Composition, form of production and packaging
The tablets covered with a film shell of pale lilac color, with engraving "CellCept 500" on one side and "Roche" - on the other.
1 tab.
mycophenolate mofetil 500 mg
[PRING] microcrystalline cellulose - 244 mg, croscarmellose sodium - 32.5 mg, povidone K90 - 24.4 mg, magnesium stearate - 12.2 mg.
Sheath composition: Opadry Lavender Y-5-10272-A (hypromellose, giprolose, titanium dioxide (E171), macrogol 400, indigo carmine dye (E132), iron oxide red (E172)) - 24 mg.
10 pieces. - blisters (5) - packs of cardboard.
Capsules hard gelatin, size 1, with an opaque brown casing and an opaque blue lid; on the body of the inscription "Roche" black, on the lid - "CellCept 250"; the contents of the capsules - a fine granular powder, partially crumpled, from white to almost white.
1 caps.
mycophenolate mofetil 250 mg
[PRING] corn pregelatinized starch - 29.76 mg, croscarmellose sodium - 11.9 mg, povidone K90 - 5.95 mg, magnesium stearate - 4.5 mg.
The composition of the capsule body: gelatin, titanium dioxide (E171), iron oxide red (E172), iron oxide yellow (E172).
Composition of capsule capsule: gelatin, titanium dioxide (E171), dye indigo carmine (E132).
Ink composition: shellac, iron oxide black oxide (E172), potassium hydroxide.
10 pieces. - blisters (10) - packs of cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2011.
PHARMACHOLOGIC EFFECT
Immunosuppressant, inhibitor of inosine monophosphate dehydrogenase - mycophenolate mofetil (MMF) is a 2-morpholinoethyl ester of mycophenolic acid (MPA).IFC is a potent selective noncompetitive and reversible inhibitor of inosine monophosphate dehydrogenase (IMPHG), which suppresses the synthesis of guanosine nucleotides de novo. The mechanism by which IFC suppresses the enzymatic activity of IMPDG appears to be due to the fact that IFC structurally imitates both the cofactor of nicotinamide dinucleotide phosphate and the catalyzing water molecule. This prevents the oxidation of IMP in xanthose-5-monophosphate - the most important stage of the biosynthesis of guanosine nucleotides de novo. IFC has a more pronounced cytostatic effect on lymphocytes than on other cells, since the proliferation of T and B lymphocytes depends very strongly on purine de novo synthesis, while other types of cells can switch to metabolic bypasses.
Efficiency
In clinical studies on the prevention of rejection after kidney, heart and liver transplants, Sellsept was administered in combination with the following drugs: immunoglobulin antitimocytic, OKT3 (orthoclone of mouse monoclonal antibodies), cyclosporine and corticosteroids. In addition, Sellsept was administered in combination with cyclosporine and corticosteroids to treat refractory rejection of the transplanted kidney. Before the start of Selsept, patients could also receive immunoglobulin antithymocyte, antilymphocytic globulin and OKT3. Later, Sellsept was used in clinical studies with daclizumab and tacrolimus.
Prevention of transplant rejection
The safety and efficacy of Sellsept in combination with corticosteroids and cyclosporine were evaluated in three randomized, double-blind, multicenter studies in adults after kidney transplantation, in one randomized, double-blind, multicentre study in patients after heart transplantation and in one randomized, double-blind, multicenter study in patients after liver transplantation.
Safety, pharmacokinetics and efficacy of Sellsept in combination with corticosteroids and cyclosporine in children after kidney transplantation were evaluated in an open, multicentre study with the participation of 100 children aged 3 months to 18 years.
Kidney Transplantation
In adults in combination with corticosteroids and cyclosporine, Selsept statistically significantly reduced the incidence of ineffective therapy during the first 6 months after transplantation and histologically proven rejection during therapy, at a dose of 2 g / day reduces the cumulative rate of graft death and mortality in 12 months after kidney transplantation, but at a dose of 3 g / day increases the frequency of premature dropout from the study for any reason.
In children (3 months to 18 years) in an open study of Sellsept (powder for suspension) with the participation of children after kidney transplantation in all age groups, reception of Sellsept was carried out in doses of 600 mg / m 2 twice a day (up to 1 g twice daily).
