title: Tacrolimus use in adult allogeneic stem cell transplant recipients receiving voriconazole: preemptive dose modification and therapeutic drug monitoring.
abstract: Concomitant use of tacrolimus and voriconazole, both competitive inhibitors of the CYP450 3A4 isoenzyme, requires tacrolimus dose reduction. On the basis of clinical observations, we developed a preemptive dose-reduction strategy in allograft recipients who received voriconazole to maintain tacrolimus concentrations within a target range. A total of 27 patients started i.v. tacrolimus at an average daily dose of 0.022 mg/kg on day -1 (30% lesser than the usual starting dose). The dose was reduced by 30-40% if the 48-h steady-state concentration was 7-10 ng/ml, and by 40-50% if it was 10-15 ng/ml. No change was made if the concentration was <7 ng/ml. Subsequently, concentrations were generally monitored 2-3 times a week with dose adjustments as necessary. None of the 170 levels (3-12 per patient; median 5) obtained between days +1 and +16 were subtherapeutic (<5 ng/ml) and only 34 levels (20%) were >15 ng/ml. Each patient required dose reduction at least twice. The dose had to be increased in only two patients after the initial dose reduction. The median tacrolimus doses in mg/kg declined with time; being 0.022, 0.008 and 0.006 on days 0, 7 and 14, respectively. We conclude that a preemptive dose-reduction strategy is effective in maintaining tacrolimus concentrations within the desired therapeutic range, although serial monitoring remains prudent.
authors: Hematopoietic Stem Cell Transplant Program, Department of Pharmacy, Northwestern Memorial Hospital, Chicago, IL 60611, USA.
authors: S M
authors: SM
authors: Trifilio
authors: M H
authors: MH
authors: Scheetz
authors: J
authors: J
authors: Pi
authors: J
authors: J
authors: Mehta
mesh_terms: D000328:Adult; D000935:Antifungal Agents; D054796:Drug Dosage Calculations; D004347:Drug Interactions; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D007166:Immunosuppressive Agents; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000627:therapeutic use*; D012189:Retrospective Studies; D016559:Tacrolimus / Q000627:therapeutic use*; D014184:Transplantation, Homologous; D014230:Triazoles / Q000627:therapeutic use*; D065819:Voriconazole
chemical_list: D000935:Antifungal Agents; D007166:Immunosuppressive Agents; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole; D016559:Tacrolimus