Certified pills 0,25mg N60
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Composition Everolimus 250 mcg. Excipients: butylhydroxytoluene - 25 mcg, lactose monohydrate - 2.225 mg, hypromellose - 10 mg, magnesium stearate - 400 mcg, crospovidone - 16 mg, anhydrous lactose - 51.1 mg. Pharmacological action Immunosuppressive drug. The active substance of the drug Certain - everolimus - is an inhibitor of the proliferative signal. Everolimus has an immunosuppressive effect by inhibiting the antigen-activated proliferation of T-cells and, accordingly, clonal expansion caused by specific T-cell interleukins, for example, interleukin-2 and interleukin-15. Everolimus inhibits the intracellular signaling pathway, which normally leads to cell proliferation triggered by the binding of these T cell growth factors to the corresponding receptors. The blockade of this signal by everolimus leads to stopping cell division at the G1 stage of the cell cycle. At the molecular level, everolimus forms a complex with the cytoplasmic protein FKBP-12. In the presence of everolimus, inhibition of phosphorylation of p70 S6 kinase stimulated by growth factor occurs. Since phosphorylation of p70 S6 kinase is under the control of FRAP (the so-called m-TOR), these data suggest that the everolimus-PKBP-12 complex is associated with FRAP. FRAP is a key regulatory protein that controls cellular metabolism, growth and proliferation. a dysfunctional FRAP, therefore, explains the stop of the cell cycle caused by everolimus. Everolimus has, therefore, a mechanism of action different from cyclosporin. In preclinical models of allotransplantation, the higher efficiency of the combination of everolimus with cyclosporine was shown than with the isolated use of each of them. The effect of everolimus is not limited to the effect on T cells. It inhibits growth factor-stimulated proliferation of both hematopoietic and non-hematopoietic cells (for example, smooth muscle cells). Stimulated growth factor proliferation of vascular smooth muscle cells, which is triggered by damage to the endothelial cells and leads to the formation of neointima, plays a key role in the pathogenesis of chronic rejection.Experimental studies have shown inhibition of neointima formation in rats with aortic allograft.
Dosage and administration
: The drug is taken orally. The recommended initial dose for adult patients with renal and cardiac transplants is 0.75 mg 2 times / day. The drug should be started as soon as possible after transplantation. The daily dose of Sertikan is always divided into 2 doses. the drug is taken either always with food, or always without it. A certificate is taken at the same time with cyclosporine in the form of a microemulsion. Correction of Sertikan's dosing regimen may be required, taking into account plasma concentrations achieved, tolerability, individual response to treatment, changes in concomitant drug therapy and the clinical situation. Correction of the dosing regimen can be carried out at intervals of 4-5 days. The incidence of acute rejection, confirmed by biopsy, was higher in the Negroid race compared to the rest. According to the limited information available, members of the Negroid race may need a higher dose of Sertikan to achieve the same effect as other patients receiving the drug at recommended adult doses. Currently available data on efficacy and safety is not enough to provide specific recommendations on the use of everolimus among members of the Negroid race. Clinical experience with Sertikan in patients aged & # 8805 .65 years is limited. However, there were no obvious differences in the pharmacokinetics of everolimus in patients aged # 8805 .65-70 years compared with younger adult patients. In patients with impaired renal function, dose adjustment is not required. In patients with liver failure, the basal concentration of everolimus in whole blood should be carefully monitored. In patients with mild and moderate liver failure (class A or B on the Child-Pugh scale), the dose of Sertican should be reduced by about 2 times compared with the average dose in cases where there is a combination of two indicators listed below: bilirubin> 34 mcmol / l (> 2 mg / dl), albumin is less than 35 g / l (less than 3.5 g / dl), prothrombin time> 1.3 INR (prolongation> 4 s).Further dose titration is carried out based on therapeutic monitoring data. In patients with severe liver failure (Child-Pugh grade C), everolimus has not been studied. Therapeutic Monitoring Regular monitoring of therapeutic concentration of everolimus in whole blood is recommended. Based on the analysis of exposure-efficacy and exposure-safety, it was found that in patients with C0> 3 ng / ml, the frequency of acute rejection of both the kidney and heart, confirmed by biopsy, was lower than in patients with C0 less than 3 ng / ml. The recommended upper limit of the range of therapeutic concentration of everolimus is 8 ng / ml. Concentrations above 12 ng / mL have not been studied. Concentrations of everolimus were determined by chromatography. It is especially important to control the concentration of everolimus in the blood of patients with hepatic insufficiency in the period of simultaneous use of strong inducers and inhibitors of CYP3A4, when switching to another dosage form and / or if the dose of cyclosporine is significantly reduced. The