Oral Ondansetron Research Articles

Evaluation of Cisplatin Induced Toxicity in Head and Neck Cancer and Cervical Cancer During Concurrent Chemoradiotherapy. Experience of National Institute of Oncology in Morocco

Background: Cisplatin is widely used as radio sensitizer in head and neck cancer (HNC) and cervical cancer. We conducted this prospective study to evaluate cisplatin induced toxicity as once-weekly regimen in HNC and cervical cancer during concurrent chemoradiotherapy (CCRT) to optimize its administration. Patients and methods: From 01 January 2015 to 11 May 2015, a data of all eligible patients treated by chemoradiation regimens containing a low dose of cisplatin were collected at the Department of radiotherapy in National Institute of Oncology in Morocco. Cisplatin was used weekly at 40 mg/m2 with adequate hydration and premedication in all patients. A complete blood count and renal function tests were done prior to each cycle of chemotherapy to evaluate toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE, version 4.0). Results: A total of 96 patients were eligible for the analysis. Mean age, PS, initial weight, enteral nutrition, cisplatin mean dose, use of oral Ondansetron and baseline serum tests did not differ significantly among the types of malignancy. However, weight loss was significantly noted among HNC group compared to cervical cancer patients with 6.06 ± 2.92 kg and 0.02 ± 0.13 kg respectively. Toxicity was observed only in 16 (20%) patients after the 4th week of treatment especially among HNC group. The neutropenia and thrombocytopenia were significantly greater for patients of HNC. However, we did not observe any renal toxicity, thrombocytopenia and ≥ grade 3 neutropenia toxicity in cervical cancer group. In multivariated analysis, only a subtype of HNC (OR, 1233; 95% CI, 16-95 103; P=0.001) and grade 2 emetogenicity (OR, 34.8; 95% CI, 2.1-583; P=0.014) were significantly associated with an increased risk for cisplatin toxicity. Whereas, less than 4 weekly cisplatin treatment (OR, 0.4; 95% CI, 0.1-0.9; P=0.046) was associated with a significantly reduced risk. Conclusion: Our data have revealed that individuals with HNC were at a significantly higher risk for cisplatininduced toxicity during CCRT and suggest that the once-weekly smaller dose of cisplatin regimen and conventional prophylactic procedures of administration might be effective for protection against the renal toxicity of cisplatin.

A Feasibility Study of the Full Outpatient Conduction of Hematopoietic Transplants in Persons with Multiple Sclerosis Employing Autologous Non-Cryopreserved Peripheral Blood Stem Cells

Background: With the goal of immune system reset, autologous hematopoietic stem cell transplantations have been done in patients with multiple sclerosis (MS).Material and methods: 131 consecutive patients with MS were autografted in a single center using non-frozen peripheral blood stem cells (PBSC) on an outpatient basis and conditioning with cyclophosphamide (Cy) and rituximab. The protocol was registered in ClinicalTrials.gov identifier NCT02674217. The PBSC mobilization schedule was done with Cy and filgrastim (G-CSF). Intravenous Cy (50 mg/Kg) was delivered on days - 11 and - 10. Subcutaneous G-CSF (10 ug / Kg / bid) was delivered on days - 9 to - 1.. The apheresis procedure was performed on day - 2. The apheresis objective was to reach at least 1 x 106 viable CD34+ cells/Kg. As outpatients and after collecting the PBSC, intravenous Cy (50 mg / Kg) was delivered along a 120 minute period, on days - 2 and - 1 followed by MESNA (1000 mg/m2 along a 180-minute period). After the intravenous Cy, oral ondansetron), oral cotrimoxazole, oral fluconazole and oral acyclovir were used in all patients until granulocytes were greater than 0.5 x 109/L. After the recovery of the granulocytes, patients were given rituximab (375 mg/m2 along a 3 h period) and subsequently rituximab (100 mg) every two months along a 12-month period. The cumulative dose of Cy is 200 mg/Kg.Results: 80 females and 51 males were included; median age was 47 years. All procedures were started on an outpatient basis and two persons were admitted to the hospital during the procedure. In order to obtain at least 1 x106 / Kg viable CD34 cells, one to four apheresis were performed (median 1). Total number of viable CD34+ cells infused ranged between 1 and 9.6 x106 / Kg (median 2.2). Patients recovered above 0.5 x109/L absolute granulocytes on median day 9 (range 6 to 12). Two individuals needed red blood cells but none needed platelet transfusions. There were no transplant related deaths, the 120-month overall survival being 100%. In a subset of 25 persons followed for 5 months or more the EDSS was assessed three months after the graft and means diminished from 5.4 to 4.9. The EDSS score improved in 11 patients (44%), remained stable in 7 (28%) and worsened in 7 (28%). A tendency to diminish the EDSS score as a function of time after the autograft was observed in this subset of individuals.Conclusions: It is possible to conduct autotrasplants for patients with MS employing non-frozen peripheral blood stem cells and outpatient conduction. Additional information is needed to assess the efficacy of these procedures in the treatment of patients with MS. DisclosuresNo relevant conflicts of interest to declare.

