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Hypertension 47% 56% 38% 43%
Urogenital
Kidney Function Abnormal 40% 27% 36% 23%
Creatinine Increased 39% 25% 24% 19%
BUN Increased 30% 22% 12% 9%
Oliguria 18% 15% 19% 12%
Urinary Tract Infection 16% 18% 21% 19%
Metabolic and Nutritional
Hypomagnesemia 48% 45% 16% 9%
Hyperglycemia 47% 38% 33% 22%
Hyperkalemia 45% 26% 13% 9%
Hypokalemia 29% 34% 13% 16%
Hemic and Lymphatic
Anemia 47% 38% 5% 1%
Leukocytosis 32% 26% 8% 8%
Thrombocytopenia 24% 20% 14% 19%
Miscellaneous
Pain 63% 57% 24% 22%
Abdominal Pain 59% 54% 29% 22%
Asthenia 52% 48% 11% 7%
Fever 48% 56% 19% 22%
Back Pain 30% 29% 17% 17%
Ascites 27% 22% 7% 8%
Peripheral Edema 26% 26% 12% 14%
Respiratory System
Pleural Effusion 30% 32% 36% 35%
Dyspnea 29% 23% 5% 4%
Atelectasis 28% 30% 5% 4%
Skin and Appendages
Pruritus 36% 20% 15% 7%
Rash 24% 19% 10% 4%
Less frequently observed adverse reactions in both liver transplantation and kidney transplantation patients are described under the subsection Less Frequently Reported Adverse Reactions.
Heart Transplantation
The incidence of adverse reactions was determined based on two trials in primary orthotopic heart transplantation. In a trial conducted in Europe, 314 patients received a regimen of antibody induction, corticosteroids and azathioprine (AZA) in combination with Tacrolimus (n=157) or cyclosporine (n=157) for 18 months. The trial population had a mean age of 51 years (range 18 to 65), the distribution was 82% male, and the composition was White (96%), Black (3%) and other(1%).
The most common adverse reactions (≥ 15%) observed in Tacrolimus-treated heart transplant patients are: abnormal renal function, hypertension, diabetes mellitus, CMV infection, tremor, hyperglycemia, leukopenia, infection, anemia, bronchitis, pericardial effusion, urinary tract infection and hyperlipemia.
Adverse reactions in heart transplant patients in the European trial are presented below:
Table 8. Heart Transplantation: Adverse Reactions Occurring in ≥ 15% of Patients Treated with Tacrolimus in Conjunction with Azathioprine (AZA)
Tacrolimus/AZA (n=157) Cyclosporine/AZA(n=157)
Cardiovascular System
Hypertension 62% 69%
Pericardial Effusion 15% 14%
Body as a Whole
CMV Infection 32% 30%
Infection 24% 21%
Metabolic and Nutritional Disorders
Diabetes Mellitus 26% 16%
Hyperglycemia 23% 17%
Hyperlipemia 18% 27%
Hemic and Lymphatic System
Anemia 50% 36%
Leukopenia 48% 39%
Urogenital System
Kidney Function Abnormal 56% 57%
Urinary Tract Infection 16% 12%
Respiratory System
Bronchitis 17% 18%
Nervous System
Tremor 15% 6%
In the European trial, the cyclosporine trough concentrations were above the pre-defined target range (i.e., 100 to 200 ng/mL) at Day 122 and beyond in 32 to 68% of the patients in the cyclosporine treatment arm, wher
