Mayscept - instructions for use, doses, side effects, contraindications

Excipients: microcrystalline cellulose, lactose, povidone (K-90), croscarmellose sodium, magnesium stearate, purified water. The tablet shell contains opadrai 03B50051 (hypromellose 6 cP, titanium dioxide dye, macrogol 400, indigo carmine dye aluminum lacquer, iron oxide red dye).

Description:

Hard gelatin capsules, size "1", with a yellow body and a gray lid containing a white or almost white powder.

Film coated tablets shell: oval tablet biconvex form, covered with a film coating of grayish-gray color with engraving "MYT 500" on one side and risk on the other.

Pharmacotherapeutic group:Immunosuppressive remedy.

ATX: & nbsp

L.04.A.A Selective immunosuppressants

Pharmacodynamics:

Immunosuppressant, inhibitor of inosine monophosphate dehydrogenase

Mycophenolate mofetil (MMF) is a 2-morpholinoethyl ester, which is a prodrug of immunosuppressive mycophenolic acid (MPA), which is produced by several species of the genus Penicillium. The mechanism of IFC action is the inhibition of purine synthesis. IFC is a reversible noncompetitive inhibitor of inosine monophosphate dehydrogenase, an enzyme that participates in the conversion of inosine monophosphate (IMP) into xanthosine monophosphate, which is a precursor of guanosine nucleotides. This leads to blockade of synthesis de novo guanosine nucleotides, which are indispensable substrates for the synthesis of DNA and RNA.Unlike other cells that can use guanosine synthesis bypasses, B- and T-lymphocytes depend on the synthesis of guanosines de novo.

Pharmacokinetics:

Mycophenolate mofetil is rapidly absorbed from the gastrointestinal tract after ingestion and is converted to an active metabolite of MFC. The MPA is further converted to the gluconide of MPA (HMFC), which is pharmacologically inactive. After oral administration, the average relative bioavailability of MPA is 94%. The maximum concentration in plasma (C_max) is achieved approximately 2 hours after ingestion. The observed secondary peak plasma concentrations are due to enterohepatic recirculation of this drug. Food reduces C_max IFC is approximately 40%, but does not affect the area under the "concentration-time" curve (AUC). The degree of binding of MPC to plasma albumin depends on its concentration. The binding of IFC to plasma proteins does not depend on the presence of such widely used immunosuppressants as ciclosporin, prednisone and tacrolimus. The binding of IFC to proteins is also not affected by other commonly used drugs, for example warfarin, digoxin and phenytoin. IFC is minimally bound to plasma lipoproteins, and this binding is independent of its concentration. IFC is converted into HMFC and three other inactive metabolites: N- (2-carboxymethyl) -morpholine, N- (2-hydroxyethyl) -morpholine and NN- (2-hydroxyethyl) -morpholine oxide. Alcoholic cirrhosis of the liver, in all likelihood, does not have a significant effect on the conversion of IFC into HMFC. IFC is eliminated mainly by the kidneys, and more than 90 % the accepted dose is excreted in the urine in the form of HMFC. After oral administration, the average apparent half-life and clearance from plasma mycophenolic acid are 17.9 h and 11.6 l / h, respectively. After taking one dose of mycophenolate mofetil AUC IFC increased almost twice in patients with severe renal dysfunction.

Hemodialysis does not have a significant effect on plasma concentrations of IFC and HMFC. However, at higher concentrations of IFPC (> 100 μg / ml), some of it can be removed.

Indications:

Allogeneic grafts: to prevent organ rejection in recipients of allogeneic grafts of the kidneys, liver or heart. Mycophenolate mofetil are used in combination with apsporin and corticosteroids.

Contraindications:

Hypersensitivity to mycophenolate mofetil, mycophenolic acid or any other ingredient in the drug.

Dosing and Administration:

Kidney transplantation: appoint 1 g orally twice a day (daily dose of 2 g). In clinical studies, a dose of 1.5 g twice daily (a daily dose of 3 g) was used, which proved to be safe and effective, but in kidney transplant recipients such a dose increase was not accompanied by an increase in the effectiveness of immunosuppressive therapy. In general, patients who received 2 grams per day, the safety profile was better than those who received 3 grams per day.

Heart transplantation: The recommended dose is 1.5 grams orally twice a day (daily dose of 3 g).

