Multi-dose Oral Ondansetron for Pediatric Gastroenteritis: study Protocol for the multi-DOSE oral ondansetron for pediatric Acute GastroEnteritis (DOSE-AGE) pragmatic randomized controlled trial.

BACKGROUND: There are limited treatment options that clinicians can provide to children presenting to emergency departments with vomiting secondary to acute gastroenteritis. Based on evidence of effectiveness and safety, clinicians now routinely administer ondansetron in the emergency department to promote oral rehydration therapy success. However, clinicians are also increasingly providing multiple doses of ondansetron for home use, creating unquantified cost and health system resource use implications without any evidence to support this expanding practice. METHODS/DESIGN: DOSE-AGE is a randomized, placebo-controlled, double-blinded, six-center, pragmatic clinical trial being conducted in six Canadian pediatric emergency departments (EDs). In September 2019 the study began recruiting children aged 6 months to 18 years with a minimum of three episodes of vomiting in the 24 h preceding enrollment, <72 h of gastroenteritis symptoms and who were administered a dose of ondansetron during their ED visit. We are recruiting 1030 children (1:1 allocation via an internet-based, third-party, randomization service) to receive a 48-h supply (i.e., six doses) of ondansetron oral solution or placebo, administered on an as-needed basis. All participants, caregivers and outcome assessors will be blinded to group assignment. Outcome data will be collected by surveys administered to caregivers 24, 48 and 168 h following enrollment. The primary outcome is the development of moderate-to-severe gastroenteritis in the 7 days following the ED visit as measured by a validated clinical score (the Modified Vesikari Scale). Secondary outcomes include duration and frequency of vomiting and diarrhea, proportions of children experiencing unscheduled health care visits and intravenous rehydration, caregiver satisfaction with treatment and safety. A preplanned economic evaluation will be conducted alongside the trial. DISCUSSION: Definitive data are lacking to guide the clinical use of post-ED visit multidose ondansetron in children with acute gastroenteritis. Usage is increasing, despite the absence of supportive evidence. The incumbent additional costs associated with use, and potential side effects such as diarrhea and repeat visits, create an urgent need to evaluate the effect and safety of multiple doses of ondansetron in children focusing on post-emergency department visit and patient-centered outcomes. TRIAL REGISTRATION: ClinicalTrials.gov: NCT03851835. Registered on 22 February 2019.

Randomized Phase II Trial to Compare the Efficacy of Haloperidol and Olanzapine in the Control of Chemotherapy-Induced Nausea and Vomiting in Nepal.

PURPOSE: The purpose of the study was to compare efficacy and toxicity of olanzapine (OLN; a higher-cost drug) and haloperidol (HAL; a lower-cost drug) in the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients who receive highly emetogenic chemotherapy (HEC). PATIENTS AND METHODS: In a randomized, phase II trial, patients were randomly assigned to receive either OLN 10 mg orally on days 1 to 4 or HAL 1 mg orally on day 1 and 0.5 mg twice daily on days 2 to 4. Both groups received ondansetron 16 mg and dexamethasone 12 mg intravenously on day 1. Patients recorded their nausea using the Edmonton Symptom Assessment Scale (ESAS) and recorded daily episodes of vomiting from day 1 to day 5. The primary end point was complete nausea prevention (CNP; ie, ESAS of 0). Secondary end point was complete emesis prevention (CEP). RESULTS: Sixty-five patients were randomly assigned, and 64 received their allocated treatment (n = 32 in each arm). There was no difference in CNP during the overall period (days 1 to 5) between OLN and HAL (68.7% v 71.8%; P = .78). In the acute period (day 1) and the delayed period (days 2 to 5), CNP was similar between OLN and HAL (acute: 84.3% v 81.2%; delayed: 68.7% v 75%). No difference was identified in the rate of CEP during the overall period (81.2% with OLN v 78.1% with HAL; P = .75), during the acute period (93.7% with OLN v 90.6% with HAL), or during the delayed period (84.3% with OLN v 84.3% with HAL). No difference in toxicities was noted between treatment arms. CONCLUSION: In this study, HAL had comparable efficacy to OLN in the management of CINV, which suggests that it is the higher-value option in patients who receive HEC in resource-scarce countries.

Assessment of absorption of transdermal ondansetron in normal research cats.

