APO-MYCOPHENOLATE MOFETIL

1 Dosing Considerations  APO-MYCOPHENOLATE MOFETIL capsules and tablets should be used concomitantly with standard cyclosporine and corticosteroid therapy.  The initial oral dose of APO-MYCOPHENOLATE MOFETIL 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 APO- MYCOPHENOLATE MOFETIL 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 receivi ng 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 recomme nded 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. Pediatrics (<18 years) Pediatric dosing is based on BSA.

5 g daily dose). 5 m2 may be dosed with APO-MYCOPHENOLATE MOFETIL capsules or tablets at a dose of 1 g twice daily (2 g daily dose). 73m2) outside the immediate post-transplant period, doses of APO-MYCOPHENOLATE MOFETIL greater than 1 g administered twice a day should be avoided.

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

3 x 103/mcL), dosing with APO-MYCOPHENOLATE MOFETIL should be interrupted or the dose reduced, appropriate diagnostic tests performed, and the patient managed appropriately. 3 Pharmacokinetics, Special Populations and Conditions, Renal Insufficiency).

4 Administration APO-MYCOPHENOLATE MOFETIL (capsules and tablets) should be administered orally, and should be taken on an empty stomach (see 10 CLINICAL PHARMACOLOGY: Absorption).

3 Pharmacokinetics, Special Populations and Conditions, Renal Insufficiency). 4 Administration APO-MYCOPHENOLATE MOFETIL (capsules and tablets) should be administered orally, and should be taken on an empty stomach (see 10 CLINICAL PHARMACOLOGY: Absorption).

5 OVERDOSAGE For management of a suspected drug overdose, contact your regional poison control centre. Reports of overdoses with mycophenolate mofetil have been received from clinical trials and during post-marketing experience. In many of these cases no adverse events were reported.

In those overdose cases in which adverse events were reported, the events fall within the known safety profile of the drug. It is expected that an overdose of mycophenolate mofetil could possibly result in oversuppression of the immune system and increase susceptibility to infections and bone marrow suppression (see 7 WARNINGS AND PRECAUTIONS: Immune).

If neutropenia develops, dosing with mycophenolate mofetil should be interrupted or the dose reduced (see 7 WARNINGS AND PRECAUTIONS: Immune). APO-MYCOPHENOLATE MOFETIL Page 7 of 68 The highest dose administered to renal transplant patients in clinical trials has been 4 g per day.

In limited experience with cardiac and hepatic transplant patients in clinical trials, the highest doses used were 4 g or 5 g per day. At doses of 4 g or 5 g per day, there appears to be a higher rate, compared to the use of 3 g per day or less, of gastrointestinal intolerance (nausea, vomiting, and/or diarrhea), and occasional hematologic abnormalities, principally neutropenia, leading to a need to reduce or discontinue dosing.

At clinically encountered concentrations, MPA and MPAG are not removed by hemodialysis. However, at high MPAG plasma concentrations (>100 mcg/mL), small amounts of MPAG are removed. By interfering with enterohepatic recirculation of the drug, bile acid sequestrants, such as cholestyramine reduce the MPA AUC.

, Immune 02/2022 TABLE OF CONTENTS Sections or subsections that are not applicable at the time of authorization are not listed. RECENT MAJOR LABEL CHANGES............................................................................................

2 TABLE OF CONTENTS .............................................................................................................. 2 PART I: HEALTH PROFESSIONAL INFORMATION .....................................................................

4 1 INDICATIONS................................................................................................................... 1 Pediatrics (<18 Years of Age) ...................................................................................

2 Geriatrics ................................................................................................................ 4 2 CONTRAINDICATIONS .....................................................................................................

4 3 SERIOUS WARNINGS AND PRECAUTIONS BOX................................................................. 4 4 DOSAGE AND ADMINISTRATION ..................................................................................... 1 Dosing Considerations.............................................................................................

2 Recommended Dose And Dosage Adjustment ......................................................... 4 Administration........................................................................................................ 6 5 OVERDOSAGE..................................................................................................................

6 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING ..................................... 7 7 WARNINGS AND PRECAUTIONS....................................................................................... 59 […]

 APO-MYCOPHENOLATE MOFETIL is contraindicated in patients with a known hypersensitivity tomycophenolate mofetil, mycophenolic acid or any component of the drug product (see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING ).  APO-MYCOPHENOLATE MOFETIL is contraindicated during pregnancy due to its mutagenic and teratogenic potential (see 7 WARNINGS and PRECAUTIONS).

 APO-MYCOPHENOLATE MOFETIL is contraindicated in women of childbearing potential not using highly effective contraceptive methods and without providing a pregnancy test result. (see 7 WARNINGS and PRECAUTIONS).  APO-MYCOPHENOLATE MOFETIL is contraindicated in women who are breastfeeding (see 7 WARNINGS and PRECAUTIONS).