Prophylaxis of acute rejection of transplants in recipients of allogeneic renal, cardiac or liver transplants in combination with ciclosporin and corticosteroids.
Composition:
1 capsule contains 250 mg mycophenolate mofetil. 1 tabl powl. contains 500 mg mycophenolate mofetil. 5 ml of the reconstituted suspension contains 1 g of mycophenolate mofetil; the suspension contains aspartame and sorbitol.
Action:
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. 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 - that is why MPA exerts a stronger cytostatic effect on lymphocytes than on other cells. After oral administration, mycophenolate mofetil is absorbed quickly and almost completely (bioavailability of about 94%), and then it is completely metabolized to the active metabolite - MPA. The immunosuppressive action of the drug is correlated with the concentration of MPA. As a result of entero-hepatic circulation, after about 6-12 hours after the drug is usually the second highest concentration of MPA in the blood. MPA binds to plasma albumin 97%. MPA is mainly metabolised by means of glucuronyl transferase into inactive phenolic glucuronide MPA (MPAG). Excretion occurs in the urine (93%) - mainly in the form of MPAG; partly with faeces (6%).
Contraindications:
Hypersensitivity to mycophenolate mofetil or mycophenolic acid or other ingredients. Breastfeeding period.
Precautions:
In order to reduce the risk of skin cancer in patients using combination immunosuppressive therapy, including mycophenolate mofetil, the skin should be protected from sunlight and UV, use protective clothing and sun protection with a high protection factor. Patients should be advised to immediately report any signs of infection, unexpected bruising, bleeding or any other manifestation of bone marrow depression. In immunosuppressive patients with deteriorating renal function or neurological symptoms, differential diagnosis should include BK associated nephropathy and progressive multidose leukoencephalopathy associated with JC virus. Patients receiving mycophenolate mofetil who develop recurrent infections should be measured for immunoglobulin levels, as reports of hypogammaglobulinemia associated with recurrent infections have been reported in patients taking the medicine in combination with other immunosuppressive drugs (in some of these cases, change of mycophenolate mofetil to another alternative drug immunosuppressant resulted in normalization of IgG values). In cases of persistent clinically significant hypogammaglobulinemia, appropriate clinical management should be considered, taking into account the strong cytostatic effect of mycophenolic acid on T and B cells. Due to the risk of bronchiectasis or interstitial lung disease and pulmonary fibrosis, it is recommended that patients with lung symptoms will develop, such as cough and shortness of breath (in some of these cases, switching to another alternative immunosuppressive drug resulted in an improvement in respiratory symptoms). Patients should be monitored for neutropenia, which may be associated with the administration of mycophenolate mofetil, concomitant therapy, viral infections or due to the coexistence of these factors. Complete blood counts should be performed: 1 time / wk. in the first month of treatment; 2 times / month in the 2nd and 3rd months of treatment; and then once / month until the end of the first year of treatment. If neutropenia (absolute neutrophil count <1.3 x 10) occurs3/ ml), it may be appropriate to discontinue or discontinue mycophenolate mofetil completely.Due to the risk of selective red cell aplasia (PRCA) in patients treated with mycophenolate mofetil in combination with other immunosuppressant agents, a dose reduction or discontinuation of therapy may be necessary; changes in treatment can only be made while maintaining proper care over recipients to minimize the risk of transplant rejection. The drug should be used with extreme caution in patients with active, serious gastrointestinal disease process (increased risk of ulceration, bleeding and perforation). Avoid use in patients with rare, congenital hypoxanthine-guanine-phosphoribosyl transferase (HGPRT) transferase, i.e. in the Lesch-Nyhana or Kelley-Seegmiller syndrome (mycophenolate mofetil is an IMPDH inhibitor of inosine monophosphate dehydrogenase). There are no data on the use of the drug in children after heart or liver transplantation. Limited data are available on the safety and efficacy of the medicine in children <2 years after kidney transplantation; data are insufficient to determine the recommended dosage, therefore the use of the drug in this age group is not recommended. The suspension contains aspartame - be cautious in patients with phenylketonuria; also contains sorbitol - do not use the suspension in patients with rare hereditary metabolic disorders with fructose intolerance.
Pregnancy and lactation:
The use of the drug in pregnancy is not recommended and should be limited to cases where no other type of therapy is possible and when the potential benefits of the drug outweigh the risk to the fetus (there is a risk of spontaneous abortions and congenital malformations, including the ears - eg incorrectly an outer / middle ear formed or missing, if the fetus is exposedin utero for combined immunosuppressive therapy, including mycophenolate mofetil). The use of the drug should be started after receiving a negative pregnancy test result. Before starting treatment, during treatment and for 6 weeks after discontinuation of the drug should use effective contraception. The use of the drug during breastfeeding is contraindicated, due to the possibility of serious side effects in fed infants.