concentration of everolimus in the blood with the use of dispersible pills may be slightly lower than with conventional pills. It is preferable to carry out the correction of the dosing regimen of Sertikan, based on the C0 values of everolimus, determined more than 4-5 days after the previous dose change. Since cyclosporine interacts with everolimus, the concentration of the latter may decrease if the concentration of cyclosporin is significantly reduced (C0 is less than 50 ng / ml). Recommendations on the dosing regimen of cyclosporine in combination therapy with the certified patient in patients after transplantation of the kidney of the Certikan should not be used for a long time with cyclosporine in the full dose. Reducing the dose of cyclosporine in patients after renal transplantation who received Certikan resulted in an improvement in renal function. Cyclosporine dose reduction should be initiated 1 month after transplantation. Based on the data obtained during the clinical study, the recommended concentration ranges of cyclosporine (the concentration of cyclosporine in the blood was determined 2 hours after the dose was taken) are determined in the protocol of this study as follows: 0-4 weeks - 1000-1400 ng / ml. 5-8 week - 700-900 ng / ml. Week 9-12 - 550-650 ng / ml. 13-52 week - 350-450 ng / ml.In this study, the basal concentrations (C0) of cyclosporine were (ng / ml): month 1 - 239 ± 114. month 3 -131 ± 85. month 6 - 82 ± 60. month 12 - 61 ± 28. It is very important that in the early period after transplantation, the concentrations of everolimus and cyclosporine do not decrease below the therapeutic range, in order to minimize the risk of no effect. Before reducing the dose of cyclosporine, one should ensure that the equilibrium C0 value of everolimus is> 3 ng / ml. There are limited data regarding dosing of Sertikan at concentrations of cyclosporin C0 less than 50 ng / ml or C2 less than 350 ng / ml in the supporting phase. If the patient does not tolerate a reduction in the dose of cyclosporine, then the subsequent use of Sertikan should be reviewed. Recommendations on the dosing regimen of cyclosporine in combination therapy with a certified patient in patients after heart transplantation For patients after heart transplantation in the supporting phase, reduce the dose of cyclosporine in order to improve kidney function. With the progression of renal dysfunction or in the event that the calculated value of creatinine clearance is less than 60 ml / min, correction of the treatment regimen is necessary on the basis of data obtained during clinical studies. In studies, Certian was prescribed in combination with reduced doses of cyclosporine and basal concentration values (C0) of cyclosporine were: in the 1st month - 200-350 ng / ml, in the 2nd month - 150-250 ng / ml, in 3-4 months - 100-200 ng / ml, in the 5-6th months - 75-150 ng / ml, in the 7-12th months - 50-100 ng / ml. Before reducing the dose of cyclosporine, one should ensure that the equilibrium C0 value of everolimus is> 3 ng / ml. With heart transplantation, there are limited data regarding the dosing of Sertikan at C0 cyclosporine 50-100 ng / mg - after 12 months. Instructions for use of the drug Tablets should be taken whole, not crushed before use. drink a glass of water. Patients who cannot swallow pills are prescribed Certican in the form of dispersible pills, from which a dispersion is prepared (fine solid particles in water). When taking dispersible pills, you can use an oral syringe. To do this, place the dispersible pills in a syringe. The maximum amount of Sertikan, from which it is possible to prepare a dispersion with a water volume of 10 ml (syringe 10 ml), is 1.25 mg. Next, add water to the 5 ml mark, wait 90 seconds, while slightly shaking the syringe. After the dispersion is formed, the contents of the syringe are injected directly into the mouth.Then rinse the syringe by typing 5 ml of water and inject the obsessively into the mouth. After that you should drink 10-100 ml of water. When taking dispersible pills, you can use a plastic cup. To do this, place Sertikan's dispersible pills in a plastic cup containing approximately 25 ml of water. The maximum amount of Sertikan, from which you can prepare a dispersion with a water volume of 25 ml, is 1.5 mg. Then you should leave the cup for about 2 minutes to form a dispersion. Shake the cup before use to allow the pills to dissolve. Then rinse the cup immediately, adding 25 ml of water, and completely drink the contents. When taking dispersible pills, you can use a naso-gastric tube. To do this, place Sertikan's dispersible pills in a small plastic medical glass containing 10 ml of water. Wait 90 seconds, slightly rotating the glass. Then the dispersion should be collected into the syringe and slowly (over 40 seconds) injected through a naso-gastric tube. Then rinse the beaker (and syringe) 3 times, taking 5 ml of water, and inject through the probe. After that wash the probe with 10 ml of water. After the introduction of Sertikan, the naso-gastric tube should be clamped for at least 30 minutes. If cyclosporine in the form of a microemulsion is also administered through a naso-gastric tube, this must be done before the administration of Sertikan. Do not mix these two drugs. Precautions During the period of treatment may worsen psoriasis. With