Rockville, MD - Roche Laboratories has warned physicians of a high incidence of acute rejection among heart-transplant recipients in a small randomized study who, after being maintained on either tacrolimus or cyclosporine along with the company's immunosuppressant mycophenolate mofetil (MMF, CellCept), had been switched to a regimen of sirolimus (Rapamune, Wyeth Pharmaceuticals) plus MMF [1].

Grade IIIA acute rejection developed in four of the seven patients for whom one of the calcineurin inhibitors had been replaced by sirolimus in the Heart Spare the Nephron (Heart STN) trial, according to a letter from the company to healthcare providers dated February 1, 2007 and reported February 22 on the US Food and Drug Administration Medwatch website [2]. Roche said it provided the safety information after discussion with the FDA.

The change in regimen occurred 12 weeks after transplantation. No episodes of acute rejection developed in the eight patients who had continued on tacrolimus or cyclosporine. All patients had been maintained on corticosteroids throughout the trial.

Three of the four patients with acute rejection, which emerged within five weeks of the regimen change, "responded well" to corticosteroid therapy, and the fourth "recovered after experiencing hemodynamic compromise," according to the letter.

The company has terminated the trial, which was designed to show whether the drug switch might help preserve renal function in patients subjected to multidrug immunosuppressive therapy. It cautions that MMF—which is approved for use after heart, kidney, or liver transplantation—should be combined with both cyclosporine and corticosteroids.