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Indian Journal of Anaesthesia Jun 2021This study was designed to compare the effectiveness of the combination of dexamethasone-ondansetron with oral aprepitant alone and triple combination therapy with all...
Effect of combinations of dexamethasone-ondansetron and dexamethasone-ondansetron-aprepitant versus aprepitant alone for early postoperative nausea and vomiting after day care gynaecological laparoscopy: A randomised clinical trial.
BACKGROUND AND AIMS
This study was designed to compare the effectiveness of the combination of dexamethasone-ondansetron with oral aprepitant alone and triple combination therapy with all three agents (dexamethasone-ondansetron and oral aprepitant) in the prevention of postoperative nausea and vomiting (PONV) in day care gynaecologic laparoscopy.
METHODS
This was a randomised clinical trial conducted at a university teaching hospital. A total of 105 female patients were randomised into the aprepitant (A), dexamethasone-ondansetron (DO) and aprepitant-dexamethasone-ondansetron (ADO) groups. The patients in the A group received only 80 mg oral aprepitant 1 h before surgery. The patients in the DO group, received dexamethasone 8 mg at induction with ondansetron 4 mg before extubation. Patients in the ADO group received 80 mg oral aprepitant 1 h before surgery, dexamethasone 8 mg at induction and ondansetron 4 mg before extubation. Incidence of nausea and vomiting was compared between groups using the Chi-square test/Fisher's test. Bellville score for severity of PONV was analysed using the Kruskall-Wallis test. value < 0.05 was regarded as significant.
RESULTS
The incidence of PONV did not show a statistically significant difference between the three groups, with a value of 0.13 (12.5%, 30.3% and 32.3% in groups ADO, DO and A, respectively). The severity of PONV measured using Bellville score was also not significantly different among the groups [median values (IQR) of 0 (0-0), 0 (0-1), and 0 (0-1)].
CONCLUSION
The combination of aprepitant, dexamethasone and ondansetron failed to demonstrate a statistically significant superiority over the other two antiemetic regimens.
PubMed: 34248190
DOI: 10.4103/ija.IJA_119_21 -
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 -
European Journal of Pharmacology Aug 2020Cisplatin is widely used chemotherapeutic drug and have some serious side effects as tissue toxicity and nausea and vomiting. Aprepitant is used in clinic as an...
Cisplatin is widely used chemotherapeutic drug and have some serious side effects as tissue toxicity and nausea and vomiting. Aprepitant is used in clinic as an anti-emetic drug for cisplatin treated patient to prevent nausea and vomiting. We aimed to investigate the protective effects of Aprepitant on cisplatin-induced nephrotoxicity and hepatotoxicity. In total 42 male rats were separated into six groups (n = 7). A single dose of cisplatin (10 mg/kg i.p.) was administered to induce toxicity on first day. Different doses of Aprepitant (5, 10 and 20 mg/kg, p.o.) were given to treatment groups during 3 days. After the experimental procedures serum enzymes (ALT, AST, ALP, BUN and Creatinin), kidney and liver oxidative parameters (SOD, GSH and MDA), inflammatory cytokines (TNF-α and NF-κB) and Cyp2e1 expressions analyzed. Histopathological investigations also performed for all groups. Cisplatin caused tissue toxicity in both kidney and liver. Serum enzymes, tissue cytokines and oxidative stress were increased after the Cis treatment. Aprepitant treatment normalized all parameters compared to cisplatin treated group. Cisplatin significantly increased the Cyp2e1 expression in the kidney while significantly decreased in the liver compared to Healthy group. Histopathologically, it was shown that cisplatin causes a lot of abnormal structures as inflammatory infiltration and necrosis on the liver and kidney. Similar the biochemical and molecular results, aprepitant showed positive effects on tissue pathological parameters. With its main anti-emetic effect, Aprepitant treatment may be an effective option for cancer patients if they have additional injury as nephrotoxicity and hepatotoxicity due to cisplatin.
