the product in the database has an inactive status
indications:
It is used in combination with ciclosporin and corticosteroids in the prevention of acute transplant rejection in patients who have received allogeneic kidney, heart or liver transplants.
An immunosuppressive drug. 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, therefore it 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 absorbed quickly and almost completely, and then completely metabolized to the active metabolite, MPA. Inhibition of acute rejection of a transplanted kidney demonstrates that the immunosuppressive effect of mycophenolate correlates with the concentration of MPA. The average oral bioavailability of mycophenolate mofetil, measured by MPA AUC, is 94% relative to intravenously administered mycophenolate mofetil. Food that is consumed at the same time does not affect the extent of absorption (AUC for MPA) of mycophenolate mofetil, administered at a dose of 1.5 g twice a day in kidney transplant patients. However, the maximum concentration of MPA is reduced by 40% in the presence of food. After oral administration, the concentration of mycophenolate mofetil in plasma can not be determined. MPA in clinically relevant concentrations is 97% bound to plasma albumin. As a result of enterohepatic circulation, after about 6-12 h after administration of the preparation, the second peak of MPA plasma concentration usually occurs. MPA is mainly metabolised by glucuronate transferase to phenolic glucuronide MPA (MPAG), which is not pharmacologically active. Small amounts (<1% of the dose) are excreted as MPA in the urine. After oral administration, 93% of the administered dose was excreted in the urine and 6% in the faeces. The major part (about 87%) of the administered dose is excreted in the urine in the MPAG form. MPA and MPAG at clinical concentrations are not removed by hemodialysis. However, when the concentration of MPAG in the plasma is large (> 100 μg / ml), small amounts of MPAG are removed. In the early post-transplant period (<40 days after transplantation) in patients after kidney, heart or liver transplantation, the mean AUC for MPA is about 30% lower and the C valuemax about 40% lower compared to the late period after transplantation (3-6 months after transplantation).
Contraindications:
Hypersensitivity to mycophenolate mofetil or to mycophenolic acid. The use of the preparation is contraindicated in breastfeeding women. The use of the preparation is not indicated during pregnancy and should be limited to cases where no other type of therapy is possible; during treatment and for 6 weeks after discontinuation of the drug, effective contraception must be used.
Precautions:
Patients receiving immunosuppressive therapy in the form of combination therapy, including mycophenolate, are at increased risk of developing lymphomas and other malignancies, particularly of the skin. The risk of cancer appears to be more related to the intensity and duration of immunosuppression than with the administration of a specific drug. The main recommendation to reduce the risk of skin cancer is to limit skin exposure to sunlight and UV by using protective clothing and sunscreens with a high protection factor. Patients receiving mycophenolate should be instructed to immediately report any signs of infection, unexpected bruising, bleeding or any other manifestation of bone marrow depression. In immunosuppressed patients, including mycophenolate, there was an increased risk of opportunistic infections (bacterial, fungal, viral and parasitic), fatal infections and sepsis.Among opportunistic infections, there is nephropathy associated with BK infection and progressive multifocal leukoencephalopathy (PML) associated with JC virus infection. These infections are often associated with a high total immunosuppressive burden and can lead to severe or life-threatening conditions that the physician should consider in the differential diagnosis of immunosuppressive patients with deteriorating renal function or neurological symptoms. Patients receiving mycophenolate should be monitored for neutropenia, which may be associated with the administration of mycophenolate alone, other medications, viral infections or due to the coexistence of these factors. Patients treated with mycophenolate on the first month should have complete blood counts once a week, twice a month for the 2nd and 3rd month of treatment, and 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 discontinue or discontinue mycophenolate completely. Cases of selective red cell aplasia (PRCA) have been reported in patients treated with mycophenolate in combination with other immunosuppressive agents. PRCA may resolve after dose reduction or discontinuation of mycophenolate therapy. The decision to change the treatment with mycophenolate should be made carefully by observing the recipients of the transplant, in order to minimize the risk of rejection of the transplanted organ. Patients should be advised about the possibility of reduced vaccine efficacy during treatment with mycophenolate and that the use of live attenuated vaccines should be avoided. Vaccination against influenza virus may be beneficial. The doctor should take into account national recommendations for vaccinations against influenza virus. Due to the increased incidence of gastrointestinal adverse events in patients with active, severe gastrointestinal disease, mycophenolate should be used with extreme caution. Mycophenolate is an inhibitor of inosine monophosphate dehydrogenase (IMPDH) - on the basis of theoretical reasons, it should be avoided in patients with rare, inherited hypoxanthine-guanine phosphoribosyltransferase (HPRT) deficiency, ie in the Lesch-Nyhana or Kelley-Seegmiller syndrome. Mycophenolate should not be given concomitantly with azathioprine because no studies have been conducted on the concomitant use of these drugs. Caution should be exercised when mycophenolate is used concomitantly with medications that have an effect on enterohepatic circulation (cholestyramine), as there is a risk of mycophenolate's effectiveness being reduced. The risk / benefit ratios for the combined use of mycophenolate mofetil with tacrolimus or sirolimus have not been established.
