Mayfortic® (Myfortic®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
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Active substanceMycophenolic acidMycophenolic acid
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  • Mayfortic®
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    Novartis Pharma AG     Switzerland
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    TECHNOLOGY OF DRUGS, LTD.     Russia
  • Felomika
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    Nanopharma Development, LLC     Russia
    • Dosage form: & nbspenteric coated tablets
    Composition:

    1 tablet, coated with enteric coating, contains: active substance: sodium mycophenolate 192.4 mg or 384.8 mg (equivalent to mycophenolic acid 180 mg and 360 mg, respectively);

    Excipients: lactose anhydrous 45.0 mg or 90.0 mg, crospovidone 32.5 mg or 65.0 mg; povidone (K-30) 20.0 mg or 40.0 mg, starch corn 10.25 mg or 20.5 mg, silicon dioxide colloid 6.6 mg or 13.2 mg, magnesium stearate 3.25 mg or 6, 5 mg;

    shell: hypromellose phthalate 42.0 mg or 65.0 mg, titanium dioxide (No77891, El71) 2.883 mg or 4.666 mg, iron oxide yellow (No77492, El 72) 0.078 mg or 0.167 mg.

    Tablets, coated with enteric coating, 180 mg contain indigocarmine (E132) - 0.039 mg.

    Tablets, coated with enteric coating, 360 mg contain iron oxide red (No77491, E172) 0.167 mg.

    Description:

    Tablets coated with enteric coating, 180 mg: light green, round, with beveled edges, one side printed with "C".

    The tablets covered with enteric coating, 360 mg: grayish-pink in color, oval in shape, on one side it is stamped "CT".

    Pharmacotherapeutic group:Immunosuppressive remedy
    ATX: & nbsp

    L.04.A.A.06   Mycophenolic acid

    Pharmacodynamics:

    Mayfortic inhibits synthesis guanosine nucleotides by selective suppression of a key Purine synthesis enzyme inosine monophosphate dehydrogenase. Due to this mechanism, it effectively suppresses the proliferation of T and B lymphocytes, and significantly more than others cells, since the proliferation of lymphocytes depends mainly on the synthesis of purines de-novo.

    Suppressing the proliferation of T and B lymphocytes by Mayfortic complements the action of inhibitors of calcineurin, disturbing the production of cytokines, and affecting T-lymphocytes in the phase of resting the cell cycle.

    Pharmacokinetics:

    Suction

    After oral administration of sodium mycophenolate is intensively absorbed. Due to the presence of enteric film coatings, the maximum concentration of mycophenolic acid (MPA) is reached after approximately 1.5-2 hours. In studies in vitro it was shown that the special composition of the enteric film coating Mayfortika prevents the release of MPA in an acidic medium, similar to the acidic environment of the stomach.

    Patients with a stable functioning kidney transplant receiving basic immunosuppressive therapy cyclosporine in the form of a microemulsion, the degree of absorption of IFC from the gastrointestinal tract (GIT) is 93%, and the bioavailability is 72%. In the dose range from 180 to 2160 mg pharmacokinetics. Mayfortics has a linear dose-dependent character. The area under the curve "concentration - time" (AUC), at reception Majfortika on an empty stomach did not differ from that at reception of a preparation with food with high the fat content (55 g fat, 1000 calories). However, the maximum concentration of MFC (Cmax) is reduced by 33%.

    Metabolism

    IFC is mainly metabolized with the participation of glucuronyltransferase to form the main pharmacologically inactive metabolite of phenol glucuronide MFC (HMFC). Patients with a stable functioning kidney transplant receiving basic immunosuppressive therapy with cyclosporine in the form of a microemulsion, about 28% of the oral dose of Mayforth is metabolized in GMPC at the "first passage "through the liver.

    Distribution and communication with blood plasma proteins

    The volume of the IFC distribution in the equilibrium state is 50 liters.Both IFC and GMPC show a high degree of binding to plasma proteins, 97% and 82%, respectively. With a decrease in the number of binding sites with proteins (with uremia, liver failure, hypoalbuminemia, simultaneous the use of drugs with high binding to blood plasma proteins) may increase the concentration of free MPC in plasma.

