Dose Of Granisetron Research Articles

Transdermal Granisetron

Granisetron is a highly selective serotonin 5-HT(3) receptor antagonist for the prevention of chemotherapy-induced nausea and vomiting. The transdermal granisetron system delivers continuous granisetron (3.1 mg/day) into the systemic circulation (via passive diffusion) for up to 7 days. In a large phase III trial in cancer patients receiving multi-day (3-5 days) moderately or highly emetogenic chemotherapy, transdermal granisetron applied 24-48 hours prior to chemotherapy and remaining in place for 7 days was noninferior to oral granisetron 2 mg once daily administered for 3-5 days 1 hour prior to chemotherapy. Efficacy was assessed according to the proportion of patients achieving complete response (no vomiting and/or retching, no more than mild nausea, no rescue medication) from the first day, until 24 hours after the start of the last day, of administration of the chemotherapy regimen. In a phase II trial in patients with cancer receiving single-day, moderately-emetogenic chemotherapy, transdermal granisetron applied at least 24 hours prior to chemotherapy and removed after 5 days was as effective as a single oral dose of granisetron 2 mg in achieving total control (no nausea, no vomiting/retching, no use of rescue medication and no study withdrawal) during the delayed (24-120 hours; primary endpoint) period after chemotherapy. Transdermal granisetron was generally well tolerated in clinical trials, with few adverse events being treatment related.

Seizure susceptibility alteration through 5-HT 3 receptor: Modulation by nitric oxide

There is some evidence that epileptic seizures could be induced or increased by 5-hydroxytryptamine (5-HT) attenuation, while augmentation of serotonin functions within the brain (e.g. by SSRIs) has been reported to be anticonvulsant. This study was performed to determine the effect of selective 5-HT 3 channel/receptor antagonist granisetron and agonist SR57227 hydrochloride on the pentylenetetrazole (PTZ)-induced seizure threshold in mice. The possible interaction of this effect with nitrergic system was also examined using the nitric oxide (NO) synthase inhibitor N G-nitro- l-arginine methyl ester ( l-NAME) and the NO precursor l-arginine. SR57227 (10 mg/kg, i.p.) significantly increased the seizure threshold compared to control group, while high dose granisetron (10 mg/kg, i.p.) proved proconvulsant. Co-administration of sub-effective doses of the 5-HT 3 agonist with l-NAME (5 and 60 mg/kg, i.p., respectively) exerted a significant anticonvulsive effect, while sub-effective doses of granisetron (3 mg/kg) was observed to have a proconvulsive action with the addition of l-arginine (75 mg/kg, i.p.). Our data demonstrate that enhancement of 5-HT 3 receptor function results in as anticonvulsant effect in the PTZ-induced seizure model, and that selective antagonism at the 5-HT 3 receptor yields proconvulsive effects. Furthermore, the NO system may play a role in 5-HT 3 receptor function.

Double-blind comparison of granisetron, promethazine, or a combination of both for the prevention of postoperative nausea and vomiting in females undergoing outpatient laparoscopies

