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

One capsule contains:	25 mg	50 mg	100 mg
Active substance:
Cyclosporin	25.00 mg	50.00 mg	100.00 mg
Excipients:
Ethanol	39.90 mg	79.80 mg	159.60 mg
Macrogol glycerol hydroxystearate	73.70 mg	147.40 mg	294.70 mg
Polyglyceryl (3) oleate	82.70 mg	165.30 mg	330.70 mg
Polyglyceryl (10) oleate	50.00 mg	100.00 mg	199.90 mg
D, L- (alpha) Tocopherol	0.25 mg	0.50 mg	1.00 mg
The gelatinous shell of one capsule consists of (mg):
Gelatin	95.1 mg	222.2 mg	315.2 mg
Glycerol 85%	44.3 mg	103.8 mg	148.3 mg
Sorbitol solution	8.6 mg	20.2 mg	28.7 mg
Iron oxide (yellow)	0.1 mg	0.8 mg	-
Iron oxide (brown)	-	-	0.7 mg
Titanium dioxide	0.8 mg	0.5 mg	3.6 mg
Glycine	1.1 mg	2.5 mg	3.6 mg

Description:

Dosage of 25 mg. Opaque, yellow, 12.5x8 mm, soft, oval gelatin capsules with a double triangle and "25 mg". The contents of the capsule are a transparent oily liquid from yellow to yellow-brown in color.

Dosage of 50 mg. Opaque, brownish-yellow, 21x8 mm, oblong soft gelatin capsules with a double triangle and "50 mg"; The contents of the capsule are a transparent oily liquid from yellow to yellow-brown in color.

Dosage of 100 mg. Opaque, brown, 26x8 mm oblong, soft gelatin capsules with a double triangle and "100 mg". The contents of capsules are a transparent oily liquid from yellow to yellow-brown in color.

Pharmacotherapeutic group:Immunosuppressive remedy.

ATX: & nbsp

Pharmacodynamics:

Ecoral® (ciclosporin A) is a cyclic polypeptide consisting of 11 amino acids and is a potent immunosuppressive agent.

At the cellular level ciclosporin suppresses the formation and release of lymphokines, including interleukin-2 (growth factor of T-lymphocytes). Cyclosporin blocks lymphocytes at rest in phase G₀ or G₁ cell cycle and suppresses the antigen-dependent release of lymphokines by activated T lymphocytes. All the data obtained indicate that ciclosporin acts on lymphocytes specifically and reversibly.

Cyclosporine does not inhibit hemopoiesis and does not affect the function of phagocytic cells.

Pharmacokinetics:

After intake of cyclosporine, the maximum concentration in the blood is noted in the range from 1 to 6 hours, with an average bioavailability of 30% (20 to 50%), and increases with increasing dose and duration of treatment. Absorption is reduced after liver transplantation, with liver diseases or gastrointestinal pathology (diarrhea, vomiting, ileus).

Intensively binds to proteins and shaped elements of blood (concentration in whole blood is 2-9 times higher than in plasma). The connection with proteins is 90% (mainly with lipoproteins). It is distributed mainly outside the bloodstream; is present in the plasma 33-47%; lymphocytes - 4-9%, in granulocytes 5-12%, in erythrocytes - 41-58%. Time to reach the maximum concentration (TC_max) in plasma - through 1,5-3,5 h after oral intake. Metabolized by the liver, enzyme P_{450 3A}, to a lesser extent the gastrointestinal system, the kidneys.It is excreted with bile; kidneys - 6% of the administered oral dose. Excreted in breast milk. Cyclosporin Intensively metabolized with the formation of 15 identified metabolites.

T1 (half-life) - 19 hours in adults and 7 hours - in children, regardless of dose or route of administration.

Indications:

Transplantation

Transplantation of solid organs: prevention of transplant rejection after allogeneic transplantation of the kidney, liver, heart, lung, pancreas, heart-lung complex. Treatment of transplant rejection in patients who have previously received other immunosuppressive agents.

