Certican

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Certican: instructions for use and reviews

1. Release form and composition
2. Pharmacological properties
3. Indications for use
4. Contraindications
5. Method of application and dosage
6. Side effects
7. Overdose
8. Special instructions
9. Application during pregnancy and lactation
10. Use in childhood
11. In case of impaired renal function
12. For violations of liver function
13. Use in the elderly
14. Drug interactions
15. Analogs
16. Terms and conditions of storage
17. Terms of dispensing from pharmacies
18. Reviews
19. Price in pharmacies

Latin name: Sertican

ATX code: L04AA18

Active ingredient: everolimus (Everolimus)

Producer: Novartis Pharma, AG (Novartis Pharma, AG) (Switzerland)

Description and photo update: 2019-09-07

Prices in pharmacies: from 2300 rubles.

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Certican is an immunosuppressant.

Release form and composition

Dosage forms of Sertican:

tablets: round, flat-cylindrical, with beveled edges, from white to yellowish, with possible marbling in color, on one side there is an engraving "NVR", on the other - "C" (dosage 0.25 mg), "CH" (dosage 0, 5 mg), "CL" (dosage 0.75 mg) or "CU" (dosage 1 mg) (in blisters of 10 pcs., In a cardboard box of 5, 6, 10 or 25 blisters);
dispersible tablets: round, flat-cylindrical, with beveled edges, from white to yellowish, with possible marbling in color, on one side there is an engraving "NVR", on the other - "I" (dosage 0.1 mg) or "JO" (dosage 0.25 mg) (in blisters of 10 pcs., In a cardboard box of 5, 6, 10 or 25 blisters).

Each pack also contains instructions for the use of Sertican.

Composition of 1 tablet:

active substance: everolimus - 0.25; 0.5; 0.75 or 1 mg;
auxiliary components: anhydrous lactose, hypromellose, lactose monohydrate, magnesium stearate, butylhydroxytoluene, crospovidone.

Composition of 1 dispersible tablet:

active substance: everolimus - 0.1 or 0.25 mg;
auxiliary components: hypromellose, crospovidone, lactose monohydrate, anhydrous lactose, magnesium stearate, anhydrous colloidal silicon dioxide, butylhydroxytoluene.

Pharmacological properties

Pharmacodynamics

Everolimus is a proliferative signal inhibitor, an immunosuppressive agent.

The immunosuppressive effect is due to the ability of the drug to inhibit antigen-activated T-cell proliferation and, as a consequence, clonal expansion caused by specific T-cell interleukins, such as interleukin-2 and interleukin-15. Everolimus blocks the intracellular signaling pathway that normally induces cell proliferation triggered by the binding of these T cell growth factors to their respective receptors. Due to the inhibition of this signal under the action of the drug, cell division is stopped at the G ₁ stage _{of the} cell cycle.

Certican promotes inhibition of phosphorylation of p70 S6 kinase stimulated by growth factor. This phosphorylation process is under the control of FRAP, a key regulatory protein that controls cell metabolism, growth, and proliferation. At the molecular level, everolimus forms a complex with the cytoplasmic protein FKBP-12. These data suggest that the everolimus - FKBP-12 complex binds to FRAP. Thus, impaired FRAP function explains the arrest of the cell cycle caused by everolimus. Therefore, everolimus has a different mechanism of action than cyclosporin. In preclinical models of allotransplantation, a higher efficiency was revealed when using the combination of everolimus + cyclosporine than when using each of them alone.

Sertican's effect is not limited to its effect on T cells. Everolimus inhibits the proliferation of hematopoietic and non-hematopoietic cells (eg, smooth muscle), stimulated by growth factors. In the pathogenesis of chronic rejection, a key role is played by the proliferation of vascular smooth muscle cells, which is triggered when endothelial cells are damaged, stimulated by a growth factor, and leads to the formation of neointima.

In experimental studies in rats with aortic allograft, everolimus inhibited neointimal formation.

Pharmacokinetics

The maximum concentration (C _max) of everolimus is observed 1–2 hours after oral administration of Sertican. In patients after transplantation, the concentration of the drug in the blood is proportional to the dose (in the range from 0.25 to 15 mg). Considering the AUC (area under the concentration-time curve), the relative bioavailability of dispersible tablets compared to tablets is 0.9 (90% confidence interval 0.76–1.07).