Postoperative nausea and vomiting (PONV) and postdischarge nausea and vomiting (PDNV) are common problems after surgery. Prophylactic combination antiemetic therapy is recommended for patients at high risk for developing PONV and PDNV. Granisetron, a serotonin antagonist, is an effective antiemetic that is devoid of sedative side effect. Although promethazine is effective, commonly used doses are associated with sedation. This study investigates the combination of low doses of granisetron and promethazine for the prevention of PONV. Women undergoing ambulatory gynecological laparoscopy were enrolled. A standard general anesthetic regimen was prescribed. Fifteen minutes before the expected end of surgery, the patients were randomly assigned to receive granisetron 0.1 mg iv, promethazine 6.25 mg iv, or a combination of the two drugs. Prophylaxis with oral promethazine 12.5 mg, granisetron 1 mg, or both was started in the respective groups 12 hr after the end of surgery and continued every 12 hr until postoperative day 3 (a total of five oral doses). The following outcomes were recorded: total response rate (defined as no vomiting, no more than mild nausea, and no use of rescue antiemetic); incidence of nausea, vomiting, and use of rescue antiemetics; severity of nausea; patient activity level; and patient satisfaction with PONV management. Patients in the combination group had a higher total response rate at 6, 24, 48, and 72 hr after surgery compared with those who received promethazine alone (at 24 hr, Combination 69.6%, Promethazine 36.2%, Granisetron 53.3%; P = 0.0079). The maximum nausea scores were also lower in the combination group at 6, 24, 48, and 72 hr (Combination 1.7 +/- 2.2, Promethazine 4.0 +/- 3.6, Granisetron 3.1 +/- 3.2 at 24 hr; P < 0.05). There was no difference in the sedation scores, incidence of drowsiness, patient activity level, and satisfaction with PONV management. Low-dose granisetron and promethazine combination was more effective in reducing PONV and PDNV than promethazine monotherapy. The combination also reduced the severity of nausea.

Chemotherapy-induced nausea and vomiting: ESMO Clinical Recommendations for prophylaxis

Chemotherapy-induced nausea and vomiting: ESMO Clinical Recommendations for prophylaxis

Changes of Hypertonic Saline–Induced Masseter Muscle Pain Characteristics, by an Infusion of the Serotonin Receptor Type 3 Antagonist Granisetron

This study aimed to investigate whether granisetron reduces masseter muscle pain and allodynia induced by hypertonic saline. Fifteen healthy women and 15 age-matched healthy men participated in this randomized, placebo-controlled, double-blinded study. They first received bilateral injections of hypertonic saline into the masseter muscles (internal control). The evoked pain intensity and the pressure-pain threshold (PPT) were recorded during 30 minutes. Granisetron was then injected on one side and placebo (normal saline) on the contralateral side. Two minutes thereafter, the hypertonic saline injections were repeated. Pain and PPT were again recorded. The first injection of hypertonic saline induced pain of similar intensity, duration, and pain area on both sides, but with larger pain area in the women (P = .017). The PPT did not change significantly. The second injection of hypertonic saline induced considerably less pain (62.5%), of shorter duration (44.1%), and of smaller area (77.4%) on the side pretreated with granisetron (P = .005). The PPT was increased on the granisetron side in the men (P = .002). The results of this study show that local injection of a single dose of granisetron attenuates masseter muscle pain induced by hypertonic saline. This article presents the changes of hypertonic saline-induced masseter muscle pain characteristics by infusion of granisetron. It appears that the pain-inducing effect in this experimental pain model is partly due to activation of 5-HT3-receptors. Hence, the results indicate that granisetron might offer a new treatment approach for localized myofascial pain.

Palonosetron (PALO) versus granisetron (GRAN), both combined with dexamethasone (DEX) in preventing chemotherapy-induced nausea and vomiting (CINV) associated with cisplatin- or anthracycline plus cyclophosphamide-based regimens: Results of a phase III trial in Japanese patients

