was further divided into 0-24 h (early phase) and 24-120 h (later phase). Moreover, the nutritional status of each patient was assessed by noting the patients' total calorie-intake per day and total parenteral nutrition. First-generation 5-HT3 RAs and palonosetron were used for treatment in 18 and 28 patients, respectively. The complete response rate and caloric oral intake of the later phase were higher in the palonosetron group than in the first-generation group. We conclude that palonosetron treatment was more effective than first-generation 5-HT3 RAs in controlling multiple-day chemotherapy-induced nausea and vomiting.

The effect of 1-mg versus 3-mg granisetron on shivering and nausea in cesarean section: a randomized, controlled, triple-blind, clinical trial.

Abstract: Introduction Intra- and postoperative nausea, vomiting and shivering are mentioned as the most common problem following spinal anesthesia. The aim of this study is to compare two different doses of granisetron to control the shivering, nausea, and vomiting caused by spinal anesthesia in women undergoing cesarean section (C/S). Method This study is a randomized, triple-blind clinical trial. The participants received 1-mg or 3-mg granisetron. Women who underwent elective C/S were enrolled. Inclusion criteria were ASA (American Society of Anesthesiologists) physical status grade I or II and age range of 18–40 years. Primary outcome was changes in the score of shivering, and nausea and vomiting. Secondary outcomes were Apgar score, mean arterial pressure, systolic blood pressure, diastolic blood pressure, temperature and heart rate. Results According to binary logistic regression, the incidence of shivering (6.9% vs. 1.5%; p-value = 0.049), and nausea and vomiting (19.2% vs. 9.2%; p-value = 0.024) was significantly higher in patients received 1-mg granisetron in comparison with 3-mg granisetron. Multinomial logistic regression showed that the occurrence of shivering, and nausea and vomiting were not associated with the dose of granisetron. There was no significant difference between the age and Apgar score of 1 (p = 0.908) and 5 (p = 0.843) minute(s) between the two groups. Conclusion This study showed that although 3-mg of granisetron reduces the incidence of intra- and postoperative shivering, nausea and vomiting after spinal anesthesia in comparison with 1-mg of granisetron, the difference was not statistically significant.

In vitro effects of tropisetron and granisetron against Echinococcus granulosus (s.s.) protoscoleces by involvement of calcineurin and calmodulin.

Abstract: Cystic echinococcosis (CE) is a disease caused by the larval stage of Echinococcus granulosus sensu lato (s.l.). The treatment of CE mainly relies on the use of benzimidazoles, which can commonly cause adverse side effects. Therefore, more efficient treatment options are needed. Drug repurposing is a useful approach for advancing drug development. We have evaluated the in vitro protoscolicidal effects of tropisetron and granisetron in E. granulosus sensu stricto (s.s.) and assessed the expression of the calcineurin (CaN) and calmodulin (CaM) genes, both of which have been linked to cellular signaling activities and thus are potentially promising targets for the development of drugs. Protoscoleces (PSC) of E. granulosus (s.s.) (genotype G1) obtained from sheep hepatic hydatid cysts were exposed to tropisetron and granisetron at concentrations of 50, 150 and 250 µM for various periods of time up to 10 days. Cyclosporine A (CsA) and albendazole sulfoxide were used for comparison. Changes in the morphology of PSC were investigated by light microscopy and scanning electron microscopy. Gene expression was assessed using real-time PCR at the mRNA level for E. granulosus calcineurin subunit A (Eg-CaN-A), calcineurin subunit B (Eg-CaN-B) and calmodulin (Eg-CaM) after a 24-h exposure at 50 and 250 µM, respectively. At 150 and 250 µM, tropisetron had the highest protoscolicidal effect, whereas CsA was most effective at 50 µM. Granisetron, however, was less effective than tropisetron at all three concentrations. Examination of morphological alterations revealed that the rate at which PSC were killed increased with increasing rate of PSC evagination, as observed in PSC exposed to tropisetron. Gene expression analysis revealed that tropisetron at 50 μM significantly upregulated Eg-CaN-B and Eg-CaM expression while at 250 μM it significantly downregulated both Eg-CaN-B and Eg-CaM expressions; in comparison, granisetron decreased the expression of all three genes at both concentrations. Tropisetron exhibited a higher efficacy than granisetron against E. granulosus (s.s.) PSC, which is probably due to the different mechanisms of action of the two drugs. The concentration-dependent effect of tropisetron on calcineurin gene expression might reflect its dual functions, which should stimulate future research into its mechanism of action and evaluation of its potential therapeutical effect in the treatment of CE.