Liver transplantation: the recommended dose is 1.5 grams orally twice a day. The patient should be given the first oral dose as soon as possible after transplantation. It is shown that food reduces C_max IFC is approximately 40%, and therefore mycophenolate mofetil it is recommended to take an empty stomach.

Have elderly and senile patients (≥ 65 years old) 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 a day.

Side effects:

The main side effects of mycophenolate mofetil are diarrhea, leukopenia, sepsis and vomiting, as well as an increased incidence of certain infections.

Rare cases of such serious life-threatening infections as meningitis and infective endocarditis are described, in addition, there was an increase in the incidence of such serious infections as tuberculosis and atypical mycobacterial infection.

Other side effects associated with ≥3% of patients receiving combined mycophenolate therapy with mofetil, cyclosporine and corticosteroids include:

For the body as a whole: pain, abdominal pain, fever, heart pain, infection.

From the cardiovascular system: stenocardia, atrial fibrillation, arterial hypotension, peripheral vascular injury, postural hypotension, tachycardia, thrombosis, vasodilation, ventricular extrasystoles, congestive heart failure, supraventricular tachycardia, ventricular tachycardia, atrial flutter, pulmonary artery hypertension, cardiac arrest, increased venous pressure, fainting, supraventricular extrasystoles, pallor, vasospasm.

From the side of the central nervous system: anxiety, depression, hypertension, paresthesia, drowsiness, emotional lability, neuropathy, convulsions, hallucinations, dizziness, tremor, insomnia.

From the skin: alopecia, fungal dermatitis, hirsutism, itching, benign skin tumors, skin hypertrophy, skin ulcers, sweating, bruising and skin cancer.

From the endocrine system: diabetes, parathyroid gland disorders, Cushing's syndrome, hypothyroidism.

Metabolic and food: edema, hypercholesterolemia, hyperproteinemia, increased ALT.

From the gastrointestinal tract: anorexia, esophagitis, flatulence, gastritis, gastroenteritis, bleeding, gingivitis, gingival hyperplasia, hepatitis, intestinal obstruction, infections, ulceration of the oral mucosa, rectal pathology, liver enlargement, dysphagia, jaundice, stomatitis, thirst, abdominal pain, nausea, constipation , diarrhea.

From the genitourinary system: albuminuria, dysuria, hydronephrosis, impotence, pain, pyelonephritis, urinary frequency, nocturia, renal failure, haematuria, urinary incontinence, prostate pathology, urinary retention, herpes and CMV disease, hyperuricemia, nefronekroz,infectious lesions of the lower sections of the urogenital tract.

From the musculoskeletal system: arthralgia, joint damage, spasms of calf muscles, myasthenia gravis.

From the respiratory system: asthma, pulmonary edema, pleural effusion, rhinitis, sinusitis, lung atelectasis, hiccups, pneumothorax, increased sputum, nosebleeds, apnea, voice change, pain, hemoptysis, tumors, cough, infections.

From the sense organs: amblyopia, cataract, conjunctivitis, pain in the ears, deafness, eye pathology, tinnitus, visual disturbances, lacrimal gland disorders, eye hemorrhages.

Other: increased abdominal pain, chills and fever, facial swelling, flu-like syndrome, bleeding, hernia, fatigue, pelvic pain, ecchymosis, erythrocytosis, neck pain, cellulitis, petechiae, phlebitis, thrombosis, increased or decreased body weight, dehydration, anemia, leukopenia, leukocytosis, thrombocytopenia.

Overdose:

Symptoms: when taking 4-5 g of mycophenolate mofetil per day, the frequency of gastrointestinal side effects (nausea, vomiting, diarrhea), as well as hematologic disorders, in particular neutropenia, increases, as compared with the intake of 3 g of this drug per day or less.

Treatment: IFC and GMPK are usually not removed from the body by hemodialysis. It should be noted, however, that at high concentrations of HMFC in the plasma (more than 100 mg / ml), small amounts of this substance are still excreted by hemodialysis. Elimination of IFC can be accelerated with the help of sequestrants of bile acids, such as cholestyramine.

Interaction:

Interactions were studied only in adults.

Acyclovir: in the administration of mycophenolate mofetil together with acyclovir, higher concentrations of IFPC and acyclovir in plasma were observed than with the administration of each drug alone. Because plasma concentrations of IFNP, acyclovir or its homologues, such as valaciclovir, increase with renal insufficiency, there is a possibility that these two drugs compete with tubular secretion, that may lead to a further increase in the concentration of both drugs.