Objectives The objective of this study was to assess the absorption of transdermal ondansetron in healthy cats. Methods Five research cats with unremarkable complete blood count, biochemistry and urinalysis were used for both single- and multiple-dose application studies. For single-dose application, 4 mg ondansetron in 0.1 ml Lipoderm gel was applied once to the internal ear pinna. Blood samples were collected via jugular catheter over a 48 h period following administration (0, 15 mins, 30 mins, 1 h, 2 h, 4 h, 8 h, 12 h, 24 h and 48 h). For multiple-dose application, 4 mg ondansetron in 0.1 ml Lipoderm gel was applied for five consecutive days before blood samples were obtained in the same manner. Serum was separated and frozen prior to analysis. Ondansetron was measured via liquid chromatography coupled to tandem mass spectrometry. Results Analysis revealed no clinically relevant drug levels in serum after either single- or multiple-dose administration of 4 mg transdermal ondansetron. Conclusions and relevance Transdermal application of 4 mg ondansetron does not result in clinically relevant serum concentrations of drug. Despite characteristics of the drug that imply suitability for transdermal application, this does not appear to be an acceptable method of drug delivery for this medication at this dose. This study highlights the importance of assessing the suitability of each medication for transdermal administration.

Pharmacokinetic modeling and Monte Carlo simulation of ondansetron following oral administration in dogs.

Ondansetron is a potent antiemetic drug that has been commonly used to treat acute and chemotherapy-induced nausea and vomiting (CINV) in dogs. The aim of this study was to perform a pharmacokinetic analysis of ondansetron in dogs following oral administration of a single dose. A single 8-mg oral dose of ondansetron (Zofran(®) ) was administered to beagles (n = 18), and the plasma concentrations of ondansetron were measured by liquid chromatography-tandem mass spectrometry. The data were analyzed by modeling approaches using ADAPT5, and model discrimination was determined by the likelihood-ratio test. The peak plasma concentration (Cmax ) was 11.5 ± 10.0 ng/mL at 1.1 ± 0.8 h. The area under the plasma concentration vs. time curve from time zero to the last measurable concentration was 15.9 ± 14.7 ng·h/mL, and the half-life calculated from the terminal phase was 1.3 ± 0.7 h. The interindividual variability of the pharmacokinetic parameters was high (coefficient of variation > 44.1%), and the one-compartment model described the pharmacokinetics of ondansetron well. The estimated plasma concentration range of the usual empirical dose from the Monte Carlo simulation was 0.1-13.2 ng/mL. These findings will facilitate determination of the optimal dose regimen for dogs with CINV.

Clinical and economic impact of oral ondansetron for vomiting in a pediatric emergency department.

In this study, we determine the clinical impact of 1 dose of oral ondansetron for children with vomiting and evaluate the economic consequences of its use. The strategies compared were administering oral ondansetron in addition to oral rehydration therapy (group A) versus oral rehydration solution alone (group B) in children attended to for vomiting in a pediatric emergency department. The study population was 1871 children between 0 and 14 years of age treated for vomiting during a 2-year period (2009-2010). Outcome measures were need for intravenous rehydration, length of stay in the emergency department, return visits, and hospitalization. Estimates of the costs in the emergency department and hospitalization were derived from administrative databases. During the study period, 580 (31%) of 1871 patients received oral rehydration therapy. Oral ondansetron before oral rehydration solution was used in 109 (18.8%) of 580 patients. An equal number of patients not receiving ondansetron were randomized and analyzed for comparison (group B). Patients of group A had a significantly decreased risk of hospitalization (relative risk, 0.22; 95% confidence interval, 0.08-0.63) and intravenous rehydration (relative risk, 0.31; 95% confidence interval, 0.14-0.63), but there were no differences in the length of stay or return visits to the emergency department. There were no differences in the medical costs between both groups in the emergency department (US $22,078 vs US $21,987, respectively). The hospitalization cost was US $9600 for group A and US $25,079 for group B, providing a 73.7% saving. In conclusion, the administration of oral ondansetron to children with vomiting in the emergency department is clinically effective and results in significant economic savings.

Oral ondansetron administration in emergency departments to children with gastroenteritis: an economic analysis.

