Therapeutic drug monitoring and safety of intravenous voriconazole formulated with sulfobutylether β-cyclodextrin in haematological patients with renal impairment.
Because of concerns about accumulation of cyclodextrin, oral voriconazole is recommended for patients with renal impairment. However, intravenous voriconazole may occasionally be imperative in critically ill patients with life-threatening invasive aspergillosis. We investigated the clinical effects of intravenous voriconazole formulated with sulfobutylether β-cyclodextrin (SBECD) in patients with renal impairment. A prospective observational study was conducted on 25 adult patients with haematological malignancies who were treated with intravenous voriconazole for invasive aspergillosis. Among them, seven patients had a baseline creatinine clearance (CrCl) <50 ml min(-1) (case). Although voriconazole trough concentrations were significantly higher in cases (5.84 mg l(-1) ) than controls (2.28 mg l(-1) ), the proportion of concentrations within the target range did not differ between two groups (4/7 and 12/18, respectively; P = 0.658). The frequency of severe adverse events in cases (3/7) was comparable to that of controls (4/18; P = 0.355). No patients showed significant deterioration in renal function after the voriconazole therapy even in patients with renal impairment. Although CrCl <50 ml min(-1) was associated with higher voriconazole concentrations, its clinical impact remains unclear. SBECD-formulated intravenous voriconazole did not lead to a higher incidence of severe adverse events including nephrotoxicity in haematological patients with CrCl <50 ml min(-1) .
Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.|Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea.|Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Incheon St. Mary's Hospital, Incheon, Korea.
Si-Hyun
SH
Kim
Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.|Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Jae-Cheol
JC
Kwon
Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Chulmin
C
Park
Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Seunghoon
S
Han
Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Dong-Seok
DS
Yim
Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.|Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Jae-Ki
JK
Choi
Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.|Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Sung-Yeon
SY
Cho
Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.|Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Hyo-Jin
HJ
Lee
Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.|Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Sun Hee
SH
Park
Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.|Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Su-Mi
SM
Choi
Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.|Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea.|Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Incheon St. Mary's Hospital, Incheon, Korea.
Jung-Hyun
JH
Choi
Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.|Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Jin-Hong
JH
Yoo
Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea. symonlee@catholic.ac.kr.|Vaccine Bio Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Korea. symonlee@catholic.ac.kr.|Catholic Blood and Marrow Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul St. Mary's Hospital, Seoul, Korea. symonlee@catholic.ac.kr.
Dong-Gun
DG
Lee
Division of Infectious Diseases, Department of Internal Medicine, College of Medicine, The Catholic University of Korea, Seoul, Korea.|Catholic Blood and Marrow Transplantation Center, College of Medicine, The Catholic University of Korea, Seoul St. Mary's Hospital, Seoul, Korea.
Jong-Wook
JW
Lee
D061605:Administration, Intravenous; D000293:Adolescent; D000328:Adult; D000935:Antifungal Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood* / Q000627:therapeutic use; D001228:Aspergillosis / Q000188:drug therapy*; D003404:Creatinine / Q000097:blood; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics; D004339:Drug Compounding; D016903:Drug Monitoring; D005260:Female; D019337:Hematologic Neoplasms / Q000150:complications / Q000382:microbiology; D006801:Humans; D000072742:Invasive Fungal Infections / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D051437:Renal Insufficiency; D065819:Voriconazole / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood / Q000627:therapeutic use*; D055815:Young Adult; D047392:beta-Cyclodextrins
D000935:Antifungal Agents; D047392:beta-Cyclodextrins; C093196:SBE4-beta-cyclodextrin; D003404:Creatinine; D065731:Cytochrome P-450 CYP2C19; D065819:Voriconazole
Therapeutic drug monitoring; intravenous voriconazole; renal impairment; safety; sulfobutylether-β-cyclodextrin