Palonosetron versus Granisetron in Combination with Aprepitant and Dexamethasone for the Prevention of Chemotherapy-Induced Nausea and Vomiting after Moderately Emetogenic Chemotherapy: A Single-Institutional Retrospective Cohort Study.

Abstract: The triplet antiemetic regimen is administered to prevent chemotherapy-induced nausea and vomiting (CINV) after moderately emetogenic chemotherapy (MEC). However, the superiority of palonosetron over first-generation 5-hydroxytryptamine-3 receptor antagonists in triplet antiemetic therapy remains unclear. In this study, we evaluated the efficacy of palonosetron (PALO) and granisetron (GRA) in triplet antiemetic therapy for CINV. This study included 267 patients who received MEC at our hospital between April 2017 and September 2020. Patients were pretreated with antiemetic therapy comprising PALO or GRA and dexamethasone on day 1 and aprepitant on days 1-3. We evaluated the rate of complete response (CR) (i.e., no vomiting and no use of rescue medication) in the acute phase (0-24 h), delayed phase (24-120 h), and overall phase (0-120 h) after first-cycle chemotherapy. Furthermore, multivariate analysis was conducted to identify risk factors for non-CR. The rate of CR in the overall and delayed phases was significantly higher in the PALO group (91.9 and 91.9%, respectively) than in the GRA group (74.1 and 75.5%, respectively). In the acute phase, the incidence was not different between the GRA and PALO groups (96.5 and 99.2%, respectively). Multivariate analysis revealed that female sex and the use of GRA were risk factors for non-CR. Subgroup analysis revealed the superiority of PALO over GRA in female patients, but not in male patients. In conclusion, PALO was more effective than GRA in triplet antiemetic therapy in preventing CINV during MEC, especially for female patients.

A phase III study of transdermal granisetron versus oral ondansetron for women with gynecologic cancers receiving pelvic chemoradiation.

Abstract: To compare rates of complete response (no emesis, retching, or rescue antiemetics) in the late phase (days 4–7 post-chemotherapy) of cycle 1 between transdermal granisetron and oral ondansetron in cervical, endometrial, or vaginal cancer survivors undergoing chemoradiation at The University of Texas MD Anderson Cancer Center and LBJ Hospital in Houston, TX. In this non-blinded parallel design trial, eligible patients received a granisetron patch replaced every 7 days or 8 mg of ondansetron thrice daily continued for 72 h after chemotherapy completion. Data were collected on medication compliance, episodes of chemotherapy-induced nausea and vomiting (CINV), use of rescue antiemetics, and effects of CINV on quality of life. Seventy-five survivors receiving chemoradiation for cervical (n = 61), endometrial (n = 12), or vaginal (n = 2) cancer were electronically randomized to transdermal granisetron (n = 41) or oral ondansetron (n = 34). In the late phase of cycle 1, the rate of complete response was 49.8% (95% CI, 35.2–64.3%) for transdermal granisetron and 39.7% (95% CI, 24.4–56.1%) for oral ondansetron. The posterior probability that transdermal granisetron achieved a higher success rate in controlling late-onset CINV compared with oral ondansetron was 82%. During the acute phase (day 1 post-chemotherapy) of cycles 2 and 3, transdermal granisetron patients used more rescue antiemetics than oral ondansetron patients (p = 0.006 and p = 0.003, respectively). Otherwise, no between-group differences in CINV events were observed. Medication compliance and the effect of CINV on quality of life were similar between groups. Transdermal granisetron was 82% more like to control CINV than oral ondansetron in the late phase of cycle 1 and performed similarly to oral ondansetron in all other cycles. Transdermal granisetron should be considered an option as prophylactic antiemetic therapy for gynecologic cancer survivors undergoing chemoradiation.