20749 Background: PALO is a pharmacologically distinct 5-HT3 receptor antagonist with unique molecular interactions with the 5-HT3 receptor compared with GRAN. Methods: This multicenter, randomized, double-blind, stratified, phase III trial assessed the efficacy/safety of a single IV dose of PALO 0.75 mg vs IV GRAN 40 μg/kg (∼3mg) administered 30 min prior to cisplatin ≥50 mg/m2 (CDDP) or anthracycline + cyclophosphamide (AC/EC). Selection of the PALO dose was based on two Phase II dose-ranging trials and the dose of GRAN is the approved dose in Japan. DEX 16 mg IV was administered before chemotherapy (CT) on day 1, and 8 mg IV (CDDP) or 4 mg orally (AC/EC) on days 2–3. Stratification factors were gender, age and CT. The study was designed to demonstrate non-inferiority on day 1 and superiority on days 2–5 of PALO vs GRAN, combined with DEX. The primary endpoint was the complete response rate (CR = no emesis, no rescue medication). Adverse events (AEs) were assessed according to NCI-Common Toxicity Criteria. Results: A total of 1,114 pts (58% women; mean age 58) were evaluated; 57% received CDDP, 43% AC/EC. The CR rate for PALO was equivalent to GRAN in acute phase and significantly greater than GRAN in delayed phase (Table). Overall CR (0–120 h) was also greater for PALO (51.5%) vs GRAN (40.4%). Time to treatment failure was significantly longer for PALO with separation in the curves at 16 hrs after CT on day 1 (Hazard Ratio: 1.30, 95% CI: 1.106-1.526). The incidence, pattern or intensity of AEs did not differ between PALO and GRAN. Conclusions: A single dose of PALO resulted in a comparable prevention of CINV to GRAN at the end of day 1, and demonstrated superior long-lasting CINV prevention in the delayed phase in patients receiving highly emetogenic CT. CR rates Period CR (%) PALO vs GRAN p-value PALO 0.75 mg (N=555) GRAN 40 μg/kg (N=559) PALO minus GRAN Acute (0–24 hrs) § 77.5 75.2 2.29 [-2.70, 7.27]† Not done Delayed (24–120 hrs) 56.8 44.5 12.3 < 0.001* § : mean of minimum squared values adjusted with stratified factors (CT, gender and age) † : lower limit >-10% indicates non-inferiority of PALO against GRAN * : Cochran-Mantel-Haenszel test stratified with CT, gender and age No significant financial relationships to disclose.

Adapting ASCO and NCCN guidelines in institutional antiemetic guidelines benefits patients receiving chemotherapy

20508 Background: The primary endpoint of the present study was to determine the impact of adapting ASCO and NCCN guidelines for antiemetics (AE) in our institutional antiemetic guidelines. Methods: The emetic risk of chemotherapy regimens was calculated using the Hesketh classification. AE guidelines were adapted and approved by a multidisciplinary team and the Drugs and Therapeutics Committee. We have compared 2 groups: patients receiving the new adapted institutional AE with those receiving non-established antiemetic treatment. Patients recorded episodes of nausea and vomiting in a diary the day of chemotherapy administration and the following 4 days. Patients also recorded rescue antiemetic medications. Patients completed the Functional Living Index- Emesis (FLIE) questionnaire at baseline and on day 6. The FLIE total scores >108 was defined as ‘no impact on daily functional‘. The main updates of the new adapted AE guidelines included the addition of aprepitant in cisplatin-based schedules, granisetron dose of 1 mg instead of 3 mg or ondansetron and dexametasone dose based on the emetic potential of each chemotherapy protocol. A delayed antiemetic protocol was recommended for each chemotherapy protocol. Results: From February 2007 to August 2007 225 consecutive patients were prospectively included in the study, 119 patients before the implementation of new AE guidelines and 106 patients after. Patients receiving the new AE guidelines achieved a trend for more complete response (defined as no nausea, no vomiting and no AE rescue): 52% vs 66.7% (p=0.065). In the cisplatin-based group, patients receiving the new AE guidelines obtained a statistically significant benefit with the new protocol (47.6% vs 73.3 % [p=0.017]), and less patients presented a reduction in the FLIE score below 108 (42 % vs 24% [p=0.142]). Conclusions: Implementation of revised AE guidelines provides a better control of CINV with higher complete response rate, especially in patients receiving cisplatin-based schedules. No significant financial relationships to disclose.

