Evaluation of palonosetron, fosaprepitant, and olanzapine as antiemetic prophylaxis for fludarabine and melphalan-based conditioning regimens prior to allogeneic hematopoietic stem cell transplants.

BACKGROUND: Limited data are available regarding efficacious antiemetic regimens to prevent chemotherapy-induced nausea and vomiting (CINV) for patients undergoing allogeneic hematopoietic stem cell transplant (HSCT). In patients aged 60 years or older, allogeneic HSCT is associated with improved survival, but tolerability of the transplant is a significant barrier. Fludarabine and melphalan (Flu-Mel) is a frequently utilized multi-day reduced intensity conditioning regimen for allogeneic HSCT. However, the optimal CINV prevention regimen is unknown. OBJECTIVE: The purpose of this study was to evaluate the efficacy of a novel CINV prophylaxis regimen prior to allogeneic HSCT with Flu-Mel compared to a historical control group. STUDY DESIGN: This was a retrospective, single-center, cohort review of 123 patients who received a Flu-Mel preparative regimen prior to allogeneic HSCT from January 1, 2019, to September 30, 2022. Fifty-nine patients received high dose ondansetron (HDO) for CINV prevention, while sixty-four patients received a combination of palonosetron, fosaprepitant, and olanzapine (PFO). The primary outcome was average number of rescue antiemetic doses administered per day. A key secondary outcome was time to first rescue antiemetic. RESULTS: The median number of antiemetic doses used per day was significantly lower in patients who received PFO compared to HDO (1.94 doses [0.31-3.60] vs 3.31 doses [1.61-4.92]; p = 0.002). In addition, use of PFO significantly prolonged the median time to first rescue antiemetic compared to HDO (41.3 h [24.3-122.7] vs 26.2 h [14.7-48.1]; p = 0.016). CONCLUSION: The combination of palonosetron, fosaprepitant, and olanzapine is an effective antiemetic regimen for patients receiving a Flu-Mel-based preparative regimen.

Associations between ondansetron and the incidence of postoperative nausea and vomiting and food intake in Japanese female undergoing laparoscopic gynecological surgery: a retrospective study.

PURPOSE: Prevention of postoperative nausea and vomiting (PONV) is important to achieve DREAM (drinking, eating, mobilization). Ondansetron inhibits PONV, but its effects on postoperative food intake have not been investigated. This study aimed to examine associations between ondansetron and PONV incidence, and postoperative food intake. METHODS: This retrospective study included adult patients (n = 632) who underwent laparoscopic gynecological surgery at Kyushu University Hospital between January 2017 and June 2023. Outcomes were PONV on the day of surgery, PONV up to the day after surgery, and food intake, which was assessed for breakfast and lunch on the day after surgery. Odds ratios (ORs) for PONV incidence and postoperative no-food intake were calculated between those with and without ondansetron during surgery. Multivariable-adjusted analysis was performed using possible confounding factors for PONV. Synergistic effects of combining ondansetron with dexamethasone or total intravenous anesthesia (TIVA) were assessed. RESULTS: Multivariable-adjusted ORs for PONV on the day of surgery and up to the day after surgery were 0.56 (95% confidence interval, 0.32-0.99, p = 0.04) and 0.52 (0.30-0.93, p = 0.03), respectively, in the ondansetron group (n = 84) compared with the non-ondansetron group (n = 548). In contrast, multivariable-adjusted ORs for no-food intake of breakfast and lunch the day after surgery in the ondansetron group compared with the non-ondansetron group were not significant. Analysis of synergistic effects on PONV showed no significant interaction between ondansetron and dexamethasone or ondansetron and TIVA combinations. CONCLUSION: Ondansetron administration during surgery was significantly associated with decreased PONV risk but was not associated with food intake the day after surgery.

Olanzapine as an add-on, pre-operative anti-emetic drug for postoperative nausea or vomiting: a randomised controlled trial.