In the case of taking Sertican with very fatty foods, C _max and AUC decreased by 60% and 16%, respectively. For the greatest decrease in the variability of these indicators, it is recommended to take the drug either constantly with food, or constantly without it.

In patients with cardiac and renal transplants receiving everolimus 2 times a day simultaneously with cyclosporine in the form of a microemulsion, the pharmacokinetics of the drug were comparable. The equilibrium state (C _ss) was noted on the 4th day, while blood concentrations were 2–3 times higher than those after the first dose. When Sertican is taken at doses of 0.75 mg and 1.5 mg 2 times a day, the C _max values are on average 11.1 ± 4.6 ng / ml and 20.3 ± 8 ng / ml, respectively, the average AUC values are respectively 75 ± 31 ng × h / ml and 131 ± 59 ng × h / ml.

When receiving Sertikana at doses of 0.75 mg and 1.5 mg 2 times a day C ₀ everolimus blood (basal concentration determined in the morning before taking the next dose) are respectively 4.1 ± 2.1 ng / ml and 7.1 ± 4.6 ng / ml. C ₀ is highly correlated with AUC. The correlation coefficient varies in the range 0.86–0.94. Everolimus exposure remains stable for the first year after transplantation. According to the analysis of the pharmacokinetics of everolimus in patients after transplantation, the total clearance is 8.8 L / h (variability - 27%), central _Vd - 110 L (variability - 36%).

The ratio of everolimus concentration in blood and in plasma can be 17–73%, which depends on the concentration values in the range of 5–5000 ng / ml. The connection with plasma proteins in healthy volunteers and patients with moderate liver dysfunction is approximately 74%. The volume of distribution (V _d) in the final phase in persons after kidney transplantation receiving maintenance therapy is 342 ± 107 L.

Everolimus is a substrate for P-glycoprotein and CYP3A4 isoenzyme. It is metabolized mainly by O-dealkylation and monohydroxylation. The two main metabolites are formed by hydrolysis of cyclic lactone and have no significant immunosuppressive activity. In the systemic circulation, only everolimus is mainly detected.

After the administration of a single dose of radiolabeled everolimus to transplant patients receiving cyclosporine, about 80% of the radioactivity was detected in the feces, about 5% was excreted in the urine. Everolimus was not detected unchanged in either feces or urine.

The half-life (T _½) is 28 ± 7 hours.

Pharmacokinetics in special clinical situations

According to the analysis of pharmacokinetics in individuals of different races, in patients of the Negroid race, the total clearance is on average 20% higher.

The clearance of everolimus increases depending on the patient's age (from 1 to 16 years), body weight (from 11 to 77 kg), and body surface area (from 0.49 to 1.92 m ²). In an equilibrium state, the clearance is 10.2 ± 3 l / h / m ², T _½ - 30 ± 11 h.

In studies, 19 patients aged 1-16 years after kidney transplantation Sertikan obtained in the form of dispersible tablets of 0.8 mg / m ² (but not more than 1.5 mg), 2 times a day simultaneously with cyclosporin in microemulsion form. The AUC of everolimus in children was 87 ± 27 ng × h / ml, which corresponds to that in adults taking the drug 2 times a day, 0.75 mg. The basal concentration at steady state was 4.4 ± 1.7 ng / ml.

In adult patients aged 16–70 years, there was a decrease in the clearance of everolimus by 0.33% per year, but this change does not require correction of the dosage regimen.

When comparing 8 healthy volunteers and 8 patients with moderately severe functional impairment of the liver (class B on the Child-Pugh scale), the latter had an approximately 2-fold increase in the AUC of everolimus. This indicator positively correlated with the concentration of bilirubin in the blood serum and an increase in prothrombin time, negatively correlated with the concentration of albumin in the serum. At a bilirubin concentration> 34 μmol / L, a prothrombin time> 1.3 INR (prolongation> 4 sec) and / or an albumin concentration <35 g / L, a tendency towards an increase in the AUC value was observed in patients with moderate hepatic insufficiency. The pharmacokinetics of everolimus in severe hepatic impairment (Child-Pugh class C) have not been studied, but the same or more pronounced change in AUC is expected.