Efficacy and Safety of 5-Hydroxytryptamine-3 Receptor Antagonists (5-HT3 RAs) for The Prevention of Chemotherapy-Induced Nausea and Vomiting in Cancer Patients: A Review

Abstract: Objective: This review provides an update review of the efficacy and safety of 5-hydroxytryptamine-3 receptor antagonists in the prevention of chemotherapy-induced nausea and vomiting (CINV) in cancer patients. Methods: The information was collected from electronic scientific search engines from PubMed, Science Direct, Scopus, and Google Scholar. The publication dates covered were from 2010 to 2020. The primary endpoint was the percentage of patients who achieved a complete response (CR), complete control (CC), no nausea, no emesis, or no rescue medication.The secondary endpoint was the percentage of patients who experience constipation related to 5-HT RA constipation, headache, diarrhea, or dizziness, as well as changes in heart rhythm. Results: Fourteen articles were identified. Palonosetron has the same effectiveness as granisetron as but more effective than ondansetron in the delayed phase and overall. Adverse effects that often occur due to the use of palonosetron, granisetron, and ondansetron are constipation and headache. Some of the articles also mentioned that palonosetron does not cause changes in heart rhythm but granisetron and ondansetron do cause changes in the electrocardiogram (ECG) at certain doses. Conclusion: Palonosetron has the same effectiveness as granisetron, and more effective than ondansetron in delayed, and overall phases. The use of palonosetron, granisetron, and ondansetron cause constipation and headaches at all doses, palonosetron does not cause ECG abnormalities whereas granisetron and ondansetron cause ECG changes. Keywords: palonosetron, ondansetron, granisetron, 5-HT3 RAs, cancer, nausea, vomiting, CINV.

Comparison of effectiveness among ondansetron, palonosetronand granisetron in preventing postoperative nauseaand vomitingfollowing laparoscopic cholecystectomy

Abstract: Postoperative nausea and vomiting (PONV) has been variously described as the “big little problem” the “nal therapeutic challenge” for anaesthesiology. The commonest cause of morbidity after anaesthesia and surgery are pain and postoperative nausea vomiting 1. To compare the incidences of PONV following laparoscopic cholecyetectomy in different groups of patients receiving ondansetron, palonosetron and Granisetron. 2. To identify the better strategy for prevention of PONV. This is a prospective randomized double blinded clinical study. Both patient and observer were blinded to the group allocation. Allocations to three groups were strictly condential and concealed. One and half year (18 months). Patients undergoing elective laparoscopic cholecystectomy under General Anaesthesia at General Surgery operation theatres of Bankura Sammilani Medical College and Hospital, Bankura The effects of palonosetron, granisetron and ondansetron in preventing PONV (postoperative nausea vomiting) were compared in patients undergoing laparoscopic cholecystectomy and it was found that palonosetron was best and granisetron better in comparison with ondansetron in preventing postoperative nausea and vomiting. Palonosetron provides more effective prophylaxis of early PON (postoperative nausea), late PON (postoperative nausea), and late POV (postoperative vomiting) compared with granisetron and ondansetron. Palonosetron could provide effective prophylactic antiemetic control to prevent PONVafter laparoscopic cholecystectomy surgery under general anesthesia.

The Potential of Granisetron in Preventing Spinal Anesthesia Induced Hypotension on Non-Obstetric Procedure

Abstract: Hypotension is a common adverse effect seen after spinal anesthesia. In recent literature the use of 5-HT3 receptor antagonists has been proposed to prevent spinal anesthesia induced hypotension (SAIH). We present the use of granisetron in several cases as prevention strategy for SAIH in our center. All 10 eligible subjects received 3 mg granisetron diluted in 10 cc normal saline 5 minutes prior to spinal anesthesia, on patients who undergone non-obstetric procedure. Eight patients showed good response without evidence of hypotension, while the other two patients had hypotension managed well with ephedrine. As many as 9 patients had no bradycardia, while shivering was noted in 3 patients. All patients didn’t suffer from nausea/vomiting, due to its effectiveness of granisetron acts as antiemetic agents. Granisetron, has great affinity specifically for 5-HT3 receptor. It blocked the Bezold Jarisch Reflex (BJR) activation that will lead to hypotension and bradycardia. In a nutshell, granisetron has shown its potential as a prevention strategy for hypotension after spinal anesthesia in the majority of our cases above.

