Dataset Information

Overestimation of the effect of (fos)aprepitant on intravenous dexamethasone pharmacokinetics requires adaptation of the guidelines for children with chemotherapy-induced nausea and vomiting.

ABSTRACT:

Purpose

Chemotherapy-induced nausea and vomiting (CINV) are common side effects in pediatric oncology treatment. Besides 5-HT₃-antagonists, both dexamethasone and aprepitant are cornerstone drugs in controlling these side effects. Based on results of adult studies, the dexamethasone dose is reduced by 50% when combined with aprepitant, because of a drug-drug interaction, even though data on the interaction in children is lacking. The current study was developed to investigate the effect of aprepitant on dexamethasone clearance (CL) in children, in order to assess if dexamethasone dose reduction for concomitant use of aprepitant is appropriate in the current antiemetic regimen.

Methods

In total, 65 children (0.6-17.9 years), receiving intravenous or oral antiemetic therapy (dexamethasone ± aprepitant) as standard of care, were included. 305 dexamethasone plasma concentrations were determined using LC-MS/MS. An integrated dexamethasone and aprepitant pharmacokinetic model was developed using non-linear mixed effects modelling in order to investigate the effect of aprepitant administration on dexamethasone CL.

Results

In this population, dexamethasone CL in patients with concomitant administration of aprepitant was reduced by approximately 30% of the uninhibited CL (23.3 L/h (95% confidence interval 20.4-26.0)). This result is not consistent with the results of adult studies (50% reduction). This difference was not age dependent, but might be related to the route of administration of dexamethasone. Future studies are needed to assess the difference in oral/intravenous dexamethasone.

Conclusion

When dexamethasone is given intravenously as a component of triple therapy to prevent CINV in children, we advise to reduce the dexamethasone dose by 30% instead of 50%.

SUBMITTER: Nijstad AL

PROVIDER: S-EPMC9607815 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature

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Publications

Overestimation of the effect of (fos)aprepitant on intravenous dexamethasone pharmacokinetics requires adaptation of the guidelines for children with chemotherapy-induced nausea and vomiting.

Nijstad A Laura AL de Vos-Kerkhof Evelien E Enters-Weijnen Catherine F CF van de Wetering Marianne D MD Tissing Wim J E WJE Tibben Matthijs M MM Rosing Hilde H Lalmohamed Arief A Huitema Alwin D R ADR Zwaan C Michel CM

Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer 20221026 12

<h4>Purpose</h4>Chemotherapy-induced nausea and vomiting (CINV) are common side effects in pediatric oncology treatment. Besides 5-HT<sub>3</sub>-antagonists, both dexamethasone and aprepitant are cornerstone drugs in controlling these side effects. Based on results of adult studies, the dexamethasone dose is reduced by 50% when combined with aprepitant, because of a drug-drug interaction, even though data on the interaction in children is lacking. The current study was developed to investigate ...[more]

PMID: 36287279

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Project description:BackgroundCoadministration of different antiemetics proved to decrease postoperative nausea and vomiting (PONV) after laparoscopic sleeve gastrectomy (LSG). This trial compared aprepitant/dexamethasone (A/D) combination vs mirtazapine/dexamethasone (M/D) combination vs dexamethasone (D) alone for prevention of PONV in morbidly obese patients undergoing LSG.MethodsNinety patients scheduled for LSG were randomly allocated to receive 8 mg dexamethasone intravenous infusion (IVI) only in the D group or in addition to 80 mg aprepitant capsule in the A/D group or in addition to 30 mg mirtazapine tablet in the M/D group. Assessment of PONV was carried out at 0-2 h (early) and 2-24 h (late). The primary outcome was the complete response 0-24 h after surgery. Collective PONV, postoperative pain, side effects and patient satisfaction score were considered as secondary outcomes.ResultsThe A/D and M/D groups were superior to the D group for a complete response within 0-24 h after surgery (79.3% for the A/D group, 78.6% for the M/D group, and 20.7% for the D group). The D group was inferior to the A/D and M/D groups regarding collective PONV and use of rescue antiemetic 0-24 h after surgery (P < 0.001, P < 0.001, respectively). The peak nausea scores (2-24 h) were significantly reduced in the M/D group in comparison to the D group (P=0.005). Patients in the M/D group showed high sedation scores, while those in the A/D group showed low pain scores (2-24 h) and less analgesic requirements (P < 0.001, P < 0.001, P < 0.001, respectively). The A/D and M/D groups were superior to the D group with regard to the patient satisfaction score (P < 0.001).ConclusionAprepitant/dexamethasone combination and mirtazapine/dexamethasone combination were superior to dexamethasone alone in alleviating postoperative nausea and vomiting in morbidly obese patients scheduled to undergo laparoscopic sleeve gastrectomy. Trial Registration: ClinicalTrials.gov identifier: NCT04013386.

Project description:BackgroundDespite guidelines for managing chemotherapy-induced nausea and vomiting (CINV), there remains a need to clarify the optimal use of neurokinin-1 (NK1) receptor antagonists. Comparing the effectiveness of NEPA (netupitant-palonosetron) plus dexamethasone with other NK1 antagonist-based regimens combined with a 5HT3 receptor antagonist and dexamethasone is crucial for informed decision-making and improving patient outcomes.MethodsWe conducted a systematic review of the literature to assess randomized controlled trials (RCTs) comparing the efficacy, safety, and cost-effectiveness of NEPA plus dexamethasone and other NK1 antagonist-based regimens combined with a 5HT3 receptor antagonist and dexamethasone. PubMed, Embase, and the Cochrane Library databases were systematically searched, with the latest update performed in December 2023. Data on patient demographics, chemotherapy regimen characteristics, and outcomes were extracted for meta-analysis using a random-effects model.ResultsSeven RCTs were analyzed. NEPA plus dexamethasone showed superior efficacy in achieving complete response in the overall (risk ratio [RR], 1.15; 95% CI, 1.02--1.30) and delayed phases (RR, 1.20; 95% CI, 1.03-1.41) of chemotherapy. It was more effective in controlling nausea (overall phase RR, 1.20; 95% CI, 1.05-1.36; delayed phase RR, 1.21; 95% CI, 1.05-1.40) and reducing rescue therapy use (overall phase RR, 1.45; 95% CI, 1.07-1.95; delayed phase RR, 1.75; 95% CI, 1.10-2.78). Adverse event rates were comparable (RR, 1.03; 95% CI, 0.96-1.10). Subgroup analysis indicated NEPA's particular efficacy in patients receiving moderately emetogenic chemotherapy (RR, 1.31; 95% CI, 1.07-1.60).ConclusionNEPA plus dexamethasone regimens exhibit superior efficacy in preventing CINV, supporting their preferential inclusion in prophylactic treatment protocols. Its effective symptom control, safety profile, and cost-effectiveness endorse NEPA-based regimens as a beneficial option in CINV management.

Dataset Information

Overestimation of the effect of (fos)aprepitant on intravenous dexamethasone pharmacokinetics requires adaptation of the guidelines for children with chemotherapy-induced nausea and vomiting.

Purpose

Methods

Results

Conclusion

Publications

Overestimation of the effect of (fos)aprepitant on intravenous dexamethasone pharmacokinetics requires adaptation of the guidelines for children with chemotherapy-induced nausea and vomiting.

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