Index of drugs

Prophylaxis of acute rejection of transplants in recipients of allogeneic renal, cardiac or liver transplants in combination with ciclosporin and corticosteroids.

1 capsule contains 250 mg mycophenolate mofetil. 1 tabl powl. contains 500 mg mycophenolate mofetil.

Immunosuppressant - 2-morpholinoethyl ester of mycophenolic acid (MPA). MPA is a potent, selective, non-competitive and reversible inhibitor of inosine monophosphate dehydrogenase and thus inhibits synthesisde novo guanine nucleotides without incorporation into the DNA structure. Proliferation of T and B lymphocytes is strongly dependent on purine synthesisde novowhile other types of cells have alternative synthetic routes. Therefore, MPA exerts a stronger cytostatic effect on lymphocytes than on other cells. After oral administration, mycophenolate mofetil is rapidly and almost completely absorbed, and is then completely metabolised to the active metabolite mycophenolic acid (MPA). The average oral bioavailability of mycophenolate mofetil, measured by MPA AUC, is 94% relative to intravenously administered mycophenolate mofetil. Food does not affect the absorption of mycophenolate mofetil, however, the maximum concentration of MPA is reduced by 40% in the presence of food. MPA binds to plasma proteins 97%. As a result of enterohepatic circulation, after 6-12 hours after administration of the drug, the maximum concentration of MPA in the blood is usually the second time. MPA is mainly metabolised by glucuronyl transferase to mycophenolic acid phenolic glucuronide (MPAG), which has no pharmacological activity. 93% of the dose is excreted in the urine and 6% in the faeces. About 87% of the administered dose is excreted in the urine in the MPAG form.

Hypersensitivity to mycophenolate mofetil, mycophenolic acid or other ingredients of the preparation. Breast-feeding.

During treatment, there is an increased risk of developing lymphomas and other cancers, especially of the skin (the risk of cancer seems to be more related to the intensity and duration of treatment than with drug administration) and the risk of opportunistic (bacterial, fungal, viral and parasitic) infections, fatal infections and sepsis. Patients should be advised to immediately report any signs of infection, unexpected bruising, bleeding or any other manifestation of bone marrow depression. In immunosuppressed patients, including mycophenolate mofetil, there was an increased risk of opportunistic infections (bacterial, fungal, viral and parasitic), fatal infections and sepsis. These infections include reactivation of latent viral infections, such as reactivation of hepatitis B or C, and polyomavirus-induced infections (BK-associated nephropathy, progressive multifocal PML leukoencephalopathy associated with JC virus). Hepatitis B or C reactivation events have been reported in carriers of patients treated with immunosuppressive drugs. The above-mentioned infections are often associated with a high total immunosuppressive load and can lead to serious or life-threatening conditions that the physician should consider in differential diagnosis in immunosuppressive patients, who have worsening kidney function or neurological symptoms. Patients should be monitored for neutropenia, which may be associated with drug administration, concomitant medication, viral infections or due to the coexistence of these factors. The first month should be performed full blood counts once a week, in the second and third month - twice a month, and then once a month until the end of the first year of treatment. If neutropenia (absolute neutrophil count <1.3 x 10) occurs³/ μl), it may be appropriate to stop or discontinue the drug completely. Combinations of red blood cell aplasia (PRCA) have been reported during combination therapy with other immunosuppressive drugs - dose reduction or discontinuation of treatment with PRCA may result in PRCA resolution, care should be taken when administering the transplant recipients to reduce the risk of transplant rejection. Special care should be taken in patients with active, serious gastrointestinal disease process.It should be avoided in patients with rare, congenital hypoxanthine-guanine-phosphoribosyl transferase (HGPRT) transferase, i.e. in the Lesch-Nyhan or Kelley-Seegmiller syndrome.Kom. free. from 12/12/2014. Hypogammaglobulinemia associated with recurrent infections has been observed in patients taking mycophenolate mofetil in combination with other immunosuppressive agents. Patients with recurrent infections should have serum immunoglobulin levels measured. In the case of persistent, clinically significant hypogammaglobulinemia, appropriate clinical management should be considered. In some of the observed cases, replacement of mycophenolate with an alternative immunosuppressant resulted in a return of serum IgG to normal values. There have been reports on the occurrence of bronchiectasis in patients taking mycophenolate mofetil in combination with other immunosuppressive drugs. Immediate testing should be performed in patients who have developed persistent lung symptoms such as coughing or shortness of breath. In some confirmed cases of bronchiectasis, replacement of mycophenolate with another immunosuppressant resulted in regression of respiratory symptoms. In addition to the occurrence of bronchiectasis, isolated cases of interstitial lung disease were also found, sometimes with fatal consequences. Therefore, clinicians are advised to consider the possibility of these diseases as part of differential diagnosis in patients with persistent lung symptoms.

The use of the drug is not recommended during pregnancy and should be limited to cases where no other type of therapy is possible. It can only be used during pregnancy if the potential benefits of the medicine outweigh the potential risks to the fetus. Cases of congenital malformations have been reported, including hearing defects in children of patients who have used mycophenolate mofetil during pregnancy with other immunosuppressant drugs. Before starting treatment, during treatment and for 6 weeks after the end of therapy, effective contraception should be used. Use while breastfeeding is contraindicated.