The frequency of histologically proven rejection was similar in different age groups (from 3 months to <6 years, from 6 years to <12 years, from 12 years to 18 years). The overall incidence of histologically proven rejection at 6 months post-transplantation period was comparable to that in adults. The total frequency of graft death (5%) and mortality (2%) for 12 months after transplantation was comparable with the values ​​observed in adults who underwent kidney transplantation.
Heart transplantation
Rejection. There were no differences in the frequency of histologically proven rejection leading to a disturbance of hemodynamics in the groups Cellsept and azathioprine.
Survival. In terms of mortality and repeated transplantations in cardiac transplantation, MMP is superior to azathioprine.
Liver transplantation
In the initial-intention-to-treat study of all included patients, Sellsept in combination with corticosteroids and cyclosporine was more effective than azathioprine, preventing acute rejection (p = 0.025) and providing the same survival as azathioprine.
Treatment of refractory rejection of transplants
MMP therapy reduced the rate of graft death or deaths 6 months after initiation of therapy by 45% (p = 0.062) in patients who underwent kidney transplantation with refractory to acute, cell-mediated rejection of the graft.
Preclinical safety data
In doses 2-3 times higher than therapeutic ones during kidney transplantation and 1.3-2 times compared to those in patients after heart transplantation, MMP did not stimulate the formation of tumors and did not affect the fertility of male rats. Two genotoxicity tests (determination of thymidine kinase in murine lymphoma cells and a test with mouse micronuclei) indicated that at doses that have a serious toxic effect, MMF is potentially capable of causing chromosomal instability. In other genotoxicity tests (bacterial mutation test, mitotic yeast gene conversion test or chromosome aberration test in Chinese hamster ovary cells), the presence of mutagenic activity in the preparation was not revealed.
In experiments on the fertility and reproductive efficiency of female rats, oral administration of the drug at a dose 0.5 times greater than the systemic dose of 2 g / day after kidney transplantation and approximately 0.3 times the systemic effect of a clinical dose of 3 g / day recommended after heart transplantation caused malformations development (including anophthalmia, agnathy and hydrocephalus) in the first generation of offspring without any toxic effect on the mother. In subsequent generations of offspring, there were no effects on fertility and reproductive performance.
In studies of teratogenicity in rats treated with a systemic dose of approximately 0.5 times the dose of 2 g / day recommended for patients after kidney transplantation and approximately 0.3 times the systemic exposure to a dose of 3 g / day recommended by the patient after transplantation heart, there was a resorption of the fetuses and congenital malformations in the offspring (including anophthalmia, agnathy and hydrocephalus in rats and malformations of the cardiovascular system, kidneys, ectopia of the heart and kidneys, diaphragmatic and umbilical hernias in the offspring of rabbits) without signs of toxic effects on the mother.
In toxicological studies of MMFN animals, the main lesions were localized in the hematopoietic and lymphoid organs and occurred at a level of system exposure of the drug that is equivalent to or less than the exposure level when taking a clinical dose of 2 g / day recommended by patients after kidney transplantation. The profile of nonclinical toxicity of MMPs falls with undesirable phenomena noted in clinical studies in humans, which allowed obtaining safety data more significant for the patient population.
PHARMACOKINETICS
Pharmacokinetic characteristics of MMP were studied in patients who underwent kidney, heart and liver transplantation. In general, the pharmacokinetic profile of IFC is the same in patients after kidney and heart transplantation. In the early posttransplant period, patients who underwent liver transplant and received MMP at a dose of 1.5 g, the concentrations of MPC are the same as in patients after kidney transplant receiving MMF at a dose of 1 g.
Suction
After oral administration, there is a rapid and complete absorption and complete presystemic metabolism of MMPs with the formation of an active metabolite - MPA.Bioavailability of MMF on oral intake, in accordance with the value of AUC IFC, is, on average, 94% of that with its intravenous administration. After oral administration, the concentrations of MMF in plasma are not determined (below the detection threshold of 0.4 Ојg / ml).
