Selsept, 250 mg capsules 100 pcs

Mycophenolate Mofetil (MMF) is a 2-morpholinoethyl ester of mycophenolic acid (MPA), an immunosuppressant, an inosine monophosphate dehydrogenase inhibitor. MMF is a potent, selective noncompetitive and reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH) that inhibits the de novo synthesis of guanosine nucleotides. The mechanism by which MFC suppresses the enzymatic activity of IMPDH appears to be related to the fact that MFC structurally mimics both the nicotinamide dinucleotide phosphate cofactor and the catalyzing water molecule. This prevents the oxidation of IMF into xanthose-5-monophosphate, a crucial step in guanosine nucleotide biosynthesis de novo. MMF has a more pronounced cytostatic effect on lymphocytes than on other cells, since the proliferation of T- and B-lymphocytes is very much dependent on the synthesis of purines de novo, while cells of other types can switch to bypass metabolic pathways.

Indications

Adults and children with body surface area >1.25 m2 (approximate age 12 years):

prevention of acute graft rejection in patients after allogeneic kidney transplantation.

For adults:

treatment of first or treatment-refractory graft rejection in patients after allogeneic kidney transplantation;
prevention of acute graft rejection and improvement of graft survival and survival of patients after allogeneic heart transplantation;
prevention of acute graft rejection in patients after allogeneic liver transplantation.

Cellcept is prescribed as a combination therapy with cyclosporine and corticosteroids.

Pharmacological effect

The immunosuppressant, inosine monophosphate dehydrogenase inhibitor – mycophenolate mofetil (MMF) is a 2-morpholinoethyl ester of mycophenolic acid (MPA). MPA is a potent, selective, noncompetitive and reversible inhibitor of inosine monophosphate dehydrogenase (IMPDH) that inhibits de novo synthesis of guanosine nucleotides. The mechanism by which MPA inhibits the enzyme activity of IMPDH appears to be due to the fact that MPA structurally mimics both the nicotinamide dinucleotide phosphate cofactor and the catalyzing water molecule. This prevents the oxidation of IMP to xanthose-5-monophosphate, a critical step in the de novo biosynthesis of guanosine nucleotides. MPA has a more pronounced cytostatic effect on lymphocytes than on other cells, since the proliferation of T and B lymphocytes is very dependent on de novo purine synthesis, while other types of cells can switch to bypass metabolic pathways.

Special instructions

As with combined immunosuppression in general, and when MMF is prescribed as a component of an immunosuppressive regimen, there is an increased risk of developing lymphomas and other malignant neoplasms, especially of the skin. This risk does not appear to be related to the use of any drug per se, but to the intensity and duration of immunosuppression.
As with all patients at increased risk of skin cancer, exposure to sunlight and ultraviolet rays should be limited by wearing appropriate, covered clothing and using sunscreens with a high protection factor.
Patients receiving MMF should be instructed to promptly report any signs of infection, bleeding, hemorrhage, or other signs of bone marrow suppression to their physician.

Active ingredient

Mycophenolate mofetil

Composition

1 caps:

Pregnancy

Category D drug (according to FDA classification – U.S. Food and Drug Administration).

Contraindications

Increased individual sensitivity to MMF, MPA and other components of the drug;
hypoxanthine guanine phosphoribosyltransferase deficiency;
concomitant use with azathioprine.

With caution: gastrointestinal diseases (in the acute phase), simultaneous use of MMF with tacrolimus, sirolimus, with drugs that affect hepatic-intestinal recirculation.

Side Effects

The side effect profile associated with the use of immunosuppressive drugs is often difficult to determine due to the presence of an underlying disease and the concomitant use of many other drugs.

Interaction

Acyclovir. With the simultaneous use of MMF and acyclovir, higher plasma concentrations of MMF and acyclovir were observed than when each drug was administered separately. Since plasma concentrations of MPAG, like acyclovir, are increased in renal failure, there is a possibility that the two drugs compete for tubular secretion, which could lead to further increases in the concentrations of both drugs.

Overdose

Data on overdose of MMF have been obtained from clinical studies and post-marketing use. In most cases, no data on adverse events were recorded. In case of overdose, no adverse effects in addition to those described below were identified.

It is expected that overdose of MMF is likely to lead to excessive immunosuppression (consequently increased susceptibility to infections) and bone marrow suppression. If neutropenia develops, CellCept should be discontinued or the dose reduced. MPA cannot be removed from the body by hemodialysis. However, at high plasma concentrations of MPAG (>100 μg/ml), small amounts are still excreted. Bile acid binders, such as cholestyramine, may help eliminate MPA from the body by increasing its excretion.

Storage conditions

The drug should be stored at a temperature not exceeding 30°C in a dry place, protected from light, out of the reach of children.

Shelf life

3 years

Manufacturer

Delfarm Milano S.r.L./Hoffmann la Roche, Italy