Bimodal Release Ondansetron for Acute Gastroenteritis Among Adolescents and Adults: A Randomized Clinical Trial.

Importance: Vomiting resulting from acute gastroenteritis is commonly treated with intravenous antiemetics in acute care settings. If oral treatment were beneficial, patients might not need intravenous administered hydration or medication. Furthermore, a long-acting treatment could provide sustained relief from nausea and vomiting. Objective: To determine whether an experimental long-acting bimodal release ondansetron tablet decreases gastroenteritis-related vomiting and eliminates the need for intravenous therapy for 24 hours after administration. Design, Setting, and Participants: This placebo-controlled, double-blind, randomized clinical trial included patients from 19 emergency departments and 2 urgent care centers in the United States from December 8, 2014, to February 17, 2017. Patients 12 years and older with at least 2 vomiting episodes from presumed gastroenteritis in the previous 4 hours and symptoms with less than 36 hours' duration were randomized using a 3:2 active to placebo ratio. Analyses were performed on an intent-to-treat basis and conducted from June 1, 2017, to November 1, 2017. Intervention: Bimodal release ondansetron tablet containing 6 mg of immediate release ondansetron and 18 mg of a 24-hour release matrix for a total of 24 mg of ondansetron. Main Outcomes and Measures: Treatment success was defined as no further vomiting, no need for rescue medication, and no intravenous hydration for 24 hours after bimodal release ondansetron administration. Results: Analysis included 321 patients (mean [SD] age, 29.0 [11.1] years; 195 [60.7%] women), with 192 patients in the bimodal release ondansetron group and 129 patients in the placebo group. Treatment successes were observed in 126 patients in the bimodal release ondansetron group (65.6%) compared with 70 patients in the placebo group (54.3%), with an 11.4% (95% CI, 0.3%-22.4%) absolute probability difference. The proportion of treatment success was 21% higher among patients who received bimodal release ondansetron compared with those who received a placebo (relative risk, 1.21; 95% CI, 1.00-1.46; P = .04). In an analysis including only patients with a discharge diagnosis of acute gastroenteritis and no major protocol violations, there were 123 treatment successes (69.5%) in the bimodal release ondansetron group compared with 67 treatment successes (54.9%) in the placebo group (relative risk, 1.27; 95% CI, 1.05-1.53; P = .01). Adverse effects were infrequent and similar to the known safety profile of ondansetron. Conclusions and Relevance: This randomized clinical trial found that a long-acting bimodal release oral ondansetron tablet was an effective antiemetic among adolescents and adults with moderate to severe vomiting from acute gastroenteritis. The drug benefits extended to 24 hours after administration. Bimodal release ondansetron may decrease the need for intravenous access and emergency department care to manage acute gastroenteritis. Trial Registration: ClinicalTrials.gov identifier: NCT02246439.

Double-blind, randomized, parallel-group study on the efficacy and safety of oral granisetron and oral ondansetron in the prophylaxis of nausea and vomiting in patients receiving hyperfractionated total body irradiation.

The efficacy and safety of granisetron and ondansetron for the prophylaxis of nausea and vomiting resulting from hyperfractionated total body irradiation (TBI) were assessed. Thirty-four patients randomly received double-blind, oral granisetron (2 mg, 1 h before first daily fraction of radiation) or ondansetron (8 mg, 1.5 h prior to each fraction of TBI). Ninety patients who received the same TBI regimen prior to bone marrow transplantation (BMT), but no 5-HT3-receptor antagonist, were identified and comprised the historical control group. By design, this study was only powered to show a difference between each of the active treatment groups and the historical control group. Significantly more patients given granisetron (33.3%) or ondansetron (26.7%) had zero emetic episodes over 4 days, the primary efficacy end point, than those in the historical control group (0%) (P < 0.01; intent-to-treat). Secondary efficacy end points were also evaluated. During the first 24 h, significantly more patients taking granisetron (61.1%) or ondansetron (46.7%) had zero emetic episodes than patients in the historical control group (6.7%) (P < 0.01). Complete emetic control (no emesis or rescue antiemetic) over 4 days was more frequent in patients taking granisetron (27.8%) or ondansetron (26.7%) compared with the historical control group (0%) (P < 0.01). Significantly fewer patients taking granisetron (18/18), but not those taking ondansetron (12/15), experienced more than five emetic episodes during the 4 days of the study compared with the historical control group (40/90; P < 0.01). Oral granisetron and ondansetron are safe and effective for the prevention of nausea and vomiting resulting from TBI.

