Mycophenolate Mofetil (Page 8 of 10)

14.2 Heart Transplantation

A double-blind, randomized, comparative, parallel-group, multicenter study in primary de novo heart transplant recipients was performed at centers in the United States (20), in Canada (1), in Europe (5) and in Australia (2). The total number of patients enrolled (ITT population) was 650; 72 never received study drug and 578 received study drug (Safety Population). Patients received mycophenolate mofetil 1.5 grams twice daily (n=289) or AZA 1.5 to 3 mg/kg/day (n=289), in combination with cyclosporine (Sandimmune® or Neoral®) and corticosteroids as maintenance immunosuppressive therapy. The two primary efficacy endpoints were: (1) the proportion of patients who, after transplantation, had at least one endomyocardial biopsy-proven rejection with hemodynamic compromise, or were re-transplanted or died, within the first 6 months, and (2) the proportion of patients who died or were re-transplanted during the first 12 months following transplantation. Patients who prematurely discontinued treatment were followed for the occurrence of allograft rejection for up to 6 months and for the occurrence of death for 1 year.

The analyses of the endpoints showed:

  • Rejection: No difference was established between mycophenolate mofetil and AZA with respect to
    biopsy-proven rejection with hemodynamic compromise.
  • Survival: Mycophenolate mofetil was shown to be at least as effective as AZA in preventing death or re-transplantation at 1 year (see Table 13).
Table 13: De Novo Heart Transplantation Study Rejection at 6 Months/Death or Re-transplantation at 1 Year

All Patients (ITT)

Treated Patients

AZA

N=323

Mycophenolate

Mofetil

N=327

AZA

N=289

Mycophenolate

Mofetil

N=289

Biopsy-proven rejection with hemodynamic compromise at 6 monthsa

121 (38%)

120 (37%)

100 (35%)

92 (32%)

Death or re-transplantation at 1 year

49 (15.2%)

42 (12.8%)

33 (11.4%)

18 (6.2%)

a Hemodynamic compromise occurred if any of the following criteria were met: pulmonary capillary wedge pressure ≥20 mm or a 25% increase; cardiac index <2.0 L/min/m2 or a 25% decrease; ejection fraction ≤30%; pulmonary artery oxygen saturation ≤60% or a 25% decrease; presence of new S3 gallop; fractional shortening was ≤20% or a 25% decrease; inotropic support required to manage the clinical condition.

14.3 Liver Transplantation

A double-blind, randomized, comparative, parallel-group, multicenter study in primary hepatic transplant recipients was performed at centers in the United States (16), in Canada (2), in Europe (4) and in Australia (1). The total number of patients enrolled was 565. Per protocol, patients received mycophenolate mofetil 1 gram twice daily intravenously for up to 14 days followed by mycophenolate mofetil 1.5 grams twice daily orally or AZA 1 to 2 mg/kg/day intravenously followed by AZA 1 to 2 mg/kg/day orally, in combination with cyclosporine (Neoral®) and corticosteroids as maintenance immunosuppressive therapy. The actual median oral dose of AZA on study was 1.5 mg/kg/day (range of 0.3 to 3.8 mg/kg/day) initially and 1.26 mg/kg/day (range of 0.3 to 3.8 mg/kg/day) at 12 months. The two primary endpoints were: (1) the proportion of patients who experienced, in the first 6 months post-transplantation, one or more episodes of biopsy-proven and treated rejection or death or re-transplantation, and (2) the proportion of patients who experienced graft loss (death or re-transplantation) during the first 12 months post-transplantation. Patients who prematurely discontinued treatment were followed for the occurrence of allograft rejection and for the occurrence of graft loss (death or re-transplantation) for 1 year.

In combination with corticosteroids and cyclosporine, mycophenolate mofetil demonstrated a lower rate of acute rejection at 6 months and a similar rate of death or re-transplantation at 1 year compared to AZA (Table 14).

Table 14: De Novo Liver Transplantation Study Rejection at 6 Months/Death or Re-transplantation at 1 Year

AZA

N=287

Mycophenolate

Mofetil

N=278

Biopsy-proven, treated rejection

at 6 months (includes death or re-transplantation)

137 (47.7%)

107 (38.5%)

Death or re-transplantation at 1 year

42 (14.6%)

41 (14.7%)

15 REFERENCES

1. “OSHA Hazardous Drugs.” OSHA. http://www.osha.gov/SLTC/hazardousdrugs/index.html

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 Handling and Disposal

Mycophenolate mofetil has demonstrated teratogenic effects in humans [see Warnings and Precautions (5.1) and Use in Specific Populations (8.1)]. Wearing disposable gloves is recommended during reconstitution and when wiping the outer surface of the bottle/cap and the table after reconstitution. Avoid inhalation or direct contact with skin or mucous membranes of the powder contained in mycophenolate mofetil for oral suspension (before or after constitution) [see Dosage and Administration (2.6)]. Follow applicable special handling and disposal procedures 1 .

16.4 Mycophenolate Mofetil for Oral Suspension

35 grams mycophenolate mofetil USP, supplied as a white to off-white powder blend for constitution to a white to off-white mixed-fruit flavor suspension. Supplied in the following presentation:

NDC Number

Size

0480-1175-22

225 mL bottle with bottle adapter and 2 oral dispensers

Storage

  • Store dry powder at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].
  • Store constituted suspension at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) for up to 60 days. Storage in a refrigerator at 2° to 8°C (36° to 46°F) is acceptable. Do not freeze.

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