Postoperative nausea or vomiting occurs in up to 40% in patients with multiple risk factors, despite prophylaxis. Olanzapine is an antipsychotic drug that is used to prevent nausea and vomiting in palliative care and to treat chemotherapy-induced nausea and vomiting. This study aimed to examine whether pre-operative olanzapine, as a prophylactic anti-emetic added to intra-operative dexamethasone, ondansetron and total intravenous anaesthesia, reduced the incidence of postoperative nausea or vomiting. We performed a multiply-blinded randomised controlled trial in patients aged 18-60 years with cancer at high risk of postoperative nausea or vomiting (three or four risk factors according to the Apfel criteria) plus a previous history of chemotherapy-induced nausea and vomiting. Patients were allocated at random to receive 10 mg olanzapine or placebo orally 1 h before surgery in addition to a two-drug regimen (dexamethasone and ondansetron) and propofol anaesthesia to prevent postoperative nausea or vomiting. The primary outcome was the incidence of postoperative nausea or vomiting in the first 24 h after surgery. In total, 100 patients were enrolled; 47 in the olanzapine group and 49 in the control group completed the study. The baseline characteristics of the groups were similar. The incidence of postoperative nausea or vomiting in the first 24 h after surgery was lower in the olanzapine group (12/47, 26%) than in the control group (31/49, 63%) (p = 0.008, RR 0.40 (95%CI 0.21-0.79)). Adding pre-operative oral olanzapine to intra-operative dexamethasone and ondansetron was highly effective in reducing the risk of postoperative nausea or vomiting in the first 24 hours after surgery in patients with a previous history of chemotherapy-induced nausea and vomiting and at least three Apfel risk factors for postoperative nausea or vomiting.

Acupuncture combined with ondansetron for prevention of postoperative nausea and vomiting in high-risk patients undergoing laparoscopic gynaecological surgery: A randomised controlled trial.

BACKGROUND: Consensus guidelines recommend the use of multiple antiemetics as prophylaxis in patients at high risk of postoperative nausea and vomiting (PONV), but the evidence regarding combining acupuncture and antiemetics as a multimodal approach was of very low quality. OBJECTIVE: This study aimed to assess the effect of combinations of acupuncture with ondansetron versus ondansetron alone for PONV prophylaxis in women at a high risk. METHODS: This parallel, randomised controlled trial was conducted in a tertiary hospital in China. Patients who had three or four PONV risk factors on the Apfel simplified risk score, undergoing elective laparoscopic gynaecological surgery for benign pathology, were recruited. Patients in the combination group received two sessions of acupuncture treatment and 8 mg intravenous ondansetron, whereas those in the ondansetron group received ondansetron alone. The primary outcome was the incidence of PONV within 24 h postoperatively. Secondary outcomes included the incidence of postoperative nausea, postoperative vomiting, adverse events etc. RESULTS: Between January and July 2021, a total of 212 women were recruited, 91 patients in the combination group and 93 patients in the ondansetron group were included in the modified intention-to-treat analysis. In the first 24 h postoperatively, 44.0% of the patients in the combination group and 60.2% of the patients in the ondansetron group experienced nausea, vomiting, or both (difference, -16.3% [95% CI, -30.5 to -2.0]; risk ratio, 0.73 [95% CI, 0.55-0.97]; p = 0.03). However, the results of the secondary outcomes showed that compared to ondansetron alone, acupuncture together with ondansetron was only effective in reducing nausea but did not have a significant impact on vomiting. The incidence of adverse events was similar between the groups. CONCLUSION: Acupuncture combined with ondansetron as a multimodal prophylaxis approach is more effective than ondansetron alone in preventing postoperative nausea in high-risk patients.

Antiemetic Administration and Its Association with Race: A Retrospective Cohort Study.

