mycophenolate

Action and Spectrum

Actions and Spectrum:

Action:

The primary action of mycophenolate is the inhibition of an enzyme called inosine monophosphate dehydrogenase (IMPDH). IMPDH synthesizes guanosine nucleotides, which are essential for replicating immune cells. By inhibiting this enzyme, mycophenolate reduces the production of guanosine nucleotides, thereby impairing the proliferation of immune cells.

Spectrum:

The spectrum of activity of mycophenolate is relatively broad, targeting both T and B lymphocytes. T lymphocytes are key players in cell-mediated immunity and are involved in organ rejection following transplantation. B lymphocytes, On the other hand, B lymphocytes are responsible for the production of antibodies and have a significant role in humoral immunity. By suppressing the activity of both cell-mediated and humoral immune responses.

Drug Interaction

Adverse Reaction

Frequency defined

>10%

Nausea (23%)

Fever (23%)

Anemia (26%)

Peripheral edema (27%)

Abdominal pain (27%)

Hypertension (28%)

Hypocalcemia (30%)

Increasing frequency of cough (31%)

Urinary tract infection (34%)

Pleural effusion (34%)

Back pain (35%)

Hyperglycemia (44%)

Increased blood urea nitrogen (BUN) (35%)

Hypercholesterolemia (41%) 

1-10%

Lymphoma (0.4-1%)

Other malignancies (0.7-2.1%)

Melanoma (1.6-4.2%)

Neutropenia

Opportunistic infection (including herpes)

Pulmonary fibrosis

GI bleeding

Progressive multifocal leukoencephalopathy

Black Box Warning

Black Box Warning:

Enhanced vulnerability to infection due to Immunosuppression

Medication raises the likelihood of developing lymphoma and skin cancer

Myfortic and CellCept have distinct absorption patterns and should not be used interchangeably

Contraindication / Caution

Contraindication/Caution:

Hypersensitivity: Drugs should not be used in individuals with a known hypersensitivity or allergic reaction to mycophenolate mofetil or any of its components. If you have experienced an allergic reaction to mycophenolate in the past, you should avoid using it.

Pregnancy and breast-feeding: Drug has been associated with an increased risk of birth defects and miscarriages when used during pregnancy. It is contraindicated in pregnant women or those who are planning to become pregnant. Additionally, its use is not recommended during breast-feeding.

Severe immunodeficiency: Drug is an immunosuppressive medication, which reduces the immune system’s activity. It should not be used in individuals with severe immunodeficiency, such as those with untreated HIV infection or other conditions that significantly impair immune function.

Severe gastrointestinal disease: Drug may cause or worsen gastrointestinal (GI) symptoms, including diarrhea, nausea, vomiting, and abdominal pain. Individuals with severe GI disease, such as inflammatory bowel disease or gastrointestinal ulcers, should use mycophenolate with caution or avoid it altogether.

Severe liver disease: Drug is primarily metabolized in the liver, and its dosage may need adjustment in patients with moderate to severe liver disease. However, it should be used with caution or avoided in individuals with severe liver disease, as there is limited data available on its safety and efficacy in such cases.

Pregnancy / Lactation

Pregnancy warnings:   

Pregnancy category: AU TGA pregnancy category: D
US FDA pregnancy category: Not assigned.

Lactation: Excreted into human milk is unknown

Pregnancy Categories:

Category A: Studies that were well-controlled and met expectations revealed no risk to the fetus in either the first or second trimester.

Category B: There were a lack of studies on pregnant women and no evidence of risk to the fetus in animal experiments.

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.

Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.

Category N: There is no data available for the drug under this category

Pharmacology

Pharmacology:

mycophenolate is an immunosuppressive medication that is commonly used in the field of transplant medicine to prevent organ rejection.

Pharmacodynamics:

mycophenolate is a prodrug that is converted in the body to its active form, mycophenolic acid (MPA). MPA inhibits an enzyme called inosine monophosphate dehydrogenase (IMPDH), which plays a critical role in the de novo synthesis of guanosine nucleotides. By inhibiting IMPDH, mycophenolate prevents the proliferation of T and B lymphocytes, which are key components of the immune response. This action suppresses the immune system and helps to prevent organ rejection.

Pharmacokinetics:

Absorption

mycophenolate mofetil, which is the prodrug version of mycophenolate, is given through oral administration. It is quickly and effectively absorbed from the gastrointestinal tract, mainly in the upper small intestine. The drug undergoes significant first-pass metabolism in the liver to produce the active metabolite called mycophenolic acid (MPA).

Distribution

MPA, the active metabolite of mycophenolate, exhibits extensive protein binding (greater than 97%) primarily to albumin. It has a relatively large volume of distribution, indicating widespread distribution in the body, including extravascular tissues.

Metabolism

The metabolism of mycophenolate primarily occurs in the liver. mycophenolate mofetil undergoes rapid and extensive hydrolysis by esterases to form MPA. MPA is then metabolized in the liver via glucuronyl transferase to form the inactive metabolite mycophenolate glucuronide (MPAG).

Excretion and Elimination

Both MPA and MPAG are eliminated primarily via the kidneys. MPA is eliminated as a combination of unchanged drug (6-9%) and glucuronide metabolite (87-94%) in the urine. MPAG is the primary metabolite excreted in the urine, accounting for approximately 75-92% of the administered dose. Only a small fraction of the drug is excreted via the feces.

Adminstartion

Administration: 

Drug can be taken with or without food. However, taking it with food may reduce the likelihood of stomach upset. Swallowing the tablets or capsules whole with a full glass of water is generally recommended.

Patient Information Leaflet

Patient information leaflet

Generic Name: mycophenolate

Why do we use mycophenolate?

Organ Transplantation: mycophenolate is commonly prescribed to transplant recipients to prevent transplanted organ rejection. It is often combined with other immunosuppressive medications, such as corticosteroids and calcineurin inhibitors like tacrolimus or cyclosporine.

Autoimmune Diseases: Drug can be used to treat various autoimmune diseases, including lupus nephritis, systemic lupus erythematosus (SLE), and certain types of vasculitis. It helps suppress the overactive immune response, leading to inflammation and tissue damage.

Dermatological Conditions: Drug may be prescribed to treat certain dermatological conditions, such as severe forms of pemphigus vulgaris and other autoimmune blistering disorders. It helps control the immune response involved in these skin conditions.

Graft-versus-Host Disease (GVHD): GVHD is a potential bone marrow or stem cell transplantation complication. drug can be used as part of the treatment regimen for GVHD to suppress the immune system and reduce the severity of symptoms.

Rheumatological Conditions: Drug may be used as an off-label treatment for rheumatological conditions like rheumatoid arthritis or psoriatic arthritis when other treatments have not been effective. However, its use for these conditions is not as common as other medications like methotrexate or biologic agents.