    Excretion

    The half-life of IFC is 11.7 hours, the clearance is 8.6 l / h. IFC is excreted mainly with urine in the form of HMFC, and very small amounts (<1.0%) in unchanged form. The half-life of HMFC is 15.7 hours, the clearance is 0.45 l / h. HMFC also secreted with bile in the intestine, where it is split (by deconjugation) by the intestinal flora. The resulting IFC cleavage can then be reabsorbed. Six to eight hours after the administration of Mayfortic, a second peak of the concentration of MPA is observed, which corresponds to the re-absorption of the deconjugated IFC.

    Pharmacokinetics in patients who underwent kidney transplantation and are on basic immunosuppressive therapy cyclosporin in the form of a microemulsion

    The table presents the average values ​​of pharmacokinetic parameters of IFC after receiving Mayfortika.The values ​​of pharmacokinetic Parameters of Mayforth with a single dose can predict the possible values ​​of these parameters for repeated and prolonged dosing. Mean values AUC and CmThe IFC measured in the early posttransplant period was approximately 50% of the values ​​determined 6 months after transplantation.

    Table. Mean values ​​of pharmacokinetic parameters of MFC after oral administration of Maisfort in patients who underwent kidney transplantation and received basic immunosuppressive therapy with cyclosporin in the form of a microemulsion.

    See Appendix 1:

    The abbreviations used in the table are:

    FROMmah - the maximum concentration in the blood plasma

    Tmah - the time to reach the maximum concentration in the blood plasma

    AUC-area under the curve "concentration-time"

    Mean values ​​of pharmacokinetic parameters of MFC after oral administration of Maisfort in patients who underwent kidney transplantation and received basic immunosuppressive therapy with cyclosporin in the form of a microemulsion.

    ADULTS

    Single dose (n=24)

    Dose

    (ingestion)

    Tmax

    (h)

    Cmax

    (μg / ml)

    AUC0- ∞ (μg / ml)

    720 mg

    2

    26,1 (12,0)

    66,5 (22,6)

    ADULTS

    Repeated doses x 6 days (2 times per day) (n = 12)

    Dose

    (ingestion)

    Tmax

    (h)

    Cmax

    (μg / ml)

    AUC0- 12 (μg / ml)

    720 mg

    2,5

    37,0 (13,3)

    67,9 (20,3)

    ADULTS

    Repeated doses x 28 days (2 times per day) (n = 36)

    Dose

    (ingestion)

    Tmax

    (h)

    Cmax

    (μg / ml)

    AUC0- 12 (μg / ml)

    720 mg

    2,5

    31,2 (18,1)

    71,2 (26,3)

    ADULTS

    Long-term therapy (2 times a day)

    (n = 48)

    Dose

    Tmax

    (h)

    Cmax

    (μg / ml)

    AUC0- 12 (μg / ml)

    14 days after transplantation

    720 mg

    2

    13,9 (8,6)

    29,1 (10,4)

    3 months after transplantation

    720 mg

    2

    24,6 (13,2)

    50,7 (17,3)

    6 months after transplantation

    720 mg

    2

    23,0 (10,1)

    55,7 (14,6)

    CHILDREN

    Single dose (n=24)

    Dose

    Tmax

    (h)

    Cmax

    (μg / ml)

    AUC0- ∞ (μg / ml)

    450 mg / m2

    2-2,5

    31,9 (18,2)

    76,2 (25,2)

    Renal insufficiency

    The pharmacokinetics of IFC does not depend on the function of the kidneys. AUC GMPK in violation of kidney function, on the contrary, increases, so in patients with anuria the values AUC GMPC is approximately 8 times higher. Hemodialysis does not affect the clearance of IFC and GMPC. With renal failure, the concentration of free MPC in blood plasma can significantly increase, which is probably due to a decrease in binding of IFC to proteins in conditions of high urea concentration in the blood.

    Liver failure

    In patients with alcoholic cirrhosis of the liver, no effect of this disease on the response glucuronation of MPA. The presence or absence of the effect of liver disease on the pharmacokinetics of IFC may depend on the nature of the disease (primary parenchyma or bile excretory system, or the like).

    Childhood

    Experience with the use of Mayforth in children is limited. The table shows the average values ​​of pharmacokinetic parameters in children with stable kidney transplant receiving a microemulsion of cyclosporine as an immunosuppressive therapy. Values Cmax and AUC for IFC in children compared with older patients showed greater variability. When taking the usual single dose of Mayforth 720 mg in children AUC IFC was higher than that in adults. The average value of the IFC clearance was about 7.7 l / h. It is expected that at a dose of Mayforth, equal to 200-300 mg / m2, the AUC of the MPC will be from 30 to 50 μg / ml.

