A drug-drug interaction study of ibrutinib with moderate/strong CYP3A inhibitors in patients with B-cell malignancies

Leukemia & Lymphoma
Jan de JongDaniele Ouellet

Abstract

This was an open-label, multicenter, phase-1 study to evaluate the drug interaction between steady-state ibrutinib and moderate (erythromycin) and strong (voriconazole) CYP3A inhibitors in patients with B-cell malignancies and to confirm dosing recommendations. During cycle 1, patients received oral ibrutinib 560 mg qd alone (Days 1-4 and 14-18), and ibrutinib 140 mg (Days 5-13; 19-27) plus erythromycin 500 mg tid (Days 5-11) and voriconazole 200 mg bid (Days 19-25). Twenty-six patients (median [range] age: 64.5 [50-88] years) were enrolled. Geometric mean ratio (90% confidence intervals) after co-administration of ibrutinib 140 mg with erythromycin and voriconazole was 74.7 (53.97-103.51) and 143.3 (107.77-190.42), respectively, versus ibrutinib 560 mg alone. The most common (≥20%) adverse events were diarrhea (27%) and neutropenia (23%). The results demonstrate that ibrutinib 140 mg with voriconazole or erythromycin provides exposure within the clinical range for patients with B-cell malignancies.

References

May 1, 1994·Clinical Pharmacology and Therapeutics·K T OlkkolaP J Neuvonen
Mar 1, 1993·Clinical Pharmacology and Therapeutics·K T OlkkolaP J Neuvonen
Apr 4, 2006·Clinical Pharmacology and Therapeutics·Teijo I SaariKlaus T Olkkola
Jan 24, 2007·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Bruce D ChesonUNKNOWN International Harmonization Project on Lymphoma
Jul 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Lee A HonigbergJoseph J Buggy
Oct 10, 2012·Journal of Clinical Oncology : Official Journal of the American Society of Clinical Oncology·Ranjana H AdvaniNathan H Fowler
Jun 21, 2013·The New England Journal of Medicine·John C ByrdSusan O'Brien
Jun 3, 2014·The New England Journal of Medicine·John C ByrdUNKNOWN RESONATE Investigators
Aug 26, 2014·The Lancet Oncology·Paolo Ghia
Dec 10, 2014·Drug Metabolism and Disposition : the Biological Fate of Chemicals·Ellen ScheersGeert Mannens
Jul 15, 2015·Pharmacology Research & Perspectives·Jan de JongErik Mannaert

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Citations

Aug 7, 2019·Clinical Pharmacokinetics·Nikki BlosserDouglas Stewart
Oct 14, 2017·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Georgios ChamilosDimitrios P Kontoyiannis
Jun 7, 2020·Journal of Hematology & Oncology·Camille Hardy-AbeloosJanice Gabrilove
Sep 19, 2020·Pharmacology Research & Perspectives·Jan de JongPeter Hellemans
May 30, 2019·American Journal of Therapeutics·Takeo YasuToyotaka Kawamata
May 29, 2020·Clinical Cancer Research : an Official Journal of the American Association for Cancer Research·Yuqin SongJun Zhu
Nov 9, 2019·Blood Reviews·Rossana MaffeiRoberto Marasca
Dec 4, 2020·Pharmaceuticals·Alejandro Cabrera-AndradeEduardo Tejera
Dec 20, 2021·Therapeutic Drug Monitoring·Benjamin KablyEliane M Billaud

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