Oral Ondansetron versus Domperidone for Acute Gastroenteritis in Pediatric Emergency Departments: Multicenter Double Blind Randomized Controlled Trial.

The use of antiemetics for vomiting in acute gastroenteritis in children is still a matter of debate. We conducted a double-blind randomized trial to evaluate whether a single oral dose of ondansetron vs domperidone or placebo improves outcomes in children with gastroenteritis. After failure of initial oral rehydration administration, children aged 1–6 years admitted for gastroenteritis to the pediatric emergency departments of 15 hospitals in Italy were randomized to receive one oral dose of ondansetron (0.15 mg/kg) or domperidone (0.5 mg/kg) or placebo. The primary outcome was the percentage of children receiving nasogastric or intravenous rehydration. A p value of 0.014 was used to indicate statistical significance (and 98.6% CI were calculated) as a result of having carried out two interim analyses. 1,313 children were eligible for the first attempt with oral rehydration solution, which was successful for 832 (63.4%); 356 underwent randomization (the parents of 125 children did not give consent): 118 to placebo, 119 to domperidone, and 119 to ondansetron. Fourteen (11.8%) needed intravenous rehydration in the ondansetron group vs 30 (25.2%) and 34 (28.8%) in the domperidone and placebo groups, respectively. Ondansetron reduced the risk of intravenous rehydration by over 50%, both vs placebo (RR 0.41, 98.6% CI 0.20–0.83) and domperidone (RR 0.47, 98.6% CI 0.23–0.97). No differences for adverse events were seen among groups. In a context of emergency care, 6 out of 10 children aged 1–6 years with vomiting due to gastroenteritis and without severe dehydration can be managed effectively with administration of oral rehydration solution alone. In children who fail oral rehydration, a single oral dose of ondansetron reduces the need for intravenous rehydration and the percentage of children who continue to vomit, thereby facilitating the success of oral rehydration. Domperidone was not effective for the symptomatic treatment of vomiting during acute gastroenteritis.

1435O - Exploration of the heterogeneity of moderately emetogenic chemotherapy on response to fosaprepitant in a randomized phase 3 trial

1435O - Exploration of the heterogeneity of moderately emetogenic chemotherapy on response to fosaprepitant in a randomized phase 3 trial