    Floor

    Clinically significant differences in pharmacokinetic parameters were not found depending on the sex of patients.

    Elderly age

    Based on preliminary research data, it is assumed that the concentration of IFC does not change clinically with age.

    Indications:

    Prevention of acute graft rejection in patients with allogeneic kidney transplants receiving basic immunosuppressive therapy with cyclosporine in the form of a microemulsion and glucocorticosteroids.

    Contraindications:

    - Hypersensitivity to mycophenolate sodium, mycophenolic acid, mycophenolate mofetil or any component of the drug.

    - Child age (efficacy and safety not studied).

    - Lactase deficiency, lactose intolerance, glucose-galactose malabsorption.

    - Pregnancy.

    - The period of breastfeeding.

    Carefully:

    Congenital insufficiency of hypoxanthine-guanine-phosphoribosyl-transferase (including Lesch-Nayhan syndrome and Kelly-Sigmiller syndrome).

    Diseases of the gastrointestinal tract tract in the phase of exacerbation.

    Use in children

    The efficacy and safety of the Mafictic® preparation in children have not been studied. There are limited data on the pharmacokinetics of IFC in children who underwent kidney transplantation. At the moment, no specific recommendations on the dosage regimen in children have been developed.

    Pregnancy and lactation:

    The use of the drug during pregnancy and during breastfeeding is contraindicated.

    With the use of the preparation Mayertics® during pregnancy there was an increased risk miscarriage, incl. spontaneous abortion, as well as the development of congenital anomalies.According to the American National Pregnancy Registry for Women after Transplantation (National Transplant Pregnancy Registry, NTPR), the average incidence of congenital malformations in children born to women who underwent organ transplantation is 4-5%. Although controlled clinical studies on the use of the drug Mayfortique® in pregnant women were not performed, according to NTPR in the use of mycophenolate mofetil in combination with other immunosuppressants during pregnancy, an increased incidence of congenital malformations - 22% (4 children from 18 newborns) compared with the average frequency. The most frequent use of mycophenolate mofetil during pregnancy in children was anomalies in the development of the inner ear, extremities, craniofacial area, including clefts of the upper lip and palate, congenital diaphragmatic hernia, heart, esophagus and kidney defects. The use of mycophenolate mofetil during pregnancy is accompanied by a high risk of spontaneous abortion. Since ingestion or intravenous administration of mycophenolate mofetil is converted to mycophenolic acid, all the above information should be taken into account when application of preparation Mayfortik®.

    In experimental preclinical studies, the animals exhibited a teratogenic effect of mycophenolic acid.

    It is not recommended to begin therapy with Mafractic® before a negative pregnancy test result is obtained. In case of an offensive pregnancy, the patient must immediately consult a doctor.

    Prior to the initiation of therapy with Mafractic®, effective contraceptive methods should be used throughout the therapy and for 6 weeks after its completion.

    It is not known whether IFC is excreted in breast milk. In connection with the fact that there is a potential risk of developing serious adverse events in the breastfed child, it is necessary to resolve the issue of either stopping the use of the drug Mayfortik®, or, given the importance of therapy with this drug for the mother, the cessation of breastfeeding throughout the therapy and within 6 weeks after its discontinuation.

    Dosing and Administration:

    Inside, the tablets are swallowed whole, without chewing; do not do it break down pills. Mayforth can be taken on an empty stomach or together with food.

    Maboptyk therapy in patients who did not receive it before, begin in the first 48 hours after transplantation. The recommended dose is 720 mg (4 tablets in enteric coating of 180 mg or 2 tablets of 360 mg) 2 times a day (daily dose of 1440 mg). In patients receiving mycophenolate mofetil (MMF) in a dose 2 g, MMF can be replaced with Mayfortik in a dose of 720 mg 2 times a day.

    Application in elderly patients

    Correction of the dosing regimen in elderly patients is not required.

    Use in patients with impaired renal function

    In patients with delayed restoration of renal function graft change dose Mayforth is not required. Careful monitoring of patients with chronic severe disability kidney function (glomerular rate filtration less than 25 ml x min x 1.73 m2).

