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Clinical Medicine (London, England) Jul 2019Nausea and vomiting in palliative care are commonly experienced symptoms, and the aetiology is often multifactorial. The most common causes are impaired gastric...
Nausea and vomiting in palliative care are commonly experienced symptoms, and the aetiology is often multifactorial. The most common causes are impaired gastric emptying, chemical causes (eg medication) and visceral causes (eg constipation). Close attention should be paid to the clinical features which may suggest the likely cause. Antiemetic therapy should be guided by the likely aetiology, although in practice, the clinical picture is often complex, and so regular reassessment is essential for adequate symptom control.
Topics: Antiemetics; Humans; Nausea; Palliative Care; Vomiting
PubMed: 31308107
DOI: 10.7861/clinmedicine.19-4-299 -
The Oncologist Aug 2023A protocol was developed to evaluate the value of an NK-1 receptor antagonist for preventing nausea and vomiting resulting from highly emetogenic chemotherapy when an... (Randomized Controlled Trial)
Randomized Controlled Trial
Olanzapine With or Without Fosaprepitant for Preventing Chemotherapy Induced Nausea and Vomiting in Patients Receiving Highly Emetogenic Chemotherapy: A Phase III Randomized, Double-Blind, Placebo-Controlled Trial (ALLIANCE A221602).
PURPOSE
A protocol was developed to evaluate the value of an NK-1 receptor antagonist for preventing nausea and vomiting resulting from highly emetogenic chemotherapy when an olanzapine-based antiemetogenic regimen was used.
MATERIALS AND METHODS
A221602, a prospective double-blind, placebo-controlled clinical trial, was developed to compare 2 -olanzapine-containing antiemetic regimens, one with an NK-1 receptor antagonist (aprepitant or fosaprepitant) and one without. Trial patients had a malignant disease for which they received intravenous highly emetogenic chemotherapy (single day cisplatin ≥ 70 mg/m2 or doxorubicin plus cyclophosphamide on 1 day). Patients on both arms received commonly administered doses of a 5-HT3 receptor antagonist, dexamethasone, and olanzapine. Additionally, patients were randomized to receive an NK-1 receptor antagonist (fosaprepitant 150 mg IV or aprepitant 130 mg IV) or a corresponding placebo. The primary objective was to compare the proportion of patients with no nausea for 5 days following chemotherapy between the 2 study arms. This trial was designed to test for the noninferiority of deleting the NK-1 receptor antagonist, with noninferiority defined as a decrease in freedom from nausea by less than 10%.
RESULTS
A total of 690 patients were entered on this trial, 50% on each arm. The proportion of patients without nausea for the complete 5-day study period was 7.4% lower (upper limit of the one-sided 95% confidence interval was 13.5%) in the arm without an NK-1 receptor antagonist compared with the arm with an NK-1 receptor antagonist.
CONCLUSION
This trial did not provide sufficient evidence to support that deletion of the NK-1 receptor antagonist was as good as keeping it, as a part of a 4-drug antiemetic regimen for highly emetogenic chemotherapy (ClinicalTrials.gov Identifier: NCT03578081).
Topics: Humans; Antiemetics; Olanzapine; Aprepitant; Prospective Studies; Receptors, Neurokinin-1; Vomiting; Nausea; Antineoplastic Agents; Double-Blind Method; Dexamethasone
PubMed: 37284847
DOI: 10.1093/oncolo/oyad140 -
Daru : Journal of Faculty of Pharmacy,... Dec 2023Chemotherapy-induced nausea and vomiting are commonly experienced side effects in breast cancer (BCa) patients. Antiemetic drugs used in BCa treatment are either...
BACKGROUND
Chemotherapy-induced nausea and vomiting are commonly experienced side effects in breast cancer (BCa) patients. Antiemetic drugs used in BCa treatment are either inhibitors or inducers of cytochrome P450 (CYP) enzymes, while anticancer drugs are metabolized by CYPs.
OBJECTIVES
The purpose of the present work was to evaluate in silico drug-drug interaction (DDI) potential between BCa chemotherapeutic drugs and antiemetic agents.
METHODS
The Drug-Drug Interaction™ module of GastroPlus™ was employed to assess CYP-related interactions between antiemetic and anticancer therapy combinations. The CYP inhibitory or inducing parameters (IC, K, EC) used in simulations were obtained from the literature.