213 Impact of Ondansetron Prescription on Return Emergency Department Visits Among Children With Acute Gastroenteritis

A single dose of oral ondansetron given in the ED for children with acute gastroenteritis (AGE) decreases vomiting and hospitalization. The objective of this study was to determine if providing ondansetron prescription to children seen in the ED with AGE is associated with reduced unscheduled ED revisits. Retrospective cohort comparative study of children 6 months to 18 years who presented to a tertiary pediatric ED between 2010 and 2015. ICD-9 codes identified eligible patients discharged home with AGE diagnosis. Patients with complex chronic conditions and those with comorbidity identified during the initial ED visit were excluded. Illness severity was determined using the institutional dehydration score, emergency severity index (ESI), and presenting symptoms. Medical records of all returning patients were reviewed for clinical history, interventions and diagnostic studies, and final diagnosis. The primary outcome was the incidence of unscheduled ED revisit within 7 days among patients discharged home initially with ondansetron prescription compared with those without a prescription. Secondary outcomes included rate of hospitalization at second presentation and alternative diagnoses. 11,785 eligible patients were seen and discharged home from the initial ED visit. 35.5% (N=4,187) of patients were discharged home with an ondansetron prescription. 48% were female, and median age was 3.5 years (IQR 1.7, 7.0). 6.0% (N=707) of patients returned to the ED within 7 days; of these, 40 were unrelated visits, 186 were related but not AGE-specific encounters, and 23 resulted in alternative diagnoses. Median duration between initial ED encounter and revisit was 2 days (IQR: 1, 3). Patients were more likely to return to the ED if they were discharged with an ondansetron prescription, after adjustment for ESI, both in the full sample (6.6% vs 5.1%; aOR [95% CI] = 1.30 [1.11, 1.52]) and when restricted to return visits for AGE-specific diagnoses (5% vs 3.3%, aOR = 1.55 [1.29, 1.87]). They were also at increased risk for admission following revisit (1.7% vs 1.2%, respectively; aOR = 1.45 [1.07, 1.98]), including when the analysis was restricted to AGE-specific diagnoses (1.3% vs 0.8%, respectively; aOR = 1.59 [1.10, 2.30]. Among patients returning to the ED, no difference was found in the proportion of alternative diagnoses among patients with versus without an ondansetron prescription (2% vs 4.1%, respectively; aOR = 0.51 [0.20, 1.31]). Providing an ondansetron prescription for children seen in the ED with suspected AGE was associated with an increased risk for return ED visits and admission following revisit.

Ondansetron for pediatric concussion; a pilot study for a randomized controlled trial.

Assess the feasibility of a study evaluating one dose of oral ondansetron to decrease post-concussion symptoms at one week and one month following concussion in children aged 8 to 17 years old. This was a pilot study for a randomized, triple-blind controlled trial of one dose of either ondansetron or placebo performed in a tertiary care pediatric emergency department. Participants were children aged 8 to 17 years who sustained a concussion in the previous 24 hours and visited a single emergency department. The outcome of interest was an increase from pre-concussion baseline of at least 3 symptoms from the Post-Concussion Symptom Inventory, measured at one week and at one month following concussion. The primary outcome was to determine the proportion of children who completed the assessment at one week following the intervention. Secondary outcome was the proportion of children who completed the assessment at one month following the intervention. All children, care givers, and those assessing the outcomes were blinded to the group assignment. Of the 218 children presenting with a concussion during the study period, we screened 108 and found 36/108 (33%) eligible to participate and 16/108 (14.8%) agreed to participate. All enrolled patients were compliant with the intervention and follow-up. In our study population, approximately one-third of the screened concussion patients were eligible to participate and approximately one half of those eligible agreed to participate. Our study found that most enrolled patients preferred electronic follow-up; the noncompliance rate was minimal.

Evaluating the Impact of Clinical Decision Tools in Pediatric Acute Gastroenteritis: A Population-based Cohort Study.

Acute gastroenteritis (AGE) is a leading cause of pediatric emergency department (ED) visits. Despite evidence-based guidelines, variation in adherence exists. Clinical decision tools can enhance evidence-based care, but little is known about their use and effectiveness in pediatric AGE. This study sought to determine if the following tools-1) pathways/order sets, 2) medical directives for oral rehydration therapy (ORT) or ondansetron, and 3) printed discharge instructions-are associated with AGE admission and ED revisits. This was a retrospective population-based cohort study of all children 3 months-18 years with an AGE ED visit in Ontario, Canada, from 2008 to 2010, using linked survey and health administrative databases. Logistic regression models associating clinical decision tools (CDTs) with hospitalizations and revisits controlling for hospital and patient characteristics were employed. Of the 57,921 patient visits during the study period, there were 2,401 hospitalizations (4.2%). A total of 55,520 patients were discharged from the ED, with 2,378 (4.3%) experiencing a 72-hour return visit. In adjusted models, none of the tools were significantly associated with admission. Medical directive for ORT was associated with lower return visit rates (adjusted odds ratio [aOR] = 0.86, 95% confidence interval [CI] = 0.79-0.94] and printed discharge instructions with higher return visits (aOR = 1.33, 95% CI = 1.08-1.65); pathways/order sets and medical directives for ondansetron had no association. Admissions in children with AGE are not associated with the presence of CDTs. While ORT medical directives are associated with lower ED revisits, printed discharge instructions have the opposite effect. The simple presence/absence of decision support tools does not guarantee improved clinical outcomes.