In post-transplant renal failure [creatinine clearance (CC) 11–107 ml / min], no changes in the pharmacokinetic characteristics of everolimus were noted.

In patients within 6 months after kidney and heart transplantation, a relationship was found between the basal concentration (C ₀) of everolimus and the incidence of thrombocytopenia and acute rejection, confirmed by biopsy.

Kidney transplant:

With ₀ ≤ 3.4 ng / ml: no rejection - 68%, thrombocytopenia (<100 × 10 ⁹ / l) - 10%;
From ₀ ≤ 3.5–4.5 ng / ml: no rejection - 81%, thrombocytopenia - 9%;
C ₀ ≤ 4.6–5.7 ng / ml: no rejection - 86%, thrombocytopenia - 7%;
C ₀ ≤ 5.8–7.7 ng / ml: no rejection - 81%, thrombocytopenia - 14%;
With ₀ ≤ 7.8-15 ng / ml: no rejection - 91%, thrombocytopenia - 17%.

Heart transplant:

With ₀ ≤ 3.5 ng / ml: no rejection - 65%, thrombocytopenia (<75 × 10 ⁹ / l) - 5%;
C ₀ ≤ 3.6–5.3 ng / ml: no rejection - 69%, thrombocytopenia - 5%;
With ₀ ≤ 5.4–7.3 ng / ml: no rejection - 80%, thrombocytopenia - 6%;
C ₀ ≤ 7.4–10.2 ng / ml: no rejection - 85%, thrombocytopenia - 8%;
With ₀ ≤ 10.3–21.8 ng / ml: no rejection - 85%, thrombocytopenia - 9%.

Indications for use

Certican is used for the prevention of heart and kidney transplant rejection in the case of low and medium immunological risk in adult patients receiving basic immunosuppressive therapy with cyclosporine in the form of a microemulsion in combination with glucocorticosteroids.

Contraindications

Absolute:

galactose intolerance, severe lactase deficiency, glucose-galactose malabsorption;
lactation period;
hypersensitivity to sirolimus;
hypersensitivity to any component of Certican tablets.

There is insufficient information on the efficacy and safety of Sertican in children and adolescents to recommend this drug to this age group of patients.

During pregnancy, Certican can be prescribed only if its use is vital, and the benefits to the mother are definitely higher than the potential risks to the fetus.

Certican, instructions for use: method and dosage

Certican should be taken orally. The tablets should be swallowed whole, without breaking or chewing, with sufficient water. Dispersible tablets are recommended for patients who, for whatever reason, are unable to swallow tablets on their own.

A dispersion is prepared from the dispersible tablets. In this case, you can take the drug in three ways:

With an oral syringe: with a volume of 10 ml water (10 ml syringe), a maximum dose of 1.25 mg can be prepared. Place the tablets in the syringe, draw up water to the 5 ml mark, wait about 90 seconds, shaking the syringe slightly at this time. Inject the dispersion directly into the mouth. Collect another 5 ml of water, rinse the syringe and drink the contents. Take the drug with 10-100 ml of water.
With a plastic cup: with a volume of water of 25 ml, a maximum dose of 1.5 mg can be prepared. Pour 25 ml of water into a cup, place the tablets there, leave for about 2 minutes to form a dispersion. Shake the contents of the cup, drink. Add another 25 ml of water, rinse the cup and drink the contents.
Using a nasogastric tube: pour 10 ml of water into a small plastic medical cup and place the tablets there. Wait about 90 seconds, while rotating the glass slightly. Draw up the dispersion into a syringe and slowly (within 40 seconds) enter through a naso-gastric tube. Three times, taking 5 ml of water, rinse the glass (and therefore the syringe) and inject the liquid through the probe. Then rinse the probe with 10 ml of water and hold it for at least 30 minutes. If the cyclosporin microemulsion is also administered through a tube, it must first be injected, and then Certican. The two drugs should not be mixed.

