*
Prograf (tacrolimus) is
indicated for the prophylaxis of organ rejection in patients receiving
allogeneic liver, kidney, or heart transplants. It is recommended that
Prograf be used concomitantly with adrenal corticosteroids. Because of
the risk of anaphylaxis, Prograf injection should be reserved for
patients unable to take Prograf capsules orally. In heart transplant
recipients, it is recommended that Prograf be used in conjunction with
azathioprine or mycophenolate mofetil. The safety and efficacy of the
use of Prograf with sirolimus has not been established.
Important Safety Information
WARNING
Increased susceptibility to infection and the possible development of
lymphoma may result from immunosuppression. Only physicians experienced
in immunosuppressive therapy and management of organ transplant
patients should prescribe Prograf. The physician responsible for
maintenance therapy should have complete information requisite for the
follow-up of the patient.
* Prograf is contraindicated in patients with a hypersensitivity to
tacrolimus. Prograf injection is contraindicated in patients with a
hypersensitivity to castor oil. Patients receiving Prograf injection
should be under continuous observation for at least the first 30
minutes following the start of infusion and at frequent intervals
thereafter. If signs or symptoms of anaphylaxis occur, the infusion
should be stopped.
* Insulin-dependent post-transplant diabetes mellitus was reported
in 11% to 22% of Prograf-treated liver, kidney, and heart transplant
patients with no prior history of diabetes mellitus. Black and Hispanic
kidney transplant patients were at increased risk. Insulin dependence
was reversible in 15% to 45% of patients at 1 year.
* Prograf has been associated with nephrotoxicity, particularly
when used in high doses. In particular, to avoid excess nephrotoxicity,
Prograf should not be used simultaneously with cyclosporine. Prograf or
cyclosporine should be discontinued at least 24 hours prior to
initiating the other. In the presence of elevated Prograf or
cyclosporine concentrations, dosing with the other drug usually should
be further delayed.
* Use of Prograf with sirolimus in heart transplant patients in a
US study was associated with increased risk of wound healing
complications, renal function impairment, and insulin-dependent
post-transplant diabetes, and is not recommended.
* A safe and effective dosing regimen of mycophenolate mofetil
(MMF) in combination with Prograf has not been established in kidney
transplantation. In one clinical study, 12-month mortality was 4.2% in
patients receiving Prograf/MMF compared with 2.4% in patients receiving
cyclosporine/MMF.
* Mild to severe hyperkalemia was reported in 31% of kidney
transplant recipients, in 45% and 13% of liver transplant recipients in
the US and European randomized trials, respectively, and in 8% of heart
transplant recipients in a European randomized trial, and may require
treatment. Serum potassium levels should be monitored and
potassium-sparing diuretics should not be used during Prograf therapy
(see PRECAUTIONS).
* Neurotoxicity, including tremor, headache, and other changes in
motor function, mental status, and sensory function, was reported in
approximately 55% of liver transplant recipients in the two randomized
studies. Tremor occurred more often in Prograf-treated kidney
transplant (54%) and heart transplant patients (15%) compared with
cyclosporine-treated patients. Seizures have occurred in adult and
pediatric patients receiving Prograf. Coma and delirium also have been
associated with high plasma concentrations of tacrolimus.
* In postmarketing experience, patients treated with tacrolimus
have been reported to develop posterior reversible encephalopathy
syndrome (PRES). If PRES is suspected or diagnosed, immediate reduction
of immunosuppression is advised. Activation of latent viral infections,
including BK virus-associated nephropathy and JC virus-associated
progressive multifocal leukoencephalopathy (PML), has also been
reported.
* The principal adverse reactions of Prograf include tremor,
headache, hypertension, gastrointestinal disturbance, abnormal renal
function, hyperglycemia, leukopenia, CMV infection, infection, and
hyperlipemia.