Oral Ondansetron in Management of Dehydrating Diarrhea with Vomiting in Children Aged 3 Months to 5 Years: A Randomized Controlled Trial

To evaluate the role of oral ondansetron in facilitating successful rehydration of under-5-year-old children suffering from acute diarrhea with vomiting and some dehydration. Children (n = 170) aged 3 months to 5 years with acute diarrhea with vomiting and some dehydration were enrolled in this double blind, randomized, placebo-controlled trial. The participants were randomized to receive either single dose of oral ondansetron (n = 85) or placebo (n = 85) in addition to standard management of dehydration according to World Health Organization guidelines. Failure of oral rehydration therapy (ORT), administration of unscheduled intravenous fluids, and amount of oral rehydration solution intake in 4 hours were the primary outcomes. Secondary outcome measures included duration of dehydration correction, number of vomiting episodes, adverse effects, and caregiver satisfaction. Failure of ORT was significantly less in children receiving ondansetron compared with those receiving placebo (31% vs 62%; P < .001; relative risk 0.50, 95% CI 0.35-0.72). Almost one-half of the children in the ondansetron group received intravenous fluids compared with those in the placebo group, but it was not statistically significant (P = .074; relative risk 0.56, 95% CI 0.30-1.07). The oral rehydration solution consumption was significantly more in the ondansetron group (645 mL vs 554 mL; mean difference 91 mL; 95% CI: 35-148 mL). Patients in the ondansetron group also showed faster rehydration, lesser number of vomiting episodes, and better caregiver satisfaction. A single oral dose of ondansetron, given before starting ORT to children <5 years of age with acute diarrhea and vomiting results in better oral rehydration. Clinical Trial Registry of India: CTRI-2011/07/001916.

Risk of Cardiac Arrythmias and Death in Patients Recieving Oral Ondansetron: A Review of the Federal Adverse Events Reporting System (FAERS)

Risk of Cardiac Arrythmias and Death in Patients Recieving Oral Ondansetron: A Review of the Federal Adverse Events Reporting System (FAERS)

Aprepitant as an add-on therapy in children receiving highly emetogenic chemotherapy: a randomized, double-blind, placebo-controlled trial.

Aprepitant, a neurokinin-1 receptor antagonist, in combination with 5 HT-3 antagonist and dexamethasone is recommended in adults receiving moderately and highly emetogenic chemotherapy to reduce chemotherapy-induced vomiting (CIV). Data for use of aprepitant in children is limited and hence aprepitant is not recommended by Pediatric Oncology Group of Ontario guidelines for prevention of CIV in children <12 years. A randomized, double-blind, placebo-controlled trial was conducted at a single center in chemotherapy naïve children (5-18 years) receiving highly emetogenic chemotherapy. All patients received intravenous ondansetron (0.15 mg/kg) and dexamethasone (0.15 mg/kg) prior to chemotherapy followed by oral ondansetron and dexamethasone. Patients randomly assigned to aprepitant arm received oral aprepitant (15-40 kg = days 1-3, 80 mg; 41-65 kg = day 1, 125 mg and days 2-3, 80 mg) 1 h before chemotherapy. Control group received placebo as add-on therapy. Primary outcome measure was the incidence of acute moderate to severe vomiting, which was defined as more than two vomiting episodes within 24 h after the administration of the first chemotherapy dose until 24 h after the last chemotherapy dose in the block. Complete response (CR) was defined as absence of vomiting and retching during the specified phase. Of the 96 randomized patients, three were excluded from analysis; 93 patients were analyzed (50 in aprepitant arm and 43 in placebo arm). Acute moderate and severe vomiting was reported in 72 % patients receiving placebo and 38 % patients receiving aprepitant (p = 0.001). Complete response rates during acute phase were significantly higher in aprepitant arm (48 vs. 12 %, p < 0.001). No major adverse effects were reported by patients/guardians. This double-blind, randomized, placebo-controlled trial shows that aprepitant significantly decreases the incidence of CIV during acute phase when used as an add-on drug with ondansetron and dexamethasone in children receiving highly emetogenic chemotherapy.

