nd Precautions (5.8)]
•Hyperkalemia [see Warnings and Precautions (5.9)]
•Hypertension [see Warnings and Precautions (5.10)]
•Anaphylaxis with Tacrolimus Injection [see Warnings and Precautions(5.11)]
•Myocardial Hypertrophy [see Warnings and Precautions (5.14)]
•Pure Red Cell Aplasia [see Warnings and Precautions (5.16)]
6.1 Clinical Studies Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. In addition, the clinical trials were not designed to establish comparative differences across study arms with regards to the adverse reactions discussed below.
Kidney Transplant
The incidence of adverse reactions was determined in three randomized kidney transplant trials. One of the trials used azathioprine (AZA) and corticosteroids and two of the trials used mycophenolate mofetil (MMF) and corticosteroids concomitantly for maintenance immunosuppression.
Tacrolimus-based immunosuppression in conjunction with azathioprine and corticosteroids following kidney transplantation was assessed in trial where 205 patients received Tacrolimus based immunosuppression and 207 patients received cyclosporine based immunosuppression. The trial population had a mean age of 43 years (mean±sd was 43±13 years on Tacrolimus and 44±12 years on cyclosporine arm), the distribution was 61% male, and the composition was White (58%), Black (25%), Hispanic (12%) and Other (5%). The 12 month post-transplant information from this trial is presented below.
The most common adverse reactions ( ≥ 30%) observed in Tacrolimus-treated kidney transplant patients are: infection, tremor, hypertension, abnormal renal function, constipation, diarrhea, headache, abdominal pain, insomnia, nausea, hypomagnesemia, urinary tract infection, hypophosphatemia, peripheral edema, asthenia, pain, hyperlipidemia, hyperkalemia and anemia.
Adverse reactions that occurred in ≥ 15% of kidney transplant patients treated with Tacrolimus in conjunction with azathioprine are presented below:
Table 4. Kidney Transplantation: Adverse Reactions Occurring in ≥ 15% of Patients Treated with Tacrolimus in Conjunction with Azathioprine (AZA)
Tacrolimus/AZA (N=205) Cyclosporine/AZA (N=207)
Nervous System
Tremor
Headache
Insomnia
Paresthesia
Dizziness 54%
44%
32%
23%
19% 34%
38%
30%
16%
16%
Gastrointestinal
Diarrhea
Nausea
Constipation
Vomiting
Dyspepsia 44%
38%
35%
29%
28% 41%
36%
43%
23%
20%
Cardiovascular
Hypertension
Chest Pain 50%
19% 52%
13%
Urogenital
Creatinine Increased
Urinary Tract Infection 45%
34% 42%
35%
Metabolic and Nutritional
Hypophosphatemia
Hypomagnesemia
Hyperlipemia
Hyperkalemia
Diabetes Mellitus
Hypokalemia
Hyperglycemia
Edema 49%
34%
31%
31%
24%
22%
22%
18% 53%
17%
38%
32%
9%
25%
16%
19%
Hemic and Lymphatic
Anemia
Leukopenia 30%
15% 24%
17%
Misce
