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.
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Trifilio, S., Scheetz, M., Pi, J. et al. Tacrolimus use in adult allogeneic stem cell transplant recipients receiving voriconazole: preemptive dose modification and therapeutic drug monitoring. Bone Marrow Transplant 45, 1352–1356 (2010). https://doi.org/10.1038/bmt.2009.345
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DOI: https://doi.org/10.1038/bmt.2009.345
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