The FDA ( Food and Drug Administration ) has informed healthcare professionals of clinical trial data that suggest increased mortality in stable liver transplant patients after conversion from a calcineurin inhibitor ( CNI )-based immunosuppressive regimen to Sirolimus ( Rapamune ). The trial was conducted by Sirolimus manufacturer, Wyeth.

Sirolimus is indicated for the prophylaxis of organ rejection in patients aged 13 years or older receiving kidney transplants. The safety and efficacy of this drug in liver or lung transplant patients have not been established by the FDA.

On March 25, 2009, Wyeth submitted to FDA results of a clinical trial, titled A Randomized, Open-Label, Comparative Evaluation Of Conversion From Calcineurin Inhibitor Treatment to Sirolimus Treatment Versus Continuation Of Calcineurin Inhibitor Treatment In Liver Allograft Recipients Undergoing Maintenance Therapy . The trial compared stable liver transplant patients who were converted from a calcineurin inhibitor to Sirolimus to patients who remained on CNI-based therapy. The trial data suggested that there may be increased mortality in patients converted from calcineurin inhibitor therapy to Sirolimus.

The trial also provided additional safety and efficacy information on Sirolimus:

a) The overall treatment failure rates at one year, defined as the occurrence of acute rejection or premature discontinuation for any reason, for the intent-to-treat population were significantly higher for the cohort of stable liver transplant patients converted to Sirolimus compared to the cohort that continued on calcineurin inhibitors.

b) Drug discontinuation due to an adverse event was also more frequent in the Sirolimus cohort compared to those patients continued on calcineurin inhibitor.

c) Peripheral edema, stomatitis, rash, and mouth ulceration were the most frequent adverse events resulting in discontinuation in the trial.

d) Mean fasting lipid concentrations increased significantly after the Sirolimus conversion, and remained elevated throughout the one year follow-up evaluation period.

Source: FDA, 2009

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