BACKGROUND: Anesthesiologists' contribution to perioperative healthcare disparities remains unclear because patient and surgeon preferences can influence care choices. Postoperative nausea and vomiting is a patient- centered outcome measure and a main driver of unplanned admissions. Antiemetic administration is under the sole domain of anesthesiologists. In a U.S. sample, Medicaid insured versus commercially insured patients and those with lower versus higher median income had reduced antiemetic administration, but not all risk factors were controlled for. This study examined whether a patient's race is associated with perioperative antiemetic administration and hypothesized that Black versus White race is associated with reduced receipt of antiemetics. METHODS: An analysis was performed of 2004 to 2018 Multicenter Perioperative Outcomes Group data. The primary outcome of interest was administration of either ondansetron or dexamethasone; secondary outcomes were administration of each drug individually or both drugs together. The confounder-adjusted analysis included relevant patient demographics (Apfel postoperative nausea and vomiting risk factors: sex, smoking history, postoperative nausea and vomiting or motion sickness history, and postoperative opioid use; as well as age) and included institutions as random effects. RESULTS: The Multicenter Perioperative Outcomes Group data contained 5.1 million anesthetic cases from 39 institutions located in the United States and The Netherlands. Multivariable regression demonstrates that Black patients were less likely to receive antiemetic administration with either ondansetron or dexamethasone than White patients (290,208 of 496,456 [58.5%] vs. 2.24 million of 3.49 million [64.1%]; adjusted odds ratio, 0.82; 95% CI, 0.81 to 0.82; P < 0.001). Black as compared to White patients were less likely to receive any dexamethasone (140,642 of 496,456 [28.3%] vs. 1.29 million of 3.49 million [37.0%]; adjusted odds ratio, 0.78; 95% CI, 0.77 to 0.78; P < 0.001), any ondansetron (262,086 of 496,456 [52.8%] vs. 1.96 million of 3.49 million [56.1%]; adjusted odds ratio, 0.84; 95% CI, 0.84 to 0.85; P < 0.001), and dexamethasone and ondansetron together (112,520 of 496,456 [22.7%] vs. 1.0 million of 3.49 million [28.9%]; adjusted odds ratio, 0.78; 95% CI, 0.77 to 0.79; P < 0.001). CONCLUSIONS: In a perioperative registry data set, Black versus White patient race was associated with less antiemetic administration, after controlling for all accepted postoperative nausea and vomiting risk factors.

Efficacy of the granisetron transdermal system for the control of nausea and vomiting induced by highly emetogenic chemotherapy: a multicenter, randomized, controlled trial.

BACKGROUND/AIMS: We compared the efficacy of the granisetron transdermal system (GTS) with that of ondansetron for controlling chemotherapy-induced nausea and vomiting (CINV) in patients treated with highly emetogenic chemotherapy (HEC). METHODS: We randomized a total of 389 patients to groups treated by GTS and ondansetron before HEC. The primary endpoint was the percentage of patients achieving complete response (CR; no retching/vomiting/rescue medication) of CINV from the time of chemotherapy initiation to 24 hours after the last administration of chemotherapy (prespecified non-inferiority margin of 15%). Quality of life (QoL) was also assessed using the Functional Living Index-Emesis (FLIE). RESULTS: The per protocol analysis included 152 (47.80%) and 166 patients (52.20%) in the GTS and ondansetron groups, respectively. In the full analysis set, the most common diagnosis, regimen, and period of chemotherapy were lung cancer (149 patients, 40.27%), cisplatin-based regimen (297 patients, 80.27%), and 1 day chemotherapy (221 patients, 59.73%). The CR rates were 86.84% and 90.36% in the GTS and ondansetron groups, respectively; the treatment difference was -3.52% (95% confidence interval, -10.52 to 3.48) and met the primary endpoint, indicating that GTS was not inferior to ondansetron. Patient satisfaction, assessed on the FLIE, showed significantly higher scores in the GTS group compared to the ondansetron group (mean ± standard deviation, 1,547.38 ± 306.00 and 1,494.07 ± 312.05 mm, respectively; p = 0.0449). CONCLUSION: GTS provided effective, safe, and well-tolerated control of CINV and improved the QoL in HEC.

Serotonin type-3 receptor antagonists selectively kill melanoma cells through classical apoptosis, microtubule depolymerisation, ERK activation, and NF-κB downregulation.