Comparative study of ondansetron, granisetron and granisetron with dexamethasone for prevention of postoperative nausea and vomiting (PONV) in patients undergoing laparoscopic cholecystectomy

Abstract: Introduction: An assortment of drugs are being used for managing postoperative nausea and vomiting after laparoscopic surgeries. Combination anti-emetic therapy using 5HT3 antagonists with dexamethasone as an adjunct is being tried owing to its improved efficacy for prevention or treatment of PONV. Methodology: This was a prospective, randomized, double blind, comparative study conducted on 150 patients aged between 18 to 65 years scheduled for laparoscopic cholecystectomy. Group O received 0.1 mg/Kg IV ondansetron upto a maximum dose of 8 mg, Group G received 0.04 mg/kg IV granisetron upto a maximum dose of 3mg, Group G+D will receive 0.04mg/kg IV granisetron and 8mg Dexamethasone. Results: The three groups were comparable in terms of demographic data. Our results showed that the patients who had received combination of granisetron and Dexamethasone showed a better complete response as compared to patients who received ondansetron and patients who received granisetron alone. This was seen in all three time periods of 2-6 hours, 6-12 hours and 12-24 hours postoperatively with a p value less than 0.001 making it statistically significant. Conclusion: Combination therapy with granisetron and dexamethasone IV used as prophylactic antiemetic is better than granisetron or ondansetron given IV alone. IV granisetron and dexamethasone combination has fewer side effects compared to ondansetron or granisetron. Need for the rescue antiemetic was least in the patients receiving granisetron and dexamethasone combination as compared to in patient receiving ondansetron and granisetron alone. Keywords: Nausea, Anti-emetics, Vomiting, Dexamethasone, Granisetron, Serotonin antagonists.

Effects of Granisetron on Spinal Anesthesia-induced Hypotension

Abstract: Objective: It was aimed to evaluate the effect of intravenous (IV) granisetron used for nausea and vomiting prophylaxis on hypotension and bradycardia caused by spinal anesthesia. Methods: 120 ASA 1-2 patients undergoing elective surgery under spinal anesthesia were randomly divided into Group G (Ganisetron; n=60) and Group P (Placebo; n=60) groups. Five minutes before spinal anesthesia, Group G received 1 mg intravenous granisetron diluted in 10 mL of isotonic sodium chloride solution and Group P received 10 mL of isotonic sodium chloride solution. Spinal anesthesia with hyperbaric bupivacaine 0.5%, 15 mg at the level of L4-5 was applied for both groups. Hemodynamic data, sensory and motor block parameters were recorded before and after spinal anaesthesia every 5 minutes during 20 minutes of surgery. Results: There was no difference in the demographic data of both groups. Although hemodynamic data showed a decrease in both groups according to initial values, blood pressure measurements in group G were significantly higher than the first measure values. There was no significant difference in heart rate values between the groups. Conclusion: Intravenous granisetron reduces hypotension after spinal anesthesia, but it has no significant effect on heart rate.

Successful Treatment of Chemotherapy-induced Symptoms with Granisetron as Alternative for Ondansetron Allergy

Abstract: Corresponding Author/Sorumlu Yazar: Öner Özdemir, E-mail: ozdemir_oner@hotmail.com Received Date/Geliş Tarihi: 01.03.2021 Accepted Date/Kabul Tarihi: 25.06.2021 Öner Özdemir1, Olena Erkun2 1Sakarya University Faculty of Medicine; Sakarya Training and Research Hospital, Department of Pediatrics, Division of Allergy and Immunology, Sakarya, Turkey 2Sakarya Training and Research Hospital, Clinic of Pediatrics, Sakarya, Turkey