Granisetron Versus Ondansetron Treatment for Breakthrough Postoperative Nausea and Vomiting After Prophylactic Ondansetron Failure: A Pilot Study

Patients with an increased risk of postoperative nausea and vomiting (PONV) are frequently given prophylactic doses of a selective 5-hydroxytryptamine-3 antagonist (5HT3). In chemotherapy patients, it has been demonstrated that after unsuccessful treatment with one 5HT3 administering a different 5HT3 alleviated symptoms. We hypothesized that we could define a benefit of a 5HT3, cross-over in a pilot study of PONV. Two-hundred-fifty female patients received prophylactic ondansetron 4 mg at the end of a surgical procedure requiring general anesthesia and were then followed postoperatively for 4 h. Eighty-eight women developed PONV and were randomly assigned to receive a repeat dose of ondansetron 4 mg (n = 30), granisetron 1 mg (n = 30), or granisetron 0.1 mg (n = 28) and then followed for 24 h. Patients receiving the repeat dose of ondansetron showed a complete response of 57%. Those receiving 1 or 0.1 mg doses of granisetron had rates of 60% and 68%, respectively. This difference was not statistically significant (P = 0.773). Unlike patients with chemotherapy-induced nausea and vomiting, perioperative patients who failed ondansetron prophylaxis did not have a significant response to cross-over dosing with granisetron.

A double-blind, crossover, randomized dose-comparison trial of granisetron for the prevention of acute and delayed nausea and emesis in children receiving moderately emetogenic carboplatin-based chemotherapy

Granisetron is a safe and effective prophylaxis for nausea and vomiting associated with moderate to highly emetogenic chemotherapy. Few trials have been conducted to determine the optimal effective dose of granisetron in children with cancer. The objective of this report was to compare two doses of granisetron in patients with optic pathway tumors receiving moderately emetogenic doses of carboplatin. In this double-blind, crossover, randomized study, antiemetic efficacy and tolerability of two dose levels (10 and 40 microg/kg) of granisetron in the prevention of acute and delayed nausea/emesis were compared in children and young adults. A total of 18 patients (13 boys) aged 1-23 years (median 7.7 years) treated with a moderately emetogenic dose of carboplatin were randomly assigned to receive either 10 or 40 microg/kg of slow granisetron intravenous (i.v.) infusions at alternating cycles of chemotherapy in a blinded fashion until the end of the study period or until their chemotherapy regimen ended. In this way, the patients acted as their own controls. Patients in the granisetron 10 and 40 microg/kg groups received 104 and 121 cycles of chemotherapy, respectively. There was no significant difference in antiemetic efficacy in terms of nausea and emesis between the dose groups in the first 5 days of chemotherapy. The treatment was well tolerated. We conclude that granisetron 10 and 40 microg/kg have comparable efficacy in controlling carboplatin-induced acute and delayed nausea/emesis and is well tolerated in children and young adults.

A meta-analysis comparing the efficacy of four 5-HT3-receptor antagonists for acute chemotherapy-induced emesis

Comparing antiemetic efficacy of different 5-HT(3)-receptor antagonists (5-HT(3)RAs) is difficult due to inter-study variability. Therefore, a meta-analysis was performed to comparatively evaluate dolasetron, granisetron, ondansetron and tropisetron for acute chemotherapy-induced nausea and vomiting (CINV). Comparisons between 5-HT(3)RAs were based on 44 randomized studies (including 12,343 patients) identified by MEDLINE, CANCERLIT or EMBASE searches and subcategorized by chemotherapy type (cisplatin- or non-cisplatin-based). When all studies were combined, granisetron was equivalent to ondansetron (n = 27), and showed an advantage vs tropisetron (p = 0.018; n = 12). Ondansetron vs tropisetron (n = 11) and ondansetron vs dolasetron (n = 3) revealed equivalence in each comparison. An advantage for 3 mg granisetron vs 8 mg ondansetron was found in non-cisplatin-based studies (p = 0.015; n = 6). Overall equivalence was seen between ondansetron, 24 or 32 mg, and granisetron, 2 or 3 mg, for all studies (n = 13). There was a possible advantage for higher (24 or 32 mg) vs lower (8 mg) ondansetron dose regimens with cisplatin-based trials (n = 6). No differences were seen between 3 and 1 mg granisetron doses (n = 6). Efficacy of 5-HT(3)RAs for preventing CINV following cisplatin- and non-cisplatin-based chemotherapy is comparable, with the exception of granisetron vs tropisetron. Some differences were noted in dosing subanalyses.

