Index of drugs

Prophylaxis of acute rejection of transplants in patients who received allogeneic kidney, heart or liver transplantation in combination with ciclosporin and corticosteroids.

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

Mycophenolate mofetil is a 2-morpholinoethyl ester of mycophenolic acid (MPA). MPA is a potent, selective, non-competitive and reversible inhibitor of inosine monophosphate dehydrogenase - inhibits synthesisde novo guanine nucleotides without incorporation into the DNA structure. Due to the fact that the proliferation of T and B lymphocytes is extremely dependent on synthesisde novo Purines, while other cell types may use alternative pathways, the cytostatic action of MPAs on lymphocytes is more potent than other cells. After oral administration, the drug is absorbed quickly and almost completely, and then it is completely metabolized to the active metabolite - MPA. The average oral bioavailability of mycophenolate administered orally based on the MPA AUC is 94% relative to intravenously administered mycophenolate mofetil. MPA in clinically relevant concentrations is 97% bound to plasma albumin. As a result of enterohepatic circulation, after about 6-12 hours after administration of the preparation, the second peak of MPA concentration in the plasma follows. MPA is mainly metabolised by glucuronate transferase to phenolic glucuronide MPA (MPAG), which is not pharmacologically active. 93% of the administered dose is excreted in the urine and 6% in the faeces. The majority (about 87%) of the administered dose is excreted in the urine in the form of MPAG. MPA and MPAG at concentrations found in clinical settings are not served by hemodialysis. 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. Breastfeeding period. The use of the drug is not recommended during pregnancy and should be limited to cases where no other treatment is possible (before the start of treatment, during and up to 6 weeks after discontinuation of the drug effective methods of contraception must be used).

Patients receiving immunosuppressive therapy in the form of combination therapy, including mycophenolate mofetil, are at increased risk of developing lymphomas and other cancers, in particular of the skin - in order to reduce the risk of skin cancer, skin exposure to sunlight and ultraviolet rays should be reduced (UV) by using appropriate protective clothing and sunscreen with a high protection factor. In the event of signs of infection, unexpected bruising, bleeding or any other signs of bone marrow depression, the patient should report to a doctor immediately. Patients treated with immunosuppressants, including mycophenolate mofetil, are at greater risk of developing opportunistic (bacterial, fungal, viral or parasitic) infections, fatal or sepsis-related infections (including BK-associated nephropathy and progressive multifocal leukoencephalopathy (PML) associated with JC virus). The above 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 immunosuppressive patients with deteriorating renal function or neurological symptoms. Patients receiving the medicine should be monitored for neutropenia: full blood counts should be performed once a week during the first month, twice monthly in the 2nd and 3rd month of treatment, and once a month until the end of the first year of treatment . In the case of neutropenia (absolute neutrophil counts <1.3 x 10)³/ μl) it may be appropriate to stop or stop taking the medicine.There have been reports of selective red cell aplasia (PRCA) in patients treated with mycophenolate mofetil in combination with other immunosuppressive agents. PRCA may resolve after dose reduction or discontinuation of mycophenolate mofetil. Changes in the treatment of mycophenolate mofetil should be undertaken carefully observing transplant recipients in order to minimize the risk of rejection of the transplanted organ. During treatment with mycophenolate mofetil, the effectiveness of vaccination may be reduced; the use of live attenuated vaccines should be avoided. Vaccination against influenza virus may be beneficial (national guidelines for influenza vaccination should be taken into account). Due to the risk of gastrointestinal side effects, caution should be exercised in patients with active, severe gastrointestinal disease. Mycophenolate mofetil is an inhibitor of IMPDH (inosinomonophosphate dehydrogenase) - should be avoided in patients with rare, inherited hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency, i.e. in the Lesch-Nyhan or Kelley-Seegmiller syndrome. Do not give mycophenolate mofetil with azathioprine (no studies). Caution should be exercised when mycophenolate mofetil is co-administered with drugs that affect enterohepatic circulation (risk of decreased efficacy of mycophenolate mofetil). The risk / benefit ratio of mycophenolate mofetil in combination with tacrolimus or sirolimus has not been established. Available data on the safety and efficacy of the preparation in children under 2 years are limited - use in this age group is not recommended. There are no data on the use of the drug in children after heart and liver transplantation.

The use of the drug is not recommended during pregnancy and should be limited to cases where no other treatment is possible. It can only be used in pregnant women if the expected benefits outweigh the potential risk to the fetus. In children of patients taking mycophenolate mofetil in combination with other immunosuppressants during pregnancy, congenital malformations, including ear defects have been reported. for example, an abnormal outer ear and / or middle ear or lack thereof. Cases of spontaneous abortions have been reported in patients taking mycophenolate mofetil. It is recommended that you do not start treatment with the preparation until you have a negative pregnancy test result. Before and for up to 6 weeks after treatment with mycophenolate mofetil, effective methods of contraception must be used. The use of the drug is contraindicated during breast-feeding.

