Prograf Dosage/Direction for Use

Prograf injection (tacrolimus injection): For Intravenous Infusion Only.
NOTE: Anaphylactic reactions have occurred with injectable containing castor oil derivatives. See WARNINGS.
In patients unable to take oral Prograf capsules, therapy may be initiated with Prograf injection. The initial dose of Prograf should be administered no sooner than 6 hours after transplantation. The recommended starting dose of Prograf injection is 0.03-0.05 mg/kg/day as a continuous 24-hour intravenous infusion. Adult patients should receive doses at the lower end of the dosing range. Concomitant adrenal corticosteroid therapy is recommended early post-transplantation. Continuous intravenous infusion of Prograf injection should be continued only until the patient can tolerate oral administration of Prograf capsules.
Preparation for Administration/Stability: Prograf injection must be diluted with 0.9% Sodium Chloride Injection or 5% Dextrose Injection to a concentration between 0.004 mg/mL and 0.02 mg/mL prior to use. Diluted infusion solution should be stored in glass or polyethylene containers and should be discarded after 24 hours. Tacrolimus is not compatible with PVC. Tubing, syringes and other equipment used to prepare or administer the tacrolimus products should not contain PVC. The diluted infusion solution stored in a PVC container decreased stability and the potential for extraction of phthalates. In situations where more dilute solutions are utilized (e.g., pediatric dosing, etc.), PVC-free tubing should likewise be used to minimize the potential for significant drug absorption onto the tubing. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Due to the chemical instability of tacrolimus in alkaline media, Prograf injection should not be mixed or co-infused with solutions of pH 9 or greater (e.g., ganciclovir or acyclovir).
Prograf capsules (tacrolimus capsules): Transplantation: See Table 11.

Click on icon to see table/diagram/image

Liver Transplantation: It is recommended that patients initiate oral therapy with Prograf capsules if possible. If intravenous therapy is necessary, conversion from intravenous to oral Prograf is recommended as soon as oral therapy can be tolerated. This usually occurs within 2-3 days. The initial dose of Prograf should be administered no sooner than 6 hours after transplantation. In a patient receiving an IV infusion, the first dose of oral therapy should be given 8-12 hours after discontinuing the IV infusion. The recommended starting oral dose of Prograf capsules is 0.10-0.15 mg/kg/day administered in two divided daily doses every 12 hours. Co-administered grapefruit juice has been reported to increase tacrolimus blood trough concentrations in liver transplant patients (see Drugs that May Alter Tacrolimus Concentrations under Interactions).
Dosing should be titrated based on clinical assessments of rejection and tolerability. Lower Prograf dosages may be sufficient as maintenance therapy. Adjunct therapy with adrenal corticosteroids is recommended early post-transplant.
Dosage and typical tacrolimus whole blood trough concentrations are in the table as previously shown; blood concentration details are described in Therapeutic Drug Monitoring: Liver Transplantation as follows.
Kidney Transplantation: The recommended starting oral dose of Prograf administered every 12 hours in two divided doses is 0.2 mg/kg/day when used in combination with azathioprine or 0.1 mg/kg/day when used in combination with MMF and IL-2 receptor antagonist (see Pharmacology: Clinical Studies under Actions). The initial dose of Prograf may be administered within 24 hours of transplantation, but should be delayed until renal function has recovered (as indicated for example by a serum creatinine ≤4 mg/dL). Black patients may require higher doses to achieve comparable blood concentrations. Dosage and typical tacrolimus whole blood trough concentrations are in the table previously shown; blood concentration details are described in Therapeutic Drug Monitoring: Kidney Transplantation as follows.
The data in kidney transplant patients indicate that the Black patients required a higher dose to attain comparable trough concentrations compared to Caucasian patients. (See Table 12.)

Click on icon to see table/diagram/image

Pediatric Patients: Pediatric liver transplantation patients without pre-existing renal or hepatic dysfunction have required and tolerated higher doses than adults to achieve similar blood concentrations. Therefore, it is recommended that therapy should be initiated in pediatric patients at a starting intravenous dose of 0.03-0.05 mg/kg/day and a starting oral dose of 0.15-0.20 mg/kg/day. Dose adjustments may be required. Experience in pediatric kidney transplantation patients is limited.
Patients with Hepatic or Renal Dysfunction: Due to the reduced clearance and prolonged half-life, patients with severe hepatic impairment (Pugh ≥10) may require lower doses of Prograf. Close monitoring of blood concentrations is warranted.
Due to the potential for nephrotoxicity, patients with renal or hepatic impairment should receive doses at the lowest value of the recommended intravenous and oral dosing ranges. Further reductions in dose below these ranges may be required. Prograf therapy usually should be delayed up to 48 hours or longer in patients with post-operative oliguria.
Conversion from One Immunosuppressive Regimen to Another: Prograf should not be used simultaneously with cyclosporine. Prograf or cyclosporine should be discontinued at least 24 hours before initiating the other. In the presence of elevated Prograf or cyclosporine concentrations, dosing with the other drug usually should be further delayed.
Therapeutic Drug Monitoring: Monitoring of tacrolimus blood concentration in conjunction with other laboratory and clinical parameters is considered an essential aid to patient management for the evaluation of rejection, toxicity, dose adjustments and compliance. Factors influencing frequency of monitoring include but are not limited to hepatic or renal dysfunction, the addition or discontinuation of potentially interacting drugs and the post-transplant time. Blood concentration monitoring is not a replacement for renal and liver function monitoring and tissue biopsies.
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.
Two methods have been used for the assay of tacrolimus, a microparticle enzyme immunoassay (MEIA) and an 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: 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: A 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.
Lupus nephritis: For adults, usually, a dose of 3 mg as tacrolimus is orally administered, once daily after supper.
In order to avoid development of adverse reactions in patients with lupus nephritis, it is recommended that the blood levels be monitored monthly for 3 months after the start of tacrolimus therapy; thereafter, the blood levels approximately 12 hours after the administration should be monitored periodically, and the dosage should be adjusted. If this product does not improve the clinical signs of nephritis, such as urinary protein excretion, or the immunological findings after continuous treatment for 2 months, the treatment with this product should be discontinued, or the patient should be switched to another product. If treatment with this product is sufficiently effective, it is recommended that the dose should be reduced to the lowest level possible that will still allow the effect to be maintained.