Ondansetron and probiotics in the management of pediatric acute gastroenteritis in developed countries.

Acute gastroenteritis (AGE) is a common and impactful disease, typically managed with supportive care. There is considerable interest in the role of adjunctive therapies, particularly ondansetron and probiotics in improving AGE outcomes. The purpose of this review is to present the latest evidence regarding the use of these agents in children with AGE in developed countries. Single-dose oral ondansetron is effective and safe in reducing hospital admissions and the use of intravenous rehydration in children with AGE in emergency-department-based trials. Ondansetron use has increased significantly; however, 'real-world' studies of effectiveness have documented less impressive clinical impacts. Similarly, probiotic consumption is growing rapidly. Although several strains appear to reduce the duration of diarrhea in hospitalized children, current data are insufficient to support the routine use of probiotics in outpatient pediatric AGE. Ondansetron and probiotics may improve patient outcomes in pediatric AGE. Appropriate strategies are needed to optimally integrate oral ondansetron into clinical practice to maximize its potential benefits. Although probiotics remain a promising option, there are challenges in generalizing the data available to patients presenting for outpatient care. Large randomized controlled trials are needed to definitively guide the clinical use of probiotics in outpatients in developed countries.

Comparison of Efficacy of Clonidine versus Ondansetron for Prevention of Nausea and Vomiting Post Thyroidectomy: A Double Blind Randomized Controlled Trial

Postoperative nausea vomiting (PONV) is the most common symptom in patients post thyroidectomy. Literature search shows conflicting results regarding use of clonidine in PONV prophylaxis. We undertook this randomized controlled double blind trial to compare the efficacy of clonidine with dexamethasone versus ondansetron with dexamethasone for PONV prophylaxis in these patients. In this prospective study, 60 consecutive patients posted for thyroidectomy from August 2013 to July 2014, were randomly assigned to two groups, ondansetron (N= 30) (Group A) and clonidine (N= 30) (Group B). Patients received either oral ondansetron 8mg or oral clonidine 150μg as premedication. At the end of surgery, both groups received dexamethasone 8mg intravenously. They were monitored for occurrence of PONV and sore throat for next 24 h. Ramsay sedation scores and total time of analgesia was noted. The primary end point was incidence of PONV in post operative for 24 h. Pearson's chi square test and Students t tests were performed using SPSS for windows version 20 (SPSS Inc., Chicago, IL). Baseline characteristics of patients were comparable. A higher proportion of patients in clonidine group developed PONV than ondansetron (36.7% vs 30%; p=0.03). Clonidine group patients experienced early nausea and vomiting (1-2hrs of postoperative period), compared to ondansetron group patients (6-12 h). Ramsay sedation scores at arrival were higher in clonidine group compared to ondansetron group (2.1 ± 0.3 versus 2.0; p=0.003). Total time of analgesia was higher with use of clonidine than ondansetron (919.5 ± 622 mins versus 642 ± 631 mins; p=0.09). Moderate sore throat was seen in 2 out of 30 patients in both groups. No major adverse events were observed in either group. Ondansetron with dexamethasone group was more effective in controlling PONV after thyroidectomy compared to clonidine with dexamethasone group. However, ramsay sedation scores and total time of analgesia were higher with clonidine than ondansetron.