In the early post-transplant period (up to 40 days after kidney, heart or liver transplantation), the mean AUC MAP values ​​were about 30% lower, and Cmax was about 40% lower than in the late post-transplant period (3-6 months after transplantation ). In patients who underwent kidney transplantation, the values ​​of AUC of IFC after iv injection of Sellsept in a dose of 1 g 2 times / day in the early posttransplant period were comparable with those for oral administration (I / O rate was as recommended for this group of patients). In patients who underwent liver transplantation, the values ​​of AUC of MPC after iv injection of Cellsept 1 g twice a day, followed by oral administration of the drug at a dose of 1.5 g twice a day did not differ from those observed in patients undergoing kidney transplantation and taking the drug at a dose of 1 g twice daily.
The intake of food does not affect the degree of absorption of MMF (AUC IFC ) when administered 1.5 g twice a day to patients after kidney transplantation.However, C max IFC when taking the drug during meals is reduced by 40%.
Distribution
As a rule, approximately in 6-12 hours after taking the drug, a secondary increase in the concentration of MPA in the plasma is observed, which indicates a hepatic intestinal recirculation of the drug. With the simultaneous administration of colestyramine AUC, IFC decreases by approximately 40%, indicating interruption of hepatic intestinal recirculation.
In clinically significant concentrations, the MPA is 97% bound to plasma albumin.
Metabolism
IFC is metabolized, mainly, under the action of glucuronyltransferase with the formation of pharmacologically inactive phenolic glucuronide MFC (IFPC). In vivo, IFPC is converted into free MPA during hepatic intestinal recirculation.
Excretion
After oral administration of radiolabeled MMP93% of the received dose is excreted in the urine, and 6% - with feces. Most (about 87%) of the administered dose is excreted in the urine in the form of MHCI. Minor quantities of the drug (<1% of the dose) are excreted in the urine in the form of an MFC.
Clinically determined concentrations of IFC and IFPC are not removed by hemodialysis. However, at higher concentrations of IFPC (> 100 Ојg / ml), some of it can be removed. Sequestants of bile acids such as colestyramine reduce the AUC of the IFC , interrupting hepatic intestinal recirculation.
Bioequivalence
When examining the bioequivalence of two oral forms of MMP release, it was shown that two 500 mg tablets are equivalent to four 250 mg capsules.
Pharmacokinetics in special clinical cases
In the study with a single dose of the drug (in the group of 6 subjects) in patients with severe chronic renal failure (glomerular filtration rate <25 ml / min / 1.73 m 2 ), the MUC AUC was 28-75% higher than in healthy volunteers and patients with less pronounced renal involvement. After receiving a single dose, the AUC of IFCG is 3-6 times greater in patients with severe renal failure than in healthy volunteers and patients with moderate renal involvement, consistent with data on renal excretion of IFHC.
Studies on the repeated administration of MMF in severe chronic renal failure have not been carried out.
In patients with delayed renal transplant function after transplant, the mean AUC value 0-12 for IFC is comparable to that in patients in whom the graft began to function after a transplant without delay. In patients with delayed renal transplant function, a transient increase in the free fraction and in the concentration of MPC in the blood plasma can be observed. Probably, there is no need to correct the dose of Sellsept В® in these patients (see the section "Dosing in special cases"). The mean AUC 0-12 for MCG in plasma was 2-3 times greater than in patients in whom the graft began to function after a transplant without delay.
In patients with a primary non-functional graft after kidney transplantation, an increase in the concentration of IFPC in the blood plasma was observed; the cumulation of IFC, if noted, is much less than in IFAC.
Patients with liver damage. In volunteers with alcoholic cirrhosis of the liver after oral administration of MMP, no changes in the pharmacokinetics of IFC and IFPC have been revealed. The influence of hepatic pathology on this process probably depends on the specific disease. In case of liver disease with a predominance of biliary tract lesions (eg, primary biliary cirrhosis), changes in the pharmacokinetics of IFC and IFPC can not be ruled out.
In patients of child age (? 18 years) who underwent kidney transplantation (in the study n = 55, patients from 1 year to 18 years), after oral administration of MMF at a dose of 600 mg / m 2 twice a day (up to 1 g two times a day) AUC for IFC is comparable to that in adult patients after kidney transplant receiving the drug at a dose of 1 g twice daily, in the early and late post-transplant period. The AUC values ​​for IFC did not differ between the age groups in the early and late transplantation period.
In elderly and senile patients (? 65 years), pharmacokinetics has not been studied.
