Fosaprepitant 150mg powder for solution for infusion vials

• Aprepitant reduces nausea, vomiting, and rescue antiemetics post-surgery. • Aprepitant increases the complete response rate within 24 hours post-surgery. • Fosaprepitant reduces vomiting but not nausea or rescue antiemetic use. • The review included 35 studies with 6241 participants under general anesthesia. • Identical time points were analyzed to assess the efficacy and safety of both drugs. Postoperative Nausea and Vomiting (PONV) is one of the patient-important outcomes, as its management reduces morbidity associated with surgery. This systematic review with meta-analysis aims to evaluate the efficacy and safety of prophylactic aprepitant and fosaprepitant within the first 24 hours after surgery in adult patients who underwent general anaesthesia. The authors The authors combined the outcomes only with identical evaluation times. The authors The authors searched six databases (MEDLINE, EMBASE, CENTRAL, WHO, ICTRP, SCIELO) for randomized controlled trials that compared aprepitant or fosaprepitant for PONV against control in different time assessments within the first 24 hours after surgery in adult patients who underwent general anaesthesia. This systematic review includes 35 articles with 6241 participants in total. The authors The authors observed that aprepitant, from 0h to 24 h after surgery, significantly reduces the incidence of nausea (RR = 0.80, 95 % CI 0.67–0.97, I 2 = 42 %, p = 0.07), vomiting (RR = 0.41, 95 % CI: 0.31–0.55, I 2 = 51 %, p = 0.008), the use of rescue antiemetics (RR = 0.79, 95 % CI 0.66–0.95, I 2 = 54 %, p = 0.009), and increases the complete response rate (RR = 1.19, 95 % CI 1.04–1.37, I 2 = 51 %, p = 0.04). On the other hand, fosaprepitant, from 0 to 24 hours after surgery, showed a reduction only in the incidence of vomiting (RR = 0.35, 95 % CI 0.19–0.64, I 2 = 33 %, p = 0.20). Aprepitant reduces the incidence of postoperative nausea, vomiting and the use of rescue antiemetics and increases the complete response rate among adult patients from 0 to 24 hours after surgery. Fosaprepitant reduces the incidence of vomiting from 0 to 24 hours after surgery. Findings primarily reflect female patients; male applicability requires further study. CRD42023427076.

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Objective To systematically evaluate the clinical efficacy and safety of fosaprepitant combined with 5-hydroxytryptamine 3 receptor antagonists (5-HT 3 RA) (with or without dexamethasone) on the chemotherapy-induced vomiting in pediatric cancer patients. Methods PubMed, Embase, Cochrane Library, China Journal full-text database (CNKI), Wanfang data knowledge service platform (Wanfang) and VIP Chinese sci-tech Journal full-text database (VIP) were searched by computer (retrieval time from database establishment to Apr. 2024), randomized controlled trials (RCTs) and cohort studies about fosaprepitant and 5-HT 3 RA with or without dexamethasone (observation group) versus 5-HT 3 RA, with or without dexamethasone, as the control group for chemotherapy-induced vomiting were collected, after data extraction and quality evaluation, meta-analysis was carried out by Rev Man 5.3 software. Results A total of 731 patients were included in 7 trials. Meta-analysis results showed that the complete response (CCR, no vomiting/rescue medication) rates were higher in the observation group compared to that in the control group during the acute [the relative risk: RR = 1.64, 95% confidence interval: 95%CI = 1.35–1.99, P < 0.00001], delayed vomiting [RR = 2.05, 95%CI = 1.32–3.17, P = 0.001] and overall phases [RR = 2.08, 95%CI = 1.69–2.57, P < 0.00001], with statistical significance (P < 0.05). The subgroup analysis of salvage treatment proportion revealed that the need for rescue medication was higher for patients in the control than fosaprepitan regimens [RR = 0.20, 95%CI = 0.08–0.54, P = 0.001] There was no difference in the incidence of adverse drug reaction between two groups [RR = 0.95, 95%CI = 0.75–1.19, P = 0.66]. Conclusion Fosaprepitant in combination with 5-HT3RA (with or without dexamethasone) has the same safety and more effective in preventing chemotherapy-induced vomiting than 5-HT3RA with or without dexamethasone.

