Less frequently observed adverse reactions in both liver transplantation and kidney transplantation patients are described under the subsection Less Frequently Reported Adverse Reactions.
Liver Transplantation

There were two randomized comparative liver transplant trials. In the U.S. trial, 263 adult and pediatric patients received Tacrolimus and steroids and 266 patients received cyclosporine-based immunosuppressive regimen (CsA/AZA). The trial population had a mean age of 44 years (range 0.4 to70), the distribution was 52% male, and the composition was White (78%), Black (5%), Asian (2%), Hispanic (13%) and Other (2%). In the European trial, 270 patients received Tacrolimus and steroids and 275 patients received CsA/AZA. The trial population had a mean age of 46 years (range 15 to 68), the distribution was 59% male, and the composition was White (95.4%), Black (1%), Asian (2%) and Other (2%).

The proportion of patients reporting more than one adverse event was > 99% in both the Tacrolimus group and the CsA/AZA group. Precautions must be taken when comparing the incidence of adverse reactions in the U.S. trial to that in the European trial. The 12-month post-transplant information from the U.S. trial and from the European trial is presented below. The two trials also included different patient populations and patients were treated with immunosuppressive regimens of differing intensities. Adverse reactions reported in ≥15% in Tacrolimus patients (combined trial results) are presented below for the two controlled trials in liver transplantation.

The most common adverse reactions (≥ 40%) observed in Tacrolimus-treated liver transplant patients are: tremor, headache, diarrhea, hypertension, nausea, abnormal renal function, abdominal pain, insomnia, paresthesia, anemia, pain, fever, asthenia, hyperkalemia, hypomagnesemia, and hyperglycemia. These all occur with oral and IV administration of Tacrolimus and some may respond to a reduction in dosing (e.g., tremor, headache, paresthesia, hypertension). Diarrhea was sometimes associated with other gastrointestinal complaints such as nausea and vomiting.

Table 7. Liver Transplantation: Adverse Reactions Occurring in ≥ 15% of Patients Treated with Tacrolimus

 U.S. TRIAL  EUROPEAN TRIAL 
  Tacrolimus Cyclosporine/ Tacrolimus Cyclosporine/
  (N=250) AZA (N=264) AZA
    (N=250)   (N=265)
Nervous System        
Headache 64% 60% 37% 26%
Insomnia 64% 68% 32% 23%
Tremor 56% 46% 48% 32%
Paresthesia 40% 30% 17% 17%
Gastrointestinal        
Diarrhea 72% 47% 37% 27%
Nausea 46% 37% 32% 27%
LFT Abnormal 36% 30% 6% 5%
Anorexia 34% 24% 7% 5%
Vomiting 27% 15% 14% 11%
Constipation 24% 27% 23% 21%
Cardiovascular       &nb