Toxicities of tacrolimus and cyclosporin A after allogeneic blood stem cell transplantation

Abstract

Summary:center experience, which included 1000 liver transplants, major adverse events potentially related to FK506 included neurotoxicity in 7%, insulin-dependent hyperglycemia in To determine how well tacrolimus (FK506) and cyclosporin A (CsA) are tolerated after HLA-identical blood 13-16%, hypertension in 29-39%, hyperkalemia in 42-47%, and significant infections in 10-36%. 7 Nephrotoxicstem cell transplantation, we performed a retrospective review of 87 adults transplanted consecutively who ity, manifested by magnesium wasting and a reduction in creatinine clearance, is the most serious side-effect of received FK506 (n = 40) or CsA (n = 47) in a nonrandomized fashion in combination with methylpredniso-FK506. Some degree of renal impairment has been reported in up to 48% of solid organ transplant recipients. 8,9 lone for graft-versus-host disease (GVHD) prophylaxis and compared the incidences of complications potenDrug-related toxicities may have a substantial impact on early morbidity and mortality after allogeneic marrow or tially related to the immunosuppressive agents. Pretransplant demographic characteristics, drug comblood stem cell transplantation. Both FK506 and CsA are effective for prevention of acute GVHD, but their toxicities pliance and rates of acute GVHD were comparable for the two groups. Following first discharge, fewer patients after marrow or blood stem cell transplantation have not been compared. To determine whether, based on toxicity in the FK506 group required antihypertensive therapy (32 vs 59%, P = 0.022), but more required insulin (34 profiles, there is any basis for preferential use of FK506 or CsA in these patients, we have reviewed the immunosupvs 10%, P = 0.014). There was also a trend for more hyperkalemia and less moderate-to-severe venopressive-related toxicities to day 100 in a consecutive series of HLA-identical blood stem cells transplant recipients. occlusive disease in the FK506 group. However, nephrotoxicity, neurotoxicity, hemolytic-uremic syndrome, and cytomegaloviral or fungal infections through the first 100 days post-transplant did not differ significantly Patients and methods between the two groups. We conclude that for allogeneic blood stem cell transplant recipients, the incidence of Patients complications related to FK506 and CsA in equallyWe retrospectively reviewed the charts of 87 adults transeffective dose schedules in combination with methylplanted over a consecutive 22-month period with unmanipprednisolone are similar with the exception of the risks ulated filgrastim-mobilized HLA-identical blood stem cells of hypertension and hyperglycemia.following administration of a myeloablative regimen for

Optimal initial dose of oral cyclosporine in relation to its toxicities for graft-versus-host disease prophylaxis following reduced-intensity stem cell transplantation in Japanese patients

“…When we discussed the optimal starting dose of cyclosporine, we must consider clearance of cyclosporine, which decreases over time during the first 2 weeks after transplantation. 11,12 When the constant cyclosporine clearance during days 22-60 is 1.00, the clearance during days 0-7, 8-14, 15-21 are 1.46, 1.32, and 1.20, respectively. 11 The change of clearance in the natural course of transplant recipients may be related to our observation that cyclosporine levels were elevated in many patients, requiring dose reduction.…”

Factors affecting the pharmacokinetics of tacrolimus (FK506) in hematopoietic cell transplant (HCT) patients

“…Nephrotoxicity and neurotoxicity secondary to tacrolimus therapy is prevalent following HCT 13 and is associated with tacrolimus blood concentrations Ͼ20 ng/ml. 14,15 Nephrotoxicity (SCr Ͼ2.0 mg/dl) occurs in 32-92.6% of patients undergoing related or unrelated donor HCT.…”

“…14,15 Nephrotoxicity (SCr Ͼ2.0 mg/dl) occurs in 32-92.6% of patients undergoing related or unrelated donor HCT. [2][3][4][5]7,13,16 In one study, the risk of developing nephrotoxicity (SCr Ͼ2 mg/dl) was increased by 84.4% when the mean tacrolimus concentration was Ͼ20 ng/ml. 14 Neurotoxicity ranging from mild tremors and paresthesia to severe manifestations such as cortical blindness and seizures are also well described following HCT.…”

“…14 Neurotoxicity ranging from mild tremors and paresthesia to severe manifestations such as cortical blindness and seizures are also well described following HCT. 3,13,[17][18][19][20][21] These toxicities underscore the need for vigilant monitoring of tacrolimus blood concentrations and accurate dose modifications.The objective of this study was to determine the population pharmacokinetic parameters of intravenous and oral tacrolimus in the first 4 months post transplant, and to evaluate relevant clinical covariates for their effects on tacrolimus clearance and bioavailability. …”

New-Onset Diabetes after Transplant (NODAT)

“…1,2 It is also called as Secondary type of diabetes mellitus since it develops secondary to use of immunosuppressant's.…”