pheochromocytoma, propranolol can be used only after taking an alpha blocker. After a long course of treatment, propranolol should be discontinued gradually, under the supervision of a physician. Against the background of treatment with propranolol, IV administration of verapamil, diltiazem should be avoided. A few days before anesthesia, you must stop taking propranolol or pick up a remedy for anesthesia with minimal negative inotropic effects. Influence on the ability to drive vehicles and control mechanisms In patients whose activities require increased attention, the question of the use of propranolol on an outpatient basis should be addressed only after evaluating the individual response of the patient.Side Effects Data on the incidence of adverse reactions were obtained in three clinical trials (pooled data from 1199 patients). In these three randomized, double-blind, controlled, multicenter clinical studies (2 studies in patients with kidney transplants de novo and 1 study in patients with de novo heart transplants), in which Certican was used at a dose of 1.5 mg / day or 3 mg / day for at least 12 months in combination with cyclosporin in the form of a microemulsion and glucocorticosteroids. Also, data on the incidence of adverse reactions were obtained in two open-label studies that examined the efficacy and safety of Sertikan at a dose of 1.5 mg / day and 3 mg / day in combination with cyclosporine at a reduced dose in patients with de novo transplantation. The following criteria were used to determine the frequency of adverse reactions: very often (& # 8805 .1 / 10). often (& # 8805 .1 / 100, less than 1/10). sometimes (& # 8805 .1 / 1000, less than 1/100). rarely (& # 8805 .1 / 10 000, less than 1/1000). very rarely (less than 1/10 000). The following are undesirable reactions that may or may be related to the use of Sertikan, which have been reported in phase III clinical studies (kidney or heart transplantation). On the part of the hematopoietic system and the lymphatic system: very often - leukopenia1. often - thrombocytopenia1, anemia1, coagulopathy, thrombotic thrombocytopenic purpura / hemolytic uremic syndrome. sometimes hemolysis. On the part of the endocrine system: sometimes - hypogonadism in men (reduced testosterone levels, increased LH levels). On the part of the metabolism: very often - hypercholesterolemia, hyperlipidemia. often - hypertriglyceridemia. Since the cardiovascular system: very often - pericardial effusion2. often - increased blood pressure, lymphocele3, venous thrombosis. On the part of the respiratory system: very often - pleural effusions2. often - pneumonia. sometimes pneumonitis. On the part of the digestive system: often - abdominal pain, diarrhea, nausea, vomiting. sometimes - hepatitis, abnormal liver function, jaundice, increased ALT, ACT, GGT. Skin and subcutaneous tissue: often - angioedema, acne, complications from surgical wounds. sometimes a rash. From the musculoskeletal system: sometimes - myalgia. Urinary system: often urinary tract infections. sometimes - necrosis of the renal tubules, pyelonephritis.Other: often - swelling, pain, viral, bacterial and fungal infections, sepsis. sometimes wound infection. 1 - a dose-dependent effect was established or this phenomenon was observed significantly more often in patients who received the drug at a dose of 3 mg / day. 2 - with a heart transplant. 3 - with kidney transplantation. 4 - mainly in patients taking simultaneously ACE inhibitors. In controlled clinical trials in which patients were observed for at least one year, lymphoma or lymphoproliferative disease developed in 1.4% of patients receiving Certican (1.5 mg or 3 mg / day) in combination with other immunosuppressants. Malignant skin neoplasms were registered in 1.3% of patients, other types of malignancy - in 1.2% of patients. The occurrence of these adverse events may depend on the degree and duration of immunosuppressive therapy. In the main studies, an increase in serum creatinine concentration was observed more frequently in patients receiving Certikan in combination with a full dose of cyclosporine in the form of a microemulsion than in patients in the control group. The overall incidence of adverse events was lower with a reduced dose of cyclosporine in the form of a microemulsion. The safety profile of Sertikan in studies using the drug along with a reduced dose of cyclosporine was the same as in the 3 main studies where the standard dose of cyclosporine was prescribed. However, when using Sertikan together with a reduced dose of cyclosporine, an increase in plasma creatinine was less common and a lower mean and median plasma creatinine concentration was observed than in other phase III studies. The use of m-TOR inhibitors, including Saryk, rarely showed lesions of the lung parenchyma, for example, inflammation of the lung parenchyma (pneumonitis) and / or pulmonary fibrosis of non-infectious etiology, in isolated cases with a fatal outcome. In most cases, after the withdrawal of therapy by Certican and / or prescription of the GCS, the disappearance of these adverse reactions was noted. Specific guidance Certican should not be used in patients with rare hereditary disorders associated with galactose intolerance, severe lactase deficiency or glucose-galactose malabsorption.Everolimus has not been studied in