Index of drugs

The drug is indicated for use in combination with ciclosporin and corticosteroids in the prevention of acute rejection of transplant recipients in allogeneic kidney, heart or liver transplants.

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. Approx. 87% of the administered dose is excreted in the urine in the MPAG form. In the early post-transplant period (<40 days after transplantation) in patients after kidney, heart or liver transplantation, the average AUC for MPA is about 30% lower and the C value is_max about 40% lower compared to the late period after transplantation (3-6 months after transplantation).

Hypersensitivity to mycophenolate mofetil or mycophenolic acid. Breast-feeding.

Patients who are on immunosuppressive therapy are at increased risk of developing lymphomas and other cancers, especially of the skin (the risk of cancer seems more related to the intensity and duration of immunosuppression than with any specific drug) and the risk of opportunistic infections ( opportunistic infections include BK-associated nephropathy and JC-associated progressive multifocal leukoencephalopathy (PML) - these infections are often associated with a high total immunosuppressive burden and can lead to severe or life-threatening conditions that should be considered in differential diagnosis in patients immunosuppressive patients with deteriorating renal function or neurological symptoms). The main recommendation to reduce the risk of skin cancer is to limit the exposure of the skin to sunlight and ultraviolet (UV) by using appropriate protective clothing and sunscreens with a high protection factor. Patients receiving the medicine should be advised to immediately report any signs of infection, unexpected bruising, bleeding or any other signs of bone marrow suppression. Patients receiving mycophenolate mofetil should be monitored for neutropenia (which may be associated with the use of mycophenolate mofetil alone, concomitant therapy, viral infections or due to the coexistence of these factors) and patients should have complete blood counts once a week during the first month, 2 times per month in the 2nd and 3rd month of treatment, then once a month until the end of the first year. In case of neutropenia (absolute neutrophil count <1.3 x 10³/ μI), it may be appropriate to discontinue or discontinue mycophenolate mofetil completely.The use of live attenuated vaccines should be avoided when using the drug. Patients should be advised about the possibility of reduced vaccination efficacy during treatment with mycophenolate mofetil. Vaccination against influenza virus may be preferred; national guidelines for influenza vaccination should be taken into account. Caution should be exercised in patients with active, severe gastrointestinal disease (increased incidence of gastrointestinal adverse events, including uncommon cases of ulceration, bleeding and perforation). Mycophenolate mofetil is an inhibitor of IMPDH (inosinomonophosphate dehydrogenase) - the drug should be avoided in patients with rare, congenital hypoxanthine-guanine-phosphoribosyl transferase (HGPRT) transferase, i.e. in the Lesch-Nyhan or Kelley-Seegmiller syndrome. Patients treated with mycophenolate mofetil in combination with other immunosuppressant agents have experienced cases of selective red cell aplasia (PRCA) (the PRCA mechanism is unknown). Decreased dosages or discontinuation of mycophenolate mofetil therapy may result in resolution of PRCA - changes in mycophenolate therapy can only be introduced by closely monitoring transplant recipients to minimize the risk of transplant rejection. There are insufficient data on the safety and efficacy of the medicine in children under 2 years of kidney transplantation; use in this age group is not recommended. There are no data available on the use of the drug in children after heart and liver transplantation.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 method of treatment is possible. The drug can be used in pregnant women only if the expected benefits of the drug outweigh the potential risk to the fetus. Data on the use of mycophenolate mofetil in pregnant women are limited. However, in children of patients who have been exposed to mycophenolate mofetil in combination with other immunosuppressive drugs during pregnancy, congenital malformations have been reported, including ear defects, e.g. malformed outer and / or middle ear or missing. Cases of spontaneous abortions have been reported in patients taking mycophenolate mofetil. Animal studies have shown reproductive toxicity. Mycophenolate mofetil has been shown to be excreted in the milk of lactating rats. It is not known whether this substance is excreted in human milk. Because of the potential for mycophenolate mofetil to produce serious side effects in breastfed babies, the drug is contraindicated in breast-feeding women. It is recommended that you do not start treatment until you have a negative pregnancy test. Before starting treatment, during treatment and for 6 weeks after its completion, effective contraception should be used.

Very common: sepsis, gastrointestinal candidiasis, urinary tract infection, herpes simplex infection, shingles; vomiting, abdominal pain, diarrhea, nausea; leukopenia, thrombocytopenia, anemia.Common: tachycardia, pancytopenia, leukocytosis, convulsions, increased muscle tone, tremors, drowsiness, myasthenic syndrome, dizziness, headache, paresthesia, taste disorder; pleural effusion, dyspnea, cough; gastrointestinal bleeding, peritonitis, intestinal obstruction, colitis, gastric ulcer, duodenal ulcer, gastritis, esophagitis, stomatitis, constipation, dyspepsia, flatulence, belching; kidney problems; skin hypertrophy, rash, acne, alopecia; arthralgia; acidosis, hyperkalemia, hypokalemia, hyperglycemia, hypomagnesaemia, hypocalcaemia, hypercholesterolemia, hyperlipidemia, hypophosphatemia, hyperuricemia, gout, anorexia; pneumonia, influenza, respiratory tract infection, respiratory moniliaza, gastrointestinal infection, candidiasis, gastroenteritis, infection, bronchitis, pharyngitis, sinusitis, fungal skin infection, skin candidiasis, vaginal candidiasis, rhinitis ; skin cancer, benign skin tumors; hypotension, hypertension, vasodilatation; swelling, fever, chills, pain, malaise, weakness; hepatitis, jaundice, hyperbilirubinaemia; agitation, confusion, depression, anxiety, thinking disorders, insomnia; increased liver enzymes, increased blood creatinine, increased lactate dehydrogenase activity, increased urea, increased alkaline phosphatase, weight loss. In addition, post-marketing has been reported - often: gingival hypertrophy, colitis, including colitis caused by CMV virus, pancreatitis; uncommon: agranulocytosis; frequency unknown: atrophy of the intestinal villi, severe life-threatening infections, including meningitis, endocarditis, tuberculosis and atypical mycobacteria, multifocal leukoencephalopathy (PML) associated with JC virus (sometimes fatal, in cases reported risk factors for PML), BK-associated nephropathy, neutropenia, aplastic anemia, bone marrow suppression (some cases fatal), hypersensitivity reactions (including angioneurotic edema and anaphylactic reactions), selective red cell aplasia (PRCA) and isolated cases of abnormal neutrophil morphology, including the acquired Pelger-Huet anomaly. In children and adolescents, the type and frequency of adverse reactions are similar to those seen in adults, however in the pediatric population, especially in children aged 2-6, diarrhea, sepsis, leukopenia, anemia and infection were more frequently observed in adults than in adults. However, elderly patients may be at increased risk of certain infections (including cytomegalovirus), possibly gastrointestinal bleeding and pulmonary edema, compared to younger patients. 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 1.5 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.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.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. 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 patients with renal transplantation with severe chronic renal failure (glomerular filtration <25 ml / min / 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 of the preparation after transplant cardiac rejection; no pharmacokinetic data are available when rejection of transplanted liver.