BACKGROUND: The use of antiemetics for children with vomiting is one of the most controversial decisions in the treatment of gastroenteritis in developed countries. Ondansetron, a selective serotonin receptor antagonist, has been found to be effective in improving the success of oral rehydration therapy. However, North American and European clinical practice guidelines continue to recommend against its use, stating that evidence of cost savings would be required to support ondansetron administration. Thus, an economic analysis of the emergency department administration of ondansetron was conducted. The primary objective was to conduct a cost analysis of the routine administration of ondansetron in both the United States and Canada. METHODS AND FINDINGS: A cost analysis evaluated oral ondansetron administration to children presenting to emergency departments with vomiting and dehydration secondary to gastroenteritis from a societal and health care payer's perspective in both the US and Canada. A decision tree was developed that incorporated the frequency of vomiting, intravenous insertion, hospitalization, and emergency department revisits. Estimates of the monetary costs associated with ondansetron use, intravenous rehydration, and hospitalization were derived from administrative databases or emergency department use. The economic burden in children administered ondansetron plus oral rehydration therapy was compared to those not administered ondansetron employing deterministic and probabilistic simulations. We estimated the costs or savings to society and health care payers associated with the routine administration of ondansetron. Sensitivity analyses considered variations in costs, treatment effects, and exchange rates. In the US the administration of ondansetron to eligible children would prevent approximately 29,246 intravenous insertions and 7,220 hospitalizations annually. At the current average wholesale price, its routine administration to eligible children would annually save society US$65.6 million (US$49.1-US$81.1) and health care payers US$61.1 million (US$46.2-US$76.3). In Canada the administration of ondansetron to eligible children would prevent 4,065 intravenous insertions and 1,003 hospitalizations annually. Its routine administration would annually save society CDN$1.72 million (CDN$1.15-CDN$1.89) and the health care system CDN$1.18 million (CDN$0.88-CDN$1.41). CONCLUSIONS: In countries where intravenous rehydration is often employed, the emergency department administration of oral ondansetron to children with dehydration and vomiting secondary to gastroenteritis results in significant monetary savings compared to a no-ondansetron policy. Please see later in the article for the Editors' Summary.

Sub-antibiotic doses of erythromycin as a prokinetic in abdominal surgeries: reviving the old.

All patients undergoing major abdominal procedures have some degree of gastricatony in the immediate postoperative period, presenting mainly with vomiting. Many prokinetic agents have been used in the past, but none is a universal remedy. Studies showed that subantibiotic doses of erythromycin, a macrolide antibiotic and motilin agonist, accelerates gastric emptying. This study investigated whether preoperative subantibiotic dose oral erythromycin (250 mg), altered residual gastric volume and postoperative adverse effects in patients scheduled for abdominal surgeries. Erythromycin was compared with the commonly used prokinetic metoclopramide and antiemetic ondansetron, in terms of prokinetic efficacy, cost and adverse effects. In a double-blind study, eighty patients (20 each) were allocated randomly to receive orally, either erythromycin 250 mg (E250) or erythromycin 500 mg (E500), or 10 mg metoclopramide (M), or 4 mg ondansetron (Z), an hour pre-induction of anesthesia. Preoperative oral erythromycin in subantibiotic dose 250 mg elicited a significntly lower residual gastric volume (P < 0.001) and a lower VAS for vomiting, compared with ondansetron. As for metoclopramide and erythromycin 500, residual gastric volume was comparable, but E 250 had a lower VAS for vomiting than both groups. Rescue remedy for vomiting was required for groups E500, M and Z (100, 10 and 10%) compared to 0% in group E250. Ultimately, subantibiotic oral dose of erythromycin (250 mg), given 1 hr preoperatively, is an inexpensive prokinetic alternative with a promising post-operative profile which may be superior to the inexpensive prokinetic metoclopramide with known adverse effects, and the expensive antiemetic ondansetron.

Omission of day 2 of antiemetic medications is a cost saving strategy for improving chemotherapy-induced nausea and vomiting control: results of a randomized phase III trial.