INDICATIONS
Adults and children with a body surface area> 1.25 m 2 (approximate age 12 years):
- prevention of acute graft rejection in patients after allogeneic kidney transplantation.
Adults:
- treatment of the first or refractory to the treatment of transplant rejection in patients after allogeneic kidney transplantation;
- prevention of acute rejection of the transplant and improvement of its survival and survival of patients after allogeneic heart transplantation;
- prevention of acute graft rejection in patients after allogeneic liver transplantation.
Sellsept is prescribed as a combination therapy with cyclosporine and corticosteroids.
DOSING MODE
Adults
Prophylaxis of kidney transplant rejection
The drug should be taken within 72 hours after the transplant operation. Patients with renal transplants are recommended to take 1 g twice a day (daily dose of 2 g).Although clinical studies have shown that a dose of 1.5 g twice a day (daily dose of 3 g) is also safe and effective, its benefits in terms of effectiveness in patients after kidney transplantation are not established. In patients receiving 2 g MMF per day, the safety profile was generally better than those receiving a daily dose of 3 g.
Prevention of heart transplant rejection
The drug should be taken within 5 days after the transplant operation. The recommended dosage regimen is 1.5 g 2 times a day (daily dose 3 g).
Prevention of liver transplant rejection
The drug should be taken as early as possible after the transplant operation (depending on the patient's ability to transfer the drug). The recommended dosing regimen is 1.5 g 2 times per day (daily dose 3 g).
Treatment of first or refractory rejection of a kidney transplant
The recommended dosing regimen is 1.5 g 2 times per day (daily dose 3 g).
After the transplantation of the kidney, heart or liver, the first dose of Sellsept should be taken as soon as possible.
Dosing in special cases
For neutropenia (absolute number of neutrophils <1300 in 1 Ојl of blood), it is necessary to interrupt the treatment of MMF or to reduce its dose and carefully observe the patient.
In patients with severe chronic renal failure (glomerular filtration rate less than 25 ml / min / 1.73 m 2 ) outside the nearest post-transplantation period or after therapy for acute or refractory rejection, doses above 1 g 2 times / day should be avoided. Data on patients with severe renal failure who underwent a heart or liver transplant are not available.
Dose adjustments for patients with delayed renal transplant function are not required.
Patients who have undergone a kidney transplant and who have a severe lesion of the liver parenchyma , dose adjustment is not required. Data on patients with severe lesions of the liver parenchyma, who underwent heart transplant, are absent.
In elderly and senile patients (? 65 years) who underwent kidney transplantation, the recommended dose is 1 g 2 times a day, and after heart or liver transplantation - 1.5 g 2 times / day.
Children
Prophylaxis of transplant rejection of kidney: pediatric patients older than 12 years who underwent a kidney transplant, while the surface area of 1.25-1.50 m? possible to assign the capsules of 750 mg twice a day (daily dose is 1.5 g); when the surface area of more than 1.50 m? possible to assign the capsules of 1 g twice a day (daily dose of 2 g);
Treatment of first or refractory rejection of kidney transplant: data on the efficacy and safety of the drug for the treatment of first or refractory rejection of kidney transplant in pediatric patients are not available;
Data on the safety and efficacy of the drug in patients with childhood after a heart transplant or a liver missing.
SIDE EFFECT
Profile of side effects associated with the immunosuppressive agents is often difficult to establish because of the underlying disease and simultaneous use of many other drugs.
Clinical Trials Data
The major adverse reactions associated with the use of MMF in combination with cyclosporin and corticosteroids for preventing the rejection of kidney, heart or liver transplant are diarrhea, leukopenia, sepsis and vomiting; There are also about increasing the data rate of certain types of infections, such as opportunistic.
MMF safety profile in treating refractory kidney rejection similar to that observed in three controlled studies for the prevention of kidney rejection by using a drug dose of 3 g / day. Diarrhea and leukopenia, followed by anemia, nausea, vomiting, abdominal pain, dyspepsia, sepsis were the predominant adverse reactions occur in patients on MMF frequently than in patients treated with intravenous corticosteroids.
