QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Résumé Extracto Full Text PDF Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Articles Ahead of Print [Order Reprint] Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Yano, R. Articles by Masada, M. Search for Related Content PubMed PubMed Citation Articles by Yano, R. Articles by Masada, M.

ONCOLOGY

Evaluation of Potential Interaction Between Vinorelbine and Clarithromycin

Chief Pharmacist, Department of Pharmacy, University of Fukui Hospital, Fukui, Japan

Daisuke Tani, MSc

Pharmacist, Department of Pharmacy, University of Fukui Hospital

Kyohei Watanabe, MSc

Chief Pharmacist, Department of Pharmacy, University of Fukui Hospital

Hitoshi Tsukamoto, BS BCICPS

Chief Pharmacist, Department of Pharmacy, University of Fukui Hospital

Toshiaki Igarashi, BS

Pharmacist, Department of Pharmacy, University of Fukui Hospital

Toshiaki Nakamura, BS

Vice Director, Department of Pharmacy, University of Fukui Hospital

Mikio Masada, PhD

Director, Department of Pharmacy, University of Fukui Hospital; Professor, Faculty of Medical Sciences, University of Fukui, Fukui

Reprints: Ryoichi Yano, Department of Pharmacy, University of Fukui Hospital, 23 Matsuokashimoaizuki, Eiheiji-cho, Fukui 910-1193, Japan, fax 81-776-61-8156, yanor{at}u-fukui.ac.jp

BACKGROUND: Myelotoxicity, a major toxicity of vinorelbine. may be related to the degree of one's exposure to vinorelbine. In theory, clarithromycin has the potential to alter vinorelbine's pharmacokinetics by inhibiting CYP3A and/or P-glycoprotein; this may result in massive exposure to vinorelbine and severe toxicity. To date, macrolide–vinorelbine drug interactions have not been reported.

OBJECTIVE: To estimate the clinical risk of a interaction between vinorelbine and clarithromycin.

METHODS: In a retrospective cohort study, we searched computerized medical records of patients who had been administered vinorelbine in the University of Fukui Hospital. The study cohort was defined as all patients with non–small-cell lung cancer who received vinorelbine between May 30, 2003, and January 31, 2008. The treatment courses were classified according to whether or not clarithromycin was concomitantly administered with vinorelbine. Nadir neutrophil counts were recorded as the major outcomes. Vinorelbine–clarithromycin interaction was defined as a significant increase in the risk of severe neutropenia when the 2 drugs were administered concomitantly.

RESULTS: A total of 12 (63.2%) and 11 (27.5%) episodes of grade 3/4 neutropenia occurred among the patients who were and were not administered clarithromycin, respectively. The incidence of grade 4 neutropenia was higher in the group administered clarithromycin than in those who did not receive it (31.6% vs 2.5%; p = 0.0033). Vinorelbine dose, concomitant clarithromycin administration, and female sex were significantly correlated with severe neutropenia, with unadjusted odds ratios of 0.07 (95% CI 0.01 to 0.59), 4.52 (95% CI 1.41 to 14.45), and 4.55 (95% CI 1.39 to 14.29), respectively.

CONCLUSIONS: Compared with patients who are administered vinorelbine alone, patients who are administered clarithromycin during chemotherapy with vinorelbine are at a higher risk for severe neutropenia. Physicians should educate their patients about this interaction. If possible, clarithromycin administration should be avoided in patients who will undergo chemotherapy with vinorelbine in the near future. However, further prospective pharmacokinetic studies are required to confirm this interaction.

Key Words: clarithromycin, drug–drug interaction, vinorelbine

Published Online, March 3, 2009. www.theannals.com, DOI 10.1345/aph.1L432