OBJECTIVES: Nausea and vomiting are important symptoms observed in cancer patients. In a previous study, we showed that delayed chemotherapy-induced nausea and vomiting control could be potentially improved by skipping the administration of a 5-hydroxytryptamine 3 (5-HT3) antagonist on day 2. We report here a trial confirming our previous findings. MATERIALS AND METHODS: A phase III randomized placebo-controlled trial was conducted in which patients received intravenously ondansetron 16 mg, dexamethasone 20 mg, and ranitidine 50 mg before highly/moderately emetogenic chemotherapy (day 1). Starting on day 2, all patients received metoclopramide 10 mg per oral every 8 hours (days 2, 3, and 4), dexamethasone 8 mg daily (days 2 and 3), and ranitidine 150 mg every 12 hours (days 2 and 3). Patients were randomized to receive either granisetron 0.5 mg per oral (days 2 and 3) (group A) or placebo instead of granisetron on day 2 and granisetron 0.5 mg on days 3 and 4 (group B). RESULTS: Seventy-three patients were enrolled. Groups were similar regarding clinical characteristics, despite better control during the acute phase of chemotherapy-induced nausea and vomiting in group A (P = 0.04). Complete delayed protection from nausea and vomiting (DCPNV) from day 2 to 5 was similar in both groups (30% vs. 32%; P = 0.5). Analyzing DCPNV by logistic regression multivariate analyses, acute complete protection from nausea and vomiting (P = 0.001) and study group (P = 0.06) were independently associated with DCPNV. Selecting patients who achieved acute complete protection from nausea and vomiting, we observed that group B had a superior DCPNV (85% vs. 50%, P = 0.02). CONCLUSION: DCPNV can be improved just by skipping day 2 of 5-HT3-antagonists. Future studies should compare this inexpensive strategy with NK1-antagonists or second generation 5-HT3-antagonists.

Comparison of the antiemetic effects of ondansetron and dexamethasone on middle ear surgery.

OBJECTIVE: To compare the antiemetic efficacy of ondansetron and dexamethasone in adults undergoing middle ear surgery. METHODS: This clinical research took place in the Faculty of Medicine, Gazi University, Turkey between January to December 2004. The study included 60 cases, classified by the American Society of Anesthesiology physical status group I-II, who underwent middle ear surgery. We carried out anesthesia induction with 5 mg x kg(-1) sodium thiopental and performed muscle relaxation with 0.5 mg x kg(-1) atracurium to be followed by orotracheal intubation. Anesthesia was maintained at 5 L x min(-1) gas flows with 2-3% sevoflurane inhalation in 70/30% O(2)/N(2)O. We randomly distributed the cases into 2 groups, and the first group (Group O) was administered with 4 mg ondansetron intravenously (IV) at the stage of surgical skin closure and the second group (Group D) with 5 mg dexamethasone IV immediately after anesthesia induction. In the first 24 hours postoperatively, nausea vomiting score (NVS) and nausea, vomiting frequency, Metamizole-Na and non-steroidal anti-inflammatory drug use, the need for additional antiemetics and cost as well as the number of cases with nausea, vomiting and the need for extra antiemetics during 0-4, 4-12 and 12-24 hours were recorded, and their distribution to groups was evaluated. RESULTS: The NVS was 0 (0-0) in group O compared with 1 (0-3) in group D (p=0.003). The use of additional antiemetics was found to be significantly lower in group O (1 +/- 0.6) compared with group D (3.70 +/- 1.02) (p=0.028). In comparing the cost, group O (9.8 dollars) was found to have a significantly higher cost compared with group D (1.1 dollars) (p<0.0001). CONCLUSION: Ondansetron had a more significant effect on nausea and vomiting in the early period, however, no difference was found after 4 hours of administration. Furthermore, dexamethasone was found to cost less compared with ondansetron.

The use of oral granisetron versus intravenous ondansetron for antiemetic prophylaxis in patients undergoing laparoscopic surgery: the effect on emetic symptoms and quality of recovery.

Based on comparative studies in patients receiving emetogenic chemotherapy, it has been suggested that granisetron would be more effective than ondansetron for the prevention of postdischarge nausea and vomiting (PDNV). However, there have been no direct comparisons of these two popular 5-HT3 antagonists with respect to PDNV and quality of recovery. We designed this randomized, double-blind study to compare the antiemetic efficacy of oral granisetron (1 mg) to a standard IV dose of ondansetron (4 mg) when administered for antiemetic prophylaxis as part of a multimodal regimen in a laparoscopic surgical population. A total of 220 patients undergoing laparoscopic surgery with a standardized general anesthetic technique were enrolled in this prospective study at two major medical centers. Patients were randomly assigned to one of two prophylactic treatment groups: the control (ondansetron) group received an oral placebo 1 h before surgery and ondansetron, 4 mg IV, at the end of the surgery, and the granisetron group received granisetron, 1 mg per os, 1 h before surgery, and normal saline, 2 mL IV, at the end of the surgery. The early recovery profiles, requirement for rescue antiemetics, incidence of PDNV, and the side effects were recorded over the 48 h study period. In addition, nausea scores were assessed using an 11-point verbal rating scale at specific intervals in the postoperative period. The quality of recovery and patient satisfaction scores were recorded at 48 h after surgery. The demographic characteristics were similar in the two prophylaxis treatment groups, as well as the recovery times to patient orientation, oral intake, and hospital discharge. The incidences of PDNV, requirements for rescue antiemetics, and quality of recovery did not differ between the two study groups. The antiemetic drug acquisition costs to achieve comparable patient satisfaction with ondansetron and granisetron were US 25.65 dollars and 47.05 dollars, respectively. Therefore, ondansetron (4 mg IV) was more cost-effective than granisetron (1 mg per os) for routine antiemetic prophylaxis as part of a multimodal regimen in patients undergoing either outpatient or inpatient laparoscopic surgery.