Side effects, possibly or possibly associated with mycophenolate mofetil, reported in patients treated with mycophenolate in combination 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 tract infection, candidiasis, gastrointestinal inflammation, 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, thinking disorders, insomnia , convulsions, increased muscle tone, tremor, drowsiness, myasthenic syndrome, dizziness, headache, paresthesia, taste disorder, tachycardia, hypotension, arterial hypertension, vasodilatation, pleural effusion, dyspnea, cough, gastrointestinal bleeding, peritonitis , no spasticity, colitis, gastric ulcer, duodenal ulcer, gastritis, oesophagitis, stomatitis, constipation, dyspepsia, flatulence, belching, hepatitis, jaundice, hyperbilirubinemia, skin hyperplasia, rash, acne, alopecia, joint pain, dysfunction 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.
Additional side effects observed post-marketing: gingival hypertrophy (common), colitis including colitis caused by CMV virus (common), pancreatitis (common) and intestinal villi atrophy. Disorders associated with immunosuppression: severe, life-threatening infections, including meningitis, endocarditis, tuberculosis and infection caused by atypical microorganismsmycobacterium. In patients treated with immunosuppressive therapy, including mycophenolate mofetil, cases of nephropathy associated with BK virus and progressive multifocal leukoencephalopathy (PML) associated with JC virus have been reported. The occurrence of agranulocytosis (uncommon) and neutropenia has been reported during treatment; cases of aplastic anemia and bone marrow depression were also reported, some of them fatal. Blood and lymphatic system disorders: cases of selective red cell aplasia (PRCA) have been reported. In addition, isolated cases of abnormal neutrophil morphology have been observed, including the acquired Pelger-Huet anomaly. These changes were not associated with neutrophil dysfunction. These changes may suggest a "left shift" of the neutrophil maturation line in hematological studies, which may be misinterpreted as a symptom of infection in immunosuppressive patients. Hypersensitivity reactions have been reported, including angioneurotic edema and anaphylactic reactions. Isolated cases of interstitial lung disease and pulmonary fibrosis have been reported in patients treated with mycophenolate in combination with other immunosuppressive drugs, some with death. Patients receiving immunosuppressive therapy in the form of combination therapy, including mycophenolate mofetil, have an increased risk of lymphomas and other malignancies, particularly of the skin. In all transplant patients, there is an increased risk of opportunistic infections, which increases as the total immunosuppressive effect increases (most commonly: yeast infections of the skin and mucous membranes, viraemia and symptomatic cytomegalovirus infection (CMV), virus infectionHerpes simplex; viral load and symptomatic CMV infection occurred in 13.5% of patients). In children and adolescents (2-18 years) who were administered mycophenolate mofetil orally at a dose of 600 mg / m² pc. Twice daily, the type and frequency of adverse reactions were usually similar to those seen in adults taking 1 g of mycophenolate 2 times a day. However, the following side effects were more frequent in children, especially in children under 6 years of age: diarrhea, sepsis, leukopenia, anemia, and infection. Elderly patients (≥ 65 years) are usually at increased risk of adverse reactions due to immunosuppression; in these patients, the risk of certain infections (including organ cytomegalovirus), gastrointestinal bleeding and pulmonary edema may be significantly increased compared to younger patients.

Treatment should be started and continued by appropriately qualified transplantologists. Orally.Use after renal transplantation. Adults: oral administration should be initiated within 72 h after transplantation. The recommended dose is 1g 2 times a day (a daily dose of 2g). Children and adolescents aged 2 to 18: the recommended dose is 600 mg / m² pc. 2 times a day (maximum daily dose is 2 g). The preparation should only be prescribed to patients whose is at least 1.25 m². Patients whose pc is 1.25-1.5 m² the preparation can be prescribed at a dose of 750 mg 2 times a day (a daily dose of 1.5 g). In patients who have pc. above 1.5 m² the dose is 1 g 2 times a day (daily dose 2 g). In this age group, some side effects are more frequent compared to adults, so you may need a temporary dose reduction or discontinuation of the drug; important clinical factors should be taken into account, including the severity of the reaction.Use after heart transplantation. Adults: administration of the drug should be started within the first 5 days after transplantation. The recommended dose is 1.5 g 2 times a day (a daily dose of 3 g).Use after liver transplantation. Adults: intravenous administration of mycophenolate mofetil should be initiated within the first 4 days after liver transplantation, oral drug administration should be started as soon as it can be tolerated. The recommended dose is 1.5 g 2 times a day (a daily dose of 3 g).In elderly patients (≥ 65 years), the recommended dose is 1g 2 times daily in kidney transplant patients and 1.5g twice daily in heart or liver transplant patients. In kidney transplant patients with severe chronic renal failure (glomerular filtration <25 ml / min / 1.73 m²), except for the period directly following kidney transplantation, administration of a dose higher than 1 g 2 times a day should be avoided. These patients should also be carefully observed. In patients who are delayed from taking a transplanted kidney, no dosage adjustment is required. There are no data on heart or liver transplant patients with severe chronic renal failure. There is no need to change the dosage in kidney transplant patients with severe interstitial hepatic injury. There are no data on heart transplant patients with severe interstitial hepatic injury. Use during an episode of acute transplant rejection: rejection of a transplanted kidney does not change the MPA pharmacokinetics; no dose reduction or discontinuation of mycophenolate mofetil is required. There is no reason to modify the dosage of mycophenolate mofetil when discarding a transplanted heart. There are no pharmacokinetic data for rejection of transplanted liver.