ACH-MYCOPHENOLATE

2 Recommended Dose and Dosage Adjustment). The development of neutropenia may be related to mycophenolate mofetil itself, concomitant medications, viral infections, or some combination of these causes. 3 x 103/mcL), dosing with mycophenolate mofetil should be interrupted or the dose should be reduced, appropriate diagnostic tests performed, and the patient managed appropriately.

Neutropenia has been observed most frequently in the period from 31 to 180 days post- transplant for patients treated for prevention of renal, cardiac and hepatic rejection. 6% hepatic transplant patients receiving mycophenolate mofetil 3g daily (see 8 ADVERSE REACTIONS).

Immune Mycophenolate mofetil has been administered in combination with the following agents in clinical trials: antithymocyte globulin [equine] (Atgam®) induction, muromonab-CD3 (Orthoclone OKT®3), cyclosporine (Sandimmune®, Neoral®), and corticosteroids.

The efficacy and safety of the use of mycophenolate mofetil in combination with other immunosuppressive agents has not been determined. Oversuppression of the immune system can also increase susceptibility to infection, including opportunistic infections, fatal infections and sepsis.

Such infections include latent viral reactivation, such as hepatitis B or hepatitis C reactivation or infections caused by polyomaviruses. Cases of hepatitis due to reactivation of hepatitis B or hepatitis C have been reported in carrier patients treated with immunosuppresants.

Cases of progressive multifocal leukoencephalopathy (PML) associated with the JC virus, sometimes fatal, have been reported in mycophenolate mofetil treated patients. The reported cases had risk factors for PML, including immunosuppressant therapies and impairment of immune function.

In immunosuppressed patients, physicians should consider PML in the differential diagnosis in patients reporting neurological symptoms and consultation with a neurologist should be considered as clinically indicated. BK virus-associated nephropathy has been observed during the use of mycophenolate mofetil in patients post renal transplant.

This infection can be associated with serious outcomes, sometimes leading to renal graft loss. Patient monitoring may help detect patients at risk for BK virus-associated nephropathy. Due to the cytostatic effect of mycophenolate mofetil on B- and T-lymphocytes, increased severity of COVID-19 may occur.

Dose reduction or discontinuation of mycophenolate mofetil in immunosuppression should be considered for patients who develop evidence of BK virus-associated nephropathy, or in cases of clinically significant COVID-19. In patients receiving mycophenolate mofetil (2 g or 3 g) in controlled studies for prevention of renal, cardiac or hepatic rejection, fatal infection/sepsis occurred in approximately 2% of renal and cardiac patients and in 5% of hepatic patients (see 8 ADVERSE REACTIONS).

3 Pharmacokinetics, Special Populations and Conditions, Renal Insufficiency). 3 Pharmacokinetics, 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. Product Monograph Page 7 of 70 ACH-Mycophenolate, mycophenolate mofetil tablets 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) 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.

6. DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING Table 1 Dosage Forms, Strengths, Composition and Packaging Route of Administration Dosage Form / Strength Non-medicinal Ingredients Oral Tablets / 500 mg Croscarmellose sodium, hydroxypropyl cellulose, hypromellose, FD&C blue #2 aluminum lake, iron oxide black, iron oxide red, magnesium stearate, purified talc, microcrystalline cellulose, polyethylene glycol, povidone, titanium dioxide Film-Coated Tablets: Composition: ACH-Mycophenolate is available for oral administration as tablets containing 500 mg of mycophenolate mofetil.

, Immune 01/2022 TABLE OF CONTENTS RECENT MAJOR LABEL CHANGES .......................................................................................... 1 Special Populations..........................................................................................

1 Pregnant Women....................................................................................... 2 Breast-feeding ........................................................................................... 3 Pediatrics...................................................................................................

4 Geriatrics ................................................................................................... 13 8 ADVERSE REACTIONS................................................................................................ 1 Adverse Reaction Overview .............................................................................

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

22 9 DRUG INTERACTIONS ............................................................................................... 2 Drug Interactions Overview ............................................................................. 3 Drug-Behavioural Interactions .........................................................................

4 Drug-Drug Interactions .................................................................................... 5 Drug-Food Interactions.................................................................................... 6 Drug-Herb Interactions ....................................................................................

). Before the start of treatment, female and male patients of reproductive potential must be made aware of the increased risk of pregnancy loss and congenital malformations and must be counseled regarding pregnancy prevention, and planning.

Women of child bearing potential should use two reliable forms of contraception simultaneously, at least one of which must be highly effective, before beginning ACH-Mycophenolate therapy, during therapy, and for six weeks following discontinuation of therapy, unless abstinence is the chosen method of contraception.

Prior to starting therapy with ACH-Mycophenolate, female patients of childbearing potential must have two negative serum or urine pregnancy tests with a sensitivity of at least 25 mIU/mL; the second test should be performed 8-10 days later.

Repeat pregnancy tests should be performed during routine follow-up visits. Results of all pregnancy tests should be discussed with the patient. Patients should be instructed to consult their physician immediately should pregnancy occur.

Limited clinical evidence is currently available on paternal exposure to mycophenolate mofetil. Based on the animal data, the risk of genotoxic effects on sperm cells cannot completely be excluded. In absence of sufficient data to exclude a risk of harm to the fetus conceived during or directly after the treatment of the father, the following precautionary measure is Product Monograph Page 12 of 70 ACH-Mycophenolate, mycophenolate mofetil tablets recommended: sexually active male patients and/or their female partners are recommended to use effective contraception during treatment of the male patient and for at least 90 days after cessation of treatment.

If pregnancy does occur during treatment, the physician and patient should discuss the desirability of continuing the pregnancy. Men should not donate semen during therapy and for 90 days following discontinuation of ACH-Mycophenolate.