Efficacy and costs of 3 anesthetic regimens in the prevention of postoperative nausea and vomiting.

STUDY OBJECTIVE: The aim of the study was to compare the antiemetic efficacy and costs associated with 3 different anesthesia regimens used in gynecologic laparoscopy. DESIGN: This was a randomized, controlled study. SETTING: The study was conducted at a university hospital. PATIENTS: We studied 150 ASA physical status I or II patients, undergoing elective gynecologic laparoscopy with general anesthesia. INTERVENTION: Patients were allocated into the following 3 groups: group P-preoperative placebo tablet, propofol induction, propofol-air/O2 maintenance; group I + O-preoperative 8-mg ondansetron tablet, thiopental induction, isoflurane-N2O maintenance; group I (control)-preoperative placebo tablet, thiopental induction, isoflurane-N2O maintenance. MEASUREMENTS: The frequency of postoperative nausea and vomiting (PONV), number needed to treat to prevent PONV, and the costs of the anesthetic drugs to prevent PONV in one additional patient were evaluated. MAIN RESULTS: The frequency of PONV within the 24-hour study period was lowest in group I + O (P, 38%; I + O, 33%; and I, 59%; P < 0.05 I + O vs I). The number needed to treat was 5 in group P and 4 in group I + O, compared with group I. The median costs of anesthetic drugs to prevent PONV in one additional patient were $65 in group P and dollar 68 in group I + O, compared with group I. CONCLUSIONS: We conclude that in gynecologic laparoscopy, propofol-air/O2 anesthesia alone, and isoflurane-N2O anesthesia combined with an oral 8-mg dose of ondansetron had similar efficacy and costs to prevent PONV. Isoflurane-N2O anesthesia without ondansetron was less expensive, but was also less efficacious.

A prospective randomized trial of the antiemetic efficacy and cost-effectiveness of intravenous and orally disintegrating tablet of ondansetron in children with cancer.

Orally disintegrating tablet (ODT) of ondansetron is a new formulation, which instantaneously disintegrates and disperses in the saliva without need for ingestion of a liquid. This makes the formulation suitable for administration in children. The objective of this study was to compare the relative efficacy and cost of ODT and intravenous (IV) formulation of ondansetron in controlling nausea and vomiting in children receiving chemotherapy regimens without cisplatin. This prospective randomized trial was performed in a single institution to compare ODT and IV formulation of ondansetron for the prevention of acute emesis in a group of 22 children. Study agents were administered 30 min before chemotherapy and 12 hourly after chemotherapy (5 mg/m2 IV or 4-8 mg oral according to body surface area in 56 and 39 courses, respectively). After randomization, IV formulation was administered to some children instead of ODT due to unavailability of this formulation. Complete and major control of emesis was obtained in 92% of patients in the IV group and 93% of patients in the ODT group. In 56 courses with grade III-IV emetogenicity, complete response rates were not different between the two treatment arms. In the courses without corticosteroids complete response rates were not also different between the two arms. The mean costs per successfully controlled courses were 121.3 USD for the IV formulation whereas 63.2 USD for the ODT formulation. The results of this study confirmed that ODT formulation of ondansetron is a safe, well-tolerated, and cost-effective antiemetic for children during non-cisplatin-containing moderately and highly emetogenic chemotherapy.

Single-dose oral granisetron versus multidose intravenous ondansetron for moderately emetogenic cyclophosphamide-based chemotherapy in pediatric outpatients with acute lymphoblastic leukemia.

