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Cancer Chemotherapy and Pharmacology Jul 2022Ifosfamide is one of the chemotherapy regimens which potentially causes neurotoxicity in patients up to 30%. Aprepitant is administered as an anti-emetic agent in... (Review)
Review
Ifosfamide is one of the chemotherapy regimens which potentially causes neurotoxicity in patients up to 30%. Aprepitant is administered as an anti-emetic agent in chemotherapy and regarding the inhibitory effect on CYP3A4, aprepitant can increase the risk of ifosfamide adverse effects. This study aims to systematically investigate the relation of ifosfamide-induced neurotoxicity and aprepitant or fosaprepitant in chemotherapy cancer patients. Four databases including PubMed, Scopus, Web of Science, and Embase were systematically reviewed without language restriction and hand searching was performed until December 2021. Total 1639 publications were retrieved and nine studies fulfilled the eligibility criteria. For quality assessment, we used Newcastle-Ottawa quality assessment scales (NOS) for retrospective cohort studies and Cochrane Collaboration tool to assess the risk of bias for a randomized controlled trial. Overall, the results of our systematic review indicated a positive enhanced trend between neurotoxicity and concomitant use of ifosfamide and aprepitant or fosaprepitant, but the association was not statistically significant. As indicated by our findings, several studies identified low albumin as a risk factor for ifosfamide-induced encephalopathy. However, further clinical studies with a larger population of patients are required to evaluate the clinical significance of ifosfamide-related neurotoxicity and aprepitant or fosaprepitant.
Topics: Aprepitant; Humans; Ifosfamide; Morpholines; Neurotoxicity Syndromes; Randomized Controlled Trials as Topic; Retrospective Studies
PubMed: 35635561
DOI: 10.1007/s00280-022-04439-x -
BioMed Research International 2017Chronic pruritus is a difficult condition to treat and is associated with several comorbidities, including insomnia, depression, and decreased quality of life. Treatment... (Review)
Review
Chronic pruritus is a difficult condition to treat and is associated with several comorbidities, including insomnia, depression, and decreased quality of life. Treatment for chronic itch includes corticosteroids, antihistamines, and systemic therapies such as naltrexone, gabapentin, UV light therapy, and immunomodulatory treatments, including azathioprine, methotrexate, and cellcept. However, some patients still remain refractory to conventional therapy. Aprepitant is a neurokinin-1 receptor antagonist approved for the prevention of chemotherapy-induced and postoperative nausea and vomiting (CINV, PONV). Recently, aprepitant has demonstrated effectiveness in several case series and open label trials in relieving pruritus for patients refractory to other treatments. Patients with pruritus associated with Sézary syndrome, mycosis fungoides, lung adenocarcinoma, breast carcinoma, sarcomas, metastatic solid tumors, chronic kidney disease, hyperuricemia, iron deficiency, brachioradial pruritus, and Hodgkin's lymphoma have experienced considerable symptom relief with short-term use of aprepitant (up to two weeks). Due to differences in reporting and evaluation of drug effects, the mechanism of aprepitant's role is difficult to understand based on the current literature. Herein, we evaluate aprepitant's antipruritic effects and discuss its mechanism of action and adverse effects. We propose that aprepitant is an alternative for patients suffering from pruritus who do not obtain enough symptom relief from conventional therapy.
Topics: Antiemetics; Aprepitant; Chronic Disease; Humans; Morpholines; Neurokinin-1 Receptor Antagonists; Pruritus; Quality of Life
PubMed: 29057261
DOI: 10.1155/2017/4790810 -
Expert Review of Clinical Pharmacology 2023Post-operative nausea and vomiting (PONV) affects 30% of all patients undergoing surgery and up to 80% of high-risk patients. Antiemetics for PONV prophylaxis target a... (Review)
Review
INTRODUCTION
Post-operative nausea and vomiting (PONV) affects 30% of all patients undergoing surgery and up to 80% of high-risk patients. Antiemetics for PONV prophylaxis target a variety of receptor systems, with varying degrees of efficacy and side effect profile. Neurokinin -1 receptor antagonists are the most recent class of compounds investigated for PONV prophylaxis, with aprepitant being the only one currently approved for this indication.
AREAS COVERED
This review covers the pathophysiology of PONV, current recommendations for PONV prophylaxis, pharmacokinetics, and pharmacodynamics of aprepitant, and the evidence for its efficacy in the management of PONV as a single agent and in combination therapy.