Malignant melanoma is a highly metastatic tumour, resistant to treatment. Serotonin type-3 (5-HT3) receptor antagonists, such as tropisetron and ondansetron, are well-tolerated antiemetic drugs commonly used to prevent nausea caused by chemotherapy or radiotherapy. We investigated the anticancer effects of these drugs on melanoma cancer cell lines WM-266-4 and B16F10 with or without paclitaxel. We constructed IC50 curves and performed Chou-Talalay analysis, using data obtained with the MTT assay. Flow cytometry and fluorescent microscopy were used to examine characteristics of the cell cycle, cell death and cytoskeleton changes. Protein levels and activation were analysed by western blotting and molecular docking studies carried out. Data were analysed by one way ANOVA and post hoc testing. Ondansetron and tropisetron showed selective concentration-dependent cytotoxicity in melanoma cell lines WM-266-4 and B16F10. The effect in combination with paclitaxel was synergistic. The drugs did not cause cell cycle arrest but did promote characteristics of classical apoptosis, including accumulation of subG1 DNA, cleaved caspase-3, mitochondrial membrane permeability and phosphatidylserine exposure. As well, the cytosolic calcium level in the melanoma cells was enhanced, phosphorylated ERK1/2 induced and NF-κB inhibited. Finally, the formation of microtubules was shown to be impaired in melanoma cells treated with ondansetron or tropisetron. Docking studies were used to predict that these drugs could bind to the colchicine binding site on the tubulin molecule. Antiemetic drugs, already given in combination with chemotherapy, may enhance the cytotoxic effect of chemotherapy, following successful delivery to the tumour site.

Combination of dexamethasone and ondansetron in prophylaxis nausea and vomiting in gynecological operation.

BACKGROUND: Postoperative nausea and vomiting occur in about 20-30% of women; however, some reports have estimated the rate at 70% in at-risk individuals. Gynecological and obstetrical operations are among the most frequent types of surgeries to be associated with nausea and vomiting postoperatively. Ondansetron and dexamethasone have been compared in a variety of studies for postoperative prophylaxis. AIM OF THE STUDY: This study was conducted in order to compare the efficacy and safety of dexamethasone and ondansetron, alone or in combination, for prevention of postoperative nausea and vomiting in a sample of Iraqi women undergoing gynecological surgeries. PATIENTS AND METHODS: The study was conducted in Al-Diwaniyah Province, a region belonging to the Mid-Euphrates sector of Iraq, at the Child and Maternity Teaching Hospital. The study started in June 2021 and the work with the research was accomplished in September 2022. The study included a total of 100 women undergoing different gynecological surgeries such as ovarian cystectomy, oophorectomy, ectopic pregnancy, total abdominal hysterectomy, and myomectomy. All participants involved in the study were categorized randomly into four groups, namely, dexamethasone, ondansetron, combined, and placebo groups. RESULTS: The rates of nausea in the different groups were analyzed. The rates of nausea in dexamethasone, ondansetron, and combined groups revealed a significant decrease compared with that of placebo group (P < 0.05), and the rate was significantly lower in combined group when compared with dexamethasone and ondansetron groups (P < 0.05). The rate of nausea in combined group was significantly lower than that of dexamethasone and ondansetron groups. The rate of vomiting in combined group was significantly lower than that of placebo group and less than that of the dexamethasone group (P < 0.05). CONCLUSION: Based on our study and previous reports, both dexamethasone and ondansetron are efficient and safe in preventing nausea and vomiting in gynecological operations; however, combination of both provides the best results.

Antiemetic prophylaxis for chemoradiotherapy-induced nausea and vomiting in locally advanced head and neck squamous cell carcinoma: a prospective phase II trial.

