Toxicity of single daily dose gentamicin in stem cell transplantation.
To determine the safety of single daily dose (SDD) gentamicin in recipients of stem cell transplantation (SCT), we evaluated all adult patients at MD Anderson Cancer Center who received SDD gentamicin for treatment of febrile neutropenia. Thirty-three patients received gentamicin 5 mg/kg i.v. every 24 h. Mean duration of therapy was 7 days (range 3-32 days). All patients received vancomycin and 17 received cisplatinum. All patients had normal renal function prior to therapy. Serum gentamicin levels were monitored only when renal function deteriorated. The incidence of nephrotoxicity and clinically significant ototoxicity was 3% and 12%, respectively. All four patients who developed ototoxicity had normal renal function before and during therapy. The mean duration of gentamicin therapy was significantly longer in patients who developed ototoxicity, 20 days vs 9 days (P = 0.001). Patients treated with SDD gentamicin for >10 days were more likely to develop ototoxicity (P = 0.045). Single daily dosing of gentamicin was associated with clinically significant ototoxicity in 12% of our patients. A larger randomized EORTC trial evaluating SDD vs MDD amikacin failed to detect a difference in ototoxicity. However, the median duration of therapy was only 8 days. The increased incidence of ototoxicity in our study may be due to prolonged therapy, type of aminoglycoside used, concomitant ototoxic agents, small sample size, or a combination of the above.
Warkentin
D
D
CSU Pharmaceutical Sciences, Vancouver Hospital and Health Sciences Center, University of British Columbia, Vancouver, Canada.
Ippoliti
C
C
Bruton
J
J
Van Besien
K
K
Champlin
R
R
D000328:Adult; D002945:Cisplatin / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage* / Q000009:adverse effects*; D006311:Hearing Disorders / Q000139:chemically induced; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007262:Infusions, Intravenous; D007674:Kidney Diseases / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D009503:Neutropenia / Q000188:drug therapy; D012189:Retrospective Studies; D014640:Vancomycin / Q000627:therapeutic use
D005839:Gentamicins; D014640:Vancomycin; D002945:Cisplatin