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.

A comparison of the costs and efficacy of ondansetron and dolasetron in the prophylaxis of postoperative vomiting in pediatric patients undergoing ambulatory surgery.

UNLABELLED: Postoperative vomiting (POV) after ambulatory surgery remains a major problem. We designed this study to determine the smallest dose of dolasetron equivalent to the Food and Drug Administration approved dose of ondansetron 100 micro g/kg IV, for the prophylaxis of POV in children undergoing surgery. In this double-blinded controlled study, 204 healthy ASA I-II children aged 2-12 yr, undergoing superficial ambulatory (day-case) surgery, were randomized to receive either ondansetron 100 micro g/kg IV, or dolasetron 45, 175, 350, or 700 micro g/kg IV during a standardized perioperative regimen. The primary end-point was the incidence of complete response, defined as the absence of POV symptoms. Costs were calculated from the perspective of the hospital using a previously described model. The incidence of early (0-6 h) and 24-h emesis was more frequent in the dolasetron 45 micro g/kg group compared with the dolasetron 350 and 700 micro g/kg groups and with the ondansetron group. Repeated POV occurred more often when dolasetron was used in a dose <350 micro g/kg. There were no significant differences in emesis rates between the dolasetron 175, 350, and 700 micro g/kg groups or between these groups and the ondansetron 100 micro g/kg group. The smallest dose of dolasetron with acceptable equivalent efficacy and patient satisfaction scores to ondansetron 100 micro g/kg was 350 micro g/kg. Institutional costs for managing POV were less with dolasetron 350 micro g/kg than with ondansetron. IMPLICATIONS: This randomized double-blinded dose-ranging study concluded that dolasetron, 350 micro g/kg IV, was the smallest dose that provided acceptable equivalent efficacy and patient satisfaction scores to ondansetron, 100 micro g/kg IV, for the prophylaxis of postoperative vomiting in children undergoing outpatient surgery. However, with this dose, the costs to the institution for managing postoperative vomiting were less.

Double-blind comparative trial of oral ondansetron versus oral granisetron versus IV ondansetron in the prevention of nausea and vomiting associated with highly emetogenic preparative regimens prior to stem cell transplantation.

The optimal management of transplantation preparative regimen-induced nausea and vomiting remains unknown. We conducted a Phase III double-blind study to determine the efficacy and costs of oral ondansetron versus oral granisetron versus IV ondansetron and PRN rescue antiemetics for the prevention/control of nausea and vomiting associated with high-dose chemotherapy or chemoradiotherapy prior to stem cell transplantation. One hundred two patients were randomized to receive either 8 mg PO ondansetron every 8 hours, 1 mg PO granisetron every 12 hours, or 32 mg IV ondansetron every 24 hours plus 10 mg IV dexamethasone daily during and 1 day after the various preparative regimens. Study arms were compared in terms of emetic episodes, subjective nausea, amount and cost of rescue antiemetics used, and total costs. Response was defined as complete response (CR), no emesis with no or mild nausea and no rescue antiemetics; major response (MR), 1 episode of emesis or moderate nausea with or without rescue antiemetics; and major efficacy (ME), CR + MR. Subjective nausea was assessed using a 100-mm visual analog scale (VAS) with 0 = no nausea. Ninety-six patients completed the study; the trial was analyzed according to intention-to-treat. Overall CR rates were: 48% for oral ondansetron, 47% for oral granisetron, and 49% for IV ondansetron. Overall ME rates were 82% for oral ondansetron, 84% for oral granisetron, and 81% for IV ondansetron. Mean VAS scores were 32 for oral ondansetron, 32 for oral granisetron, and 27 for IV ondansetron. None of the differences were statistically significant. A cost analysis revealed significant differences among all arms (P = .0001, all comparisons). All 3 regimens had similar efficacy in this BMT population; oral ondansetron was the most cost-effective.

Computerized system for outcomes-based antiemetic therapy in children.