Malignancies.As well as on the background of combined immunosuppression in general, and in the appointment of MMF as a component of immunosuppressive schemes, there is an increased risk of developing lymphomas and other malignancies, particularly of the skin. In controlled clinical studies in patients undergoing transplantation of kidney, heart or liver, and observed for at least 1 year, lymphoproliferative disease or lymphoma developed in 0.4-1% of patients treated with MMF (in doses of 2 or 3 g per day) in combination with other immunosuppressive . skin cancer (excluding melanoma) was observed in 1.6-3.2% of patients with malignancies of other types - in 0.7-2.1% of patients. Three-year safety data in patients after kidney transplantation or heart did not reveal any unexpected changes in incidence rates of malignant neoplasms, compared with growth rates.After a liver transplant patients were followed for at least 1 year but less than 3 years.
In controlled trials of treatment of refractory renal rejection rate of lymphomas at a mean follow up of 42 months was 3.9%.
Opportunistic infections. The risk of opportunistic infections increased in all post-transplant patients and increases with the degree of immunosuppression. In controlled clinical trials when assigning MMF (2 or 3 g per day) in combination with other immunosuppressive drugs in patients followed for one year after kidney transplantation (at a dose of 2 g / day), the heart and the liver, the most frequent infections were skin candidosis and mucous membranes, cytomegalovirus (CMV) infection: CMV viremia / CMV syndrome (13.5%), and infection caused by the herpes simplex virus.
Children (3 months-18 years).Type undesired reactions and the frequency of their occurrence in a clinical trial, the oral administration of 600 mg / m 2 MMF 2 times / day for children aged 3 months to 18 years (N = 100) did not differ from those of adult patients receiving the drug in a dose of 1 g of 2 times / day. However, such side effects as diarrhea, leukopenia, sepsis, infection, anemia were more common (≥10%) in children, especially those younger than 6 years.
In patients elderly (≥65 years of age) in the treatment of MMF as part of combination immunosuppressive therapy, the risk of certain infections (including tissue invasive forms of symptomatic CMV infection) and possibly gastrointestinal haemorrhage and pulmonary edema is higher than in patients over young age.
Adverse events reported in? 10% and 3-10% of patients treated with MMF in combination with cyclosporine and corticosteroids in controlled studies for the prevention of kidney transplant rejection (3 studies, data on daily doses of 2 and 3 mg) in a controlled study of heart transplants and in a controlled study of liver transplant.
Adverse events after kidney transplantation (n = 991) * Adverse events after heart transplantation (n = 289) ** Adverse events after liver transplantation (n = 277) ***
Body as a Whole? 10% of fatigue, fever, headache, infection, pain (abdominal, back, chest), edema, sepsis, fatigue, fever, chills, headache, infection, pain (abdominal, back, chest), edema, sepsis ascites, asthenia, fever, chills, bloating, headache, infection, pain (abdominal, back, chest), edema, sepsis, hernia, peritonitis
3 - <10% cyst (including lymphocele and hydrocele), facial swelling, flu-like symptoms, bleeding, hernia, malaise, pelvic pain, bloating cellulitis, cysts (including lymphocele and hydrocele) facial swelling, flu-like symptoms, bleeding, hernia, bloating, malaise, pelvic pain, neck pain, pale skin abscesses, cellulitis, cyst (including lymphocele and hydrocele), flu syndrome, hemorrhage, malaise, pain in the neck
of the blood system and the lymphatic system ? 10% anemia (including gipohro mnaya), leukocytosis, leukopenia, thrombocytopenia, anemia (including hypochromic), leukocytosis, leukopenia, thrombocytopenia, anemia ecchymosis (including hypochromic), leukocytosis, leukopenia, thrombocytopenia
3 - <10% ecchymosis, polycythemia petechiae, increased prothrombin and thromboplastin time ecchymosis, prolonged prothrombin time, pancytopenia