    Use in patients with impaired liver function

    Patients with severe liver disease associated with primary parenchyma involvement do not require a dose adjustment for Mayfortics.

    Episodes of rejection reaction

    Reaction rejection of the graft does not lead to a change in the pharmacokinetics of mycophenolic acid. In these cases, changes in the dosing regimen not required.

    Side effects:

    The following adverse events were observed in two studies of the safety of the preparation Mifortic® and MMF in 423 patients with a recently transplanted kidney,previously untreated therapy (patients with renal transplant de novo), and in 322 patients with kidney transplant who had previously received maintenance therapy. The incidence of adverse events was similar in both groups of patients. With the use of the preparation Mayfortik® in combination with cyclosporine and glucocorticosteroids very often (> 10%) observed such undesirable phenomena as leukopenia (19,2%) and diarrhea (23,5%).

    In elderly patients, the risk of side effects is generally higher due to immunosuppression.

    Malignant neoplasms

    Have patients, receiving immunosuppressive therapy several drugs, including IFC, increased the risk of developing lymphomas and other neoplasms, in particular, the skin. In the course of research, malignant neoplasms developed against the background of taking Mifrotic® with the following frequency: lymphoproliferative diseases or lymphomas developed in two patients with a renal transplant de novo (0.9%) and in two patients (1.3%) with a transplanted kidney who received maintenance therapy for up to 1 year; Non-melanoma skin carcinomas developed in 0.9% with a renal transplant de novo and 1.8% of patients with kidney transplant who had previously received Supportive therapy with Mafractic® for up to 1 year; other malignant neoplasms developed in 0.5% of patients with a renal transplant de novo and 0.6% patients with a transplanted kidney who received maintenance therapy.

    Infectious diseases (opportunistic infections)

    Have patients with a recently transplanted kidney, who received the Mayfortic ® preparation as part of complex immunosuppressive therapy for 1 year, the most frequent infection was cytomegalovirus (CMV), candidiasis and infection caused by the herpes simplex virus. During the study, it was shown that CMV infection (confirmed serologically by viremia or clinical data) was noted with a frequency of 21.6% in patients with a recently transplanted kidney and 1.9% in patients with a stable functioning transplant on the background of long-term maintenance therapy.

    Other undesirable phenomena

    Below are the undesirable events detected during the administration of Mafractic® at a dose of 1440 mg / day for 12 months in combination with a cyclosporine microemulsion and corticosteroids in two clinical studies in patients with a kidney transplant de novo and in patients with kidney transplant who received previous maintenance therapy.These phenomena had a possible or probable cause-and-effect relationship with the use of the preparation Mayertics®. Undesirable phenomena are given in accordance with the classification of organs and systems for MedDRA (medical dictionary terminology of regulatory activities) and are listed by frequency.

    The frequency of unwanted reactions is estimated as follows: very often ≥ 10%; often ≥ 1% and <10%; infrequently ≥ 0.1% and <1%; rarely ≥ 0.01% and <0.1%; very rarely <0.01%, including individual messages.

    Infectious and parasitic diseases

    Very often: viral, bacterial and fungal infections: urinary tract infections, herpes zoster, candidiasis of the oral mucosa, sinusitis, gastroenteritis, herpes simplex, nasopharyngitis.

    Often: infections of the upper respiratory tract, pneumonia.

    Infrequent: wound infections, sepsis *, osteomyelitis *.

    Violations of the blood and lymphatic system

    Very often: leukopenia.

    Often: anemia, thrombocytopenia.

    Infrequent: lymphocele *, lymphopenia *, neutropenia *, lymphadenopathy *.

    Disorders of the psyche

    Often: irritability.

    Infrequently: delusional perception *.

    Disturbances from the nervous system

    Often: dizziness, headache.

    Infrequently: tremor, insomnia *.

    Disturbances from the respiratory system, chest and mediastinal organs

    Often: cough, shortness of breath, shortness of breath with physical activity.

    Infrequently: interstitial lung disease, including lung fibrosis with fatal outcome, "stagnant" lung *, stridor *.

    Disorders from the gastrointestinal tract

    Very often: diarrhea.

    Often: bloating, abdominal pain, constipation, dyspepsia, flatulence, gastritis, loosening of the stool, nausea, vomiting.