Patients with cardiac and renal transplants at the beginning of treatment are prescribed the drug 0.75 mg 2 times a day. It is recommended to start using Sertican as early as possible after transplantation. The daily dose should always be divided into 2 doses and the drug should be taken in the same way - either always with food, or always without food. Certican is indicated to be taken at the same time as cyclosporine microemulsion.

The doctor may adjust the dose of Sertican depending on the clinical situation, the plasma concentrations of everolimus achieved, the individual response to treatment and its tolerance, and changes in concomitant drug therapy. It is permissible to change doses at intervals of 4–5 days.

Patients of the black race may need to use a higher dose of Sertican to achieve an effect similar to that of the rest of the population. This is due to the fact that, according to the limited information available, the incidence of biopsy-confirmed acute rejection is higher in the Negroid race.

Elderly persons and patients with impaired renal function do not require dosage adjustment.

In patients with functional impairment of the liver, the basal concentration of everolimus in whole blood should be regularly monitored. In mild to moderate hepatic impairment, the dose of Sertican should be halved if there is a combination of two indicators of the following: albumin <35 g / L (34 μmol / L (> 2 mg / dL), prothrombin time> 1.3 INR (prolongation> 4 sec.) Further dose titration may be required depending on the individual characteristics of the patient, efficacy and tolerability of therapy.

In patients with severe hepatic impairment, the safety and efficacy of everolimus have not been studied.

Therapeutic monitoring

It is recommended that the therapeutic concentration of everolimus in whole blood be checked periodically during treatment. According to the analysis of the ratios "exposure - efficacy" and "exposure - safety", in patients with _C0 <3 ng / ml, the frequency of biopsy-confirmed acute heart / kidney rejection is higher than in patients with _C0 > 3 ng / ml.

It is recommended to adhere to therapeutic concentrations of everolimus in the range of up to 8 ng / ml. Concentrations above 12 ng / ml have not been studied. The drug concentrations were determined by chromatography.

It is especially important to control the level of everolimus in the blood in patients with hepatic insufficiency during the period of joint administration of strong inhibitors / inducers of CYP3A4, the transition from one dosage form to another and / or a significant reduction in the dose of cyclosporine.

In patients receiving Certican in dispersible tablet form, the concentration of everolimus in the blood may be slightly lower than in patients taking conventional tablets. It is preferable to adjust the dosage regimen based on the values of the basal concentrations of the drug, determined no later than 4-5 days after the previous dose change. Due to drug interactions, with a significant decrease in the concentration of cyclosporine (C ₀ <50 ng / ml), a decrease in the concentration of everolimus is also possible.

Cyclosporine dosing in kidney transplant patients receiving Certican

Certican should not be used in combination with cyclosporine at full dose for a long time Clinical experience shows that reducing the dose of cyclosporine during therapy with everolimus leads to an improvement in renal function.

It is recommended to start reducing the dosage of cyclosporine 1 month after transplantation. The recommended concentration ranges of this drug (determined in the blood 2 hours after administration) in accordance with the clinical study protocol:

0-4 weeks - 1000-1400 ng / ml;
5-8 weeks - 700-900 ng / ml;
9-12 weeks - 550-650 ng / ml;
13–52 weeks - 350–450 ng / ml.

The basal cyclosporine concentrations in this study were:

1 month - 239 ± 114 ng / ml;
3 months - 131 ± 85 ng / ml;
6 months - 82 ± 60 ng / ml;
12 months - 61 ± 28 ng / ml.

It is imperative to maintain concentrations of everolimus and cyclosporine so that they do not fall below the therapeutic range in the early post-transplant period. This minimizes the risk of reducing the effectiveness of therapy.

Before starting to reduce the dose of cyclosporine, it is necessary to ensure that the equilibrium basal concentration of everolimus exceeds 3 ng / ml.

There are limited data on the use of Sertican at concentrations of cyclosporine in the maintenance phase C ₀ <50 ng / ml or C ₂ <350 ng / ml. If the patient does not tolerate a reduction in the dose of cyclosporine, consideration should be given to the appropriateness of further use of Sertican.

Cyclosporine dosing in heart transplant patients receiving Certican

After heart transplantation, the dose of cyclosporine is reduced in the maintenance phase to improve renal function.

