AG-MYCOPHENOLATE

1 Dosing Considerations • AG-Mycophenolate (mycophenolate mofetil) should be used concomitantly with standard cyclosporine and corticosteroid therapy. AG-Mycophenolate Tablets • The initial oral dose of AG-Mycophenolate should be given as soon as possible following renal, cardiac or hepatic transplantation.

Food had no effect on MPA AUC, but has been shown to decrease MPA Cmax by 40%. It is recommended that AG- Mycophenolate be administered on an empty stomach. 2 Recommended Dose and Dosage Adjustment Adults Renal Transplantation A dose of 1 g administered orally twice a day (daily dose of 2 g) is recommended for use in renal transplant patients.

5 g administered twice daily (daily dose of 3 g) was used in clinical trials and was shown to be safe and effective, no efficacy advantage could be established for renal transplant patients. Patients receiving 2 g per day of mycophenolate mofetil in these trials demonstrated an overall better safety profile than did patients receiving 3 g per day of mycophenolate mofetil.

5 g twice daily oral (daily dose of 3 g) is recommended for use in adult cardiac transplant patients. 5 g twice daily oral (daily dose of 3 g) is recommended for use in adult hepatic transplant patients. 5 m2 may be dosed with AG-Mycophenolate tablets at a dose of 1 g twice daily (2 g daily dose).

73m2) outside the immediate post-transplant period, doses of mycophenolate mofetil greater than 1 g administered twice a day should be avoided.

These patients should also be carefully observed (see CLINICAL PHARMACOLOGY:

Pharmacokinetics, Special Populations and Conditions, Renal Insufficiency). No data are available for cardiac or hepatic transplant patients with severe chronic renal impairment. AG-Mycophenolate should be used for cardiac or hepatic transplant patients with severe chronic renal impairment if the potential benefits outweigh the potential risks.

3 x 103/mcL), dosing with AG-Mycophenolate should be interrupted or the dose reduced, appropriate diagnostic tests performed, and the patient managed appropriately. (See WARNINGS AND PRECAUTIONS: Immune, Monitoring and Laboratory Tests and ADVERSE REACTIONS) Delayed Renal Graft Function Post Transplant No dose adjustment is recommended for these patients, however, they should be carefully observed (see CLINICAL PHARMACOLOGY: Pharmacokinetics, Special Populations and Conditions, Renal Insufficiency).

2 Recommended Dose and Adjustment Pediatrics). 4 Geriatrics Geriatric patients may be at an increased risk of adverse events such as certain infections (including cytomegalovirus tissue invasive disease) and possibly gastrointestinal AG-Mycophenolate (mycophenolate mofetil) Page 13 of 66 haemorrhage and pulmonary oedema, compared with younger individuals.

1 Adverse Reaction Overview The adverse event profile associated with the use of immunosuppressive drugs is often difficult to establish owing to the presence of underlying disease and the concurrent use of many other medications. The principal adverse reactions associated with the administration of mycophenolate mofetil include diarrhea, leukopenia, sepsis and vomiting, and there is evidence of a higher frequency of certain types of infections.

2 Clinical Trial Adverse Reactions Clinical trials are conducted under very specific conditions. The adverse reaction rates observed in the clinical trials; therefore, may not reflect the rates observed in practice and should not be compared to the rates in the clinical trials of another drug.

Adverse reaction information from clinical trials may be useful in identifying and approximating rates of adverse drug reactions in real-world use. Mycophenolate Mofetil (oral) The incidence of adverse events for mycophenolate mofetil was determined in randomized comparative double-blind trials in prevention of rejection in renal (2 active, 1 placebo controlled trials), cardiac (1 active controlled trial) and hepatic (1 active controlled trial) transplant patients.

Safety data are summarized below for all active controlled trials in renal (2 trials), cardiac (1 trial) and hepatic (1 trial) transplant patients. Approximately 53% of renal patients, 65% of the cardiac patients and 45% of the hepatic patients have been treated for more than one year.

, Immune 05-2023 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed . 1 Pediatrics (2-18 years of age) ............................................................................................

2 Geriatrics ........................................................................................................................... 1 Dosing Considerations ......................................................................................................

2 Recommended Dose and Dosage Adjustment .................................................................... 4 Administration ...................................................................................................................

1 Special Populations ......................................................................................................... 1 Pregnant Women ............................................................................................................

2 Breast-feeding ................................................................................................................. 3 Pediatrics .........................................................................................................................

4 Geriatrics ......................................................................................................................... 12 8 ADVERSE REACTIONS ............................................................................................................

1 Adverse Reaction Overview ............................................................................................ 2 Clinical Trial Adverse Reactions .......................................................................................

3 Less Common Clinical Trial Adverse Reactions ............................................................... 5 Post-Market Adverse Reactions .........................................................................................

• AG-Mycophenolate (mycophenolate mofetil) is contraindicated in patients with a known hypersensitivity to mycophenolate mofetil, mycophenolic acid or any component of the drug product (see DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING).

• AG-Mycophenolate is contraindicated during pregnancy due to its mutagenic and teratogenic potential (see WARNINGS and PRECAUTIONS). • AG-Mycophenolate is contraindicated in women of childbearing potential not using highly effective contraceptive methods and without providing a pregnancy test result.

(see WARNINGS and PRECAUTIONS). • AG-Mycophenolate is contraindicated in women who are breastfeeding (see WARNINGS and PRECAUTIONS). AG-Mycophenolate (mycophenolate mofetil) Page 5 of 66