    Infrequent: abdominal wall tension, pancreatitis, belching, halitosis * (bad breath), intestinal obstruction *, esophagitis *, peptic ulcer *, subillus *, gastrointestinal bleeding, dry mouth *, ulceration of the lips *, blockage of the excretory duct parotid salivary gland *, gastro-oesophageal reflux disease *, gingival hyperplasia *, peritonitis *.

    General disorders and disorders at the site of administration

    Often: fatigue, peripheral edema, pyrexia.

    Uncommon: flu-like illness, swelling of lower limbs *, pain, thirst *, weakness *.

    Disorders from the metabolism and nutrition

    Very often: hypocalcemia, hypokalemia, hyperuricum.

    Often: hyperkalemia, hypomagnesemia.

    Uncommon: anorexia, hyperlipidemia, diabetes mellitus *, hypercholesterolaemia, hypophosphatemia *.

    Disturbances from the skin and subcutaneous tissues

    Infrequently: alopecia, bruises *, acne.

    Disturbances from the liver and bile ducts

    Often: abnormalities in the results of functional liver tests.

    Heart Disease

    Infrequent: tachycardia, pulmonary edema *.

    Vascular disorders:

    Very often: increased blood pressure, lower blood pressure.

    Often: increased severity of hypertension.

    Disturbances on the part of the organ of sight

    Infrequently: conjunctivitis *, "blurring" of vision *.

    Disturbances from musculoskeletal system and connective tissue

    Often: arthralgia, asthenia, myalgia.

    Infrequent: back pain *, muscle cramps.

    Benign, malignant and unspecified neoplasms

    Infrequent: skin papilloma *, basal cell carcinoma *, Kaposi's sarcoma *, lymphoproliferative disorders, scaly cell carcinoma *.

    Disorders from the kidneys and urinary tract

    Often: increased levels of creatinine in the blood.

    Infrequent: hematuria *, necrosis of renal tubules *, urethral stricture.

    * - this undesirable phenomenon was registered only in one patient out of 372.

    The profile of adverse events was not different in patients with kidney transplantation de novo and in patients who previously received maintenance therapy, however, the incidence of adverse events was lower in the second group.

    The following undesirable phenomena revealed during post-marketing observations (frequency unknown) are listed below:

    Disturbances from the skin and subcutaneous tissues: rash.

    Side effects observed against the background of the use of mycophenolic acid derivatives ("class-effects"):

    Infectious and parasitic diseases: severe, sometimes life-threatening infectious diseases (in some cases, with a fatal outcome), including meningitis, infective endocarditis, tuberculosis, atypical infections caused by mycobacteria. The development of poliomavirus nephropathy (especially associated with VC virus) has been reported.

    When using mycophenolate mofetil (a derivative of mycophenolic acid - the active substance of the drug Mayfortic®) reported on cases development of progressing multifocal leukoencephalopathy, associated with JC-virus, in some cases with a fatal outcome.

    Violations from the blood and lymphatic system: agranulocytosis, neutropenia, pancytopenia. When applying derivatives of mycophenolic acid in combination with other immunosuppressant cases of development partial red cell aplasia of the bone marrow.

    Violations from side of the digestive system: colitis, esophagitis (including CMV-colitis and CMV-esophagitis), CMV gastritis, pancreatitis, perforation of the intestinal wall, gastrointestinal bleeding, stomach and / or duodenal ulcer, intestinal obstruction.

    Overdose:

    In case of an overdose of Mafractic®, signs of hyperimmunosuppression and increased susceptibility to various infections, including those leading to death, as well as sepsis. Although the inactive metabolite of GMPA is excreted by hemodialysis, it should not be expected that this method will effectively excrete clinically significant amounts of active IFC.This is largely due to a high degree (97%) of binding of MPC to plasma proteins. Kolestyramine and other bile acid sequestrants disrupt the absorption of IFC from the intestine and, therefore, can lead to a decrease in its concentration in the blood.

    Interaction:

    Azathioprine. Since special research interactions Mayforth and azathioprine have not been performed, these drugs should not be prescribed simultaneously.

    Live vaccines. Do not use live vaccines in patients with a compromised immune response. With the use of other vaccines, the production of antibodies can be reduced.

