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Dosing Regimen Study Shows Extended Release Tacrolimus To Be Safe, Well Tolerated

BOSTON, May 16 /PRNewswire/ -- Results of a Phase II (dosing regimen) study in stable liver transplant recipients presented at the 5th American Transplant Congress today show a standard regimen of Prograf® (tacrolimus)*, administered twice daily, and the Modified Release (MR) tacrolimus, administered once daily, have similar drug exposure, as measured by blood levels, and the conversions were safe and well-tolerated. MR tacrolimus is an extended release version of the original Prograf formulation.

Immediately following transplant surgery, patients are prescribed and expected to manage a multitude of daily medications, including an anti- rejection regimen that consists of several immunosuppressant agents. Because their medication regimens are often complicated, many patients find adherence difficult. Low adherence to an immunsuppression regimen can result in graft rejection and/or graft loss.

"Multiple times a day, a transplant recipient takes a variety of anti- rejection medications," said Sander Florman, M.D., lead investigator for the study. "The availability of a once daily formulation of comparable dosage immunosuppressants, such as MR tacrolimus, can directly relate to a patient's ability to adhere to the regimen and ultimately maintain a successful transplant. In addition, a 1:1 dosing ratio would simplify conversion from Prograf to MR tacrolimus for prescribers."

Results

Seventy patients participated in the replicate design study to evaluate the 24 hour pharmacokinetic profiles of tacrolimus for the Prograf BID and MR QD AM regimens. Eighty percent of patients did not require any dose adjustments with either the MR tacrolimus or any concomitant immunosuppressants during the 56 day treatment period. Of these patients, there was only one acute rejection. The trough whole blood levels were highly correlated to exposure to the drug (AUC or area under the curve) for both Prograf and MR tacrolimus. MR tacrolimus had less intra-patient variability than twice a day Prograf. In addition, trough levels were comparable, regardless of gender during all patient visits and serum creatinine levels (a key indicator of renal function) and hepatic function remained stable post- conversion.

Study Design

The Phase II, open-label, multi-center study was designed to determine the pharmacokinetics, safety, and tolerability of tacrolimus in patients converted from Prograf's twice daily regimen to MR tacrolimus once in the morning. Study participants (n=70) continued their prescribed Prograf dosing for the first two weeks of the study and again on days 29-42. Patients were converted to the same mg-for-mg (1:1) once daily dose of MR tacrolimus on days 15-28 and 43-56. Patients were then maintained on MR tacrolimus long-term. The goal was to maintain tacrolimus trough levels of 5-20 ng/mL. Eligibility criteria included: 18 to 65 years of age, >6 months post transplant, stable Prograf doses BID (administered twice daily), stable renal and hepatic function (serum creatinine

About Prograf and Fujisawa Healthcare, Inc.

Prograf is indicated for the prophylaxis of organ rejection in patients receiving kidney or liver transplant and has been marketed in North America, Europe and Japan. Worldwide, Prograf is commercially available in 68 countries. Currently more than 60% of new kidney transplant recipients take Prograf. Only experienced physicians and qualified facilities should mange patients prescribed Prograf. Increased susceptibility to infection and the possible development of lymphoma may result from immunosuppression. Insulin dependent post transplant diabetes occurred in up to 20% of patients but was reversible in some patients. Black and Hispanic kidney transplant patients were at an increased risk. Common adverse reactions are nephrotoxicity, neurotoxicity, gastrointestinal disturbances, hypertension and infection. Prograf is contraindicated in patients with a hypersensitivity to tacrolimus. Prograf injection is contraindicated in patients with a hypersensitivity to castor oil. For full prescribing information, visit http://www.prograf.com/ or contact Fujisawa Healthcare, Inc. at 1-800-727-7003.

Source: Fujisawa Healthcare, Inc.

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