EXPERT OPINION
Aprepitant is effective for PONV prophylaxis. It has superior antivomiting efficacy, long half-life, and favorable side effect profile. Data on antiemetic combinations involving aprepitant are limited, and it is not clear if the addition of other antiemetics to aprepitant results in improved PONV prophylaxis. The oral route of administration of aprepitant is a potential limitation in a busy clinical practice. However, the recent approval of an intravenous formulation could provide a more convenient route of administration. Aprepitant remains more expensive than other antiemetics, and there are no studies assessing the cost effectiveness of its use.
Topics: Humans; Aprepitant; Antiemetics; Postoperative Nausea and Vomiting; Morpholines; Vomiting; Neurokinin-1 Receptor Antagonists
PubMed: 37128935
DOI: 10.1080/17512433.2023.2209722 -
Postgraduate Medical Journal Feb 2016Postoperative nausea and vomiting (PONV) is an important clinical problem. Aprepitant is a relatively new agent for this condition which may be superior to other... (Meta-Analysis)
Meta-Analysis Review
Postoperative nausea and vomiting (PONV) is an important clinical problem. Aprepitant is a relatively new agent for this condition which may be superior to other treatment. A systematic review was performed after searching a number of medical databases for controlled trials comparing aprepitant with conventional antiemetics published up to 25 April 2015 using the following keywords: 'Aprepitant for PONV', 'Aprepitant versus 5-HT3 antagonists' and 'NK-1 versus 5-HT3 for PONV'. The primary outcome for the pooled analysis was efficacy of aprepitant in preventing vomiting on postoperative day (POD) 1 and 2. 172 potentially relevant papers were identified of which 23 had suitable data. For the primary outcome, 14 papers had relevant data. On POD1, 227/2341 patients (9.7%) patients randomised to aprepitant had a vomiting episode compared with 496/2267 (21.9%) controls. On POD2, the rate of vomiting among patients receiving aprepitant was 6.8% compared with 12.8% for controls. The OR for vomiting compared with controls was 0.48 (95% CI 0.34 to 0.67) on POD1 and 0.54 (95% CI 0.40 to 0.72) on POD2. Aprepitant also demonstrated a better profile with a lower need for rescue antiemetic and a higher complete response. Efficacy for vomiting prevention was demonstrated for 40 mg, 80 mg and 125 mg without major adverse effects. For vomiting comparison there was significant unexplainable heterogeneity (67.9% and 71.5% for POD1 and POD2, respectively). We conclude that (1) aprepitant reduces the incidence of vomiting on both POD1 and POD2, but there is an unexplained heterogeneity which lowers the strength of the evidence; (2) complete freedom from PONV on POD1 is highest for aprepitant with minimum need for rescue; and (3) oral aprepitant (80 mg) provides an effective and safe sustained antivomiting effect.
Topics: Antiemetics; Aprepitant; Humans; Morpholines; Patient Satisfaction; Postoperative Nausea and Vomiting; Quality of Health Care; Treatment Outcome
PubMed: 26627976
DOI: 10.1136/postgradmedj-2015-133515 -
The Oncologist Apr 2015Chemotherapy-induced nausea and vomiting (CINV) is a common adverse event associated with anticancer treatment that can have a significant adverse impact on patient... (Review)
Review
Chemotherapy-induced nausea and vomiting (CINV) is a common adverse event associated with anticancer treatment that can have a significant adverse impact on patient health-related quality of life and that can potentially undermine the effectiveness of chemotherapy. Traditional regimens to prevent CINV generally involved a combination of a corticosteroid plus a 5-hydroxytryptamine (5HT3) receptor antagonist (RA). In the past 10 years, antiemetic treatment has greatly advanced with the availability of the neurokinin-1 receptor antagonist (NK1 RA) aprepitant and its prodrug fosaprepitant. NK1 RAs have a different mechanism of action in CINV than corticosteroids and 5HT3 RAs, thus their use can complement traditional antiemetic drugs and can enhance control of CINV. This review examined accumulated data regarding the safety and efficacy of aprepitant and fosaprepitant over the decade since the first regulatory approval. Data from key studies of aprepitant and fosaprepitant in the prevention of CINV in patients receiving moderately and highly emetogenic chemotherapy were explored, as were recommendations in currently available guidelines for their use. In addition, their use as antiemetic therapy in special patient populations was highlighted. Future perspectives on potential uses of aprepitant and fosaprepitant for indications other than CINV are presented.