RESULTS
Analyses of twenty-three BCa drugs indicated that 22% of the chemotherapeutic drugs do not need an antiemetic agent due to their low emetogenicity, whereas 30% of the anticancer drugs are not metabolized by CYPs. The remaining eleven anticancer drugs metabolized by CYPs generated ninety-nine combinations with nine antiemetics. Simulation of DDIs suggest that about half of the pairs did not demonstrate any potential for DDI, whereas 30%, 10%, and 9% of the pairs showed weak, moderate, and strong interaction potential, respectively. In the present study, netupitant was the only antiemetic that showed strong inhibitory interactions (predicted AUC ratio > 5) with CYP3A4-metabolzied anticancer therapies (e.g., docetaxel, ribociclib, olaparib). Moderate to no interactions were observed with ondansetron, aprepitant, rolapitant, and dexamethasone in combination with anticancer agents.
CONCLUSION
It is critical to recognize that these interactions can get amplified in cancer patients because of the severity of the disease and chemotherapy toxicities. Clinicians need to be aware of the DDI likelihood of the drug combinations used in BCa treatment.
Topics: Humans; Female; Antiemetics; Breast Neoplasms; Antineoplastic Agents; Aprepitant; Drug Interactions
PubMed: 37223851
DOI: 10.1007/s40199-023-00463-1 -
The Cochrane Database of Systematic... Sep 2010Nausea and vomiting are the most common symptoms experienced in early pregnancy, with nausea affecting between 70 and 85% of women. About half of pregnant women... (Review)
Review
BACKGROUND
Nausea and vomiting are the most common symptoms experienced in early pregnancy, with nausea affecting between 70 and 85% of women. About half of pregnant women experience vomiting.
OBJECTIVES
To assess the effects of different methods of treating nausea and vomiting in early pregnancy.
SEARCH STRATEGY
We searched the Cochrane Pregnancy and Childbirth Group trials register (December 2002) and the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 4, 2002).
SELECTION CRITERIA
Randomised trials of any treatment for nausea and/or vomiting in early pregnancy.
DATA COLLECTION AND ANALYSIS
Two reviewers assessed the trial quality and extracted the data independently.
MAIN RESULTS
Twenty-eight trials met the inclusion criteria. For milder degrees of nausea and vomiting, 21 trials were included. These trials were of variable quality. Nausea treatments were: different antihistamine medications, vitamin B6 (pyridoxine), the combination tablet Debendox (Bendectin), P6 acupressure and ginger. For hyperemesis gravidarum, seven trials were identified testing treatments with oral ginger root extract, oral or injected corticosteroids or injected adrenocorticotropic hormone (ACTH), intravenous diazepam and acupuncture. Based on 12 trials, there was an overall reduction in nausea from anti-emetic medication (odds ratio 0.16, 95% confidence interval 0.08 to 0.33).
AUTHORS' CONCLUSIONS
Anti-emetic medication appears to reduce the frequency of nausea in early pregnancy. There is some evidence of adverse effects, but there is very little information on effects on fetal outcomes from randomised controlled trials. Of newer treatments, pyridoxine (vitamin B6) appears to be more effective in reducing the severity of nausea. The results from trials of P6 acupressure are equivocal. No trials of treatments for hyperemesis gravidarum show any evidence of benefit. Evidence from observational studies suggests no evidence of teratogenicity from any of these treatments.
Topics: Antiemetics; Female; Humans; Hyperemesis Gravidarum; Nausea; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Pregnancy Trimester, Second; Randomized Controlled Trials as Topic; Vomiting
PubMed: 20824826
DOI: 10.1002/14651858.CD000145.pub2 -
Cancer Medicine Sep 2023This study aims to develop a risk prediction model for chemotherapy-induced nausea and vomiting (CINV) in cancer patients receiving highly emetogenic chemotherapy (HEC)...
A deep learning-based interpretable decision tool for predicting high risk of chemotherapy-induced nausea and vomiting in cancer patients prescribed highly emetogenic chemotherapy.
OBJECTIVE
This study aims to develop a risk prediction model for chemotherapy-induced nausea and vomiting (CINV) in cancer patients receiving highly emetogenic chemotherapy (HEC) and identify the variables that have the most significant impact on prediction.