Comparasion of granisetron and metoclopramide for prevention of nausea and vomiting following total cystectomy and ileal conduit

The objective of this study was to examine the use of granisetron in actual clinical practice and to compare effect of dose of 1 mg granisetron after total cystectomy plus ileal conduit with group of patients which received metoclopramide. Granisetron established total contol of PONV in 93,33% patients. Granisetron is 40% more effective in PONV control than metoclopramide. Only minimal nausea epizodes were observed in early postoperative period in patients who had received low dose of granisetron (1 mg i.v.).

A Meta-analysis of the Efficacy of Granisetron 0.1 mg for Postoperative Nausea and Vomiting (PONV)

This meta-analysis of published randomized clinical trials (RCTs) compared the efficacy of granisetron 0.1 mg versus ≥ 1.0 mg for prevention of postoperative nausea and vomiting (PONV). Efficacy data (proportion of patients without PONV or requiring rescue medication) were extracted and stratified by the postoperative period (i.e., early, late, and overall). Meta-analytic techniques were used to integrate findings and estimate pooled efficacy. Ten RCTs met inclusion criteria, but only 2 directly compared granisetron 0.1 mg versus 1.0 mg, which was insufficient for meta-analysis, necessitating indirect comparisons between pairwise sets of granisetron 0.1 mg and granisetron 1.0 mg with common comparators: placebo and granisetron dose levels > 1.0 mg. Granisetron 0.1 mg appears to be at least as effective as granisetron 1.0 mg during the early and overall postoperative periods. There were insufficient data for meta-analysis of any outcomes during the late postoperative period. CONFLICT OF INTEREST DISCLOSURE The author received in the past financial support (Independent Investigator Grant) from Roche Pharmaceuticals (maker of Kytril-granisetron).

흰쥐를 이용한 Granisetron함유 경비 투여제제의 평가 및 그 적용

Granisetron is a selective 5-HT3 receptor antagonist that is used therapeutically for the prevention of vomiting and nausea associated with emetogenic cancer chemotherapy. Although this drug is commercially available for intravenous and oral dosage, there is a need for intranasal delivery formulations in specific patient populations in which the use of these dosage forms may be unfeasible and/or inconvenient. A rapid and specific high-performance liquid chromatography method with mass spectrometric detection(LC-MS) was developed and validated for the analysis of granisetron in plasma after nasal administration in rats. This method has been validated for concentrations ranging from 5 to 1000 ng/ml with simple treatment. This technique has high level reproducibility, accuracy, and sensitivity. The method described was found to be suitable for the analysis of all samples collected during preclinical pharmacokinetic investigations of granisetron in rats after nasal administration. This study was aimed to investigate the feasibility of nasal delivery of granisetron for the elimination of vomiting. The effects of osmolarity, dosage volume at the same dose and applied dose on the nasal absorption of granisetron in rats were observed. No significant difference in the effect of osmolarity and dosage volume at the same dose was observed. As the applied dose of granisetron in nasal formulation increased, the absorption increased linearly. Based on these results it appears that only the applied dose(drug mass) determines the nasal absorption of granisetron. The bioavailability of granisetron on nasal administration of 4 mg/kg appeared to be comparable to that of intravenous administration of the same dose. These results suggest that granisetron can be efficiently delivered nasally and the development of nasal formulation will be feasible.

Efficacy of Granisetron for the Treatment of Postoperative Nausea and Vomiting in Women Undergoing Breast Surgery