OBJECTIVE: To introduce a computerized data collection system used for an outcomes-based approach to antiemetic therapy in children, and to present data collected with this system in support of a new antiemetic dosing regimen. METHODS: A validated nausea/vomiting survey was used to collect data on nausea severity (NSEV), vomiting severity (VSEV), daily activity interference (DAI), and the number of vomiting episodes. NSEV, VSEV, and DAI were rated as 0 = none to 3 = severe. All children and/or their parents were surveyed following the completion of each highly emetogenic chemotherapy regimen. This survey was computerized and transferred to a handheld data entry unit. Time and motion studies were performed to compare the time required to collect nausea/vomiting data and transfer the data to a computerized database with the hand-held system versus traditional paper (manual) surveys. The hand-held technology was used to collect survey data for children receiving a new antiemetic regimen (daily ondansetron and dexamethasone [OD]), which was then compared with data obtained with a previously employed regimen (thrice-daily ondansetron and daily methylprednisolone [OM]). Statistical analysis and a cost-effectiveness analysis (CEA) were performed to compare the two antiemetic regimens. RESULTS: The mean time required for total data entry with the manual system was 5.2 minutes per survey versus 2.4 minutes with the hand-held technology (p = 0.0026). A total of 376 nausea/vomiting surveys in 78 children receiving the OM antiemetic regimen were compared with 153 surveys in 38 children treated with the OD regimen. The mean survey scores were as follows: NSEV (1.2 vs. 0.8), VSEV (1.0 vs. 0.7), DAI (1.0 vs. 0.7), and number of vomiting episodes (4.3 vs. 2.1) for OM and OD, respectively; all were significantly lower with the OD regimen (p < 0.05). The percentage of patients with complete control of nausea and vomiting (19.2% vs. 39.2%) and good control (55.6% vs. 65.4%) were significantly greater with the OD regimen (p < 0.05). The CEA revealed that the OD resulted in a reduction of approximately $31 per patient for good protection and a $258 reduction for complete protection from nausea and vomiting. CONCLUSIONS: A computerized outcomes-based system aided by handheld technology allowed for more prompt and efficient collection of nausea/vomiting data. The OD antiemetic regimen was shown to be a more cost-effective alternative for children receiving severely emetogenic chemotherapy.

Comparison of granisetron, ondansetron and tropisetron for control of vomiting and nausea induced by cisplatin.

Severe nausea and vomiting are common and one of the most feared side effects of cisplatin-based chemotherapy. A total of 106 patients were randomized to receive a single dose of 8 mg ondansetron or 3 mg granisetron or 5 mg tropisetron intravenously as prevention of cisplatin-induced acute nausea and vomiting. Antiemetic therapy was done within 30 minutes before initiating chemotherapy. A questionnaire evaluating nausea, vomiting and retches was administered to patients and the responses were categorized as complete, partial or failure. The response determination was repeated in the first 24 hours, and within 24-72 hours following cisplatin administration. The complete response rates for ondansetron, granisetron and tropisetron in the first 24 hours were 51.4%, 65.7% and 61.1% respectively. All three agents were highly effective against cisplatin-induced acute and late vomiting and the results were statistically significant. This study demonstrated no significant difference in effectiveness of these three antiemetics. 5-HT3 (5-hydroxytryptamine 3) receptor antagonists have similar efficacy in the prevention of nausea and vomiting due to cisplatin. Thus, we recommend that drug choice be based on cost-benefit and patient tolerance.

Balancing efficacy with cost: antiemetic control in the pediatric stem cell transplant (SCT) population.

We studied the practice patterns regarding intravenous (i.v.) ondansetron in children receiving stem cell transplants (SCT) at The Children's Hospital, Boston to identify cost efficiencies. The pharmacy provided information on material and preparation costs on 36 patients who received i.v. ondansetron during 41 SCT in 1995. We examined the effects of frequency, duration, and route of administration on costs. There were 498 days of ondansetron administration costing $49,083 (95$). Tremendous variation existed in frequency and duration with one third receiving i.v. ondansetron once daily, despite published evidence of equivalence of once a day and divided dosing. A switch to once daily i.v. dosing for all patients would have resulted in >/=28% savings. The median duration of use was 11 days (range 1-48); placing a cap for 7-10 days based on the length of SCT conditioning regimens, would produce savings of 48-60% over current use. By shifting administration route from i.v. to oral, a savings of 67% over current use, without a cap on duration, would be realized. Identifying areas for cost savings can be achieved after thorough analysis of all the component costs. We demonstrated that significant cost reductions could be realized by simple changes in prescribing practices without jeopardizing efficacy. These savings are achieved by standardizing dosing interval, route of administration and duration of treatment without altering daily dosage or access to an effective antiemetic. Bone Marrow Transplantation (2000) 25, 553-557.