Topics: Animals; Antiemetics; Antineoplastic Agents; Aprepitant; Chemical and Drug Induced Liver Injury; Cisplatin; Cytochrome P-450 CYP2E1; Kidney; Kidney Diseases; Liver; Male; NF-kappa B; Rats, Wistar; Tumor Necrosis Factor-alpha
PubMed: 32423870
DOI: 10.1016/j.ejphar.2020.173168 -
Journal of Chromatography. B,... May 2021A pharmacokinetic study was set up to investigate the pharmacokinetics of the anti-emetic agents aprepitant and dexamethasone and the drug-drug interaction between these...
Development and validation of a combined liquid chromatography tandem-mass spectrometry assay for the quantification of aprepitant and dexamethasone in human plasma to support pharmacokinetic studies in pediatric patients.
A pharmacokinetic study was set up to investigate the pharmacokinetics of the anti-emetic agents aprepitant and dexamethasone and the drug-drug interaction between these drugs in children. In order to quantify aprepitant and dexamethasone, a liquid chromatography-tandem mass spectrometry assay was developed and validated for the simultaneous analysis of aprepitant and dexamethasone. Protein precipitation with acetonitrile-methanol (1:1, v/v) was used to extract the analytes from plasma. The assay was based on reversed-phase chromatography coupled with tandem mass spectrometry detection operating in the positive ion mode. The assay was validated based on the guidelines on bioanalytical methods by the US Food and Drug Administration and European Medicines Agency. The calibration model was linear and a weighting factor of 1/concentration was used over the range of 0.1-50 ng/mL for aprepitant and 1-500 ng/mL for dexamethasone. Intra-assay and inter-assay bias were within ±20% for all analytes at the lower limit of quantification and within ±15% at remaining concentrations. Dilution integrity tests showed that samples exceeding the upper limit of quantification can be diluted 100 times in control matrix. Stability experiments showed that the compounds are stable in the biomatrix for 25 h at room temperatures and 89 days at -20 °C. This assay is considered suitable for pharmacokinetic studies and will be used to study the drug-drug interaction between aprepitant and dexamethasone in pediatric patients.
Topics: Adolescent; Aprepitant; Child; Chromatography, Liquid; Dexamethasone; Female; Humans; Linear Models; Male; Reproducibility of Results; Sensitivity and Specificity; Tandem Mass Spectrometry
PubMed: 33756449
DOI: 10.1016/j.jchromb.2021.122639 -
Pediatric Neurology Sep 2020Aprepitant is a neurokinin-1 receptor antagonist approved for the treatment of chemotherapy-induced nausea. We aimed to investigate the safety and efficacy of aprepitant... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Aprepitant is a neurokinin-1 receptor antagonist approved for the treatment of chemotherapy-induced nausea. We aimed to investigate the safety and efficacy of aprepitant in patients with subacute sclerosing panencephalitis.
METHODS
A randomized, double-blind, placebo-controlled study was conducted in patients with subacute sclerosing panencephalitis assigned to receive two courses of aprepitant 250 mg/day orally or placebo for 15 days with an interval of two months between courses. Primary end points were safety and tolerability, and secondary end point was clinical improvement or stabilization assessed by subacute sclerosing panencephalitis scoring system. Electroencephalography (EEG), brain magnetic resonance imaging, and cerebrospinal fluid measles-specific immunoglobulin G index were evaluated before and after treatment.
RESULTS
Sixty-two patients with subacute sclerosing panencephalitis were allocated to aprepitant (n = 31, median age 18 years) or placebo (n = 31, median age 22 years) group. Fifteen patients left the study within the first six months and 12 patients left between six and 12 months. Aprepitant was well tolerated and treatment-associated adverse events were similar to those described in the treatment of nausea. Clinical status at six and 12 months' follow-up did not differ between aprepitant and placebo groups. Post-treatment EEG scores at 12 months were better in the aprepitant group (P = 0.015). Cerebral atrophy on magnetic resonance imaging increased in both groups, whereas measles-specific immunoglobulin G index decreased in the placebo group.