patients with severe liver failure. It is recommended to carefully monitor the concentration of everolimus in the blood plasma of patients with impaired liver function. Regular monitoring of renal function is recommended for all patients. With an increase in serum creatinine concentration, consideration should be given to correcting the immunosuppressive regimen, in particular, reducing the dose of cyclosporine. Caution should be exercised while the use of other drugs that have a negative effect on kidney function. Treatment with Certican should be initiated and performed only by physicians experienced in immunosuppressive therapy after organ transplantation, and who have the ability to monitor the concentration of everolimus in whole blood. In clinical studies, Certified was used simultaneously with cyclosporine in the form of a microemulsion, basiliximab, and glucocorticosteroids. The use of Sertikan in combination with other immunosuppressive agents has not been sufficiently studied. The use of Sertikan in patients with high immunological risk is not well understood. Combined use of Sertikan with strong inhibitors of CYP3A4 (for example, ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, ritonavir) and inducers (for example, rifampicin, rifabutin) is not recommended unless the expected benefit of such therapy exceeds the potential risk. It is recommended to control the concentration of everolimus in whole blood with simultaneous use with inducers or inhibitors of CYP3A4 and after their withdrawal. In patients receiving immunosuppressive therapy, including Certican, there is an increased risk of developing lymphomas and other malignant diseases, especially skin. Absolute risk is associated more with the duration and intensity of immunosuppression than with the use of a particular drug. Patients should be monitored regularly to detect skin lesions, recommend minimizing exposure to ultraviolet radiation, sunlight, and use appropriate sunscreen. Hyperimmunosuppression, including and when using Sertican-based treatment regimens, it predisposes to the development of infections, especially those caused by opportunistic pathogens.There are reports of the development of fatal infections and sepsis with Sertikan. In clinical studies of Sertikan, the development of pneumonia caused by Pneumocystis carinii was prevented for 12 months after transplantation. Prevention of the development of cytomegalovirus infection was recommended for 3 months after transplantation, especially in patients with an increased risk of developing this infection. The combined use of Sertikan with cyclosporine in the form of a microemulsion in patients after transplantation was associated with an increase in serum cholesterol and triglycerides, which may require appropriate treatment. Patients receiving Certified should be monitored to identify hyperlipidemia and, if necessary, to carry out treatment with lipid-lowering drugs and prescribe an appropriate corrective diet. It is necessary to evaluate the risk / benefit ratio for patients who have hyperlipidemia before initiating therapy with immunosuppressive agents, including Certikan. You should also evaluate the risk / benefit ratio of continuing the treatment with Certican in patients with severe refractory hyperlipidemia. Patients receiving HMG-CoA reductase inhibitors and / or fibrates should be monitored for the development of adverse events caused by the above drugs. Use in pediatrics Data on the use of Sertican in children and adolescents is not enough to recommend the use of the drug in this category of patients. However, there are limited data on the use of Sertikan in pediatrics for kidney transplantation. Impact on the ability to drive motor vehicles and control mechanisms Research on the influence of Sertikan on the ability to drive motor vehicles and driving mechanisms have not been conducted. Use during pregnancy and breastfeeding There are no data on the use of Sertikan during pregnancy. Experimental studies have shown the presence of toxic effects on reproduction, including embryotoxicity and fetotoxicity. It is not known whether there is a potential risk to a person. Do not use Certikan during pregnancy except in cases where the expected benefit from therapy outweighs the potential risk to the fetus.Women of childbearing age should be advised to use effective contraceptive methods during the period of treatment with Certican and for 8 weeks after the end of therapy. It is not known whether everolimus is excreted in human breast milk. Experimental studies have shown that everolimus and / or its metabolites rapidly penetrated the milk of lactating rats. Therefore, women who receive a Certificate should not breastfeed. Type: Drug Quantity in the package, pcs: 60 Shelf life: 36 months Active ingredient: Everolimus Everolimus Route of administration: Oral Vacation procedure: Prescription Release form: Prescription Storage conditions: In a dry place, In a dark place, Keep out of reach of children Maximum storage temperature, ° С: 30 Pharmacological group: L04AA18 Everolimus Minimum age: 18 yearsActive ingredients
Release form
Pills
Composition
Everolimus 250 mcg Auxiliary substances: butylhydroxytoluene - 25 mcg, lactose monohydrate - 2.225 mg, hypromellose - 10 mg, magnesium stearate - 400 mcg, crospovidone - 16 mg, anhydrous lactose - 51.1 mg.