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BACKGROUND: Postoperative nausea and vomiting (PONV) is a major problem after surgery. Even with double prophylactic therapy including dexamethasone and a 5-hydroxytryptamine-3 receptor antagonist, the incidence is still high in many at-risk patients. Fosaprepitant, a neurokinin-1 receptor antagonist, is an effective antiemetic, but its efficacy and safety in combination antiemetic therapy for preventing PONV remain unclear. METHODS: In this randomised, controlled, double-blind trial, 1154 participants at high risk of PONV and undergoing laparoscopic gastrointestinal surgery were randomly assigned to either a fosaprepitant group (n=577) receiving fosaprepitant 150 mg i.v. dissolved in 0.9% saline 150 ml, or a placebo group (n=577) receiving 0.9% saline 150 ml before anaesthesia induction. Dexamethasone 5 mg i.v. and palonosetron 0.075 i.v. mg were each administered in both groups. The primary outcome was the incidence of PONV (defined as nausea, retching, or vomiting) during the first 24 postoperative hours. RESULTS: The incidence of PONV during the first 24 postoperative hours was lower in the fosaprepitant group (32.4% vs 48.7%; adjusted risk difference -16.9% [95% confidence interval: -22.4 to -11.4%]; adjusted risk ratio 0.65 [95% CI: 0.57 to 0.76]; P<0.001). There were no differences in severe adverse events between groups, but the incidence of intraoperative hypotension was higher (38.0% vs 31.7%, P=0.026) and intraoperative hypertension (40.6% vs 49.2%, P=0.003) was lower in the fosaprepitant group. CONCLUSIONS: Fosaprepitant added to dexamethasone and palonosetron reduced the incidence of PONV in patients at high risk of PONV undergoing laparoscopic gastrointestinal surgery. Notably, it increased the incidence of intraoperative hypotension. CLINICAL TRIAL REGISTRATION: NCT04853147.

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Importance: Unlike substantial evidence in the prevention of chemotherapy-induced nausea and vomiting (CINV), research in the prevention of nausea and vomiting caused by concurrent chemoradiotherapy (CCRT) is currently lacking. Objective: To compare the efficacy and safety of fosaprepitant weekly vs every 3 weeks for the prevention of nausea and emesis caused by CCRT among patients with nasopharyngeal carcinoma. Design, Setting, and Participants: This pilot randomized clinical trial was conducted at a single cancer center from November 24, 2020, to July 26, 2021, among patients with nasopharyngeal carcinoma who had achieved CINV control after 2 to 3 cycles of induction chemotherapy. Efficacy analyses were performed in the intention-to-treat population. Data were analyzed on November 4, 2022. Interventions: Eligible patients were randomly assigned (1:1) to receive fosaprepitant either weekly or every 3 weeks. Main Outcomes and Measures: The primary end point was the proportion of patients with sustained complete response (defined as no emesis and no rescue therapy) during CCRT. Secondary end points were sustained no emesis, no nausea, no significant nausea, mean time to first emetic episode, quality of life, and 1-year progression-free survival (PFS). Results: A total of 100 patients (mean [SD] age, 46.6 [10.9] years; 83 [83.0%] male) who had achieved CINV control after induction chemotherapy were randomly assigned to receive fosaprepitant weekly (50 patients) or every 3 weeks (50 patients). There was no significantly significant difference in cumulative risk of emesis or rescue therapy in the group that received weekly fosaprepitant compared with those who received fosaprepitant every 3 weeks (subhazard ratio, 0.66 [95% CI, 0.43-1.02]; P = .06). The proportion of patients with sustained no emesis (38% vs 14%; P = .003) or no significant nausea (92% vs 72%; P = .002) was significantly higher in the group that received fosaprepitant weekly vs those who received fosaprepitant every 3 weeks. Treatments were well tolerated. Patients in the weekly group had improved scores for multiple quality-of-life measures. There was no significant difference in survival outcomes between groups (91.8% vs 93.7%; P = .99). In the mean brainstem dose subgroups, a possible treatment interaction effect was observed in sustained complete response (mean brainstem dose ≥36 Gy: hazard ratio [HR], 0.32 [95% CI, 0.15-0.69]; mean brainstem dose <36 Gy: HR, 0.95 [95% CI, 0.55-1.63]) and sustained no emesis (mean brainstem dose ≥36 Gy: HR, 0.21 [95% CI, 0.08-0.53]; mean brainstem dose <36 Gy: HR, 0.73 [95% CI, 0.41-1.28]). Conclusions and Relevance: In this pilot randomized clinical trial, there was no statistically significant difference in the complete response primary end point, but patients receiving weekly fosaprepitant were less likely to experience emesis compared with those who received fosaprepitant every 3 weeks, especially in the subgroup with a mean brainstem dose of 36 Gy or more. Weekly fosaprepitant was well tolerated and improved quality of life of patients without compromising survival. Trial Registration: ClinicalTrials.gov Identifier: NCT04636632.