In case of progression of renal impairment or a decrease in the calculated CC value below 60 ml / min, the correction of the therapy regimen is carried out on the basis of data obtained during clinical trials.

In studies, Certican was prescribed with reduced doses of cyclosporine. Basal cyclosporine concentrations were:

1 month - 200-350 ng / ml;
2 months - 150–250 ng / ml;
3-4 months - 100-200 ng / ml;
5-6 months - 75-150 ng / ml;
7-12 months - 50-100 ng / ml.

After 12 months, with basal ciclosporine concentrations of 50–100 ng / ml, data on the use of Sertican are limited.

Before starting to reduce the dose of cyclosporine, it is necessary to ensure that the equilibrium basal concentration of everolimus exceeds 3 ng / ml.

Side effects

Certican is used as part of a combination therapy, therefore, the side effects described below may be related to its intake, but this has not been reliably established. The frequency of their development was determined by the following criteria: very often - ≥ 1/10, often - from ≥ 1/100 to <1/10, sometimes - from ≥ 1/1000 to <1/100, rarely - from ≥ 1/10 000 up to <1/1000, very rarely - <1/10 000.

The following side effects have been reported in phase III clinical trials (kidney or heart transplant):

on the part of the hematopoietic and lymphatic system: very often - leukopenia ¹; often - anemia ¹, thrombocytopenia ¹, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura, coagulopathy; sometimes hemolysis;
from the respiratory system: very often - pleural effusion ²; often pneumonia; sometimes pneumonitis;
on the part of the cardiovascular system: very often - pericardial effusion ²; often - lymphocele ³, increased blood pressure, venous thrombosis;
on the part of the skin and subcutaneous tissue: often - complications from a surgical wound, acne, angioedema ⁴; sometimes a rash;
from the digestive system: often - nausea, diarrhea, abdominal pain, vomiting; sometimes - jaundice, liver dysfunction, increased activity of liver enzymes, hepatitis;
from the side of metabolism: very often - hyperlipidemia, hypercholesterolemia; often - hypertriglyceridemia;
from the urinary system: often - urinary tract infections; sometimes - pyelonephritis, renal tubular necrosis;
from the endocrine system: sometimes in men - hypogonadism (increased luteinizing hormone levels, decreased testosterone levels);
from the musculoskeletal system: sometimes - myalgia;
others: often - fungal, viral and bacterial infections, pain, edema, sepsis; sometimes a wound infection.

¹ The development of these disorders depended on the dose and was significantly more often observed in patients who took Certican at a daily dose of 3 mg.

² These reactions were noted in patients after heart transplantation.

³ These reactions have been reported in kidney transplant patients.

⁴ Angioneurotic edema was diagnosed mainly in patients who received angiotensin-converting enzyme (ACE) inhibitors during the period of immunosuppressive therapy.

In controlled clinical trials in which patients who received Certican (in a daily dose of 1.5 or 3 mg) in combination with other immunosuppressants were followed up for at least 1 year, lymphoproliferative diseases or lymphoma were recorded in about 1.4% of cases. Malignant neoplasms of the skin were detected in 1.3% of patients, other types of malignancy accounted for 1.2% of cases.

In the main studies, an increase in serum creatinine concentration was more often observed in patients taking Certican together with a full dose cyclosporine microemulsion than in the control group. The overall incidence of side effects is lower with a reduced dose of cyclosporine.

Studies have shown that the safety profile of Sertican in combination with a reduced dose of cyclosporine is broadly similar to that of the three main studies using the full dose of cyclosporine. However, in the first case, an increase in plasma creatinine concentration was noted less often, as well as a lower mean and median plasma creatinine concentration, than in other phase III studies.

Against the background of everolimus therapy, lesions of the lung parenchyma are rarely noted (for example, pulmonary fibrosis of non-infectious etiology and pneumonitis), in isolated cases with a fatal outcome. These adverse reactions usually disappear after the withdrawal of Sertican and / or the appointment of glucocorticosteroids.

Overdose

Experimental studies have shown that everolimus has a low potential for toxicity. A single oral dose of 2000 mg / kg in rats and mice did not cause severe toxicity and death.