Bone marrow transplantation: prevention of graft rejection after bone marrow transplantation; prevention and treatment of the "graft versus host" reaction (GVHD).

Indications not related to transplantation

Endogenous uveitis (active, vision-threatening uveitis of the middle and posterior region of the eye of non-infectious etiology, if conventional therapy does not produce a result or leads to severe adverse reactions); uveitis of Behcet (with recurrent attacks of inflammation affecting the retina).

Nephrotic syndrome: steroid-dependent and steroid-resistant nephrotic syndrome caused by glomerular pathology such as minimal changes nephropathy, focal and segmental glomerulosclerosis or membranous glomerulonephritis (to achieve and support remission, and to support remission caused by glucocorticosteroids, which will allow the elimination of glucocorticosteroid therapy).

Rheumatoid arthritis: severe forms of high activity rheumatoid arthritis in the case when traditionally slow acting antirheumatic drugs are ineffective or their application is impossible.

Psoriasis: severe forms of psoriasis, when traditional therapy is ineffective or impossible.

Atopic dermatitis: severe forms of atopic dermatitis, when traditional therapy is ineffective or impossible.

Contraindications:

hypersensitivity to the drug components malignant neoplasms and precancerous skin diseases chicken pox
Herpes Zoster (risk of generalization of the process)
severe liver failure
hyperkalemia
uncontrolled hypertension
malabsorption syndrome
infectious diseases in acute phase.

Pregnancy and lactation:

The experience with cyclosporine in pregnant women is limited. In pregnant women who have undergone transplantation and are receiving immunosuppressive drugs, including ciclosporin, the risk of preterm delivery (less than 37 weeks) is increased. There is a limited number of observations of children up to the age of 7 years, whose mothers took ciclosporin during pregnancy. Indices of kidney function and blood pressure in these children were within the age limit. However, there is no information on the efficacy and safety of cyclosporine in pregnant women, so do not use ciclosporin at pregnancy, except for that cases when the expected advantage for mother exceeds potential risk for a fetus.

Ciclosporin penetrates into breast milk. Breastfeeding should be stopped when cyclosporine is needed.

Dosing and Administration:

The daily dose of Ecoral® should be divided into 2 divided doses. The following dosage ranges for oral administration of Ecoral® should be considered only as a guideline.Conventional monitoring of the concentration of cyclosporin in the blood should be performed. Based on the results obtained, determine the dose necessary to achieve the desired level of concentration of cyclosporine in different patients. Capsules of the preparation Ecoral® should be washed down with water and swallowed whole.

Because of the possible interaction with the P450-dependent enzyme system, grapefruit or grapefruit juice should not be consumed one hour before taking the dose of the drug.

Transplantation

When transplanting solid organs, treatment with Ecoral® should be started 12 hours before the operation at a dose of 10-15 mg / kg divided into two doses. Within 1-2 weeks after the operation, the drug is prescribed daily in the same dose, after which the dose is gradually reduced under the control of the concentration of cyclosporine in the blood, until a maintenance dose of 2-6 mg / kg / day (in 2 doses) is reached.

In cases where the preparation Ecoral® is prescribed in combination with glucocorticosteroids, as well as in a three-component or four-component therapy, the dose of the drug can be reduced even at the initial stage of therapy (3-6 mg / kg / day in 2 administrations) or is corrected in the process treatment taking into account the concentration of cyclosporine in the blood and the dynamics of safety indicators (urea concentration,serum creatinine and blood pressure).

When bone marrow transplantation, the initial dose should be prescribed one day before the operation. The daily dose of Ecoral® should be 12.5 mg / kg, divided into 2 divided doses. Maintenance therapy is performed for at least 3 months (preferably 6 months), after which the dose of cyclosporine is gradually reduced to zero within 1 year.

Indications not related to transplantation

With endogenous uveitis, to achieve remission, the drug is administered at an initial daily dose of 5 mg / kg orally in 2 divided doses until the signs of active inflammation disappear and visual acuity is improved. In cases that are difficult to treat, the dose may be increased to 7 mg / kg / day for a short period.

