3 - Mycophenolate Mofetil

Question 1

MMF is a prodrug

Answer 1

True

Question 2

The active antimetabolite of MMF is mycophenolic acid

Answer 2

True

Question 3

Mycophenolic acid has antibacterial properties

Answer 3

True

Question 4

Mycophenolic acid has antiviral properties

Answer 4

True

Question 5

Mycophenolic acid has antifungal properties

Answer 5

True

Question 6

Mycophenolic acid has antitumour properties

Answer 6

True

Question 7

Mycophenolic acid has immunosuppressive properties

Answer 7

True

Question 8

MMF has greater bioavailability and tolerability than Mycophenolic acid

Answer 8

True

Question 9

MMF is an ester of mycophenolic acid

Answer 9

True

Question 10

MMF is converted to mycophenolic acid by esterases in the plasma, liver and kidney

Answer 10

True

Question 11

Mycophenolic acid is inactivated in the liver via glucuronidation

Answer 11

True

Question 12

Mycophenolic acid is inactivated in the liver

Answer 12

True

Question 13

Glucuronidation of mycophenolic acid in the liver yields the inactive compound mycophenolic acid glucuronide

Answer 13

True

Question 14

Mycophenolic acid glucuronide (inactive metabolite of mycophenolic acid) is secreted into bile and recycled to the liver via enterohepatic recirculation

Answer 14

True

Question 15

The enterohepatic recirculation of mycophenolic acid glucuronide is vital for maintaining mycophenolic acid serum levels

Answer 15

True

Question 16

Mycophenolic acid glucuronide (inactive metabolite) is converted back to mycophenolic acid by beta-glucuronidase

Answer 16

True

Question 17

The high levels of beta-glucuronidase (to convert mycophenolic acid glucuronide to mycophenolic acid) found in the epidermis accounts for the efficacy of MMF

Answer 17

True

Question 18

The high levels of beta-glucuronidase (to convert mycophenolic acid glucuronide to mycophenolic acid) found in the GI tract accounts for the most common adverse effects of MMF

Answer 18

True

Question 19

The first peak of MMF plasma levels occurs in the first hour

Answer 19

True

Question 20

A second MMF plasma level peak occurs after 6-12 hours due to enterohepatic recirculation of mycophenolic acid glucuronide

Answer 20

True

Question 21

Over 90% of the administered MMF dosage is excreted in urine as mycophenolic acid glucuronide (inactive metabolite)

Answer 21

True

Question 22

Dose reduction of MMF is not necessary in renal impairment

Answer 22

True (renal impairment does not have a significant impact on mycophenolic acid)

Question 23

MMF and mycophenolic acid is bound to serum albumin

Answer 23

True

Question 24

A decrease in MMF dosing may be necessary in situations which alter albumin levels

Answer 24

True (altered albumin levels may occur in liver or renal disease or concomitant use of medications that compete for albumin binding sites)

Question 25

Exposure to increased amounts of unbound mycophenolic acid (active metabolite/drug) may be a predictor of infections

Answer 25

True

Question 26

Exposure to increased amounts of unbound mycophenolic acid (active metabolite/drug) may be a predictor of haematologic toxicity

Answer 26

True

Question 27

Mycophenolic acid inhibits inosine monophosphate dehydrogenase in the de novo purine synthesis pathway

Answer 27

True (just like MTX - an antimetabolite)

Question 28

By inhibiting inosine monophosphate dehydrogenase in the purine synthesis pathway, mycophenolic acid deprives T and B lymphocytes of purine metabolites necessary for growth and replication (hence causes selective immunosuppression)

Answer 28

True

Question 29

The immunosuppressive effects of MMF are related to the effects of purine biosynthesis affecting lymphocytes

Answer 29

True

Question 30

By selectively inhibiting the de novo purine synthesis pathway within activated lymphocytes, MMF targets the lymphocytes most responsible for disease whilst having a minimal effect on other organs and cell types

Answer 30

True

Question 31

MMF also reduces the recruitment of inflammatory cells

Answer 31

True

Question 32

MMF is used off label for dermatologic diseases

Answer 32

True (as a steroid-sparing agent and for severe refractory disease that has failed other treatment regimens)

Question 33

MMF is comparable to other immunosuppressants as a corticosteroid-sparing agent in treatment of Pemphigus

Answer 33

True

Question 34

MMF is not first line treatment in psoriasis

Answer 34

True

Question 35

Azathioprine is associated with a significantly higher rate of elevated LFTs as compared to MMF in the treatment of bullous pemphigoid

Answer 35

True

Question 36

MMF shows promise in the treatment of the associated interstitial lung disease in dermatomyositis

Answer 36

True

Question 37

MMF is efficacious in the treatment of interstitial lung disease associated with diffuse systemic sclerosis, although efficacy is less convincing for cutaneous disease