Data on overdose of Sertican in humans are limited. Accidental ingestion of 1.5 mg everolimus by a 2-year-old child has been reported. No side effects followed.

After a single oral administration of the drug in doses up to 25 mg, patients after transplantation showed acceptable tolerance of everolimus.

Recommendations in the event of an overdose are of a general nature: symptomatic and supportive therapy, careful monitoring of the patient's condition.

special instructions

Only a physician who has experience in treating patients after organ transplantation can prescribe a Certican. Therapy should be performed under close medical supervision, including monitoring the concentration of everolimus in whole blood.

During treatment, constant monitoring of renal function is indicated. In case of an increase in serum creatinine concentration, it is necessary to consider adjusting the immunosuppressive therapy regimen, in particular, a reduction in the dose of cyclosporine is recommended. Particular care should be taken when concomitantly prescribing drugs that can negatively affect renal function.

Immunosuppressive drugs increase the risk of malignant diseases (especially skin) and lymphomas. The absolute risk is more likely due to the duration and intensity of the therapy, rather than taking a specific drug. In this regard, it is recommended to observe patients for the timely detection of any skin lesions. Patients should avoid exposure to sunlight and ultraviolet radiation, use sunscreen.

Hyperimmunosuppression is a risk factor for the development of infections, especially those caused by opportunistic pathogens. Cases of sepsis and infections with fatal outcomes have been reported in patients treated with Certican.

In clinical trials, prophylactic treatment was carried out to prevent the development of pneumonia caused by Pneumocystis carinii within 12 months after organ transplant. Prevention of cytomegalovirus infection, especially in patients at risk, is recommended to be carried out within 3 months after transplantation.

The use of Sertican in combination with cyclosporin microemulsion is associated with the likelihood of increased serum cholesterol and triglyceride levels. During the period of treatment, patients should be observed for the development of hyperlipidemia, if necessary, a corrective diet and appropriate lipid-lowering agents should be prescribed. If hyperlipidemia is diagnosed before the initiation of immunosuppressive therapy, it is necessary to assess the benefits of the forthcoming treatment and the possible risks. Comparison of the benefits of continuing therapy with Certican and the potential risks is also necessary for patients with severe refractory hyperlipidemia.

Influence on the ability to drive vehicles and complex mechanisms

The effect of the components of Certican tablets on human cognitive and psychomotor functions has not been studied.

Application during pregnancy and lactation

There is no experience of using Sertican during pregnancy. However, in experimental animal studies, everolimus has shown reproductive toxicity, including fetotoxicity and embryotoxicity. In this regard, the appointment of Sertican is contraindicated for pregnant women, except in cases of the absolute necessity of its use, when the benefits of the forthcoming therapy definitely outweigh the potential risk to the fetus.

In experimental studies on rats, it was found that everolimus and / or its metabolites quickly pass into milk. If it is necessary to use Sertican, breastfeeding should be discontinued.

Women of childbearing age are advised to use reliable contraceptive methods during treatment and for 8 months after treatment.

Pediatric use

There is insufficient information on the efficacy and safety of Sertican in children and adolescents to recommend this drug to this age group of patients. There is only limited data on the use of Sertican in pediatrics after kidney transplantation.

With impaired renal function

No dose adjustment is required in patients with impaired renal function.

For violations of liver function

With mild to moderate hepatic impairment (class A or B on the Child-Pugh scale), the dose of Sertican should be halved if there is a combination of two indicators of the following: albumin <35 g / l (34 μmol / l (> 2 mg / dl), prothrombin time> 1.3 INR (prolongation> 4 sec) Further dose titration may be required depending on the individual patient, efficacy and tolerability of therapy. During treatment, the basal concentration of everolimus in whole blood should be regularly monitored.

In patients with severe hepatic impairment (Child-Pugh class C), the safety and efficacy of everolimus have not been studied.

Use in the elderly

There is little clinical experience in treating patients over 65 with the drug. However, in studies, significant differences in pharmacokinetics compared with younger individuals were not noted, so there is no need to adjust the dose of Sertican.