Topics: Administration, Intravenous; Administration, Oral; Antiemetics; Antineoplastic Agents; Aprepitant; Drug Interactions; Guidelines as Topic; Humans; Morpholines; Nausea; Stem Cell Transplantation; Vomiting
PubMed: 25795636
DOI: 10.1634/theoncologist.2014-0229 -
Expert Opinion on Pharmacotherapy Dec 2003Recently, a new class of agents, the substance P antagonists, has heralded a novel approach for the control of emesis. Aprepitant (Emend, Merck & Co., Inc.), the first... (Review)
Review
Recently, a new class of agents, the substance P antagonists, has heralded a novel approach for the control of emesis. Aprepitant (Emend, Merck & Co., Inc.), the first of this class, was recently approved by the FDA for the prevention of both acute and delayed chemotherapy-induced nausea and vomiting (CINV). Of interest is the vast array of processes in which substance P is involved such as pain, anxiety, depression and inflammation and the potential wide applicability of substance P antagonists to a number of medical conditions outside of the nausea and vomiting realm. The following review provides an overview of aprepitant including pharmacokinetics, pharmacology and clinical evidence for its use in CINV. A brief discussion of other possible indications for aprepitant will also be presented.
Topics: Antiemetics; Antineoplastic Agents; Aprepitant; Clinical Trials as Topic; Drug Interactions; Humans; Morpholines; Nausea; Neurokinin-1 Receptor Antagonists; Vomiting
PubMed: 14640927
DOI: 10.1517/14656566.4.12.2279 -
The Netherlands Journal of Medicine Apr 2018In the current guidelines to prevent hemotherapyinduced nausea and vomiting, multiple antiemetic drugs are administered simultaneously. In patients who receive highly... (Review)
Review
In the current guidelines to prevent hemotherapyinduced nausea and vomiting, multiple antiemetic drugs are administered simultaneously. In patients who receive highly emetogenic chemotherapy, aprepitant, an NK1-receptor antagonist, is combined with ondansetron and dexamethasone. Aprepitant can influence the pharmacokinetics of other drugs, as it is an inhibitor and inducer of CYP3A4. Some anticancer drugs and other co-medication frequently used in cancer patients are CYP3A4 or CYP29C substrates. We give an overview of the metabolism and current data on clinically relevant drug-drug interactions with aprepitant during chemotherapy. Physicians should be aware of the potential risk of drug-drug interactions with aprepitant, especially in regimens with curative intent. More research should be performed on drug-drug interactions with aprepitant and their clinical consequences to make evidence-based recommendations.
Topics: Analgesics; Anticoagulants; Antiemetics; Antineoplastic Agents; Aprepitant; Chemoprevention; Dexamethasone; Drug Interactions; Glucocorticoids; Humans; Neoplasms; Neurokinin-1 Receptor Antagonists; Psychotropic Drugs; Vomiting
PubMed: 29667586
DOI: No ID Found -
Drugs 2004Aprepitant (Emend) is the first commercially available drug from a new class of agents, the neurokinin NK(1) receptor antagonists. Oral aprepitant, in combination with... (Review)
Review
Aprepitant (Emend) is the first commercially available drug from a new class of agents, the neurokinin NK(1) receptor antagonists. Oral aprepitant, in combination with other agents, is indicated for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) associated with highly emetogenic chemotherapy in adults. In three randomised, double-blind, placebo-controlled trials comparing aprepitant (125 mg day 1, 80mg once daily on days 2 and 3 or 2-5) plus standard therapy (intravenous ondansetron and oral dexamethasone) with standard therapy plus placebo, overall complete responses (primary endpoint, defined as no emesis and no rescue therapy) were seen in significantly more patients in the aprepitant arms (63-73% versus 43-52%, p < 0.01 for all comparisons). Complete responses and complete protection during the acute and delayed phase, and overall complete protection were also observed in significantly more patients in the aprepitant arms. The difference between treatment groups was more marked in the overall and delayed phases than in the acute phase. The antiemetic efficacy of aprepitant plus standard therapy in the prevention of CINV was maintained for up to six cycles of chemotherapy. Where assessed, more patients in the aprepitant plus standard therapy arms than the standard therapy plus placebo arms reported no impact of CINV on daily life, as assessed by the Functional Living Index-Emesis. Aprepitant is generally well tolerated. The most common adverse events in randomised trials were asthenia or fatigue. Other adverse events experienced by aprepitant recipients include anorexia, constipation, diarrhoea, nausea (after day 5 of the study) and hiccups. In addition to being a substrate for cytochrome P450 (CYP) 3A4, aprepitant is also a moderate inhibitor and inducer of this isoenzyme as well as an inducer of CYP2C9. Thus, aprepitant has the potential to interact with other agents metabolised by hepatic CYP isoenzymes. In one trial, there was a higher incidence of serious infection or febrile neutropenia in the aprepitant plus standard therapy arm than the standard therapy plus placebo arm; this was attributed to a pharmacokinetic interaction between aprepitant and dexamethasone. In subsequent trials, a modified dexamethasone regimen was used. In conclusion, when added to standard therapy (a serotonin 5-HT(3) receptor antagonist and a corticosteroid), aprepitant is effective and generally well tolerated in the prevention of CINV associated with highly emetogenic chemotherapy in adults. Despite marked advances in the prevention of CINV, standard therapy does not protect all patients. The addition of aprepitant to standard therapy provides an advance in the prevention of both acute and delayed CINV in adults with cancer.