Antacids containing magnesium hydroxide and aluminum: when taken together with antacids, the absorption of mycophenolate mofetil decreases.

Cholestyramine: after administration of a single dose of mycophenolate mofetil in 1.5 g to healthy volunteers, previously taking 4 g of cholestyramine 3 times a day for 4 days, there was a decrease in AUFROM_IFC on 40%.

Drugs acting on the intrahepatic circulation: when combined with mycophenolate mycophenolate mofetil noted a decrease in the effect of the latter.

Ganciclovir: based on the results of research with a one-time oral administration of the recommended dose of mycophenolate mofetil and intravenous ganciclovir, taking into account the well-known effect of renal impairment on the pharmacokinetics of mycophenolate mofetil (. See "Pharmacokinetics" and "Precautions") and ganciclovir, it can be assumed that the simultaneous use of two These drugs (competing in the tubular secretion process) will lead to an increase in the concentrations of IFPC and ganciclovir. A significant change in the pharmacokinetics of IFC is not expected, so adjust the dose of mycophenolate mofetil is not necessary. If mycophenolate mofetil, ganciclovir and its analogues, such as valganciclovir, appoint patients with renal insufficiency, it is necessary to adhere to the recommended dosing regimen for ganciclovir and carefully monitor patients.

Cyclosporin A: mycophenolate mofetil does not affect the pharmacokinetics of cyclosporin A.

Observations have shown that the use of cyclosporin A reduces AUFROM_IFC by 19-38%, probably because of inhibition of bile secretion, which reduces intrahepatic circulation.

Tacrolimus: the patients with a transplanted kidney: with the combined use of cyclosporine and mycophenolate mofetil, an increase in AUC_IFC by 30%, but when it is replaced ciclosporin on tacrolimus the maximum concentration of IFC does not change, and IFPC - is reduced by 20%. In part, this may be due to increased biliary secretion of IFGC in combination with increased hepatic intestinal recirculation of MPA, as the increase in MPC concentrations after tacrolimus administration was more pronounced near the end of the concentration-time curve (4-12 hours after administration). In patients receiving tacrolimus, the dose of MMF should not exceed 1 g twice a day.

Patients with transplanted liver: The interaction of mycophenolate mofetil and tacrolimus is small andit is trained. When studying the pharmacokinetics of mycophenolate mofetil together with tacrolimus in labile patients with transplanted liver, an increase in AUC_tacrolimus by 20%, after prolonged use of mycophenolate mofetil in a dose of 1.5 g 2 times a day.

Other interactions: with simultaneous administration of probenecid and mycophenolate mofetil monkeys, an increase in AUC_IFCG in plasma in 3 times. Thus, other drugs undergoing tubular secretion can compete with IFPC, which leads to an increase in the plasma concentration of IFPC or another drug that also undergoes tubular secretion.

Live vaccines: should not be administered to patients in a state of immunosuppression.

Antibody formation in response to other vaccines can be reduced.

Special instructions:

Precautionary measures

Monitoring: a complete blood test is done weekly during the first month of treatment, every two weeks during the second and third months of treatment and further once a month during the first year of therapy.

Gastrointestinal bleeding: mycophenolate treatment with mycophenolate is accompanied by an increased incidence of gastrointestinal side effects, including infrequent gastrointestinal ulceration, bleeding and perforation, and should therefore be used with caution in patients suffering from active serious gastrointestinal diseases.

Delayed recovery of renal allograft function: these patients do not need to reduce the dose of mycophenolate mofetil, but it is necessary to closely monitor their condition.

Since MMF is an inhibitor of IMPDG, from the theoretical point of view, it should not be prescribed to patients with a rare, genetically determined hereditary deficiency of hypoxanthine guanine phosphoribosyltransferase (Lesch-Nienen syndrome and Kelly-Zygmiller syndrome).

It is not recommended to combine the use of mycophenolate mofetil with aziotioprine, as they both cause bone marrow suppression. Their joint application has not been studied.