Pharmacological effect
Immunosuppressive drug. The active substance of the drug Certain - everolimus - is an inhibitor of the proliferative signal. Everolimus has an immunosuppressive effect by inhibiting the antigen-activated proliferation of T-cells and, accordingly, clonal expansion caused by specific T-cell interleukins, for example, interleukin-2 and interleukin-15. Everolimus inhibits the intracellular signaling pathway, which normally leads to cell proliferation triggered by the binding of these T cell growth factors to the corresponding receptors. The blockade of this signal by everolimus leads to stopping cell division at the G1 stage of the cell cycle. At the molecular level, everolimus forms a complex with the cytoplasmic protein FKBP-12. In the presence of everolimus, inhibition of phosphorylation of p70 S6 kinase stimulated by growth factor occurs. Since phosphorylation of p70 S6 kinase is under the control of FRAP (the so-called m-TOR), these data suggest that the everolimus-PKBP-12 complex is associated with FRAP. FRAP is a key regulatory protein that controls cellular metabolism, growth and proliferation. a dysfunctional FRAP, therefore, explains the stop of the cell cycle caused by everolimus. Everolimus has, therefore, a mechanism of action different from cyclosporin.In preclinical models of allotransplantation, the higher efficiency of the combination of everolimus with cyclosporine was shown than with the isolated use of each of them. The effect of everolimus is not limited to the effect on T cells. It inhibits growth factor-stimulated proliferation of both hematopoietic and non-hematopoietic cells (for example, smooth muscle cells). Stimulated growth factor proliferation of vascular smooth muscle cells, which is triggered by damage to the endothelial cells and leads to the formation of neointima, plays a key role in the pathogenesis of chronic rejection. Experimental studies have shown inhibition of neointima formation in rats with aortic allograft.
Indications
- prevention of kidney and heart transplant rejection in adult recipients with low and medium immunological risk, receiving basic immunosuppressive therapy with cyclosporine in the form of a microemulsion and glucocorticosteroids.
Contraindications
- hypersensitivity to everolimus, sirolimus or other components of the drug.
Use during pregnancy and lactation
Data on the use of Sertikan during pregnancy are not available. Experimental studies have shown the presence of toxic effects on reproduction, including embryotoxicity and fetotoxicity. It is not known whether there is a potential risk to a person. Do not use Certikan during pregnancy except in cases where the expected benefit from therapy outweighs the potential risk to the fetus. Women of childbearing age should be advised to use effective contraceptive methods during the period of treatment with Certican and for 8 weeks after the end of therapy. It is not known whether everolimus is excreted in human breast milk. Experimental studies have shown that everolimus and / or its metabolites rapidly penetrated the milk of lactating rats. Therefore, women who receive a Certificate should not breastfeed.