Women undergoing general anaesthesia for breast surgery are especially at risk of experiencing postoperative nausea and vomiting (PONV). This study was undertaken to assess the efficacy of granisetron, a selective serotonin type 3 receptor antagonist, for the treatment of postoperative nausea and vomiting after breast surgery. This was a prospective, randomised, double-blind, placebo-controlled study carried out in a university-affiliated teaching hospital. The study included women who experienced nausea lasting >10 minutes and/or vomiting during the first 3 hours after recovery from anaesthesia for breast surgery. Patients intravenously received either placebo or granisetron at four different doses (10 microg/kg, 20 microg/kg, 40 microg/kg and 80 microg/kg). Patients were observed for 24 hours after administration of the study drug. A total of 100 women were enrolled in this study. Complete control of established PONV, defined as no emetic symptoms and no need for a rescue antiemetic, was observed in 50% of women receiving granisetron 10 microg/kg (p = 0.5 vs placebo), 85% of women receiving granisetron 20 microg/kg (p = 0.009 vs placebo), 90% of women receiving granisetron 40 microg/kg (p = 0.003 vs placebo), and 85% of women receiving granisetron 80 microg/kg (p = 0.009 vs placebo), compared with 45% of placebo recipients. The efficacies of granisetron 20 microg/kg, granisetron 40 microg/kg, and granisetron 80 microg/kg for the treatment of established PONV were superior to that of granisetron 10 microg/kg (all p < 0.05). No serious adverse effects were observed in any group. The minimum effective dose of granisetron for the treatment of PONV in women undergoing breast surgery was 20 microg/kg. Increasing the granisetron dose to 80 microg/kg provided no further benefit.

Contribution to the treatment of nausea and emesis induced by chemotherapy in children and adolescents with osteosarcoma

Chemotherapy-induced emesis is a limiting factor in treating children with malignancies. Intensive chemotherapy regimens along with emetogenic drug administration have increased the frequency and severity of emesis and nausea. Our study was designed to consider the importance of this problem and the need for improvement in emesis treatment for patients receiving chemotherapy. Our objective was to compare the efficacy and safety of the antiemetic drug granisetron and a regimen of metoclopramide plus dimenhydrinate. Open, prospective and randomized study at Instituto de Oncologia Pediátrica, Department of Pediatrics, Universidade Federal de São Paulo. From February to August 1994, 26 patients (mean age: 14 years) with osteosarcoma received 80 chemotherapy cycles of iphosphamide (2,500 mg/m2) plus epirubicin (75 mg/m2) or carboplatin (600 mg/m2), or epirubicin (75 mg/m2) plus carboplatin (600 mg/m2). Eighty chemotherapy treatments were analyzed regarding nausea and vomiting control. Patients were randomized to receive either a single dose of granisetron (50 microg/kg) or metoclopramide (2 mg/kg) plus dimenhydrinate (5 mg/kg infused over eight hours). Emesis and nausea were monitored for 24 hours by means of the modified Morrow Assessment of Nausea and Emesis. Statistical analysis utilized the chi-squared, Student t and Mann-Whitney tests, plus data exploration techniques. 62.5% of the patients undergoing chemotherapy responded completely to granisetron, whereas 10% responded to metoclopramide plus dimenhydrinate (p < 0.0001). No severe adverse reactions were found in either of the treatments given. In children and adolescents with osteosarcoma, granisetron was safe and more efficient than metoclopramide plus dimenhydrinate for controlling chemotherapy-induced emesis and nausea.

A randomized, double-blind, dose-ranging, pilot study of intravenous granisetron in the prevention of postoperative nausea and vomiting in patients undergoing abdominal hysterectomy 1

Postoperative nausea and vomiting (PONV) is a frequent and unpleasant experience that may increase postoperative complications and costs. For surgical procedures with a high risk of PONV, prevention is preferable to treatment. In this study, the authors explore the dose-response relationship between granisetron administered just prior to the end of surgery and post-operative nausea and vomiting in patients undergoing abdominal hysterectomy. This was a randomized, double-blind, placebo-controlled, pilot study of post-operative nausea and vomiting prevention. Patients undergoing elective open abdominal hysterectomy requiring general anaesthesia received a single dose of granisetron 0.1, 0.2 or 0.3 mg or placebo administered approximately 15 min prior to the end of surgery. The primary efficacy end-point was the proportion of patients with no vomiting in the 0--6 h interval following medication administration. No inferential statistics were planned. The proportion of patients with no vomiting episode in the 0--6 h interval after administration of study medication was higher in each granisetron treatment group (>90%) than in the placebo group (77%). Proportions of patients with no vomiting episodes in the 0--24 h interval were similar across treatment groups. Results of analyses of proportions of patients with no moderate or severe nausea episodes, proportions of those requiring rescue medication and times to first use of rescue medication suggested a treatment effect of granisetron relative to placebo in both the 0--6 and 0--24 h intervals. Similar proportions of patients in each treatment group reported at least one adverse event. Granisetron at doses of 0.1, 0.2 and 0.3 mg administered just prior to the end of surgery suggested a trend of improved efficacy compared to placebo in preventing postoperative nausea and vomiting in the first 6 h after abdominal hysterectomy. This pilot study did not identify a dose-response relationship.