Genitourinary tract 10% hematuria, necrosis of the renal tubules, urinary tract infections renal dysfunction (decrease in renal function, increased concentration of serum creatinine)? , oliguria, urinary tract infections renal dysfunction (decrease in renal function, increased concentration of serum creatinine), oliguria, urinary tract infection
3 - <10% albuminuria, dysuria, hydronephrosis, impotence, pyelonephritis, frequent urination, dysuria, hematuria, impotence, nocturia, renal failure, urinary frequency, incontinence, and urinary retention, acute renal failure, dysuria, hematuria, renal insufficiency, scrotal swelling, frequent urination, urinary incontinence,
cardiovascular system ? 10% increase in blood pressure arrhythmia, bradycardia, heart failure, rise and fall of blood pressure, pericardial effusion rise and fall in blood pressure, tachycardia
3 - <10% angina, atrial fibrillation, reducing blood pressure, orthostatic hypotension, tachycardia, thrombosis, vasodilatation angina, arrhythmias (supraventricular and ventricular extrasystoles, atrial flutter and atrial fibrillation, supraventricular and ventricular tachycardia), heart failure, congestive heart failure, Orthostatic hypotension, pulmonary hypertension, syncope, vasospasm, increased venous pressure, arterial thrombosis, atrial fibrillation, arrhythmia, bradycardia, vasodilation, syncope
About varied substances ? 10% acidosis (metabolic or respiratory) hypervolemia, increased body mass narusheniezazhivleniya wounds
3 - <10% acidosis (metabolic or respiratory), dehydration, hypervolemia, weight gain violation wound healing, alkalosis, dehydration, gout, hypovolemia, hypoxia, respiratory acidosis, thirst, weight loss acidosis (metabolic or respiratory), dehydration, hypervolemia, hypoxia, hypovolemia, weight gain, weight loss
Laboratory findings? 10% of hypercholesterolemia, hyperglycemia, hyperkalemia, hypokalemia, hypophosphatemia hyperbilirubinemia, increased residual nitrogen, increase serum creatinine concentration, increased activity of enzymes (LDH, AST, ALT) in blood serum, hypercholesterolemia, hyperglycemia, hyperkalemia, hyperlipidemia, hyperuricemia, hypokalemia, hypomagnesemia, hyponatremia hyperbilirubinemia, increased residual nitrogen, increase serum creatinine concentration, hyperglycemia, hyperkalemia, hypokalemia, hypocalcemia, hypoglycemia, hypomagnesemia, hypo osfatemiya, hypoproteinemia
3 - <10% increase in the activity of alkaline phosphatase, increased activity of enzymes (gammaglutamiltranspeptidazy, LDH, ALT and AST) in serum, increased concentration of serum creatinine, hypercalcemia, hyperlipidemia, hypocalcemia, hypoglycemia, hypoproteinemia, hyperuricemia increased activity of alkaline phosphatase, hypocalcemia, chloropenia, hypoglycemia, hypoproteinemia, hypophosphatemia increase in alkaline phosphatase activity, increased activity of enzymes (AST and ALT) in serum, hypercholesterolemia, giperlip Come on, hyperphosphatemia, hyponatremia
Gastrointestinal tract? 10% of constipation, diarrhea, dyspepsia, nausea and vomiting, candidiasis of the oral mucosa constipation, diarrhea, dyspepsia, flatulence, nausea and vomiting, mucosal oral candidiasis anorexia, cholangitis, cholestatic jaundice, constipation, diarrhea, dyspepsia, flatulence, hepatitis, nausea and vomiting, candidiasis of the oral mucosa, improving liver function tests (including AST, ALT)
3 - <10% of anorexia, flatulence, gastroenteritis, gastrointestinal bleeding, candidiasis gastrointestinal, gingivitis, gingival hyperplasia, hepatitis, ileus, stomatitis, esophagitis, increased liver function tests (including AST, ALT), anorexia, dysphagia, gastroenteritis , gingivitis, gingival hyperplasia, jaundice, melena, stomatitis, esophagitis, increased liver function tests (including AST, ALT), dysphagia, gastritis, gastrointestinal bleeding, intestinal obstruction, jaundice, melena, ulceration of the oral mucosa, esophagitis, hitting of colon, stomach ulcer
Respiratory? 10% increased cough, dyspnea, pharyngitis, pneumonia, bronchitis, asthma, cough increased, dyspnea, pharyngitis, pleural effusion, pneumonia, rhinitis, sinusitis, increased cough, dyspnea, pharyngitis, pneumonia, pleural effusion, sinusitis, atelectasis
3 - <10% asthma, pleural effusion, pulmonary edema, rhinitis, sinusitis, sleep apnea, atelectasis, bronchitis, epistaxis, hemoptysis, hiccups, neoplasm, pneumothorax, pulmonary edema, increased sputum, change of voice asthma, bronchitis, epistaxis, hyperventilation, pneumothorax, pulmonary edema candidiasis respiratory n Tay, rhinitis