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Background: Neurokinin-1 receptor antagonists have improved the management of chemotherapy-induced nausea and vomiting (CINV), but to date there has been no prospective comparison between oral aprepitant and intravenous fosaprepitant in pediatric oncology patients. Methods: Our study was a double-parallel study, and the distribution ratio was 1:1. Children aged 2–12 years who were undergoing moderate or highly emetogenic chemotherapy (MEC or HEC) were randomly assigned to receive ondansetron and dexamethasone combined with either a single dose of intravenous fosaprepitant (arm A), or 3 days of oral aprepitant (arm B). The primary outcome measure was the rate of complete response (CR) of CINV within the acute phase, defined as from the start through 24 hours after the last chemotherapy dose. Response during the delayed phase, overall response, and use of rescue antiemetics were also assessed. Results: We prospectively evaluated 108 eligible patients, including 55 receiving fosaprepitant. Study observations were made during a single cycle for each patient. The occurrence of CR in the acute phase was statistically higher for patients receiving fosaprepitant (95% vs. 79%, P=0.018<0.05). Modest differences were seen in CR rates during the delayed phase (71% vs. 66%, P=0.586), and overall response rate (69% vs. 57%, P=0.179). The use of antiemetic rescue medicines was similar between arms A (11%) and B (7%). Conclusions: Fosaprepitant produced more CRs of CINV in the acute phase than did aprepitant, although there were no statistical differences in delayed phase response, overall response, or use of rescue antiemetics. This study confirms the safety, efficacy, and potential advantages of fosaprepitant in reducing CINV in pediatric oncology patients. Trial Registration: ClinicalTrials.gov identifier: NCT04873284.

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PURPOSE: Prevention of chemotherapy-induced nausea and vomiting with currently recommended NK1 receptor antagonist-based triplet during carboplatin (AUC ≥4) chemotherapy appears inadequate. A comparative study between olanzapine and NK1 receptor antagonist-based combination is lacking. METHODS: This was a single-center, phase III, prospective randomized, double-blind, placebo-controlled superiority study comparing olanzapine (olanzapine, ondansetron, dexamethasone [OOD]-experimental arm) with fosaprepitant (fosaprepitant, ondansetron, dexamethasone [FOD]-standard arm) in combination with ondansetron and dexamethasone among chemotherapy-naïve patients (age ≥18 years) receiving carboplatin (AUC ≥4) during the first cycle of single-day chemotherapy. The OOD arm received olanzapine 5 mg per oral once daily (day 1-4), ondansetron 8 mg with dexametahsone 12 mg intravenous (IV) once daily (20 mg with paclitaxel; day 1), and matching placebo for fosaprepitant (day 1). The FOD arm received fosaprepitant 150 mg IV once daily, with the combination (day 1) and matching placebo for olanzapine (days 1-4). The primary outcome was no nausea during the overall period (0-120 hours). RESULTS: = .19) in the overall period (0-120 hours). Complete response rates and total control rates were also similar in both arms. One patient had grade 3 sedation in the olanzapine arm. CONCLUSION: Olanzapine, in comparison with NK1 antagonist, is not superior for nausea control during carboplatin-induced emesis. It may act as an effective oral alternative for prevention.

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PURPOSE: Cisplatin-based chemoradiotherapy (CRT) is standard treatment for head and neck squamous cell carcinoma (HNSCC). However, IMRT may increase chemotherapy-induced nausea and vomiting (CINV). The purpose of this study is to investigate the effect of fosaprepitant in preventing CINV. METHODS: An infusion of 150 mg fosaprepitant was given through a 30 min. We assessed acute toxicity using CTCAE v.4 and the incidence of CINV using the FLIE questionnaire. The evaluation of CINV was done at the second and fifth weeks of CRT and 1 week after the end. The EORTC QLQ-HN 43 questionnaire was administered before treatment beginning (baseline), at second (T1) and fifth (T2) weeks. A dosimetric analysis was performed on dorsal nucleus of vagus (DVC) and area postrema (AP). RESULTS: Between March and November 2020, 24 patients were enrolled. No correlation was found between nausea and DVC mean dose (p = 0.573), and AP mean dose (p = 0.869). Based on the FLIE questionnaire, patients reported a mean score of 30.5 for nausea and 30 for vomiting during week 2 and 29.8 for nausea and 29.2 for vomiting during week 5. After treatment ended, the mean scores were 27.4 for nausea and 27.7 for vomiting. All patients completed the EORTC QLQ-HN 43. Significantly higher scores at T2 assessment than baseline were observed. CONCLUSIONS: The use of fosaprepitant in preventing CINV reduced incidence of moderate to severe nausea and vomiting. No correlation has been found between nausea and median dose to DVC and AP.

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In recent years, chemotherapy-induced nausea and vomiting (CINV) has become the most common adverse effect of chemotherapy in oncology patients. The CINV may reduce the quality of life in mild cases, or even make the patients resist or delay further treatment. Fosaprepitant is a newly marketed neurokinin-1 receptor antagonist (NK-1RA), which can be combined with 5-hydroxytryptamine 3 receptor antagonists (5-HT3RAs) and dexamethasone to prevent chemotherapy-induced vomiting. The dimeglumine salt form of fosaprepitant can be utilized as an intravenous injectable drug, which surpasses aprepitant's oral admistration limits. Fosaprepitant is effective and safe in the control of CINV in cancer patients receiving highly emetogenic chemotherapy (HEC), and may be an alternative option for antiemetic therapy. In general, fosaprepitant is worthy of clinical promotion and has a large market potential. This article reviews the clinical studies on fosaprepitant conducted in recent years, with the aim of providing a basis for the rational clinical selection of antiemetic drugs.

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