Retrospective Cohort Study of Granisetron Administration for PONV Prophylaxis and Treatment

Postoperative nausea and vomiting (PONV) frequently complicates surgical recovery and is considered to be one of the least desirable surgical side effects. Granisetron (Kytril) 1 mg intravenously (IV) was approved by the FDA for the prevention and treatment of PONV in August 2002. Objective This cohort study evaluated outcomes and utilization associated with granisetron use for PONV prevention and treatment. Methods This was a retrospective cohort study of 400 patient records from 10 US hospitals. Patients included were those greater than or equal to 18 years of age having elective surgery under general anesthesia with granisetron administered IV for prevention or treatment of PONV. Excluded were those with concurrent radiation or chemotherapy, or those observed less than 2 hours in the post anesthesia care unit. Results Mean age was 50 y ± 17 with 272 females (68%). The majority was at moderate-high (n = 230; 58%) or mild-moderate risk of PONV (n = 155; 39%). Granisetron was administered predominantly perioperatively and at 0.1 mg dose (n = 382; 96%) from prefilled syringes extemporaneously prepared from 4 mg/4 mL vials. Total control (absence of nausea and vomiting) was experienced in 330 patients (83%), with 16 (4%) having a vomiting episode. In 167 patients at lower risk of PONV, symptoms were prevented in 148 (less than 90%). Regression analysis indicates that, in addition to absence of key risk factors, combination antiemetic prophylaxis was highly associated with optimal outcome. Granisetron dose did not impact outcome. Conclusion The majority of granisetron use for PONV was prophylactic, administered perioperatively at a 0.1 mg dose. Most patients experienced excellent control, even in the highest risk groups, particularly when granisetron was administered in combination with dexamethasone or metoclopramide.

RETRACTED: Effects of granisetron in the treatment of nausea and vomiting after laparoscopic cholecystectomy: A dose-ranging study

Patients undergoing general anesthesia for laparoscopic cholecystectomy are at high risk for postoperative emetic symptoms (nausea, vomiting, and retching). Antihistamines, butyrophenones, dopamine receptor antagonists, and selective serotonin receptor antagonists (SSRAs) have been investigated for the prevention and treatment of emetic symptoms. However, these drugs are associated with undesirable adverse effects (AEs), such as excessive sedation, hypotension, dry mouth, dysphoria, hallucinations, and extrapyramidal signs. Granisetron hydrochloride is a newer SSRA developed for the prevention and treatment of cytotoxic drug-induced emetic symptoms, but its effects in postoperative laparoscopic cholecystectomy have not been studied. The aims of this study were to assess the efficacy and tolerability of 4 doses of granisetron, and to determine the minimum effective dose, for the control of established emetic symptoms in patients undergoing general anesthesia for laparoscopic cholecystectomy. This prospective, randomized, double-blind, placebo-controlled, dose-ranging study was conducted in the Departments of Anesthesiology and Surgery, Toride Kyodo General Hospital (Toride, Japan). Male and female patients aged 23 to 68 years with American Society of Anesthesiologists physical status I (no organic, physiologic, biochemical, or psychiatric disturbance) who were experiencing nausea lasting >10 minutes or retching or vomiting within 3 hours after recovery from general anesthesia for laparoscopic cholecystectomy were enrolled. Patients were randomized to receive a single IV dose of placebo or granisetron at 1 of 4 doses (10, 20, 40, or 80 microg/kg). Patients were monitored for 24 hours after study drug administration. One hundred patients (60 women, 40 men; mean [SD] age, 48 [10] years [range, 23-68 years]; mean [SD] height, 158 [7] cm [range, 145-177 cm]; mean [SD] body weight, 56 [8] kg [range, 43-75 kg]) were enrolled. No significant differences in baseline demographic or clinical characteristics were found between the study groups. The proportions of patients who were free of emetic symptoms were significantly higher with granisetron 20, 40, and 80 microg/kg than with placebo (P = 0.02, 0.007, and 0.007, respectively). The difference between the granisetron 10-microg/kg group and the placebo group was not significant. No clinically significant AEs were reported in any group. Granisetron 20 microg/kg was the minimum effective dose for the treatment of established postoperative emetic symptoms in patients undergoing laparoscopic cholecystectomy. Increasing the dose to 80 microg/kg provided no further benefit.