A prospective survey of knowledge and perceptions of ondansetron: what do health care workers know about this drug?

Ondansetron is a relatively new drug whose optimal use is dependent on an understanding of its characteristics and role relative to traditional antiemetics. To assess perceptions and knowledge regarding ondansetron, we conducted a prospective written survey involving 56 physicians, pharmacists, and nurses at this hospital. Pharmacists claimed to be exposed to ondansetron promotion by industry more than the other groups. Apart from industry, pharmacists were considered to be the most common source of drug information. Nurses were less aware of dosage form equivalence than the other groups (p = 0.042). Physicians were more aware of twice daily dosing efficacy than other respondents (p = 0.0006). Nurses were able to better identify the relative duration of antiemetic benefit over metoclopramide (p = 0.008); however, most participants tended to be misinformed on this issue. Pharmacists were more familiar with the side effect profile while physicians were more cognizant of oral (p = 0.001) and parenteral (p = 0.018) drug costs than other groups. Overall, survey scores for physicians and pharmacists were higher than those for nurses (p = 0.007). There is an apparent difference across health care profession disciplines in the perceptions and knowledge about ondansetron. Specific misconceptions could lead to suboptimal drug use and warrant efforts to ensure a good understanding of the attributes and relative role of this agent.

Prophylactic antiemetic treatment with ondansetron in children undergoing tonsillectomy.

BACKGROUND: Children undergoing tonsillectomy are at high risk for postoperative vomiting. This study was undertaken to compare ondansetron with metoclopramide and droperidol for the prevention of postoperative vomiting after tonsillectomy. METHODS: Two hundred fifty-six pediatric patients, ages 2-12 years, scheduled for outpatient tonsillectomy were enrolled in a prospectively randomized, double-blinded investigation and assigned to one of four treatment regimens: placebo (saline), ondansetron 0.15 mg.kg-1, metoclopramide 0.5 mg.kg-1, or droperidol 0.075 mg.kg-1. Study drugs were administered intravenously after inhalation induction of anesthesia with halothane, nitrous oxide, and oxygen. No premedication or neuromuscular blocking agents were used. Tracheal extubation was performed while patients were still deeply anesthetized. Acetaminophen and meperidine were given for postoperative pain. Patients were observed in the recovery room for a minimum of 4 h before discharge. Parents were contacted by telephone 24 h later for follow-up. RESULTS: Ondansetron reduced the incidence of postoperative emesis from 62% to 27% (relative risk 0.45, 95% confidence interval 0.29 to 0.70, P < 0.001). Metoclopramide and droperidol had no significant effect on postoperative vomiting. CONCLUSIONS: The intravenous administration of ondansetron 0.15 mg.kg-1 is highly effective in reducing postoperative emesis in children undergoing tonsillectomy. Metoclopramide and droperidol at the doses tested are ineffective in this population.

Effects of ondansetron in the prevention of postoperative nausea and vomiting in children.