    Acyclovir. In patients with impaired renal function may increase blood concentrations of both HMFC and acyclovir. Perhaps, both drugs compete when excreted from the body (a similar way of excretion - tubular secretion). Such patients require careful observation.

    Antiulcer drugs (including antacid preparations and proton pump inhibitors):

    Antacid preparations containing magnesium hydroxide and aluminum. With simultaneous administration with antacids, the absorption of sodium mycophenolate is reduced, resulting in AUC MFC is reduced by 37% and CmOh - by 25%. Caution should be exercised when combining Maiscotica with antacid preparations containing magnesium hydroxide and aluminum.

    Proton pump inhibitors. In healthy volunteers with the combined use of mycophenolate mofetil in dose of 1000 mg and pantoprazole at a dose of 40 mg 2 times a day, there was a decrease AUC and FROMmOh mycophenolic acid by 27% and 57%, respectively. However, with the appointment of these patients, Mayforth, along with pantoprazole, there was no change pharmacokinetic parameters of mycophenolic acid.

    Kolestyramin and drugs that affect the intestinal-hepatic circulation. In connection with its ability to bind bile acids in the intestine colestramine can reduce the concentration of IFC in the blood and AUC. In connection with the possible decrease in the effectiveness of Mayfortik, caution should be exercised when it is combined with colestyramine and preparations affecting the hepatic intestinal circulation.

    Ganciclovir. Joining Ganciclovir does not affect the pharmacokinetics of IFC and HMFC. When the therapeutic The concentration of IFC clearance of ganciclovir does not change.Nevertheless, with the combined appointment of Mayfortik and ganciclovir, patients with impaired renal function may need to adjust the dosage regimen of ganciclovir, and such patients should be carefully monitored.

    Tacrolimus. Patients with stable kidney transplant in a study with cross-sectional design studied the pharmacokinetics of Mayforth in equilibrium state, with its simultaneous application with Sandimmunom Neoral and tacrolimus.

    Mean values AUC IFC for joint reception of Mayforth and tacrolimus were 19% higher than when a joint reception of Mayforth and Sandimmune Neoral, and the values ​​of CmOh IFC - 20% lower. For HMPA values AUC and CmOh amounted to 30,% lower when taking Mayforth with tacrolimus than when taking Mayforth with Sandimmunom Neoral.

    Oral contraceptives. Oral contraceptives metabolized by oxidation reactions, while Mafractic - through glucuronation. Influence of oral contraceptives on the pharmacokinetics of Mayforth is unlikely, and, therefore, it is unlikely that one can expect any clinically significant interactions.With another If we take into account the fact that the effect of prolonged therapy Mayfortikom on pharmacokinetics oral contraceptives have not yet been We can not exclude the possibility of reducing the effectiveness of contraceptives.

    Cyclosporine. In studies in patients with a stable renal transplant it was shown that against the background of equilibrium concentrations of Mayforth the pharmacokinetics of cyclosporine did not change.

    Special instructions:

    Therapy with Mafractic ® should be performed only by qualified transplant doctors.

    In patients receiving combined immunosuppressive therapy, including, and the preparation of Mafractic®, the risk of developing lymphomas and other malignant tumors, especially the skin, is increased.

    There are data on the genotoxic effect of the preparation Mayertics®. This risk is most likely associated not with the use of the drug, but with the intensity and duration of immunosuppressive therapy. To reduce exposure to sunlight and ultraviolet radiation to reduce the risk of skin cancer, it is recommended to protect the skin with clothing and use sunscreens with a high protective factor.

    Patients treated with Mafractic® should be instructed to immediately notify the doctor of all cases of infection, sudden onset of bruising, bleeding, and any other manifestations of bone marrow depression.

