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

Autor: Nijstad AL; Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht, The Netherlands.; Department of Pharmacology, Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands., de Vos-Kerkhof E; Princess Máxima Center for Pediatric Oncology, Postbus 113, 3720 AC, Bilthoven, Utrecht, The Netherlands., Enters-Weijnen CF; Princess Máxima Center for Pediatric Oncology, Postbus 113, 3720 AC, Bilthoven, Utrecht, The Netherlands.; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands., van de Wetering MD; Princess Máxima Center for Pediatric Oncology, Postbus 113, 3720 AC, Bilthoven, Utrecht, The Netherlands., Tissing WJE; Princess Máxima Center for Pediatric Oncology, Postbus 113, 3720 AC, Bilthoven, Utrecht, The Netherlands.; Department of Pediatric Oncology and Hematology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands., Tibben MM; Department of Pharmacy & Pharmacology, Netherlands Cancer Institute, Amsterdam, The Netherlands., Rosing H; Department of Pharmacy & Pharmacology, Netherlands Cancer Institute, Amsterdam, The Netherlands., Lalmohamed A; Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht, The Netherlands.; Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands., Huitema ADR; Department of Clinical Pharmacy, University Medical Center Utrecht, Utrecht, The Netherlands.; Department of Pharmacology, Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.; Department of Pharmacy & Pharmacology, Netherlands Cancer Institute, Amsterdam, The Netherlands., Zwaan CM; Princess Máxima Center for Pediatric Oncology, Postbus 113, 3720 AC, Bilthoven, Utrecht, The Netherlands. c.m.zwaan@prinsesmaximacentrum.nl.; Department of Pediatric Oncology, Erasmus MC-Sophia Children's Hospital, Rotterdam, The Netherlands. c.m.zwaan@prinsesmaximacentrum.nl.
Jazyk: angličtina
Zdroj: Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer [Support Care Cancer] 2022 Dec; Vol. 30 (12), pp. 9991-9999. Date of Electronic Publication: 2022 Oct 26.
DOI: 10.1007/s00520-022-07423-6
Abstrakt: Purpose: Chemotherapy-induced nausea and vomiting (CINV) are common side effects in pediatric oncology treatment. Besides 5-HT 3 -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%.
(© 2022. The Author(s).)
Databáze: MEDLINE
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