PKP-001 Tacrolimus plasma levels in adults during haematopoietic stem cell allotransplantation

Abstract

Background When an unrelated donor is used for an allogeneic hematopoietic stem cell transplant (AlloHSCT) highly immunosuppressive treatment is needed during the early post-transplant period as prophylaxis against acute graft versus host disease (aGVHD). Tacrolimus is one the drugs used with a target level of 5–15 ng/mL. Purpose To compare the accuracy of real plasma tacrolimus levels with target levels in the immediate post-transplant period. Materials and methods A retrospective review was made between 2008/01/01 and 2013/09/30 of all aGVHD prophylaxis that included tacrolimus. Data were obtained from the electronic medical history records and the Pharmacy Unit intravenous database. Results Tacrolimus was used in 46 patients (17 women) with a median of 51 years old (17–69). First dose of tacrolimus was administered on day -1 at 0.03 mg/kg/day by continuous intravenous infusion. Only half of patients, 23 (50%), were within the therapeutic range when the first measure was made. Supratherapeutic levels were found in 15 patients and infratherapeutic in 8 patients. This first tacrolimus plasma level was obtained between day + 2 and + 11. Conditioning was done with myeloablative regimens (fludarabine-busulfan: 13 patients; total body irradiation and cyclophosphamide: 5 patients) and non myeloablative regimens (fludarabine-melphalan: 7 patients; fludarabine-busulfan: 17 patients; fludarabine-cyclophosphamide: 4 patients). Antibiotic prophylaxis was administered in all cases with ciprofloxacin and antifungal prophylaxis was fluconazole, voriconazole and caspofungin for 42, 3 and 1 patient, respectively. A direct relationship has not been found between the day of measurement, conditioning regimen, antibiotic or antifungal prophylaxis and the tacrolimus plasma level obtained. Conclusions There is great discordance between theoretical tacrolimus plasma levels and real levels. Renal function doesn’t affect tacrolimus pharmacokinetics, although it is potentially nephrotoxic, which might require dose adjustment. After this review a pharmacokinetic drug interaction among drugs used during conditioning or antibiotic or antifungal prophylaxis was excluded. A thorough investigation of how tacrolimus samples are obtained and handled is mandatory. No conflict of interest.