METHODS
Data from Tianjin Medical University General Hospital were collected and subjected to stepwise data preprocessing. Deep learning algorithms, including deep forest, and typical machine learning algorithms such as support vector machine (SVM), categorical boosting (CatBoost), random forest, decision tree, and neural network were used to develop the prediction model. After training the model and conducting hyperparameter optimization (HPO) through cross-validation in the training set, the performance was evaluated using the test set. Shapley additive explanations (SHAP), partial dependence plot (PDP), and Local Interpretable Model-Agnostic Explanations (LIME) techniques were employed to explain the optimal model. Model performance was assessed using AUC, F1 score, accuracy, specificity, sensitivity, and Brier score.
RESULTS
The deep forest model exhibited good discrimination, outperforming typical machine learning models, with an AUC of 0.850 (95%CI, 0.780-0.919), an F1 score of 0.757, an accuracy of 0.852, a specificity of 0.863, a sensitivity of 0.784, and a Brier score of 0.082. The top five important features in the model were creatinine clearance (Ccr), age, gender, anticipatory nausea and vomiting, and antiemetic regimen. Among these, Ccr had the most significant predictive value. The risk of CINV decreased with increased Ccr and age, while it was higher in the presence of anticipatory nausea and vomiting, female gender, and non-standard antiemetic regimen.
CONCLUSION
The deep forest model demonstrated good discrimination in predicting the risk of CINV in cancer patients prescribed HEC. Kidney function, as represented by Ccr, played a crucial role in the model's prediction. The clinical application of this predictive tool can help assess individual risks and improve patient care by proactively optimizing the use of antiemetics in cancer patients receiving HEC.
Topics: Humans; Antiemetics; Deep Learning; Antineoplastic Agents; Vomiting; Nausea; Neoplasms
PubMed: 37609808
DOI: 10.1002/cam4.6428 -
Asian Pacific Journal of Cancer... Mar 2021Fosaprepitant, an NK1 receptor antagonist, inhibits and induces cytochrome P450 3A4 (CYP3A4) as its substrate. Contrarily dexamethasone is metabolized by CYP3A4....
BACKGROUND
Fosaprepitant, an NK1 receptor antagonist, inhibits and induces cytochrome P450 3A4 (CYP3A4) as its substrate. Contrarily dexamethasone is metabolized by CYP3A4. Therefore, in combination therapy wherein both agents interact with each other, it is recommended that the dexamethasone dose be reduced in the first two days. Thus far, there are only a few studies on the optimum dose of dexamethasone after day 3. Thus, we aimed to determine the pharmacokinetics of dexamethasone on day3 when administered together with fosaprepitant and investigate the dose-dependent differences in its antiemetic effect in patients with cancer.
METHODS
Twelve patients with esophageal, stomach, or lung cancer received primary highly emetogenic chemotherapy (HEC). We intravenously administered 9.9 mg and 6.6 mg of dexamethasone on days 1 and 2, respectively, and 6.6 mg or 13.2 mg on day 3 together with the administration of 150 mg fosaprepitant and 0.75 mg palonosetron. We assessed the pharmacokinetics of dexamethasone on day 3 by dose and examined the dose-dependent antiemetic effect.
RESULTS
No differences were observed in the time-to-maximum concentration and blood half-life of dexamethasone between patient groups that received dexamethasone at doses of 6.6 mg and 13.2 mg. In contrast, the area under the blood concentration-time curve and the maximum concentration of dexamethasone correlated with its dose. Moreover, the blood dexamethasone concentration on day 3 increased by twofold after the administration of a higher dose than after a lower dose. The severity of nausea in the delayed phase significantly decreased in a dose-dependent manner.
CONCLUSION
Administration of a higher dexamethasone dose on day 3 improved the antiemetic effect of the combined regimen in patients with cancer who underwent HEC.
.Topics: Aged; Antiemetics; Antineoplastic Agents; Cytochrome P-450 CYP3A; Cytochrome P-450 CYP3A Inducers; Cytochrome P-450 CYP3A Inhibitors; Dexamethasone; Dose-Response Relationship, Drug; Drug Interactions; Esophageal Neoplasms; Female; Humans; Lung Neoplasms; Male; Middle Aged; Morpholines; Nausea; Stomach Neoplasms; Vomiting
PubMed: 33773552
DOI: 10.31557/APJCP.2021.22.3.871 -
The Cochrane Database of Systematic... Jul 2006Drugs can prevent postoperative nausea and vomiting, but their relative efficacies and side effects have not been compared within one systematic review. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Drugs can prevent postoperative nausea and vomiting, but their relative efficacies and side effects have not been compared within one systematic review.