Single-Dose Oral Granisetron Versus MultiDose Intravenous Ondansetron for Moderately Emetogenic Cyclophosphamide-Based Chemotherapy in Pediatric Outpatients with Acute Lymphoblastic Lukemia

This prospective study was designed to compare the efficacy of ondansetron with granisetron in terms of complete emesis control and time spent in an ambulatory care setting in children with acute lymphoblastic leukemia (ALL) undergoing moderately emetogenic cyclophosphamide-based chemotherapy.The costs for both treatments are also examined. A total of 33 children (mean age: 7.8 ± 4.9 year) were studied during 66 chemotherapy cycles. Analysis was based on 33 courses of a single oral dose of granisetron and 33 courses of ondansetron incorporating 2 intravenous doses of ondansetron 0.15 mg/kg followed by 1 dose of the same dosage orally. There was no significant difference between the 2 treatments in terms of overall efficacy (McNemar's chi-square test). Twenty of 33 patients (60.6%) receiving granisetron and 15 of 33 patients (45.5%) receiving ondansetron experienced no emesis 24 h after chemotherapy (p = .227). Boys experienced greater rates of vomiting than did girls despite antiemetic treatment; however, no apparent reason for the gender discrepancy was noted. Both antiemetic regimens have similar antiemetic efficacy for treating the moderately emetogenic effects associated with cyclophosphamide-based chemotherapy. It is possible that the granisetron regimen may be preferable because it is simpler to administer and more cost-effective.

Granisetron: is there a dose-response effect on nausea and vomiting?

Nausea and vomiting are two of the most debilitating side effects of cytotoxic chemotherapy. Prevention of nausea and vomiting is, thus, very important to ensure that cancer patients continue to receive optimal cytotoxic therapy while seeking to maintain their quality of life. Significant advances in antiemetic therapy have been achieved since the introduction of the 5-HT(3) receptor antagonists, and these agents are currently regarded as first-line antiemetic agents. The aim of this article is to examine the hypothesis that there is a dose-response effect of granisetron for preventing chemotherapy-induced nausea and vomiting in cancer patients. A literature review of relevant publications was undertaken to provide a comprehensive review of issues related to the control of chemotherapy-induced emesis with escalating doses of granisetron. There is evidence to suggest that there is a significant trend towards an improved efficacy of granisetron-in both the control of emesis and secondary end-points such as nausea and anorexia-with increasing doses, up to 40 micro g/kg, in adults. At this dose, the likelihood of treatment success may be enhanced for most patients regardless of their individual emetogenic risk. Additionally, incremental doses of granisetron (up to 9 mg) have been shown to be effective and well tolerated in patients with refractory emesis. Those patients experiencing inadequate control of nausea and vomiting following granisetron may also benefit from retreatment with supplementary doses of granisetron, and over subsequent chemotherapy cycles, these patients should receive granisetron 40 micro g/kg to ensure emesis protection.