CONCLUSIONS
In this first clinical trial of aprepitant treatment in patients with subacute sclerosing panencephalitis, the drug was safe and well tolerated. No clinical effect was observed. A modest improvement in EEG findings might justify trials for longer periods because EEG changes can precede clinical findings in subacute sclerosing panencephalitis.
Topics: Adolescent; Adult; Aprepitant; Atrophy; Double-Blind Method; Electroencephalography; Female; Follow-Up Studies; Humans; Magnetic Resonance Imaging; Male; Neurokinin-1 Receptor Antagonists; Outcome Assessment, Health Care; Subacute Sclerosing Panencephalitis; Young Adult
PubMed: 32718528
DOI: 10.1016/j.pediatrneurol.2020.05.009 -
Dermatitis : Contact, Atopic,... 2023As treatment with immune checkpoint inhibitors (CPIs) for cancer increases, so has the incidence of immune-related cutaneous adverse events (irCAEs). These toxicities... (Review)
Review
As treatment with immune checkpoint inhibitors (CPIs) for cancer increases, so has the incidence of immune-related cutaneous adverse events (irCAEs). These toxicities can significantly impact quality of life and may be dose-limiting. Current guidelines for irCAEs offer only corticosteroids or CPI discontinuation. Evidence supports biologic immunomodulatory therapies when corticosteroids fail or need avoidance. A review of literature from 2010 to 2020 yielded 45 articles, resulting in 185 irCAEs, including bullous pemphigoid-like eruption (n = 55), psoriasis/psoriasiform dermatitis (n = 41), and maculopapular rash (n = 31). Treatments included immunomodulators, intravenous immunoglobulin, aprepitant, acitretin, tetracyclines, and biologic agents. Overall, 92.3% of patients saw improvement or resolution of their rash. Bullous pemphigoid-like eruptions were treated with a tetracycline +/- niacinamide (94.7% success [18/19]), omalizumab (100% success [7/7]), and rituximab (100% success [10/10]). Although prospective research is required, this review provides a comprehensive list of successful, non-corticosteroid treatment options for irCAEs to improve compliance with lifesaving cancer therapy.
Topics: Humans; Immune Checkpoint Inhibitors; Pemphigoid, Bullous; Quality of Life; Prospective Studies; Exanthema; Neoplasms; Adrenal Cortex Hormones; Anti-Bacterial Agents
PubMed: 34405836
DOI: 10.1097/DER.0000000000000776 -
Chinese Clinical Oncology Oct 2020The goal of this study was to evaluate aprepitant usage in the context of routine clinical practice with dose/regimens at the discretion of prescribers for...
Safety and efficacy of aprepitant as mono and combination therapy for the prevention of emetogenic chemotherapy-induced nausea and vomiting: post-marketing surveillance in China.
BACKGROUND
The goal of this study was to evaluate aprepitant usage in the context of routine clinical practice with dose/regimens at the discretion of prescribers for chemotherapy-induced nausea and vomiting (CINV) treatments.
METHODS
In this single arm, multicenter prospective study 1,000 patients with solid malignancies were enrolled across 21 centers in China. The primary endpoint was the rate of adverse events (AEs), including drug related AEs and serious AEs (SAEs). Secondary efficacy endpoints included the proportion of patients achieving complete response (CR; no vomiting, no nausea, and no use of rescue medication) within 120 h after highly emetogenic chemotherapy, the rates of no nausea and no vomiting, as well as quality of life (QoL). Multivariable logistic regression analysis was carried out to determine factors associated with the overall (0-120 h), acute (0-24 h) and delayed (25-120 h) CR.