Drug interactions

Cyclosporine (a CYP3A4 / P-glycoprotein inhibitor) significantly increases the bioavailability of everolimus. After a single dose of cyclosporine microemulsion (Sandimmun Neoral), there was an increase in C _{max of} everolimus by 82% (from 25 to 158%) and AUC by 168% (from 46 to 365%), compared with taking only everolimus. Changing the cyclosporine dose may require a dose adjustment of everolimus.

The effect of Sertican on the pharmacokinetic parameters of cyclosporine (in the form of a microemulsion) in patients after kidney / heart transplantation is minimal.

In addition to cyclosporine, in clinical studies, Certican was used simultaneously with glucocorticosteroids and basiliximab. Concomitant use with other immunosuppressive agents has not been studied enough.

Certican is not recommended for use in conjunction with strong inducers of CYP3A4 (for example, rifabutin, rifampicin) and strong inhibitors of CYP3A4 (for example, ritonavir, clarithromycin, ketoconazole, voriconazole, itraconazole, telithromycin), since they can have a significant effect on absorption and eliimus. Caution should be exercised with the simultaneous use of CYP3A4 and CYP2D6 substrates, which have a narrow therapeutic index. It is required to control the concentrations of everolimus in whole blood with their combined use and after their withdrawal. All in vivo interaction studies were conducted without the combined use of cyclosporine.

CYP3A4 inducers such as anticonvulsants (phenobarbital, phenytoin, carbamazepine), St. John's wort, drugs for the treatment of HIV (nevirapine, efavirenz) can enhance the metabolism of everolimus and reduce its concentration in the blood.

Moderate inhibitors of CYP3A4 and P-glycoprotein, such as protease inhibitors (indinavir, nelfinavir, amprenavir), macrolide antibiotics (erythromycin), antifungal agents (fluconazole), calcium channel blockers (nerapazemilipine), diltiapine, are capable of increasing the concentration of everolimus in the blood.

Grapefruit (including juice from it) affects the activity of P-glycoprotein and cytochrome P ₄₅₀, therefore, the properties of everolimus, therefore, their combined intake should be avoided.

After taking a single dose of Sertican in healthy volunteers together with pravastatin (a substrate of P-glycoprotein) or atorvastatin (a substrate of CYP3A4), there were no changes in either the pharmacokinetics of each drug or the general bioreactivity of HMG-CoA reductase in plasma. However, these results cannot be taken into account when using other inhibitors of HMG-CoA reductase, therefore, in the case of joint use of such inhibitors, patients should be carefully monitored for the development of side effects, including rhabdomyolysis.

When using fibrates together, patients should be monitored for the development of adverse events caused by taking these funds.

Like other immunosuppressants, Certican may decrease the response to vaccination. It is recommended to avoid the administration of live vaccines during therapy.

Analogs

Sertican's analogues are: Advagraf, Grastiva, Mayfortic, Pangraf, Prograf, Rapamun, Soliris, Tacrolimus, Takrosel, Ekoral, Yakvinus, etc.

Terms and conditions of storage

Store in a place protected from moisture and light, out of the reach of children, at a temperature not exceeding 30 ° C.

The shelf life is 3 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Certicane

There are no reviews from patients about Certicane on specialized medical forums and websites.

There are some reports from surgeons who write that they do not use this drug in their practice and are unlikely to ever use it. According to them, Certican is a specific immunosuppressant used exclusively in transplantation after heart and kidney transplants. To be able to treat with this drug, physicians must have not only the experience, but also the resources to monitor the concentration of everolimus in whole blood.

Price for Certican in pharmacies

Depending on the region of sale and the pharmacy network, the price for Certican (tablets, 60 pcs. In a package) may be: dosage 0.25 mg - 3400-5050 rubles, dosage 0.5 mg - 6500-7770 rubles, dosage 0, 75 mg - 11 400-14 600 rubles.

Certican: prices in online pharmacies

Drug name

Price

Pharmacy

Certican 0.25 mg tablets 60 pcs.

2300 RUB

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Certican 0.5 mg tablets 60 pcs.

4280 RUB

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Certican 0.75 mg tablets 60 pcs.

RUB 12,900

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Maria Kulkes Medical journalist About the author

Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!