Dosage and administration
The drug is taken orally. The recommended initial dose for adult patients with renal and cardiac transplants is 0.75 mg 2 times / day. The drug should be started as soon as possible after transplantation.The daily dose of Sertikan is always divided into 2 doses. the drug is taken either always with food, or always without it. A certificate is taken at the same time with cyclosporine in the form of a microemulsion. Correction of Sertikan's dosing regimen may be required, taking into account plasma concentrations achieved, tolerability, individual response to treatment, changes in concomitant drug therapy and the clinical situation. Correction of the dosing regimen can be carried out at intervals of 4-5 days. The incidence of acute rejection, confirmed by biopsy, was higher in the Negroid race compared to the rest. According to the limited information available, members of the Negroid race may need a higher dose of Sertikan to achieve the same effect as other patients receiving the drug at recommended adult doses. Currently available data on efficacy and safety is not enough to provide specific recommendations on the use of everolimus among members of the Negroid race. Clinical experience with Sertikan in patients aged & # 8805 .65 years is limited. However, there were no obvious differences in the pharmacokinetics of everolimus in patients aged # 8805 .65-70 years compared with younger adult patients. In patients with impaired renal function, dose adjustment is not required. In patients with liver failure, the basal concentration of everolimus in whole blood should be carefully monitored. In patients with mild and moderate liver failure (class A or B on the Child-Pugh scale), the dose of Sertican should be reduced by about 2 times compared with the average dose in cases where there is a combination of two indicators listed below: bilirubin> 34 mcmol / l (> 2 mg / dl), albumin is less than 35 g / l (less than 3.5 g / dl), prothrombin time> 1.3 INR (prolongation> 4 s). Further dose titration is carried out based on therapeutic monitoring data. In patients with severe liver failure (Child-Pugh grade C), everolimus has not been studied. Therapeutic Monitoring Regular monitoring of therapeutic concentration of everolimus in whole blood is recommended.Based on the analysis of exposure-efficacy and exposure-safety, it was found that in patients with C0> 3 ng / ml, the frequency of acute rejection of both the kidney and heart, confirmed by biopsy, was lower than in patients with C0 less than 3 ng / ml. The recommended upper limit of the range of therapeutic concentration of everolimus is 8 ng / ml. Concentrations above 12 ng / mL have not been studied. Concentrations of everolimus were determined by chromatography. It is especially important to control the concentration of everolimus in the blood of patients with hepatic insufficiency in the period of simultaneous use of strong inducers and inhibitors of CYP3A4, when switching to another dosage form and / or if the dose of cyclosporine is significantly reduced. The concentration of everolimus in the blood with the use of dispersible pills may be slightly lower than with conventional pills. It is preferable to carry out the correction of the dosing regimen of Sertikan, based on the C0 values of everolimus, determined more than 4-5 days after the previous dose change. Since cyclosporine interacts with everolimus, the concentration of the latter may decrease if the concentration of cyclosporin is significantly reduced (C0 is less than 50 ng / ml). Recommendations on the dosing regimen of cyclosporine in combination therapy with the certified patient in patients after transplantation of the kidney of the Certikan should not be used for a long time with cyclosporine in the full dose. Reducing the dose of cyclosporine in patients after renal transplantation who received Certikan resulted in an improvement in renal function. Cyclosporine dose reduction should be initiated 1 month after transplantation. Based on the data obtained during the clinical study, the recommended concentration ranges of cyclosporine (the concentration of cyclosporine in the blood was determined 2 hours after the dose was taken) are determined in the protocol of this study as follows: 0-4 weeks - 1000-1400 ng / ml. 5-8 week - 700-900 ng / ml. Week 9-12 - 550-650 ng / ml. 13-52 week - 350-450 ng / ml. In this study, the basal concentrations (C0) of cyclosporine were (ng / ml): month 1 - 239 ± 114. month 3 -131 ± 85. month 6 - 82 ± 60. month 12 - 61 ± 28. It is very important that in the early period after transplantation, the concentrations of everolimus and cyclosporine do not decrease below the therapeutic range, in order to minimize the risk of no effect.Before reducing the dose of cyclosporine, one should ensure that the equilibrium C0 value of everolimus is> 3 ng / ml. There are limited data regarding dosing of Sertikan at concentrations of cyclosporin C0 less than 50 ng / ml or C2 less than 350 ng / ml in the supporting phase. If the patient does not tolerate a reduction in the dose of cyclosporine, then the subsequent use of Sertikan should be reviewed. Recommendations on the dosing regimen of cyclosporine in combination therapy with a certified patient in patients after heart transplantation For patients after heart transplantation in the supporting phase, reduce the dose of cyclosporine in order to improve kidney function. With the progression of renal dysfunction or in the event that the calculated value of creatinine clearance is less than 60 ml / min, correction of the treatment regimen is necessary on the basis of data obtained during clinical studies. In studies, Certian was prescribed in combination with reduced doses of cyclosporine and basal concentration values (C0) of cyclosporine were: in the 1st month - 200-350 ng / ml, in the 2nd month - 150-250 ng / ml, in 3-4 months - 100-200 ng / ml, in the 5-6th months - 75-150 ng / ml, in the 7-12th months - 50-100 ng / ml. Before reducing the dose of cyclosporine, one should ensure that the equilibrium C0 value of everolimus is> 3 ng / ml. With heart transplantation, there are limited data regarding the dosing of Sertikan at C0 cyclosporine 50-100 ng / mg - after 12 months. Instructions for use of the drug Tablets should be taken whole, not draw