Pregnancy and lactation:
Therapy with mycophenolate should be started after a negative pregnancy test result. Before starting treatment with mycophenolate mofetil, effective contraception must be used during treatment and for 6 weeks after discontinuation. The use of mycophenolate is not indicated during pregnancy and should be limited to cases where no other type of therapy is possible. Mycophenolate can be used in pregnant women only if the possible benefits of the preparation outweigh the risks to the fetus. Data on the use of mycophenolate mofetil in pregnant women are limited. However, in children of patients who were exposed to mycophenolate mofetil in combination with other immunosuppressive drugs in the fetal period, congenital malformations, including ear deformities, i.e. an abnormal outer ear and / or middle ear or a lack thereof, were observed. Cases of spontaneous abortions have been reported in patients taking mycophenolate mofetil. Animal studies have shown reproductive toxicity. The preparation is contraindicated in breastfeeding women.
Side effects:
Side effects, probably or probably associated with the administration of 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, improper thinking, insomnia , convulsions, increased muscle tone, tremor, drowsiness, myasthenic syndrome, dizziness, headache, paresthesia, taste disorder, increased heart rate, hypotension, arterial hypertension, vasodilatation, pleural effusion, dyspnea, cough, gastrointestinal bleeding, behind peritonitis, obstruction, colitis, gastric ulcer, duodenal ulcer, gastritis, oesophagitis, stomatitis, constipation, dyspepsia, bloating, belching, hepatitis, jaundice, hyperbilirubinemia, skin hyperplasia, rash, acne, alopecia, joint pain , renal dysfunction, edema, fever, chills, pain, malaise, weakness, increased liver enzymes, increased blood creatinine, increased blood lactate dehydrogenase, increased blood urea, increased alkaline phosphatase in the blood, reduced body weight. 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 and progressive multifocal leukoencephalopathy 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 patients treated with mycophenolate. 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. Single cases of interstitial lung disease and pulmonary fibrosis have been reported in patients treated with mycophenolate in combination with other immunosuppressive agents; some ended with death. Patients receiving immunosuppressive therapy in the form of combination therapy, including mycophenolate, are at increased risk of lymphomas and other malignancies, particularly of the skin. Lymphoproliferative disease or lymphoma developed in 0.6% of patients receiving mycophenolate (2 g or 3 g per day) in combination with other immunosuppressants, in controlled clinical trials after renal transplantation (data on 2 g), after a heart or liver transplant, at least 1 year. Skin cancers other than melanoma were diagnosed in 3.6% of patients, other cancers in 1.1% of patients. 3-year safety data in patients after kidney or heart transplantation do not show unexpected changes in the incidence of tumors compared to one-year results. Patients after liver transplantation were observed for at least 1 year but less than 3 years. In all patients after transplantation there is an increased risk of opportunistic infections, which increases as the total immunosuppressive effect increases.In controlled clinical trials in kidney transplant patients (2g dose data), heart and liver, mycophenolate (2g or 3g daily) in combination with other immunosuppressants, during at least one-year follow-up, the most common opportunistic infections were : yeast infections of the skin and mucous membranes, viraemia and symptomatic cytomegalovirus infection (CMV), virus infectionHerpes simplex. Wiremia 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, compared to adults: diarrhea, sepsis, leukopenia, anemia, and infection. Elderly patients (≥ 65 years) are usually at increased risk of adverse reactions due to immunosuppression. In elderly patients in whom mycophenolate is a component of combination immunosuppressive therapy, the risk of certain infections (including the organ form of CMV infection), gastrointestinal bleeding and pulmonary edema may be significantly increased compared to younger patients.
Dosage:
Treatment with mycophenolate should be started and continued by transplantologists with appropriate clinical experience.Use after renal transplantation. Adults: oral mycophenolate should be initiated within 72 h after transplantation. The dose recommended in kidney transplant patients is 1g 2 times a day (a daily dose of 2g). Children and adolescents (from 2 to 18 years of age): the recommended dose of mycophenolate mofetil is 600 mg / m2 pc. orally 2 times a day (up to 2 g daily). Mycophenolate mofetil capsules should only be prescribed to patients who have 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). Mycophenolate mofetil tablets should only be prescribed to patients who have is above 1.5 m2 pc at a dose of 1 g 2 times daily (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 medicine; important clinical factors should be taken into account, including the severity of the reaction. Available data on the safety and efficacy of the preparation in children under 2 years of age are limited; data are insufficient to determine the recommended dosage, therefore use in this age group is not recommended.Use after heart transplantation. Adults: administration of mycophenolate should be started within the first 5 days after transplantation. The recommended dose is 1.5 g 2 times a day (daily dose 3 g). No data on children after heart transplantation.Use after liver transplantation. Adults: intravenous mycophenolate mofetil should be initiated within the first 4 days after hepatic transplantation, oral mycophenolate should be initiated as soon as it can be tolerated. The recommended oral dose is 1.5 g 2 times a day (a daily dose of 3 g). No data on children after liver transplantation. In elderly patients, 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.