Topics: Animals; Aprepitant; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Double-Blind Method; Drug-Related Side Effects and Adverse Reactions; Humans; Morpholines; Multicenter Studies as Topic; Nausea; Neurokinin-1 Receptor Antagonists; Randomized Controlled Trials as Topic; Receptors, Neurokinin-1; Vomiting
PubMed: 15025555
DOI: 10.2165/00003495-200464070-00013 -
Journal of Perianesthesia Nursing :... Oct 2015Postoperative nausea and vomiting (PONV) affects as many as 30% of surgical patients. Aprepitant, an antagonist of the neurokinin-1 receptor with a 40% half-life, may be... (Review)
Review
PURPOSE
Postoperative nausea and vomiting (PONV) affects as many as 30% of surgical patients. Aprepitant, an antagonist of the neurokinin-1 receptor with a 40% half-life, may be effective for prophylaxis for PONV. This review describes the evidence of adding aprepitant to antiemetic therapy for PONV prophylaxis.
METHODS
A literature search was conducted to answer the population-intervention-comparison-outcome-time (PICOT) question: In adult patients undergoing general anesthesia (P), does aprepitant (I) decrease PONV (O) postoperatively (T) as compared to patients receiving other antiemetic therapy or a placebo (C)?
RESULTS
Eight randomized controlled trials, one prognostic study, and one post hoc analysis were appraised. Perioperatively, aprepitant decreased the severity and number of episodes of PONV.
DISCUSSION
Aprepitant appears to be more effective in decreasing the incidence of PONV postoperatively as compared with ondansetron. It is recommended that aprepitant is used to treat patients at risk for PONV and for whom PONV could lead to catastrophic adverse outcomes.
Topics: Antiemetics; Aprepitant; Evidence-Based Medicine; Female; Humans; Male; Morpholines; Postoperative Nausea and Vomiting
PubMed: 26408515
DOI: 10.1016/j.jopan.2014.11.013 -
Journal of Neuroinflammation Aug 2022Pyroptosis is a programmed cell death mediated by inflammasomes. Previous studies have reported that inhibition of neurokinin receptor 1 (NK1R) exerted neuroprotection...
BACKGROUND
Pyroptosis is a programmed cell death mediated by inflammasomes. Previous studies have reported that inhibition of neurokinin receptor 1 (NK1R) exerted neuroprotection in several neurological diseases. Herein, we have investigated the role of NK1R receptor inhibition using Aprepitant to attenuate NLRC4-dependent neuronal pyroptosis after intracerebral hemorrhage (ICH), as well as the underlying mechanism.
METHODS
A total of 182 CD-1 mice were used. ICH was induced by injection of autologous blood into the right basal ganglia. Aprepitant, a selective antagonist of NK1R, was injected intraperitoneally at 1 h after ICH. To explore the underlying mechanism, NK1R agonist, GR73632, and protein kinase C delta (PKCδ) agonist, phorbol 12-myristate 13-acetate (PMA), were injected intracerebroventricularly at 1 h after ICH induction, and small interfering ribonucleic acid (siRNA) for NLRC4 was administered via intracerebroventricular injection at 48 h before ICH induction, respectively. Neurobehavioral tests, western blot, and immunofluorescence staining were performed.
RESULTS
The expression of endogenous NK1R and NLRC 4 were gradually increased after ICH. NK1R was expressed on neurons. Aprepitant significantly improved the short- and long-term neurobehavioral deficits after ICH, which was accompanied with decreased neuronal pyroptosis, as well as decreased expression of NLRC4, Cleaved-caspase-1, GSDMD (gasdermin D), IL-1β, and IL-18. Activation of NK1R or PKCδ abolished these neuroprotective effects of Aprepitant after ICH. Similarly, knocking down NLRC4 using siRNA produced similar neuroprotective effects.
CONCLUSION
Aprepitant suppressed NLRC4-dependent neuronal pyroptosis and improved neurological function, possibly mediated by inhibition of NK1R/PKCδ signaling pathways after ICH. The NK1R may be a promising therapeutic target for the treatment of ICH.
Topics: Animals; Aprepitant; Cerebral Hemorrhage; Disease Models, Animal; Mice; Neurons; Neuroprotective Agents; Pyroptosis; RNA, Small Interfering
PubMed: 35922848
DOI: 10.1186/s12974-022-02558-z