Concurrent use of proton pump inhibitors or H2 blockers did not adversely affect nilotinib efficacy in patients with chronic myeloid leukemia

Ophelia Q.P. Yin, Frank J. Giles, Michele Baccarani, Philipp Le Coutre, Ovidiu Chiparus, Neil Gallagher, Giuseppe Saglio, Timothy P. Hughes, Andreas Hochhaus, Hagop M. Kantarjian, Richard A. Larson

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Purpose The impact of proton pump inhibitors (PPIs) and histamine H2 receptor antagonists (H2 blockers) on the efficacy of nilotinib was evaluated. Methods Retrospective analyses were performed in patients with newly diagnosed Philadelphia chromosomepositive (Ph?) chronic myeloid leukemia in chronic phase (CML-CP; N = 492) and in patients with imatinib-resistant or imatinib-intolerant Ph? CML-CP (N = 256) treated with nilotinib. Results In the newly diagnosed population, 87 (17.7 %) and 49 (10.0 %) patients received PPIs and H2 blockers, respectively. Major molecular response at 12 months was achieved by 59 (49.6 %) patients who received at least one PPI or H2 blocker (n = 119) and 153 (41.0 %) patients who did not receive any comedication (n = 373; P = 0.13). PPIs and H2 blockers were used by 77 (30.1 %) and 17 (6.6 %) patients with imatinib-resistant or imatinibintolerant CML-CP, respectively. Major cytogenetic response by 12 months was achieved by 55 (64.0 %) patients who received at least one PPI or H2 blocker (n = 86) versus 98 (57.6 %) patients who did not receive any comedication (n = 170; P = 0.40); 39 (45.3 %) versus 65 (38.2 %), respectively, achieved complete cytogenetic response by 12 months (P = 0.34). Similar findings were observed in patients who received comedication for >50 % of the time on nilotinib therapy. Nilotinib steadystate trough concentration was not affected by the presence of PPIs or H2 blockers. Conclusions Concurrent use of PPIs or H2 blockers did not affect the pharmacokinetics and efficacy of nilotinib in patients with Ph? CML-CP.

Original languageEnglish (US)
Pages (from-to)345-350
Number of pages6
JournalCancer chemotherapy and pharmacology
Volume70
Issue number2
DOIs
StatePublished - Aug 1 2012

Keywords

  • Chronic myeloid leukemia
  • Drug-drug interactions
  • H2 blockers
  • Nilotinib
  • Proton pump inhibitors

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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    Yin, O. Q. P., Giles, F. J., Baccarani, M., Le Coutre, P., Chiparus, O., Gallagher, N., Saglio, G., Hughes, T. P., Hochhaus, A., Kantarjian, H. M., & Larson, R. A. (2012). Concurrent use of proton pump inhibitors or H2 blockers did not adversely affect nilotinib efficacy in patients with chronic myeloid leukemia. Cancer chemotherapy and pharmacology, 70(2), 345-350. https://doi.org/10.1007/s00280-012-1881-3