    Excess immunosuppression increases the likelihood of developing infections, including opportunistic infections, as well as sepsis and fatal infections. In patients who received immunosuppressive therapy with mycophenolic acid derivatives, including Mifrotic ® and mycophenolate with mofetil, reactivation of the infection caused by hepatitis B and C viruses was observed. Infected patients should be monitored for clinical symptoms and laboratory indicators of the activity of the infectious process. Patients treated with mycophenolic acid derivatives, including Mafictic® and mycophenolate with mycophenolate, have reported cases of progressive multifocal leukoencephalopathy (PML) associated with JCa virus, in some cases with a fatal outcome. Cases of development of PML against the background of treatment with mycophenolic acid derivatives (mycophenolate mofetil and sodium mycophenolate) were noted mainly in patients with risk factors for PML development,including therapy with immunosuppressive drugs and immune disorders. Doctors should consider the possibility of developing PML on the background of drug therapy in patients with reduced immunity and, if necessary, refer patients with neurologic disorders to a consultation with a neurologist. Development of poliomavirus nephropathy, especially associated with BK virus, should be take into account in the differential diagnosis of the causes of liver function disorders in patients receiving immunosuppressive therapy. When developing PML or polyomavirus nephropathy, the doctor should consider the possibility of reducing the intensity immunosuppressive therapy. However, in patients after transplantation, a decrease in immunosuppression may increase the risk of rejection transplant.

    In patients receiving therapy with Mafractic®, development of neutropenia caused by exposure to the mycophenolic acid itself, as well as concomitant medications, viral infections or a combination of these factors is not excluded. In patients receiving the preparation of Mafractic®, a regular blood test should be performed on a regular basis (to detect neutropenia or anemia): during the first month of therapy - weekly, during the second and third months - twice a month, then, during the first year - once a month. With the development of neutropenia (absolute number of neutrophils <1.5 x 10 / mm ) or anemia with Mafractic® it is advisable to interrupt or terminate.

    When using the derivatives Mycophenolic acid (mycophenolate mofetil and sodium mycophenolate), in combination with other immunosuppressants, cases of development partial red cell aplasia of the bone marrow. At present, there is no known mechanism for the development of partial red cell aplasia of the bone marrow against the background of therapy with mycophenolic acid derivatives, as well as the role of other immunosuppressants and their combinations. However, it should be borne in mind that mycophenolic acid derivatives can cause neutropenia and anemia. In a number of cases, with a reduction in the dose or discontinuation of therapy with mycophenolic acid derivatives, the patient's condition was normalized. The change in the dosage regimen of Miforetic® should only be carried out under proper control of the patient's condition in order to reduce the risk of rejection of the transplant.

    Patients should be warned that during vaccination with mycophenolic acid derivatives, vaccination may be less effective and that the use of live attenuated vaccines should be avoided. Vaccination against the influenza virus should be conducted in accordance with the recommendations of local health authorities regarding vaccination against influenza.

    Since the use of the preparation Mayfortic® may be accompanied by side reactions from the gastrointestinal tract (ulceration of the gastrointestinal mucosa, gastrointestinal bleeding, gastrointestinal perforation), care must be taken when it is used in patients with diseases of the digestive tract at the stage of exacerbation.

    The drug Mayfortic ® was used in combination with the following drugs: antitimocyte globulin, basiliximab, ciclosporin (in the form of a microemulsion) and glucocorticoids.

    The efficacy and safety of the Mafractic® preparation when used with other immunosuppressive drugs has not been studied.

    Effect on the ability to drive transp. cf. and fur:

    The effect of taking Miffortic® on the ability to drive vehicles and work with mechanisms has not been established.The mechanism of action of the preparation Mayfortic®, its pharmacodynamic effects and registered undesirable phenomena indicate a low probability of such influence. Nevertheless, patients should be warned about possible adverse events drug and the need for caution in works requiring concentration of attention.

    Form release / dosage:Tablets, covered with enteric coating, 180 mg, 360 mg.
    Packaging:

    Tablets coated with enteric coating, 180 mg: 10 tablets per blister (Al / Al). By 5, 6, 10, 12, 25 blisters together with instructions for use in a cardboard box.

    Tablets coated with enteric coating, 360 mg: 10 tablets per blister (Al / Al). By 5, 6, 10, 12, 25 blisters together with instructions for use in a cardboard box.

    Storage conditions:

    At a temperature of no higher than 30 ° C.

    The drug should be stored out of the reach of children.

    Shelf life:

    30 months.

    Do not use after the expiration date.

    Terms of leave from pharmacies:On prescription
    Registration number:П N016017 / 01
    Date of registration:01.10.2009 / 09.10.2017
    Expiration Date:Unlimited
    The owner of the registration certificate:Novartis Pharma AGNovartis Pharma AG Switzerland
    Manufacturer: & nbsp
    Representation: & nbspNOVARTIS PHARMA LLCNOVARTIS PHARMA LLC
    Information update date: & nbsp25.03.2018
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