RESULTS
Of the 1,000 highly emetogenic chemotherapy treated patients enrolled in the study ≥1 AE, ≥1 drug related AE, ≥1 SAE and drug related SAE rates in 998 patients were 45.9%, 2.5%, 4.0% and 0.1%, respectively. Approximately half of the patients (455/990, 46.0%) received aprepitant as part of a 3-drug anti-CINV regimen consistent with prescribing guidelines. The overall CR (0 to 120 h) for anti-emetic drug use was 41.0%, with an acute CR of 66.0% and a delayed CR of 46.5%. The rates of no vomiting and no nausea after solely aprepitant anti-emetic therapy from 0 to 120 h were 70.9% and 43.0%, for dual anti-emetic therapy 86.9% and 64.6%, and for triple therapy 86.4% and 69.5%, respectively. Multivariate regression analysis revealed that triple anti-emetic therapy (P=0.038), male gender (P<0.001) and a history of chemotherapy (P=0.016) were significantly associated with the overall acute CR.
CONCLUSIONS
Especially as a combination treatment, aprepitant is safe and efficient for preventing CINV in patients receiving highly emetogenic chemotherapy.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antiemetics; Aprepitant; China; Female; Humans; Male; Middle Aged; Nausea; Product Surveillance, Postmarketing; Vomiting; Young Adult
PubMed: 33161724
DOI: 10.21037/cco-20-160 -
Drug Design, Development and Therapy 2021The stability of aprepitant injectable emulsion is evaluated in various admixture bags and solutions, under different storage conditions, and when combined with other...
PURPOSE
The stability of aprepitant injectable emulsion is evaluated in various admixture bags and solutions, under different storage conditions, and when combined with other antiemetics.
METHODS
A volume of 18 mL aprepitant injectable emulsion was added to infusion bags (either non-di-(2-ethylhexyl) phthalate [DEHP], polyvinyl chloride [PVC]-containing bags or non-DEHP, non-PVC bags) containing 100, 130, or 250 mL of 0.9% normal saline solution (NSS) or 5% dextrose in water (D5W). Bags were stored at controlled room temperature (20-25°C) for up to 12 hours or refrigerated (2-8°C) for up to 72 hours. Compatibility/stability was also assessed in admixtures combined with either dexamethasone or palonosetron. At specified time points, bags were tested for appearance, pH, assay for aprepitant (ie, percent label claim of aprepitant) and aprepitant-related substances, Z-average particle size, globule size distribution, particulate matter, and DEHP content (PVC bags). In separate analyses to assess microbial burden, bags containing aprepitant were inoculated with seven different organisms and assessed for microbial growth.
RESULTS
There was no detectable impact on the physicochemical properties or potential to promote microbial growth of aprepitant when diluted with various amounts of either NSS or D5W and when admixed with either dexamethasone or palonosetron at room temperature for at least 6 hours or during refrigeration for up to 72 hours in either PVC- or non-PVC-containing bags.
CONCLUSION
Aprepitant-containing admixtures are stable under these conditions, a finding that may improve patient and provider convenience and reduce medication wastage.
Topics: Antiemetics; Aprepitant; Dexamethasone; Diethylhexyl Phthalate; Drug Combinations; Drug Incompatibility; Drug Packaging; Drug Stability; Drug Storage; Emulsions; Hydrogen-Ion Concentration; Palonosetron; Polyvinyl Chloride; Refrigeration; Temperature; Time Factors
PubMed: 34163138
DOI: 10.2147/DDDT.S282058 -
Naunyn-Schmiedeberg's Archives of... Dec 2020Aprepitant is a selective SP/NK-1 receptor antagonist and used in postoperative and chemotherapeutics induced emesis and vomiting. The aim of our study is to show...