BACKGROUND: There is sparse research reporting effective interventions for preventing nausea and emesis caused by concurrent chemoradiotherapy (CCRT) in locally advanced head and neck squamous cell carcinoma (LA-HNSCC). METHODS: Treatment-naïve LA-HNSCC patients received intensity-modulated radiotherapy with concomitant cisplatin 100 mg/m2 (33 mg/m2/days [d]1-3) every 3 weeks for two cycles. All patients were given oral aprepitant 125 mg once on d1, then 80 mg once on d2-5; ondansetron 8 mg once on d1; and dexamethasone 12 mg once on d1, then 8 mg on d2-5. The primary endpoint was complete response (CR). Pursuant to δ = 0.2 and α = 0.05, the expected CR rate was 80%. RESULTS: A total of 43 patients with LA-HNSCC were enrolled. The median age was 53 years, and 86.0% were male. All patients received radiotherapy and 86.0% of patients completed both cycles as planned. The overall CR rate was 86.0% (95% confidence interval [CI]: 72.1-94.7). The CR rates for cycles 1 and 2 were 88.4% (95% CI: 74.9-96.1) and 89.2% (95% CI: 74.6-97.0). The complete protection rate in the overall phase was 72.1% (95% CI: 56.3-84.7). The emesis-free and nausea-free responses in the overall phase were 88.4% (95% CI: 74.9-96.1) and 60.5% (95% CI: 44.4-75.0), respectively. The adverse events related to antiemetics were constipation (65.1%) and hiccups (16.3%), but both were grade 1-2. There was no grade 4 or 5 treatment-related toxicity with antiemetic usage. CONCLUSION: The addition of aprepitant into ondansetron and dexamethasone provided effective protection from nausea and emesis in patients with LA-HNSCC receiving radiotherapy and concomitant high-dose cisplatin chemotherapy.

A pharmacogenomic investigation of the cardiac safety profile of ondansetron in children and pregnant women.

BACKGROUND: Ondansetron is a highly effective antiemetic for the treatment of nausea and vomiting. However, this medication has also been associated with QT prolongation. Pharmacogenomic information on therapeutic response to ondansetron exists, but no investigation has been performed on genetic factors that influence the cardiac safety of this medication. METHODS: Three patient groups receiving ondansetron were recruited and followed prospectively (pediatric post-surgical patients n = 101; pediatric oncology patients n = 98; pregnant women n = 62). Electrocardiograms were conducted at baseline, and 5- and 30-min post-ondansetron administration, to determine the effect of ondansetron treatment on QT interval. Pharmacogenomic associations were assessed via analyses of comprehensive CYP2D6 genotyping and genome-wide association study data. RESULTS: In the entire cohort, 62 patients (24.1%) met the criteria for prolonged QT, with 1.2% of the cohort exhibiting unsafe QT prolongation. The most significant shift from baseline occurred at five minutes post-ondansetron administration (P = 9.8 × 10-4). CYP2D6 activity score was not associated with prolonged QT. Genome-wide analyses identified novel associations with a missense variant in TLR3 (rs3775291; P = 2.00 × 10-7) and a variant linked to the expression of SLC36A1 (rs34124313; P = 1.97 × 10-7). CONCLUSIONS: This study has provided insight into the genomic basis of ondansetron-induced cardiac changes and has emphasized the importance of genes that have been implicated in serotonin-related traits. These biologically-relevant findings represent the first step towards understanding this adverse event with the overall goal to improve the safety of this commonly used antiemetic medication.

Efficacy and Safety of Olanzapine in Children Receiving Highly Emetogenic Chemotherapy: A Randomized, Double-blind Placebo-controlled Phase 3 Trial.

BACKGROUND: In this trial, we evaluated the safety and efficacy of olanzapine in children receiving highly emetogenic chemotherapy. MATERIALS AND METHODS: In this study, patients aged 3 to 18 years were randomly assigned to either the olanzapine group or the placebo group. All patients received intravenous ondansetron and dexamethasone 30 minutes before highly emetogenic chemotherapy, followed by oral ondansetron for 48 hours. Participants in the olanzapine group received olanzapine once daily on days 1 and 2, while those in the control group received a placebo in the same dosage and schedule. The primary objective was: (a) to compare the complete control rates of vomiting in the delayed phase and (b) to compare the complete control rates of vomiting in acute and overall phases. The secondary objective was to evaluate the safety of olanzapine and the need for rescue medications. RESULTS: A total of 128 patients were randomly assigned either to the olanzapine group (n=63) or the control group (n=65). Complete control of vomiting between olanzapine and placebo group was 73% versus 48% ( P =0.005) in the delayed phase, 60% versus 54% ( P =0.46) in the acute phase, and 48% versus 34% ( P =0.117) in the overall phase, respectively. Grades 1 and 2 sedation was greater in the olanzapine group (46% vs. 14%; P <0.001). A significantly higher proportion of patients in the placebo group required rescue medications for vomiting compared with in the olanzapine group ( P =0.025). CONCLUSIONS: Olanzapine significantly improved complete control of vomiting in the delayed phase. A considerably lesser proportion of patients in the olanzapine group needed rescue medications.