Pregnancy:

Pregnant women did not undergo adequate and well-controlled studies of mycophenolate mofetil. This drug can be given to a pregnant woman only if the potential benefit to a future mother outweighs the possible risks to the fetus. For 1 week or less before the start of treatment for mycophenolate mofetil in women capable of childbearing, the result of a urine test for pregnancy with a sensitivity of at least 50 mIU / ml should be negative.Mycophenolate therapy with mycophenolate can not be started until a negative pregnancy test result is obtained. An effective contraception before the treatment of mycophenolate mofetil, during treatment and for 6 weeks after the end of treatment. This rule extends even for women suffering from infertility, except when the latter is due to hysterectomy. In the absence of abstinence from sexual activity, two effective methods of preventing pregnancy should be used simultaneously. In case of pregnancy during treatment with mycophenolate mofetil, the patient should discuss with the doctor the advisability of maintaining a pregnancy.

Lactation:

Studies in rats receiving mycophenolate mofetil, showed that mycophenolic acid penetrates into the milk. It is not known whether this substance is capable of penetrating the breast milk of women. Feeding infants with mothers who receive mycophenolate mofetil, can, in principle, cause? serious side effects, and therefore in such situations it is necessary to solve the dilemma - to refuse breastfeeding or to cancel mycophenolate mofetil, taking into account the importance of treating a woman with this drug.

Children:

At present, there is no data on the safety and efficacy of mycophenolate mofetil in children.

Lymphomas and malignant neoplasms:

In patients receiving immunosuppressive therapy, in particular the combination of mycophenolate mofetil with other immunosuppressants, increased risk of lymphoma and other malignancies, particularly skin. This risk appears to depend on the intensity and duration of immunosuppression, and not on the use of a specific immunosuppressant. In addition, hypersuppression of the immune system increases the susceptibility of patients to various infections.

As with all patients with an increased risk of skin cancer, exposure to sunlight and ultraviolet rays should be limited by wearing appropriate closed clothing and using sunscreens with a high protective factor.

Neutropenia:

In patients receiving mycophenolate mofetil, it is necessary to regularly do blood tests to monitor neutropenia. Neutropenia can be caused by mycophenolate mofetil, concomitant medications, viral infections and various combinations of these factors.

Impaired renal function:

It should avoid the use of mycophenolate mofetil in doses of more than 1 g twice daily, you should also carefully monitor the patient's condition.

In elderly patients, the risk of adverse events may be higher than in younger patients.

To prevent rejection after kidney, heart and liver transplantation, treatment of refractory rejection of the transplanted kidney, MMP is prescribed in combination with antitimocytic globulin, OKT3 (orthoclone of mouse monoclonal antibodies), cyclosporine and corticosteroids.

Abnormal laboratory indicators:

Increased levels of alkaline phosphatase, creatinine, gamma-glutamyltranspeptidase, lactate dehydrogenase, ACT and ALT, hypercalcemia, hyperlipidemia, hyperuricemia, hypervolemia, hypocalcemia, hypoproteinemia, acidosis, hypoxia, hypophosphatemia, alkalosis and hypochloremia.

Treatment with the drug:

Because the mycophenolate mofetil in an experiment on rats and rabbits showed a teratogenic effect, Misept should not be broken and violated the integrity of the capsule or tablet.It is necessary to avoid inhaling the powder contained in capsules / Mayscept tablets or direct exposure to the skin or mucous membranes. If this happens, you need to thoroughly rinse this area with soap and water, and your eyes - just water.

Form release / dosage:

Tablets of 500 mg, toapsules of 250 mg each.

Packaging:

Tablets of 500 mg: 10 tablets per blister of PVC / Aluminum foil. By 3, 5, 10 blisters with instructions for use in a cardboard box.

Capsules of 250 mg: 10 capsules per blister of PVC / Aluminum foil. By 3, 5, 10 blisters with instructions for use in a cardboard box.

Storage conditions:

In a dry, the dark place at a temperature of no higher than 30 ° C.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use the drug after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:LSR-003305/07

Date of registration:22.10.2007 / 23.06.2015

Expiration Date:Unlimited

The owner of the registration certificate:Panacea Biotech Co., Ltd.Panacea Biotech Co., Ltd. India

Manufacturer: & nbsp

PANACEA BIOTEC, Ltd. India

Representation: & nbspKORAL-MED, CJSCKORAL-MED, CJSC

Information update date: & nbsp28.09.16

Illustrated instructions

Instructions

Misept (Mysept)