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.
Data from a Phase 3 study of Prograf 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 7-20 ng/mL, and then between 5-15 ng/mL, through 1 year.
In a separate clinical trial of Prograf in conjunction with MMF and daclizumab, approximately 80% of patients maintained tacrolimus whole blood concentrations between 4-11 ng/mL through 1 year post-transplant.
In another clinical trial of Prograf in conjunction with MMF and basiliximab, approximately 80% of patients maintained tacrolimus whole trough blood concentrations between 6-16 ng/mL during month 1-3 and, then, between 5-12 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 evaluation of toxicity and efficacy failure.
Data from a European Phase 3 study indicate that trough concentrations of tacrolimus in whole blood, as measured by IMx® were most variable during the first week of dosing. From 1 week to 3 months post transplant, approximately 80% of patients maintained trough concentrations between 8-20 ng/mL and, from 3 months through 18 months post transplant, approximately 80% of patients maintained trough concentrations between 6-18 ng/mL.
The relative risk of toxicity; for example, nephrotoxicity and post-transplant diabetes mellitus, is increased with higher trough concentrations. Therefore, monitoring of whole blood trough concentrations is recommended to assist in the clinical evaluation of toxicity.
(containing the equivalent of 1 mg anhydrous tacrolimus)
|branding on capsule cap/body|| |
|100 count bottle||NDC 21695-170-00|
Made in Japan
Store at 25°C (77°F); excursions permitted to 15°C-30°C (59°F-86°F).
(for IV infusion only)
NDC 0469-3016-01 Product Code 301601
5 mg/mL (equivalent of 5 mg of anhydrous tacrolimus per mL) supplied as a sterile solution in a 1 mL ampule, in boxes of 10 ampules
Made in Ireland
Store between 5°C and 25°C (41°F and 77°F).
Astellas Pharma US, Inc.
Deerfield, IL 60015-2548
Revised: August 2009
Rebel Distributors Corp
Thousand Oaks, CA 91320
1.CDC: Recommendations of the Advisory Committee on Immunization Practices: Use of vaccines and immune globulins in persons with altered immunocompetence. MMWR 1993;42(RR-4):1-18.
|PROGRAF tacrolimus capsule, gelatin coated|
|Labeler — Rebel Distributors Corp (118802834)|
|Rebel Distributors Corp||118802834||RELABEL, REPACK|
Revised: 12/2010 Rebel Distributors Corp
All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.