OBJECTIVES
The objective of this review was to assess the prevention of postoperative nausea and vomiting by drugs and the development of any side effects.
SEARCH STRATEGY
We searched The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 2, 2004), MEDLINE (January 1966 to May 2004), EMBASE (January 1985 to May 2004), CINAHL (1982 to May 2004), AMED (1985 to May 2004), SIGLE (to May 2004), ISI WOS (to May 2004), LILAC (to May 2004) and INGENTA bibliographies.
SELECTION CRITERIA
We included randomized controlled trials that compared a drug with placebo or another drug, or compared doses or timing of administration, that reported postoperative nausea or vomiting as an outcome.
DATA COLLECTION AND ANALYSIS
Two authors independently assessed trial quality and extracted outcome data.
MAIN RESULTS
We included 737 studies involving 103,237 people. Compared to placebo, eight drugs prevented postoperative nausea and vomiting: droperidol, metoclopramide, ondansetron, tropisetron, dolasetron, dexamethasone, cyclizine and granisetron. Publication bias makes evidence for differences among these drugs unreliable. The relative risks (RR) versus placebo varied between 0.60 and 0.80, depending upon the drug and outcome. Evidence for side effects was sparse: droperidol was sedative (RR 1.32) and headache was more common after ondansetron (RR 1.16).
AUTHORS' CONCLUSIONS
Either nausea or vomiting is reported to affect, at most, 80 out of 100 people after surgery. If all 100 of these people are given one of the listed drugs, about 28 would benefit and 72 would not. Nausea and vomiting are usually less common and, therefore, drugs are less useful. For 100 people, of whom 30 would vomit or feel sick after surgery if given placebo, 10 people would benefit from a drug and 90 would not. Between one to five patients out of every 100 people may experience a mild side effect, such as sedation or headache, when given an antiemetic drug. Collaborative research should focus on determining whether antiemetic drugs cause more severe, probably rare, side effects. Further comparison of the antiemetic effect of one drug versus another is not a research priority.
Topics: Antiemetics; Humans; Postoperative Nausea and Vomiting; Randomized Controlled Trials as Topic
PubMed: 16856030
DOI: 10.1002/14651858.CD004125.pub2 -
BMJ Open Jun 2022Chemotherapy-induced nausea and vomiting (CINV) decrease patients' quality of life and negatively impact treatment outcomes. Although standard prophylactic antiemetic...
Factors affecting the implementation of guideline-based prophylactic antiemetic therapy for chemotherapy-induced nausea and vomiting in Japan: a protocol for a hospital-based qualitative study.
INTRODUCTION
Chemotherapy-induced nausea and vomiting (CINV) decrease patients' quality of life and negatively impact treatment outcomes. Although standard prophylactic antiemetic therapy for acute CINV recommended by guidelines is effective, poor guideline implementation is a worldwide problem. In Japan, prophylactic antiemetic therapy is relatively well implemented for chemotherapy associated with high emetogenic risk, while implementation gaps are observed for that with low emetogenic risk.Although most reports on factors influencing appropriate antiemetic prescription focus on physicians' attitudes and behaviours, a more comprehensive exploration is needed since chemotherapy is expected to involve pharmacists, nurses and eventually hospital directors. The purpose of this qualitative study is to comprehensively explore the factors that influence the implementation of appropriate prophylactic antiemetic procedures at cancer care hospitals in Japan.
METHODS AND ANALYSIS
This study is a hospital-based qualitative study using semistructured individual interviews. The target population will be hospital directors, and chiefs (including proxies) of departments of oncology and/or chemotherapy, pharmacy and nursing, working in the hospitals, selected by purposive sampling. We will obtain information on antiemetics in chemotherapy regimens, antiemetic routine use and awareness of guidelines using prequestionnaires. Interviews will then be conducted online using an interview guide. The Consolidated Framework for Implementation Research will be used to collect and analyse the interview data. We will also create new codes inductively, as required. In addition, we will refer to the aggregate results of the Quality Indicator survey to determine the implementation of recommended antiemetic prescriptions for each hospital and discuss the relationship with influencing factors.
ETHICS AND DISSEMINATION
This study has been approved by the National Cancer Centre Ethics Approval Committee (approval number: 2020-305). The study findings will be disseminated via peer-reviewed journal publications and presentations to academics, policy-makers, and clinicians at scientific conferences.