Pharmacogenetic and clinical predictors of ondansetron failure in a diverse pediatric oncology population.

PURPOSE: Chemotherapy-induced nausea and vomiting (CINV) is a frequently seen burdensome adverse event of cancer therapy. The 5-HT3 receptor antagonist ondansetron has improved the rates of CINV but, unfortunately, up to 30% of patients do not obtain satisfactory control. This study examined whether genetic variations in a relevant drug-metabolizing enzyme (CYP2D6), transporter (ABCB1), or receptor (5-HT3) were associated with ondansetron failure. METHODS: DNA was extracted from blood and used to genotype: ABCB1 (3435C > T (rs1045642) and G2677A/T (rs2032582)), 5-HT3RB (rs3758987 T > C and rs45460698 (delAAG/dupAAG)), and CYP2D6 variants. Ondansetron failure was determined by review of the medical records and by patient-reported outcomes (PROs). RESULTS: One hundred twenty-nine patients were approached; 103 consented. Participants were less than 1 to 33 years (mean 6.85). A total of 39.8% was female, 58.3% was White (22.3% Black, 19.4% other), and 24.3% was Hispanic. A majority had leukemia or lymphoma, and 41 (39.8%) met the definition of ondansetron failure. Of variants tested, rs45460698 independently showed a significant difference in risk of ondansetron failure between a mutant (any deletion) and normal allele (p = 0.0281, OR 2.67). Age and BMI were both predictive of ondansetron failure (age > 12 (OR 1.12, p = 0.0012) and higher BMI (OR 1.13, p = 0.0119)). In multivariate analysis, age > 12 was highly predictive of ondansetron failure (OR 7.108, p = 0.0008). rs45460698 was predictive when combined with an increased nausea phenotype variant of rs1045642 (OR 3.45, p = 0.0426). CONCLUSION: Select phenotypes of 5-HT3RB and ABCB1, age, and potentially BMI can help predict increased risk for CINV in a diverse pediatric oncology population.

Predictors of Postoperative Nausea and Vomiting After Endoscopic Skull Base Surgery.

OBJECTIVES/HYPOTHESIS: The objective of this study is to evaluate the impact of patient and surgical factors, including approach and reconstruction type, on postoperative nausea and vomiting episodes following endoscopic skull base surgery. STUDY DESIGN: Retrospective review. METHODS: We performed a retrospective chart review from July 2018 to August 2020 of 99 consecutive patients undergoing endoscopic skull base surgery at a tertiary academic skull base surgery program. All patients were treated with a standardized postoperative protocol consisting of scheduled ondansetron, along with promethazine and scopolamine for breakthrough nausea and vomiting episodes. Cumulative nausea and vomiting episodes throughout hospital stay were recorded for each patient. RESULTS: Of the 99 patients identified, the mean number of nausea and vomiting episodes per patient were 0.4 ± 1.2 and 0.3 ± 0.7, respectively. Female sex (ß = .65, P = .034) and extended surgical approach (ß = .90, P = .027) were associated with increased risk for postoperative nausea. Furthermore, female sex (ß = .44, P = .018), cavernous sinus dissection (ß = .52, P = .002), and extended approach (ß = .79, P = .025) significantly increased odds of postoperative vomiting episodes. There was no association between total operative time or total postoperative opioid dose and nausea and vomiting episodes (all Ps > .05). Neither increased nausea nor vomiting episodes significantly increased odds of prolonged hospitalization (P = .105 and .164, respectively). CONCLUSION: This report highlights novel risk factors for patients undergoing endoscopic skull base surgery. Upfront standing antiemetic therapy may be considered when treating patients with independent predictors of postoperative nausea and vomiting, including female sex, cavernous sinus dissection, and extended surgical approach. LEVEL OF EVIDENCE: 4 Laryngoscope, 132:761-768, 2022.

