title: Itraconazole may increase the risk of early-onset bortezomib-induced peripheral neuropathy.
abstract: Bortezomib (BOR) is an effective drug for the treatment of multiple myeloma and BOR-induced peripheral neuropathy (BIPN) is a major adverse event. BIPN tends to occur after two or three cycles of treatment (late-onset BIPN), but may occur during the first treatment cycle (early-onset BIPN). BIPN severity was retrospectively assessed and graded in 48 patients with relapsed or refractory multiple myeloma treated with BOR for the first time between June 2007 and February 2011 at Keio University Hospital. PN grade 2 or higher occurring within the first cycle of BOR was defined as early-onset severe BIPN. Early-onset severe BIPN occurred in 13 patients. Concomitant use of itraconazole [ITCZ: odds ratio (OR) 29.14 (3.02-281.56), p = 0.004] and a proton pump inhibitor [OR 9.00 (1.05-77.1), p = 0.04] were identified by univariate analysis, as risk factors for developing early-onset severe BIPN. Based on multivariate analysis, concomitant use of ITCZ was the only significant risk factor for developing early-onset severe BIPN [OR 19.00 (1.89-190.96), p = 0.01]. Concomitant use of ITCZ with BOR significantly increased the incidence of early-onset severe BIPN in our study population, suggesting that administration of ITCZ in patients receiving BOR should be avoided.
authors.affiliation: Division of Hematology, Department of Medicine, Keio University School of Medicine, 35 Shinano-machi, Tokyo, 160-8582, Japan.
authors.forename: Norisato
authors.initials: N
authors.lastname: Hashimoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Yokoyama
authors.forename: Ken
authors.initials: K
authors.lastname: Sadahira
authors.forename: Tomoki
authors.initials: T
authors.lastname: Ueda
authors.forename: Yuiko
authors.initials: Y
authors.lastname: Tsukada
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Okamoto
mesh_terms: D000328:Adult; D000368:Aged; D000935:Antifungal Agents / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D000069286:Bortezomib; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003907:Dexamethasone / Q000008:administration & dosage; D048909:Diabetes Complications / Q000188:drug therapy; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008658:Inactivation, Metabolic; D015994:Incidence; D017964:Itraconazole / Q000009:adverse effects* / Q000493:pharmacokinetics / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000601:surgery; D009181:Mycoses / Q000209:etiology / Q000517:prevention & control; D009894:Opportunistic Infections / Q000209:etiology / Q000517:prevention & control; D036102:Peripheral Blood Stem Cell Transplantation; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000453:epidemiology; D011480:Protease Inhibitors / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D054328:Proton Pump Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D012189:Retrospective Studies; D012307:Risk Factors; D016879:Salvage Therapy
chemical_list: D000935:Antifungal Agents; D000970:Antineoplastic Agents; D001897:Boronic Acids; D011480:Protease Inhibitors; D054328:Proton Pump Inhibitors; D011719:Pyrazines; D017964:Itraconazole; D000069286:Bortezomib; D003907:Dexamethasone; D003577:Cytochrome P-450 Enzyme System