Answer 37

True

Question 38

Peptic ulcer disease is a relative contraindication of MMF

Answer 38

True

Question 39

Cholestyramine (interferes with enterohepatic recirculation) is relatively contraindicated with MMF

Answer 39

True

Question 40

Concomitant administration of Azathioprine with MMF increases risk of bone marrow suppression

Answer 40

True

Question 41

The risk of MMF in causing lymphoproliferative disorders and NMSCs is unclear

Answer 41

True

Question 42

The risk of malignancy associated with MMF (lymphoproliferative disorders and NMSCs) likely relates to the effects of cumulative immunosuppression from multiple drugs rather than an MMF specific effect

Answer 42

True

Question 43

GI symptoms are most common with MMF

Answer 43

True

Question 44

GI symptoms associated with MMF are dose related

Answer 44

True

Question 45

Adverse GI effects associated with MMF improve over time

Answer 45

True

Question 46

Administration of MMF with food and BD or TDS dosing improves GI tolerability

Answer 46

True

Question 47

MMF is not hepatotoxic although elevated transaminases have been reported

Answer 47

True (the significance of the elevated transaminases is unclear)

Question 48

MMF can cause elevated transaminases

Answer 48

True (though significance is unclear)

Question 49

MMF is less hepatotoxic than Azathioprine

Answer 49

True

Question 50

MMF does not cause nephrotoxicity

Answer 50

True

Question 51

Haematologic toxicity associated with MMF is dose-dependant

Answer 51

True

Question 52

The haematologic toxicity associated with MMF is rapidly reversible with cessation of therapy

Answer 52

True

Question 53

Risk of Infections with MMF are more common in transplant patients used as anti-rejection treatment

Answer 53

True

Question 54

Progressive multifocal leukoencephalopathy was associated in patients on MMF with transplanted organs and long-standing SLE on concomitant immunosuppression

Answer 54

True

Question 55

The role of MMF to the development of progressive multifocal leukoencephalopathy is unclear

Answer 55

True (occurred in transplant patients and SLE patients already at increased risk for this condition)

Question 56

Fetal malformations are associated with MMF (teratogenic)

Answer 56

True

Question 57

Antacids and PPIs reduce serum levels of mycophenolic acid

Answer 57

True (MMF requires gastric acidity for conversion to the active metabolite mycophenolic acid)

Question 58

Oral iron supplementation does not affect serum MMF levels

Answer 58

True (although it is advisable to give MMF 1 hour before iron containing products)

Question 59

Salicylic acid competes with mycophenolic acid for albumin binding sites and can increase the free active fraction of mycophenolic acid

Answer 59

True

Question 60

Phenytoin competes with mycophenolic acid for albumin binding sites and can increase the free active fraction of mycophenolic acid and vice versa increase free phenytoin levels

Answer 60

True

Question 61

Xanthine bronchodilators (theophylline) compete with mycophenolic acid for albumin binding sites and can increase the free active fraction of mycophenolic acid and vice versa increase free levels of theophylline

Answer 61

True

Question 62

Antivirals (acyclovir, ganciclovir, valganciclovir) inhibit renal tubular secretion of mycophenolic acid and thus increase the serum levels of mycophenolic acid

Answer 62

True (caution with co-administration especially in renal impairment)

Question 63

There is a potential risk of neutropenia with both valacyclovir and MMF

Answer 63

True

Question 64

There is a risk of decreased serum levels of levonorgestrel (progestin component of OCP) with Co-administration with MMF

Answer 64

True

Question 65

Co-administration of MMF does not affect the serum levels of desogestrel, gestodene and ethinyl oestradiol

Answer 65

True (in contrast to levonorgestrel, levels of these do not appear to be affected by MMF although caution is still advised)

Question 66

Live vaccines are contraindicated in patients on MMF

Answer 66

True (risk of reduced immunologic response or increased risk of disseminated viral infection)

Question 67

MMF may increase levels of Cyclosporine

Answer 67

True

Question 68

Antibacterials may reduce serum levels of mycophenolic acid because of reduced enterohepatic recirculation

Answer 68

True (multiple classes including metronidazole, cephalosporins, aminoglycosides, macrolides, etc)

Question 69

Bile acid sequestrants I.e. Cholestyramine reduces the enterohepatic recirculation of mycophenolic acid glucuronide (hence reduce serum levels of mycophenolic acid)

Answer 69

True

Question 70

Probenecid competes with mycophenolic acid for renal tubular secretion and thus increase the serum levels of mycophenolic acid

Answer 70

True

Question 71

Concomitant use of MMF and narcotics may increase risk of seizures

Answer 71

True

Question 72

MMF has been linked to rising Hep C viral titres and Hep C induced acute hepatitis

Answer 72

True (although MMF is safe to use in patients infected with Hep B and C)

Question 73

MMF has been associated with reactivation of latent TB

Answer 73

True

Question 74

MMF may cause genitourinary symptoms I.e. Urgency, frequency, dysuria

Answer 74

True