Effect of Oral Ondansetron on Vomiting Associated with Intramuscular Ketamine Sedation in Children: A Double-Blind, Randomized, Placebo-Controlled Trial

Purpose The purpose of this study is to investigate the effect of oral ondansetron on the incidence of vomiting in children who receive intramuscular (IM) ketamine for procedural sedation and analgesia in the emergency department (ED). Methods In this double-blind, randomized, placebo-controlled trial in a children's hospital ED, patients receiving IM ketamine (5 mg/kg) for ED procedures were randomized to receive either oral ondansetron (2 mg or 4 mg) or placebo 15 minutes before the ketamine injection. We recorded whether vomiting occurred in the ED postsedation or up to 12 hours after discharge with telephone follow-up and compared ED length of stay and parental satisfaction. Results Thirty two children were randomized to placebo and 31 to ondansetron. The groups were similar in age, sex, and fasting duration. ED vomiting was no significant difference with ondansetron: 7 of 31 (22.6%) versus 6 of 32 (18.8%), P=0.707, difference -3.8 (95% confidence interval -23.8% to 16.2%). Follow-up completed in 82.5%. The vomiting in the ED or after discharge in two groups, there was no significant difference: 7 of 27 (25.9%) versus 12 of 25 (48.0%), P=0.165, difference 22.1% (95% confidence interval -3.5% to 47.7%). ED length of stay and parental satisfaction were similar between groups. Conclusion There is no significant reduction of the incidence of vomiting in oral ondansetron group with IM ketamine procedural sedation in children. Key Words: Ketamine; Conscious Sedation; Vomiting

Efficacy of acupuncture in prevention of delayed chemotherapy induced nausea and vomiting in gynecologic cancer patients

ObjectiveTo compare the efficacy between acupuncture and ondansetron in the prevention of delayed chemotherapy induced nausea and vomiting (CINV). Methods70 patients were randomized to receive either 1) acupuncture at P6 point before chemotherapy infusion or 2) ondansetron 8mg intravenously 30min before chemotherapy infusion in their first cycle with cross-over of antiemetic regimen in the consecutive cycle. All patients received dexamethasone 5mg orally twice a day for 3days. Patients were given additional does of ondansetron 4mg orally every 12h if they experienced emesis. Emetic episode, severity of nausea score of 0–10 and adverse events were recorded. Complete response was defined as no nausea, no vomiting and no requirement of additional antiemetic drugs. FACT-G scale was used to evaluate quality of life (QOL) 7days after each cycle of chemotherapy. ResultsThe acupuncture group had a significantly higher rate of complete response in the prevention of delayed CINV (52.8% and 35.7%, P=0.02). Compared to another group, the acupuncture group reported significantly lower delayed nausea (45.7% and 65.7%, P=0.004), nausea score (P<0.001) and fewer dosages of additional oral ondansetron (P=0.002). Adverse effects were also significantly lower in the acupuncture group with less frequent constipation (P=0.02) and insomnia (P=0.01). Overall FACT-G scores were significantly higher in the acupuncture group. ConclusionAcupuncture is effective in preventing delayed CINV and in promoting better QOL. With fewer adverse effects, it may be used as an alternative treatment option for CINV.

Is a single dose of oral ondansetron effective in reducing rates of intravenous rehydration in children with gastroenteritis?

Is a single dose of oral ondansetron effective in reducing rates of intravenous rehydration in children with gastroenteritis?

English

Spinal anesthesia is the most commonly performed anesthesia technique in patients undergoing cesarean sections. Postdural puncture headache (PDPH) is one of the common complications following spinal anesthesia more so in in obstetric patients. It is preventable complication, hence the study is undertaken to know the incidence of PDPH in patients undergoing cesarean sections.100 patients belonging to ASA grade I & II, age group ranging from 20-40 years who are subjected to LSCS considered for the study. Patients with acute or chronic headache, otolaryngeal, ophthalmic and neurological problems are excluded from this study. Study is conducted in District hospital attached to Belgaum Institute of Medical Sciences. 0.5% Bupivacaine hydrochloride is injected at L3-L4 level using 25G Quincke needle. In the postoperative period only 3% of cases developed PDPH.2 patients had mild headache and one patient developed moderate headache with vomiting, which was managed by analgesic oral paracetamol, antiemetic ondansetron and fluids.