Effect of domperidone, ondansetron, olanzapine-containing antiemetic regimen on QTC interval in patients with malignancy: a prospective, observational, single-group, assessor-blinded study.

Domperidone, ondansetron and olanzapine can prolong the QT interval. The clinical use of combinations of these drugs is not uncommon. Our study aimed to determine the presence of any QTc prolonging effect of the combination when used as antiemetic in patients receiving cancer chemotherapy. We carried out a prospective, observational study of patients with malignancy who were to receive domperidone, ondansetron and olanzapine-containing antiemetic regimen. Electrocardiograms were recorded before and during the administration of antiemetics, for three consecutive days. A blinded assessor determined the QTc interval using Bazett and Fridericia formulae. Thirty-six patients completed the study; 23 (63.9%) were females. There was a statistically significant change in QTc with time (Fridericia, χ2(4) = 15.629, p = 0.004; Bazett, χ2(4) = 15.910, p = 0.003); QTc on Day 1 was more than that during baseline (p < 0.001); these differences were significant in females (Fridericia, χ2(4) = 13.753, p = 0.008; Bazett, χ2 (4) = 13.278, p = 0.010) but not in males (Fridericia, χ2 (4) = 4.419, p = 0.352; Bazett, χ2(4) = 4.280, p = 0.369). Two female patients had an absolute QTc prolongation (Bazett correction) of > 500 ms. However, no clinically significant adverse events occurred. The findings show that QTc prolongation is a concern with olanzapine alone and in combination with domperidone and ondansetron, and needs to be investigated further.

Acute, severe dystonia after strabismus surgery in a patient on propofol, ondansetron, and bupropion.

Acute, severe dystonia is a frightening and potentially life-threatening surgical complication. We describe the case of a 41-year-old woman who experienced postoperative drug-induced dystonia after elective strabismus surgery. In this case, the medications likely responsible were propofol, ondansetron, and, possibly, bupropion.

Randomized, double-blind, placebo-controlled study of aprepitant versus two dosages of olanzapine with ondansetron plus dexamethasone for prevention of chemotherapy-induced nausea and vomiting in patients receiving high-emetogenic chemotherapy.

PURPOSE: We assessed the efficacy of aprepitant (APR) or 10 or 5 mg OLN (OLN10 or OLN5) plus ondansetron and dexamethasone for chemotherapy-induced nausea/vomiting (CINV) prophylaxis in patients receiving high-emetogenic chemotherapy (HEC). METHODS: Patients who received doxorubicin + cyclophosphamide or cisplatin were given intravenous ondansetron and dexamethasone prior to chemotherapy and oral dexamethasone on days 2-4 and randomized 1:1:1 to receive APR125 on day 1 and APR80 on days 2-3 or OLN10 or OLN5 on days 1-4. Matched placebo controls were used. The primary endpoint was no nausea in ≤ 120 h. Secondary endpoints included CINV severity, complete response (CR) rate, adverse effects (AE), and quality of life. RESULTS: Of 141 patients, 104 received AC and 37 received cisplatin. The no-nausea rates were 33% (APR), 43.2% (OLN10; p = 0.24), and 37% (OLN5; p = 0.87). Grades 2-4 nausea were experienced by fewer patients for OLN10 than for APR (24-120 h, 8.7% vs. 27.7%, respectively; p = 0.02; overall period, 19.6% vs. 40.4%, respectively; p = 0.03). The median visual analog scale nausea score from 24 to 120 h was significantly lower for OLN10 (2.3) than for APR (1.2, p = 0.03). The degrees of vomiting, CR, and AE were similar between the APR and OLN10 groups. CINV was similar between the OLN5 and APR groups. CONCLUSIONS: Nausea was less severe for OLN10 than for APR in patients receiving HEC, but other measures were similar. CINV prevention efficacy was comparable between OLN5 and APR.