Side effects:
The most important adverse reactions occurring in combination with ciclosporin and corticosteroids include diarrhea, leukopenia, sepsis and vomiting, and more frequent occurrence of infections, especially opportunistic infections (infection of the skin and mucous membranes).Candida spp., viraemia, symptomatic CMV infection, virus infectionHerpes simplex). There is also an increased risk of lymphomas and other cancers, especially of the skin. The following side effects are likely or possibly related to drug administration in patients with kidney, heart or liver transplantation treated with mycophenolate mofetil in combination with ciclosporin and corticosteroids. 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, inflammation of the gastrointestinal tract, infections, 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 disorders, increased heart rate, hypotension, hypertension, vasodilatation, pleural effusion, dyspnea, cough, gastrointestinal bleeding, peritonitis , not really incidence, colitis, gastric ulcer, duodenal ulcer, gastritis, oesophagitis, stomatitis, constipation, dyspepsia, flatulence, belching, hepatitis, jaundice, hyperbilirubinemia, skin hyperplasia, rash, acne, alopecia, joint pain, renal failure , 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.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 following side effects have been reported after marketing: gingival hyperplasia, colitis (including CMV-induced), pancreatitis, intestinal villi atrophy, severe life-threatening infections (meningitis, endocarditis, tuberculosis, atypical infection)mycobacterium), BK-associated nephropathy, progressive multifocal leukoencephalopathy associated with JC virus, agranulocytosis, neutropenia, aplastic anemia and bone marrow suppression (including fatal), selective red cell aplasia (PRCA), abnormal neutrophil morphology (including acquired Pelger's anomaly) Hueta), hypersensitivity reactions (including angioneurotic edema and anaphylactic reactions). Hypogammaglobulinemia (frequency unknown), pulmonary distension in children and adults (frequency not known), as well as isolated cases of interstitial lung disease and pulmonary fibrosis (some with fatal outcome) have also been reported.
Dosage:
Orally. Treatment should be started and continued by physicians experienced in the management of patients after organ transplantation.Kidney transplantation. Adults: administration of the drug should be started within 72 hours after transplantation. The recommended dose is 1g 2 times a day (2g / day).Children and adolescents (aged 2-18 years): 600 mg / m2 pc. 2 times a day (up to 2 g / day). The medicine in capsules or tablets should only be prescribed to patients with a body surface area of at least 1.25 m2. Patients whose body surface area is from 1.25 to 1.5 m2 may be prescribed at a dose of 750 mg 2 times a day (1.5 g / day). Patients who have a surface area> 1.5 m2 may be prescribed medicine in capsules or tablets at a dose of 1g 2 times a day. 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 response.Children <2 years: limited data, do not use.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 (3 g / day).Children: no data.Liver transplantation. Adults: intravenous infusion should be started within the first 4 days after transplantation, oral administration should be started as soon as it can be tolerated. The recommended oral dose is 1.5 g 2 times a day (3 g / day).Children: no data.Special groups of patients. Elderly patients (≥65 years). Use the usual dose, i.e. 1g twice daily, in kidney transplant patients and 1.5g twice daily in heart or liver transplant patients.Patients with renal insufficiency. In renal transplant patients with severe chronic renal failure (GFR <25 ml / min / 1.73 m2), apart from the period immediately following renal transplantation, doses higher than 1 g 2 times a day should be avoided; these patients should be carefully observed. In patients who are delayed by the transplanted organ, no dose adjustment is required. There are no data on heart or liver transplant patients with severe chronic renal failure.Patients with severe hepatic impairment. There is no need to change the dose in patients after kidney transplantation with severe damage to the liver parenchyma. There are no data on heart transplant patients with severe damage to the liver parenchyma.Use during an episode of acute transplant rejection. MPA (mycophenolic acid) is the active metabolite of mycophenolate mofetil. Rejection of a transplanted kidney does not lead to changes in the MPA pharmacokinetics; no dose reduction or discontinuation is required. There is no basis for modifying the dose of the drug after the occurrence of rejection of the transplanted heart.There are no data on pharmacokinetics when rejection of transplanted liver.Way of giving. If desired, the oral suspension can be administered via a naso-gastric tube of at least 8 French (internal diameter of at least 1.7 mm).
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