Impact of Increasing Ondansetron Use on Clinical Outcomes in Children With Gastroenteritis

Ondansetron hydrochloride use in children with gastroenteritis is increasing rapidly; however, little is known about its impact on outcomes. To determine whether increasing emergency department ondansetron use has resulted in a reduction in intravenous rehydration rates. Retrospective observational analysis of eligible visits included in the Pediatric Health Information System administrative database. Eligible institutions included 18 emergency departments geographically distributed across the United States, and participants included 804,000 patients aged 0 to 18 years who were diagnosed as having gastroenteritis in an emergency department at an eligible participating institution between January 1, 2002, and December 31, 2011. The presence or absence of oral ondansetron administration was identified for each patient through database review. Visits were categorized based on institutional ondansetron use: low (<5% administered ondansetron), medium (5%-25%), or high (>25%). We conducted hospital-level analyses of the associations between ondansetron use and 3 outcomes: intravenous rehydration (primary), hospitalization, and emergency department revisits within 3 days. Time-series regression models were used, adjusting for demographic characteristics, laboratory testing, diagnostic imaging, and rotavirus infection. A total of 804,000 eligible patient visits were identified. Oral ondansetron use increased from a median institutional rate of 0.11% (interquartile range, 0.04%-0.44%) of patient visits in 2002 to 42.2% (interquartile range, 37.5%-49.1%) in 2011 (P < .001). Intravenous rehydration was administered to 43,413 of 232,706 children (18.7%) during the low ondansetron period compared with 59,450 of 334,264 (17.8%) during the high ondansetron period (adjusted percentage change = -0.33%; 95% CI, -1.86% to 1.20%). During the transition from low to high ondansetron use, we observed no change in the hospitalization rate (adjusted percentage change = -0.33%; 95% CI, -0.95% to 0.29%), but emergency department revisits decreased (adjusted percentage change = -0.31%; 95% CI, -0.49% to -0.13%). The change in all 3 outcomes varied widely between low and high ondansetron use categories at an institutional level. Oral ondansetron was provided to 13.5% (95% CI, 13.3% to 13.7%) of children administered intravenous rehydration. Although ondansetron use increased during the study period, intravenous rehydration rates were unchanged. Most children administered intravenous fluids did not receive oral ondansetron. Our findings highlight the need to focus efforts to administer ondansetron to children at greatest risk for oral rehydration failure.

Does ondansetron have an effect on intramuscular ketamine‐associated vomiting in children? A prospective, randomised, open, controlled study

Ketamine is one of the most commonly used sedatives for facilitating painful procedures for paediatric patients in the emergency department (ED). However, the use of ketamine is associated with a common, though not serious, adverse event usually called ketamine-associated vomiting (KAV). The purpose of this study is to evaluate the anti-emetic effect of adjunctive ondansetron in paediatric patients receiving ketamine sedation in the ED. We conducted a prospective, randomised, open, controlled study in children from 1 to 18 years of age who had undergone intramuscular ketamine sedation in the ED. The patients were randomised into two groups: a ketamine-only group and a ketamine/ondansetron group. The patients in the first group received ketamine alone, while those in the second group received ketamine with oral ondansetron. The incidence of KAV was estimated in the ED and after discharge, and the time to resumption of a normal diet was measured after sedation. A total of 237 patients were analysed. The incidence of KAV was 29.7% in the ketamine-only group and 25.2% in the ketamine/ondansetron group (P = 0.47). After administration of ketamine, the mean time to resumption of a normal diet was 8 h 54 min in the ketamine-only group and 8 h 39 min in the ketamine/ondansetron group (P = 0.67). A relatively high rate of KAV (29.7%) was observed, and the time to resumption of a normal diet after ketamine sedation was rather long. It turned out that, however, the adjunctive administration of ondansetron did not effectively reduce the incidence of KAV.