BACKGROUND: Postoperative nausea and vomiting (PONV) is a commonly observed adverse effect of general anesthesia. Recently, ondansetron, a new serotonin3 (5-hydroxytryptamine3) receptor antagonist was shown to be effective in the prophylaxis and prevention of chemotherapy-induced nausea and vomiting in children and adults as well as of PONV in adults. The aim of the current study was to evaluate the capacity of ondansetron to prevent PONV in pediatric patients. METHODS: Two hundred children (132 boys and 68 girls) 2-10 yr of age received general inhalational anesthesia for surgical procedures (the extremities; ear, nose, and throat; inguinal hernia and phimosis; and dentistry) of an expected duration of less than 90 min. This study was divided into two phases: prophylaxis and rescue treatment. For prophylaxis, patients were randomly assigned to two groups: one group received an intravenous injection of 0.1 mg/kg ondansetron, and the other group received a placebo before surgical incision under double-blind conditions. For rescue treatment, only placebo patients were included; as a rescue medication they received an intravenous injection of 0.1 mg/kg ondansetron or 0.02 mg/kg droperidol according to a prestudy randomization under double-blind conditions. Incidence and severity of PONV (PONV score 0 = no nausea and no retching; 1 = complaining of sickness and retching; 2 = vomiting one or two time in 30 min; 3 = vomiting more than two times in 30 min) was recorded over a 4-h period in the postanesthesia care unit. Within 72 h of the procedure, a follow-up nurse interviewed the parents for late-onset nausea in the children. RESULTS: With regard to prophylaxis, 10% of patients receiving ondansetron had PONV during the 4-h observation period versus 40% of those receiving placebo (P < 0.001). The incidence of vomiting alone (PONV score > or = 2) was 5% and 25%, respectively (P < 0.001). There were no significant differences between ondansetron and droperidol in the treatment of PONV. However, at the end of the 4-h period, ondansetron patients were less sedated than were patients who had received droperidol (P < 0.01). Interviews with parents could be performed for 143 of 200 children (76 ondansetron and 67 placebo). Twenty-four children (15 ondansetron and 9 placebo) showed late-onset PONV after the 4-h observation period but within 24 h of the procedure (19.7% vs. 13.4%; P not significant). CONCLUSIONS: Ondansetron is effective in the prevention of PONV in pediatric patients for the first 4 h after general anesthesia. Lower sedation scores with ondansetron compared with droperidol may be an advantage, especially in ambulatory surgery. However, the incidence of late-onset PONV (> 4-24 h) was not influenced by prophylactic treatment with one dose of ondansetron preoperatively.

Evaluation of ondansetron prescribing in US academic medical centers.

BACKGROUND: The study objectives were to characterize the use of the antiemetic ondansetron, a serotonin subtype 3 receptor antagonist, in US academic medical centers, and to assess ondansetron prescribing with consensus-derived prescribing guidelines used as evaluation criteria. METHODS: A multicenter, prospective, observational study was conducted in the inpatient and outpatient care areas of 23 US academic medical centers. A total of 670 patients received ondansetron (508 inpatients and 162 outpatients). The use of ondansetron was compared with consensus-derived prescribing guidelines on the basis of indication for use and dose administered. RESULTS: Only 253 (37.8%) of the 670 patients satisfied for prescribing guidelines for both indication for use and dose administered. The remainder of the patients did not satisfy the guidelines, in whole or in part. If all ondansetron use had met the prescribing guidelines in the patients studied, a reduction in ondansetron use of 31% (16 185/52 260 mg) would have been realized. At an estimated cost of $5 per milligram, this reduction represents a potential cost savings of nearly $81,000, or $121 per patient studied. CONCLUSION: Since its introduction in 1991, ondansetron has become a commonly used antiemetic in US academic medical centers. Although ondansetron is safe and effective in improving patients' tolerance of emetogenic therapies, including cancer chemotherapy, its high cost has added a significant burden to the pharmaceutical budgets of many institutions. The study data suggest that compliance with ondansetron prescribing guidelines, with elimination of indiscriminant use, could result in significant cost savings.

Ondansetron for efficient emesis control during total body irradiation.

Ondansetron is a 5-hydroxytryptamine receptor antagonist which has shown activity in the prevention of emesis following cytotoxic and radiation therapy for cancer. We describe our experience using ondansetron in 25 patients undergoing fractionated total body irradiation (TBI) 12 Gy/3 days as conditioning for bone marrow transplantation. Antiemetic efficiency was investigated during the 3 days of TBI prior to high-dose cytotoxic chemotherapy. Twenty-two of the 25 patients (88%) achieved sufficient emesis control with less than three emetic episodes whereas the remaining 12% experienced three to five emetic events during their worst 24-h period. Eleven patients (44%) had complete control with no vomiting at all. Of 75 'patient days', 52 (69%) were without any emesis, 20 (27%) were associated with one to two and only three (4%) with three to five emetic episodes. Headache occurred in four patients (16%). No other significant adverse effects were seen, in particular no extrapyramidal reactions due to ondansetron. Our data confirm that ondansetron plays a major role in the antiemetic management of patients undergoing TBI.