The most important adverse reactions occurring in combination with ciclosporin and corticosteroids include diarrhea, leukopenia, sepsis and vomiting. There was also a higher incidence of infections, especially opportunistic infections (most commonly skin and mucous membrane infections)Candida, viraemia and symptomatic CMV infection, virus infectionHerpes simplex). There is also an increased risk of lymphomas and other cancers, especially of the skin. The side effects are likely or possibly related to drug administration in patients treated with mycophenolate mofetil with ciclosporin and corticosteroids, after kidney, heart or liver transplantation. Very common: sepsis, gastrointestinal candidiasis, urinary tract infection, herpes simplex virus infection, herpes zoster, leukopenia, thrombocytopenia, anemia, vomiting, abdominal pain, diarrhea, nausea. Common: pneumonia, influenza, respiratory tract infection, respiratory monilia, gastrointestinal infection, candidiasis, inflammation of the gastrointestinal tract, infection, bronchitis, pharyngitis, sinusitis, fungal skin infection, skin candidiasis, vaginal candidiasis, rhinitis , skin cancer, benign skin tumors, pancytopenia, leukocytosis, acidosis, hyperkalemia, hypokalemia, hyperglycemia, hypomagnesaemia, hypocalcemia, hypercholesterolemia, hyperlipidemia, hypophosphatemia, hyperuricemia, gout, anorexia, agitation, confusion, depression, anxiety, improper thinking, insomnia , convulsions, increased muscle tone, tremor, drowsiness, myasthenic syndrome, headache and dizziness, paresthesia, dysgeusia, cardiac acceleration, hypotension, hypertension, vasodilatation, pleural effusion, dyspnea, cough, gastrointestinal bleeding, peritonitis, niedrożnoś gastrointestinal tract, colitis, gastric ulcer, duodenal ulcer, gastritis, oesophagitis, stomatitis, constipation, dyspepsia, flatulence, belching, hepatitis, jaundice, hyperbilirubinemia, skin hyperplasia, rash, acne, alopecia, joint pain, insufficiency kidney, swelling, fever, chills, pain, malaise, weakness, increased liver enzymes, increased blood creatinine, increased blood lactate dehydrogenase, increased blood urea, increased alkaline phosphatase in the blood, weight loss.The following have also been reported during post-marketing experience: Gingival hyperplasia, colitis (including CMV-induced), pancreatitis, intestinal villi atrophy, severe life-threatening infections, such as meningitis, endocarditis, tuberculosis, infection atypicalmycobacterium, BF-associated nephropathy, progressive multifocal leukoencephalopathy (PML), sometimes fatal, agranulocytosis, neutropenia, aplastic anemia and bone marrow suppression, sometimes with fatal outcome, hypersensitivity reactions (including angioneurotic edema and anaphylactic reactions). In addition, cases of selective red cell aplasia, abnormal neutrophil morphology, including acquired Pelger-Huet anomaly, cases of interstitial lung disease and pulmonary fibrosis, including fatal cases, have been reported. In children of patients who used mycophenolate mofetil during concomitant administration with other immunosuppressants, cases of congenital malformations, including hearing defects, have been reported. In children and adolescents aged 2-18 years, the type and frequency of adverse drug reactions were generally similar to those observed in adult patients with the exception of diarrhea, sepsis, leukopenia, anemia, and infections that occurred more frequently in pediatric patients. In elderly patients, compared to younger patients, there may be a significantly increased risk of certain infections (including the organ form of CMV infection), gastrointestinal bleeding and pulmonary edema. The review of case reports and published studies showed that mycophenolate mofetil in combination with other immunosuppressive drugs may cause hypogammaglobulinemia and bronchiectasis (Comp.No. Of 12.12.2014).

Treatment with the preparation should be started and continued by specialists in the field of transplantation.
Orally.After kidney transplantation. The preparation should be started within 72 hours after transplantation. Adults: the recommended dose is 1g 2 times a day. Children and adolescents aged 2-18: the recommended dose is 600 mg / m² pc. 2 times a day, up to 2 g a day. The preparation should only be prescribed to patients with a body surface area of ​​at least 1.25 m². Patients whose body surface area is 1.25-1.5 m² they can be prescribed at a dose of 750 mg twice daily; patients whose body surface area is above 1.5 m² may be prescribed at a dose of 1g 2 times a day. In this age group, a temporary dose reduction or discontinuation of the drug may be needed compared to adults due to the increased incidence of certain adverse reactions. There are insufficient data on the safety and efficacy of the medicine in children under the age of 2 years. Data are insufficient to determine the dosage, therefore the use of the drug in this age group is not recommended.After heart transplantation. Administration of the preparation should begin within the first 5 days after transplantation. Adults: the recommended dose is 1.5 g 2 times a day. Children: no data available.After liver transplantation. The intravenous formulation should be administered within the first 4 days after hepatic transplantation, oral administration should be started as soon as it can be tolerated. Adults: the recommended dose is 1.5 g 2 times a day. Children: no data available.
Elderly patients do not need to modify their dosage. There is no need to change the dose in patients after kidney transplantation with severe hepatic injury; there is no data on heart transplant patients with severe liver damage. In renal transplant patients with severe chronic renal failure (glomerular filtration <25 ml / min x 1.73 m²), with the exception of the time immediately following renal transplantation, administration of a dose higher than 1 g twice daily should be avoided; in patients who are delayed by the transplanted organ, no dose adjustment is necessary; there is no data on heart or liver transplant patients with severe chronic renal failure. There is no reason to modify the dose after rejection of a transplanted kidney or heart; no pharmacokinetic data are available when rejection of transplanted liver.