cle enzyme immunoassay (MEIA) and ELISA. Both methods have the same monoclonal antibody for tacrolimus. Comparison of the concentrations in published literature to patient concentrations using the current assays must be made with detailed knowledge of the assay methods and biological matrices employed. Whole blood is the matrix of choice and specimens should be collected into tubes containing ethylene diamine tetraacetic acid (EDTA) anti-coagulant. Heparin anti-coagulation is not recommended because of the tendency to form clots on storage. Samples which are not analyzed immediately should be stored at room temperature or in a refrigerator and assayed within 7 days; if samples are to be kept longer they should be deep frozen at -20° C for up to 12 months.
Liver Transplantation
Although there is a lack of direct correlation between tacrolimus concentrations and drug efficacy, data from Phase II and III studies of liver transplant patients have shown an increasing incidence of adverse events with increasing trough blood concentrations. Most patients are stable when trough whole blood concentrations are maintained between 5 to 20 ng/mL. Long-term post-transplant patients often are maintained at the low end of this target range.
Data from the U.S. clinical trial show that tacrolimus whole blood concentrations, as measured by ELISA, were most variable during the first week post-transplantation. After this early period, the median trough blood concentrations, measured at intervals from the second week to one year post-transplantation, ranged from 9.8 ng/mL to 19.4 ng/mL.
Therapeutic Drug Monitoring, , 1995, Volume 17, Number 6 contains a consensus document and several position papers regarding the therapeutic monitoring of tacrolimus from the 1995 International Consensus Conference on Immunosuppressive Drugs. Refer to these manuscripts for further discussions of tacrolimus monitoring.
Kidney Transplantation
Data from a Phase 3 study of tacrolimus in conjunction with azathioprine indicate that trough concentrations of tacrolimus in whole blood, as measured by IMx® were most variable during the first week of dosing. During the first three months of that trial, 80% of the patients maintained trough concentrations between 7 to 20 ng/mL, and then between 5 to 15 ng/mL, through 1 year.
In a separate clinical trial of tacrolimus in conjunction with MMF and daclizumab, approximately 80% of patients maintained tacrolimus whole blood concentrations between 4 to 11 ng/mL through 1 year post-transplant.
In another clinical trial of tacrolimus in conjunction with MMF and basiliximab, approximately 80% of patients maintained tacrolimus whole trough blood concentrations between 6 to 16 ng/mL during month 1 to 3 and, then, between 5 to 12 ng/mL from month 4 through 1 year.
The relative risks of toxicity and efficacy failure are related to tacrolimus whole blood trough concentrations. Therefore, monitoring of whole blood trough concentrations is recommended to assist in the clinical eva luation of toxicity and efficacy failure.
HOW SUPPLIED
Tacrolimus Capsules
strength 0.5 mg
(containing the equivalent of 0.5 mg monohydrate tacrolimus) 1 mg
(containing the equivalent of 1 mg monohydrate tacrolimus) 5 mg
(containing the equivalent of 5 mg monohydrate tacrolimus)
shape/color capsule/light yellow capsule/white capsule/pink
branding on capsule cap/body “TCR” on cap
