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tacrolimus are unaffected by renal function, no dose adjustment should be required. However, owing to the nephrotoxic potential of tacrolimus careful monitoring of renal function is recommended (including serial serum creatinine concentrations, calculation of creatinine clearance and monitoring of urine output).Paediatric patientsIn general, paediatric patients require doses 1½ - 2 times higher than the adult doses to achieve similar blood levels.Elderly patientsThere is no evidence currently available to indicate that dosing should be adjusted in elderly patients.Conversion from ciclosporinCare should be taken when converting patients from ciclosporin-based to tacrolimus-based therapy. Tacrolimus therapy should be initiated after considering ciclosporin blood concentrations and the clinical condition of the patient. Dosing should be delayed in the presence of elevated ciclosporin blood levels. In practice, tacrolimus therapy has been initiated 12-24 hours after discontinuation of ciclosporin. Monitoring of ciclosporin blood levels should be continued following conversion as the clearance of ciclosporin might be affected.Target whole blood trough concentration recommendationsDosing should primarily be based on clinical assessments of rejection and tolerability in each individual patient.As an aid to optimise dosing, several immunoassays are available for determining tacrolimus concentrations in whole blood including a semi-automated microparticle enzyme immunoassay (MEIA). Comparisons of concentrations from the published literature to individual values in clinical practice should be assessed with care and knowledge of the assay methods employed. In current clinical practice, whole blood levels are monitored using immunoassay methods.Blood trough levels of tacrolimus should be monitored during the post-transplantation period. When dosed orally, blood trough levels should be drawn approximately 12 hours post-dosing, just prior to the next dose. The frequency of blood level monitoring should be based on clinical needs. As tacrolimus is a medicinal product with low clearance, adjustments to the dosage regimen may take several days before changes in blood levels are apparent. Blood trough levels should be monitored approximately twice weekly during the early post-transplant period and then periodically during maintenance therapy. Blood trough levels of tacrolimus should also be monitored following dose adjustment, changes in the immunosuppressive regimen, or following co-administration of substances which may alter tacrolimus whole blood concentrations.Clinical study analysis suggests that the majority of patients can be successfully managed if tacrolimus blood trough levels are maintained below 20 ng/ml. It is necessary to consider the clinical condition of the patient when interpreting whole blood levels.In clinical practice, whole blood trough levels have generally been in the range 5-20 ng/ml in liver transplant recipients and 10-20 ng/ml in kidney and heart transplant patients in the early post-transplant period. Subsequently, during maintenance therapy, blood concentrations have generally been in the range of 5-15 ng/ml in liver, kidney and heart transplant recipients.
Contra Indications
Hypersensitivity to tacrolimus or other macrolides.Hypersensitivity to any of the excipients.
Special Precautions
During the initial post-transplant period, monitoring of the following parame |