Tolerability and Pharmacokinetic Properties of Ondansetron Administered Subcutaneously With Recombinant Human Hyaluronidase in Minipigs and Healthy Volunteers

BackgroundSubcutaneous ondansetron facilitated by recombinant human hyaluronidase PH20 (rHuPH20) is an alternative for treating nausea/vomiting in patients who cannot receive ondansetron by other routes of administration. ObjectiveBased on preclinical results in minipigs, a Phase I study was designed to assess the tolerability and pharmacokinetic properties of subcutaneous ondansetron + rHuPH20 compared with intramuscular, intravenous, or oral ondansetron monotherapy in healthy volunteers. MethodsIn a crossover design, 3 minipigs were dosed with subcutaneous ondansetron 0.08 mg/kg + rHuPH20, or as intramuscular or intravenous monotherapy, for the evaluation of plasma ondansetron concentrations and local tolerability. In a randomized, open-label, 4-way crossover study, subjects received a randomized sequence of SC ondansetron 4 mg + rHuPH20, or ondansetron monotherapy IM (4 mg), IV (4 mg), or PO (8 mg), over 4 daily visits. Study participants included healthy volunteers aged 19 to 65 years with adequate venous access in both upper extremities and no history of QT-interval prolongation. Primary tolerability end points (administration-site observations, systemic adverse events [AEs], and subject-assessed pain) were assessed, and pharmacokinetic parameters (AUC, Cmax, Tmax, t½) were computed to compare relative rate and extent of systemic exposure. Results were described using summary statistics, and bioequivalence was determined with a linear mixed-effects model. ResultsIn the preclinical study, no adverse events or significant local reactions were observed. The Cmax (45.8 ng/mL at 0.08 hour) with subcutaneous administration + rHuPH20 was 83% greater and was achieved 68% faster than with intramuscular administration (Cmax = 25 ng/mL at 0.25 hour). In the clinical study, a total of 12 subjects (7 women, 5 men; white majority; mean age, 44.8) were randomized. The majority of AEs were at the injection site, mild in severity, and transient. After subcutaneous administration of ondansetron + rHuPH20, geometric mean Cmax was 35% higher than with intramuscular ondansetron, 43% lower than with intravenous ondansetron, and 126% higher than with oral ondansetron (corrected for dose). Bioequivalence tests demonstrated that systemic exposure after subcutaneous administration was similar to that after intramuscular or intravenous administration and significantly greater than that after oral administration. ConclusionsSubcutaneous ondansetron + rHuPH20 was generally well-tolerated. Subcutaneous dosing resulted in an extent of systemic exposure similar to that with intramuscular or intravenous dosing and greater than that with oral administration, and may be an option for clinical administration of ondansetron. ClinicalTrials.gov identifier: NCT01572012.

Oral, subcutaneous, and intravenous pharmacokinetics of ondansetron in healthy cats

Ondansetron is a 5-HT3 receptor antagonist that is an effective anti-emetic in cats. The purpose of this study was to evaluate the pharmacokinetics of ondansetron in healthy cats. Six cats with normal complete blood count, serum biochemistry, and urinalysis received 2 mg oral (mean 0.43 mg/kg), subcutaneous (mean 0.4 mg/kg), and intravenous (mean 0.4 mg/kg) ondansetron in a cross-over manner with a 5-day wash out. Serum was collected prior to, and at 0.25, 0.5, 1, 2, 4, 8, 12, 18, and 24 h after administration of ondansetron. Ondansetron concentrations were measured using liquid chromatography coupled to tandem mass spectrometry. Noncompartmental pharmacokinetic modeling and dose interval modeling were performed. Repeated measures anova was used to compare parameters between administration routes. Bioavailability of ondansetron was 32% (oral) and 75% (subcutaneous). Calculated elimination half-life of ondansetron was 1.84 ± 0.58 h (intravenous), 1.18 ± 0.27 h (oral) and 3.17 ± 0.53 h (subcutaneous). The calculated elimination half-life of subcutaneous ondansetron was significantly longer (P < 0.05) than oral or intravenous administration. Subcutaneous administration of ondansetron to healthy cats is more bioavailable and results in a more prolonged exposure than oral administration. This information will aid management of emesis in feline patients.