The effects of ondansetron versus dexamethasone on electrocardiographic markers of ventricular repolarization in children undergoing cochlear implant.

INTRODUCTION: Congenital hearing loss is associated with cardiac rhythm disturbances namely long Q-T syndrome. This study was designed to investigate the effect of anti-emetic doses of ondansetron and dexamethasone on ECG recordings in children undergoing cochlear implant surgery. METHODS: Sixty-three pediatric patients scheduled for elective cochlear implantation were enrolled in the study. Two patients were excluded as their baseline ECG showed long QT syndrome. Anesthesia was induced with fentanyl, propofol and atracurium and maintained with propofol. Dexamethasone 0.1 mg.kg-1or ondansetron 0.2 mg.kg-1was randomly administered for the participants approximately 30 min before the end of surgery. ECG recording was performed 15 min after induction of anesthesia and 15 min after dexamethasone/ondansetron administration. RR interval, QRS duration, QT interval, and Tp-e interval were measured by a blinded cardiologist. RESULTS: Ondansetron resulted in no significant changes in RR, JTc and QTc intervals; while prolongedTp-e interval. Multivariable logistic regression analysis showed that use of ondansetron was an independent predictor of QTc prolongation after adjustment for age, gender and baseline QTc (OR = 17.94, CI 95% 1.97-168.70, p = 0.011). The incidence of postoperative retching/vomiting in ondansetron group was significantly lower than dexamethasone group. (3.2% vs. 26.7%, p = 0.011). CONCLUSION: The risk of arrhythmias with the use of ondansetron in otherwise healthy candidates of cochlear implant is very low. However, the drug may induce significant changes in ECG parameters. The clinical significance of these changes in patients with cardiac conduction abnormalities should be investigated in further studies.

The efficacy and safety of the addition of olanzapine to ondansetron and dexamethasone for prevention of chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy.

OBJECTIVE: To evaluate the efficacy and safety of the addition of olanzapine to ondansetron and dexamethasone for chemotherapy-induced nausea vomiting (CINV) prevention in patients receiving highly emetogenic chemotherapy (HEC). METHODS: In this randomized, double-blind, placebo-controlled, crossover study, we randomly assigned chemotherapy-naïve patients receiving HEC to receive olanzapine or placebo in addition to ondansetron and dexamethasone. All subjects were crossed over to another treatment arm on second-cycle chemotherapy. The primary endpoint was complete response (CR) rate defined as no vomiting and no use of rescue drugs. RESULTS: At the first cycle, there were significantly more patients with CR in the olanzapine group than in the placebo group in overall phase (68.7% vs. 25.0%, p < 0.001), acute phase (0-24 h) (75.0% vs. 31.2%, p < 0.001) and delayed phase (24-120 h) (68.7% vs. 43.7%, p = 0.038). After crossover, there were significantly more patients with CR in the olanzapine group than in the placebo group in overall phase (67.2% vs. 25.0%, p < 0.001), acute phase (71.9% vs. 32.8%, p < 0.001) and delayed phase (67.2% vs. 37.5%, p < 0.001). In crossover analysis, the olanzapine group had significantly lower mean nausea (1.28 vs. 3.05, p < 0.001) and fatigue (3.5 vs. 4.58, p < 0.001) scores but higher mean appetite (2.5 vs. 1.55, p = 0.003) and sleepiness (3.26 vs. 2.2, p < 0.001) scores. There were no grade 3 and 4 anti-emetic-drug-related toxicities. Mean QT interval changes did not different between two groups (-4.30 vs. -1.86, p = 0.69). CONCLUSION: The addition of olanzapine to ondansetron and dexamethasone significantly improved CINV prevention and was safe in patients receiving HEC.