llaneous
Infection 45% 49%
Peripheral Edema
Asthenia
Abdominal Pain
Pain
Fever
Back Pain 36%
34%
33%
32%
29%
24% 48%
30%
31%
30%
29%
20%
Respiratory System
Dyspnea Cough Increased 22%
18% 18%
15%
Musculoskeletal
Arthralgia 25% 24%
Skin
Rash Pruritus 17%
15% 12%
7%
Two trials were conducted for Tacrolimus-based immunosuppression in conjunction with MMF and corticosteroids. In the non-US trial (Study 1), the incidence of adverse reactions was based on 1195 kidney transplant patients that received Tacrolimus (Group C, n=403), or one of two cyclosporine (CsA) regimens (Group A, n=384 and Group B, n=408) in combination with MMF and corticosteroids; all patients, except those in one of the two cyclosporine groups, also receivedinduction with daclizumab. The trial population had a mean age of 46 years (range 17 to 76), the distribution was 65% male, and the composition was 93% Caucasian. The 12 month post-transplant information from this trial is presented below.
Adverse reactions that occurred in ≥ 10% of kidney transplant patients treated with Tacrolimus in conjunction with MMF in Study 1 [Note: This trial was conducted entirely outside of the United States. Such trials often report a lower incidence of adverse reactions in comparison to U.S. trials] are presented below:
Table 5. Kidney Transplantation: Adverse Reactions Occurring in ≥ 10% of Patients Treated with Tacrolimus in Conjunction with MMF (Study 1)
Tacrolimus Cyclosporine Cyclosporine
(Group C) (Group A) (Group B)
(N=403) (N=384) (N=408)
Diarrhea 25% 16% 13%
Urinary Tract Infection 24% 28% 24%
Anemia 17% 19% 17%
Hypertension 13% 14% 12%
Leukopenia 13% 10% 10%
Edema Peripheral 11% 12% 13%
Hyperlipidemia 10% 15% 13%
Key: Group A = CsA/MMF/CS, B = CsA/MMF/CS/Daclizumab, C=Tac/MMF/CS/Daclizumab CsA = Cyclosporine, CS = Corticosteroids, Tac = Tacrolimus, MMF = mycophenolate mofetil
In the U.S. trial (Study 2) with Tacrolimus-based immunosuppression in conjunction with MMF and corticosteroids, 424 kidney transplant patients received Tacrolimus (n=212) or cyclosporine (n=212) in combination with MMF 1 gram twice daily, basiliximab induction, and corticosteroids. The trial population had a mean age of 48 years (range 17 to 77), the distribution was 63% male, and the composition was White (74%), Black (20%), Asian (3%) and other (3%). The 12 month post-transplant information from this trial is presented below.
Adverse reactions that occurred in ≥15% of kidney transplant patients treated with Tacrolimus in conjunction with MMF in Study 2 are presented below:
Table 6. Kidney Transplantation: Adverse Reactions Occurring in ≥ 15% of Patients Treated with Tacrolimus in Conjunction with MMF (Study 2)
Tacrolimus/MMF Cyclosporine/MMF
(N=212) (N=212)
Gastrointestinal Disorders
Diarrhea 44% 26%
Nausea 39% 47%
Constipation 36% 41%
Vomiting 26% 25%
Dyspepsia 18% 15%
Injury, Poisoning, and Procedural Complications
Post-Procedural Pain 29% 27%
Incision Site Complication 28% 23%
Graft Dysfunction 24% 18%
Metabolism and Nutrition Disorders
Hypomagnesemia 28% 22%
Hypophosphat