Skin and appendages ? 10% of acne, herpes simplex, acne, herpes simplex, herpes zoster, rash, hives, itching, povyshennayapotlivost
3- <10% hair loss, benign skin tumors, fungal dermatitis, herpes zoster, hirsutism, pruritus, skin cancer, skin hypertrophy (including actinic keratosis), excessive sweating, skin sores, rashes benign skin tumors, fungal dermatitis , hemorrhage, pruritus, skin cancer, skin hypertrophy, excessive sweating, skin ulcers, acne, fungal dermatitis, hemorrhage, herpes simplex, herpes zoster, hirsutism, benign skin tumors, skin ulcers, vesicles, bullous rash
Nervous system ? 10% of heads servation, insomnia, tremor, agitation, anxiety, confusion, depression, dizziness, hypertonia, insomnia, paresthesia, somnolence, tremor, anxiety, confusion, depression, dizziness, insomnia, paraesthesia, tremor
3 <10% anxiety, depression, hypertonia, paresthesia, drowsiness, convulsions, emotional lability, hallucinations, neuropathy, thought disorder, vertigo, agitation , seizures, delirium, dry mouth, hypertonia, hypoesthesia, neuropathy, psychosis, somnolence, thinking disorders
Bone -Muscular system ? 10% ~ leg cramps, muscle pain, muscle weakness ~
3 <10% joint pain, leg cramps, muscle pain, muscle weakness, joint pain joint pain, leg cramps, pain muscles, muscle weakness, osteoporosis
sense organs ? 10% ~ Amble Pia ~
3 <10% amblyopia, cataract, conjunctivitis, blurred vision, conjunctivitis, deafness, ear pain, bleeding in the eye, ringing in the ears of violations, amblyopia, conjunctivitis, deafness
endocrine system ? 10% ~ ~ ~
3 <10% sugar diabetes, parathyroid disease (increased levels of parathyroid hormone) diabetes, Cushing's syndrome, hypothyroidism, diabetes mellitus
* (total n = 1483) , ** (total n = 578) , *** (total n = 564)
in the three controlled studies prevention of kidney transplant rejection safety profile MMF in a daily dose of 2 g was MULTI of better than a daily dose of 3 g
Post-marketing application of the drug
On the part of the digestive system: colitis (sometimes etiology cytomegalovirus), pancreatitis, isolated cases of intestinal villous atrophy.
Immune system : individual cases of severe, life-threatening infections (meningitis, infectious endocarditis), increase in the frequency of some infections such as tuberculosis and atypical mycobacterial infections.
Cases of progressive multifocal leukoencephalopathy (PML), sometimes fatal, have been observed in patients treated with CellCept. The reports of these cases, there is information about the presence in patients of additional risk factors for PML, including immunosuppressant therapies and impairment of immune status.
In patients treated with CellCept, we observed cases of nephropathy associated with the BK-virus (BKvirus-associatednephropathy). The infection can lead to serious consequences, sometimes to the death of a kidney transplant.
Cases of partial red cell aplasia (PKKA) were observed in patients treated with CellCept in combination with other immunosuppressive agents.
Developmental anomalies: reported cases of fetal malformations (including ear malformations Development) in patients treated with MMF during pregnancy in combination with other immunosuppressants.
Other adverse reactions observed with the use of the drug post-registration do not differ from undesired reactions reported in controlled clinical trials.
CONTRAINDICATIONS
- increased sensitivity to individual MMF, IFC and other ingredients;
- lack hypoxanthine;
- Simultaneous reception with azathioprine.
With caution: gastrointestinal disease (exacerbation), simultaneous with MMF tacrolimus, sirolimus, with drugs affecting the intestinal and hepatic recirculation.
PREGNANCY AND LACTATION
The drug category D (classification FDA - US FoodandDrugAdministration).
Found an increased risk of spontaneous abortion in the I trimester of pregnancy, as well as an increased risk of birth defects, including malformations of the external ear, "palate", "cleft lip", distal extremities, heart abnormalities, kidney and esophagus.
The patient, planning a pregnancy should not take CellCept as long as the effect of
