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Drug–drug interaction profile of components of a fixed combination of netupitant and palonosetron: Review of clinical data
Neurokinin-1 (NK(1)) receptor antagonists (RAs) are commonly coadministered with serotonin (5-HT(3)) RAs (e.g. palonosetron (PALO)) to prevent chemotherapy-induced nausea/vomiting. Netupitant/palonosetron (NEPA), an oral fixed combination of netupitant (NETU)—a new NK(1) RA—and PALO, is currently un...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
SAGE Publications
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4843089/ https://www.ncbi.nlm.nih.gov/pubmed/25998320 http://dx.doi.org/10.1177/1078155215586824 |
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author | Natale, James J Spinelli, Tulla Calcagnile, Selma Lanzarotti, Corinna Rossi, Giorgia Cox, David Kashef, Kimia |
author_facet | Natale, James J Spinelli, Tulla Calcagnile, Selma Lanzarotti, Corinna Rossi, Giorgia Cox, David Kashef, Kimia |
author_sort | Natale, James J |
collection | PubMed |
description | Neurokinin-1 (NK(1)) receptor antagonists (RAs) are commonly coadministered with serotonin (5-HT(3)) RAs (e.g. palonosetron (PALO)) to prevent chemotherapy-induced nausea/vomiting. Netupitant/palonosetron (NEPA), an oral fixed combination of netupitant (NETU)—a new NK(1) RA—and PALO, is currently under development. In vitro data suggest that NETU inhibits CYP3A4 and is a substrate for and weak inhibitor of P-glycoprotein (P-gp). This review evaluates potential drug–drug interactions between NETU or NEPA and CYP3A4 substrates/inducers/inhibitors or P-gp substrates in healthy subjects. Pharmacokinetic (PK) parameters were evaluated for each drug when NETU was coadministered with PALO (single doses) and when single doses of NETU or NEPA were coadministered with CYP3A4 substrates (erythromycin (ERY), midazolam (MID), dexamethasone (DEX), or oral contraceptives), inhibitors (ketoconazole (KETO)), or inducers (rifampicin (RIF)), or a P-gp substrate (digoxin (DIG)). Results showed no relevant PK interactions between NETU and PALO. Coadministration of NETU increased MID and ERY exposure and significantly increased DEX exposure in a dose-dependent manner; NETU exposure was unaffected. NEPA coadministration had no clinically significant effect on oral contraception, although levonorgestrel exposure increased. NETU exposure increased after coadministration of NEPA with KETO and decreased after coadministration with RIF; PALO exposure was unaffected. NETU coadministration did not influence DIG exposure. In conclusion, there were no clinically relevant interactions between NETU and PALO, or NEPA and oral contraceptives (based on levonorgestrel and ethinylestradiol exposure). Coadministration of NETU or NEPA with CYP3A4 inducers/inhibitors/substrates should be done with caution. Dose reduction is recommended for DEX. Dose adjustments are not needed for NETU coadministration with P-gp substrates. |
format | Online Article Text |
id | pubmed-4843089 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | SAGE Publications |
record_format | MEDLINE/PubMed |
spelling | pubmed-48430892016-05-24 Drug–drug interaction profile of components of a fixed combination of netupitant and palonosetron: Review of clinical data Natale, James J Spinelli, Tulla Calcagnile, Selma Lanzarotti, Corinna Rossi, Giorgia Cox, David Kashef, Kimia J Oncol Pharm Pract Review Articles Neurokinin-1 (NK(1)) receptor antagonists (RAs) are commonly coadministered with serotonin (5-HT(3)) RAs (e.g. palonosetron (PALO)) to prevent chemotherapy-induced nausea/vomiting. Netupitant/palonosetron (NEPA), an oral fixed combination of netupitant (NETU)—a new NK(1) RA—and PALO, is currently under development. In vitro data suggest that NETU inhibits CYP3A4 and is a substrate for and weak inhibitor of P-glycoprotein (P-gp). This review evaluates potential drug–drug interactions between NETU or NEPA and CYP3A4 substrates/inducers/inhibitors or P-gp substrates in healthy subjects. Pharmacokinetic (PK) parameters were evaluated for each drug when NETU was coadministered with PALO (single doses) and when single doses of NETU or NEPA were coadministered with CYP3A4 substrates (erythromycin (ERY), midazolam (MID), dexamethasone (DEX), or oral contraceptives), inhibitors (ketoconazole (KETO)), or inducers (rifampicin (RIF)), or a P-gp substrate (digoxin (DIG)). Results showed no relevant PK interactions between NETU and PALO. Coadministration of NETU increased MID and ERY exposure and significantly increased DEX exposure in a dose-dependent manner; NETU exposure was unaffected. NEPA coadministration had no clinically significant effect on oral contraception, although levonorgestrel exposure increased. NETU exposure increased after coadministration of NEPA with KETO and decreased after coadministration with RIF; PALO exposure was unaffected. NETU coadministration did not influence DIG exposure. In conclusion, there were no clinically relevant interactions between NETU and PALO, or NEPA and oral contraceptives (based on levonorgestrel and ethinylestradiol exposure). Coadministration of NETU or NEPA with CYP3A4 inducers/inhibitors/substrates should be done with caution. Dose reduction is recommended for DEX. Dose adjustments are not needed for NETU coadministration with P-gp substrates. SAGE Publications 2015-05-20 2016-06 /pmc/articles/PMC4843089/ /pubmed/25998320 http://dx.doi.org/10.1177/1078155215586824 Text en © The Author(s) 2015 http://creativecommons.org/licenses/by-nc/3.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 License (http://www.creativecommons.org/licenses/by-nc/3.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access page(https://us.sagepub.com/en-us/nam/open-access-at-sage). |
spellingShingle | Review Articles Natale, James J Spinelli, Tulla Calcagnile, Selma Lanzarotti, Corinna Rossi, Giorgia Cox, David Kashef, Kimia Drug–drug interaction profile of components of a fixed combination of netupitant and palonosetron: Review of clinical data |
title | Drug–drug interaction profile of components of a fixed combination of netupitant and palonosetron: Review of clinical data |
title_full | Drug–drug interaction profile of components of a fixed combination of netupitant and palonosetron: Review of clinical data |
title_fullStr | Drug–drug interaction profile of components of a fixed combination of netupitant and palonosetron: Review of clinical data |
title_full_unstemmed | Drug–drug interaction profile of components of a fixed combination of netupitant and palonosetron: Review of clinical data |
title_short | Drug–drug interaction profile of components of a fixed combination of netupitant and palonosetron: Review of clinical data |
title_sort | drug–drug interaction profile of components of a fixed combination of netupitant and palonosetron: review of clinical data |
topic | Review Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4843089/ https://www.ncbi.nlm.nih.gov/pubmed/25998320 http://dx.doi.org/10.1177/1078155215586824 |
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