Topics: Antiemetics; Antineoplastic Agents; Hospitals; Humans; Japan; Nausea; Neoplasms; Quality of Life; Vomiting
PubMed: 35667723
DOI: 10.1136/bmjopen-2021-055473 -
Expert Opinion on Drug Safety May 2013Ondansetron is a 5-HT₃ receptor antagonist commonly used as an antiemetic to prevent nausea and vomiting associated with anti-cancer drugs, cancer radiotherapy or... (Review)
Review
INTRODUCTION
Ondansetron is a 5-HT₃ receptor antagonist commonly used as an antiemetic to prevent nausea and vomiting associated with anti-cancer drugs, cancer radiotherapy or postoperatively. Recently, the US Food and Drug Administration (FDA) issued a warning for ondansetron due to a potential for prolongation of the QT interval of the electrocardiogram (ECG), a phenomenon that is associated with an increased risk of the potentially fatal arrhythmia torsade de pointes.
AREAS COVERED
The authors undertook a review of the cardiac safety of ondansetron. Their primary sources of information were PubMed (with downloading of full articles) and the Internet.
EXPERT OPINION
The dose of ondansetron that the FDA has concerns about is 32 mg i.v. (or several doses that are equivalent to this), which is only used in preventing nausea and vomiting associated with cancer chemotherapy. This suggests that ondansetron may be safe in lower doses used to prevent nausea and vomiting in radiation treatment or postoperatively. However, as there is a report that a lower dose of ondansetron prolonged the QT interval in healthy volunteers, this needs to be clarified by the FDA. More research needs to be undertaken on the relationship between QT prolongation and torsades in order that the FDA can produce clear-cut evidence of proarrhythmic risk when introducing warnings for this.
Topics: Antiemetics; Antineoplastic Agents; Arrhythmias, Cardiac; Humans; Nausea; Ondansetron; Randomized Controlled Trials as Topic
PubMed: 23578248
DOI: 10.1517/14740338.2013.780026 -
Drug Design, Development and Therapy 2020High-dose myeloablative conditioning prior to autologous hematopoietic stem cell transplantation (autoHSCT) in pediatric patients is usually highly emetogenic. The...
BACKGROUND
High-dose myeloablative conditioning prior to autologous hematopoietic stem cell transplantation (autoHSCT) in pediatric patients is usually highly emetogenic. The antiemetic neurokinin-1 receptor antagonist fosaprepitant was safe and effective in children receiving highly emetogenic chemotherapy. Data on fosaprepitant during autoHSCT in children are currently not available.
METHODS
A total of 35 consecutive pediatric patients, who received an antiemetic prophylaxis with fosaprepitant (4 mg/kg; single dose, max. 1 x 150 mg/kg BW) and ondansetron (24-hours continuous infusion; 8-32 mg/24h) or granisetron (2 x 40 µg/kg∙d) during highly emetogenic conditioning chemotherapy before autoHSCT were retrospectively analyzed, and their results were compared with a control group comprising 35 consecutive pediatric patients, who received granisetron or ondansetron only. The antiemetic efficacy and the safety of the two prophylaxis regimens were compared with respect to three time periods after the first chemotherapy administration (0-24h, >24-120h, >120-240h).
RESULTS
Clinical adverse events and clinically relevant increases/decreases of laboratory markers were similarly low and did not significantly differ between the two study groups (>0.05). The registered number of vomiting events was significantly higher in the control group in the time periods of 0-24h (64 vs 22 events; <0.01), >24-120h (135 vs 78 events; <0.0001), >120-240h (268 vs 105 events; <0.0001), and the whole observation period 0-240h (467 vs 205 events; <0.0001). The percentage of patients experiencing vomiting was higher in the control group during the time period of >24-120h (100% vs 74.3%) but not the other analyzed time periods (>0.05).
CONCLUSION
The fosaprepitant-based antiemetic prophylaxis was safe, well tolerated and significantly reduced vomiting in children undergoing highly emetogenic chemotherapy prior to autoHSCT. Prospective randomized trials are necessary to confirm these results.
Topics: Adolescent; Antibiotic Prophylaxis; Antiemetics; Child; Child, Preschool; Female; Hematopoietic Stem Cell Transplantation; Humans; Infant; Male; Morpholines; Neoplasms; Retrospective Studies; Serotonin 5-HT3 Receptor Antagonists; Transplantation, Autologous
PubMed: 33061297
DOI: 10.2147/DDDT.S260887