Evaluation of potential interaction between vinorelbine and clarithromycin.
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.
Yano
Ryoichi
R
Department of Pharmacy, University of Fukui Hospital, Fukui, Japan. yanor@u-fukui.ac.jp
Tani
Daisuke
D
Watanabe
Kyohei
K
Tsukamoto
Hitoshi
H
Igarashi
Toshiaki
T
Nakamura
Toshiaki
T
Masada
Mikio
M
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy; D017291:Clarithromycin / Q000008:administration & dosage / Q000009:adverse effects*; D015331:Cohort Studies; D004347:Drug Interactions; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D012189:Retrospective Studies; D012307:Risk Factors; D012727:Sex Characteristics; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077235:Vinorelbine
D014747:Vinblastine; D017291:Clarithromycin; D000077235:Vinorelbine