Aprepitant is a selective SP/NK-1 receptor antagonist and used in postoperative and chemotherapeutics induced emesis and vomiting. The aim of our study is to show aprepitant may have beneficial effects on gastrointestinal complaints in cancer patients undergoing chemotherapeutics by indomethacin-induced gastric ulcer model. A total of 48 rats were fasted 24 h for ulcer experiment. Aprepitant doses of 5, 10, 20, and 40 mg/kg were evaluated for their antiulcer activity. Omeprazole (20 mg/kg) was used as a positive control group. Six hours after 25 mg/kg indomethacin administration, all stomachs were dissected out. After macroscopic analyses, tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), COX-1, and COX-2 mRNA levels and SOD activity, and GSH and MDA levels of stomachs were determined. Histopathological examinations were evaluated. Aprepitant administration exerted 48.14%, 49.62%, 65.92%, and 76.77% ulcer inhibition effects at 5, 10, 20, and 40 mg/kg, respectively. Aprepitant administration decreased oxidative stress and inflammatory parameters in stomach tissues dose dependently. Aprepitant administration increased stomach COX-2 mRNA levels at 20 and 40 mg/kg doses. Although aprepitant appears to be disadvantageous in terms of treating gastric ulcer due to COX enzyme inhibition according to the previous studies, aprepitant has been shown to have ulcer healing effect in our study. When aprepitant is given as an anti-nausea and vomiting drug to cancer patients undergoing chemotherapy, we can argue that it will not be necessary to add a new gastric protective agent as it also shows beneficial effects in gastrointestinal complaints.
Topics: Animals; Antiemetics; Aprepitant; Gastric Mucosa; Inflammation Mediators; Male; Nausea; Rats; Rats, Wistar; Stomach Ulcer; Vomiting
PubMed: 32743741
DOI: 10.1007/s00210-020-01956-5 -
Therapeutic Drug Monitoring Jun 2021Aprepitant, an antiemetic selective neurokinin-1 receptor antagonist, is primarily metabolized to the active N-dealkylated form (ND-AP) and then converted to its...
BACKGROUND
Aprepitant, an antiemetic selective neurokinin-1 receptor antagonist, is primarily metabolized to the active N-dealkylated form (ND-AP) and then converted to its carbonyl form (ND-CAP) in humans. This study developed a simple liquid chromatography-tandem mass spectrometry method using electrospray ionization for the quantitation of plasma total and free aprepitant and its N-dealkylated metabolites and used them to analyze patient plasma.
METHODS
Free aprepitant and ND-AP in plasma were fractionated using centrifugal ultrafiltration. The analytes in plasma or their ultrafiltered specimens treated with triethylamine/acetonitrile were isocratically separated using a 3-μm octadecylsilyl column with a total run time of 10 minutes and scanned using positive ion electrospray ionization.
RESULTS
The calibration curves of total aprepitant, ND-AP, and ND-CAP were prepared at concentration ranges of 50-2500, 20-1000, and 5-250 ng/mL, respectively, whereas that of free aprepitant and ND-AP were at a concentration range of 2-150 ng/mL. The intraassay and interassay accuracy and imprecision values were 93.5%-107.7% and 94.6%-103.3%, and 2.1%-7.5% and 1.0%-8.9%, respectively. Aprepitant and its metabolites did not exhibit any matrix effects or instabilities in the plasma specimens. In cancer patients receiving oral aprepitant, the plasma concentration ranges of total aprepitant, ND-AP, and ND-CAP, and free aprepitant and ND-AP were 137-2170, 104-928, 22.4-97.6, 8.11-60.0, and 3.53-56.0 ng/mL, respectively. The median plasma free fraction proportion of aprepitant and ND-AP was 4.14% and 4.90%, respectively.
CONCLUSIONS
The present developed method showed an acceptable analytical performance and can be used to evaluate total and free aprepitant and its N-dealkylated metabolites in patient plasma.
Topics: Aprepitant; Calibration; Chromatography, Liquid; Humans; Plasma; Reproducibility of Results; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry
PubMed: 32960546
DOI: 10.1097/FTD.0000000000000815