If the situation can not be controlled with monotherapy with the drug Ecoral®, systemic glucocorticosteroids can be added to the complex therapy to achieve initial remission or to stop an attack of inflammation in a daily dose of 0.2-0.6 mg / kg of prednisolone (or another glucocorticosteroid drug in an equivalent dose).

In the course of maintenance therapy, the dose should be slowly reduced to the lowest effective dose, which during the remission period should not exceed 5 mg / kg per day.

In the nephrotic syndrome, to achieve remission, the recommended daily dose is 5 mg / kg for adults and 6 mg / kg for children (in 2 divided doses) with normal renal function. In patients with impaired renal function, the initial dose should not exceed 2.5 mg / kg / day.

If one can not achieve a satisfactory effect with the use of one Ecoral® preparation, especially in steroid-resistant patients, it is recommended that it be combined with oral glucocorticoids in low doses. If after 3 months of treatment failed to achieve improvement, the preparation of Ecoral® should be canceled.

In rheumatoid arthritis during the first 6 weeks of treatment, the recommended dose is 3 mg / kg / day in 2 divided doses. In case of insufficient effect, the daily dose can be gradually increased, if tolerability allows, but should not exceed 5 mg / kg. To achieve full effectiveness, a 12-week treatment with Ecoral® may be required.

For maintenance therapy, the dose should be selected individually, depending on the tolerability of the drug.

The drug Ecoral® can be administered in combination with low doses of glucocorticoids and / or NSAIDs (non-steroidal anti-inflammatory drugs).The preparation Ecopal® can also be combined with a weekly course of methotrexate in low doses in patients with an unsatisfactory response to methotrexate monotherapy. The initial dose of Ecoral® is 2.5 mg / kg / day (in 2 divided doses), and the dose can be raised to a level that is limited by tolerability.

In psoriasis, due to the variability of this disease, treatment should be selected individually. To induce remission, the recommended initial dose is 2.5 mg / kg / day in 2 divided doses. If there is no improvement after 1 month of therapy, the daily dose can be gradually increased, but should not exceed 5 mg / kg. Treatment should be discontinued unless a satisfactory response is obtained from psoriasis after 6 weeks of treatment with a dose of 5 mg / kg / day, or if the effective dose meets the established safety parameters.

The use of an initial dose of 5 mg / kg / day is justified in patients whose condition requires a speedy improvement. If a satisfactory answer is reached, then the preparation of Ecoral® can be canceled, and the subsequent relapse can be treated with the repeated administration of this drug at the previous effective dose.Some patients may require long-term maintenance therapy.

For maintenance therapy, doses should be individually selected at the lowest effective level and should not exceed 5 mg / kg / day.

Atopic dermatitis due to the variability of this condition, treatment should be selected individually. The range of the recommended initial dose is 2.5-5 mg / kg / day in 2 divided doses. If the initial dose of 2.5 mg / kg / day does not allow a satisfactory response within 2 weeks, the daily dose can be rapidly increased to a maximum of 5 mg / kg. In very severe cases, rapid and adequate control of the disease can be achieved by initially applying a dose of 5 mg / kg / day. When a satisfactory response is achieved, the dose should be gradually reduced and, if possible, the drug should be discontinued. In case of relapse, a second course can be conducted.

Despite the fact that a course of treatment of 8 weeks can be sufficient to cleanse the skin, it has been shown that therapy with a duration of up to 1 year is effective and well tolerated, provided that all necessary indicators are monitored.

Side effects:

Many of the side effects associated with the use of cyclosporine are dose-dependent and reversible with decreasing dose. The spectrum of side effects is generally the same when used for different indications, however, the frequency and severity of side effects may vary. In patients after transplantation, due to the use of higher doses and longer duration of treatment, side effects occur more often and are usually more pronounced than in patients taking ciclosporin on indications not related to transplantation.

In patients receiving immunosuppressive treatment with cyclosporine or combination therapy, including ciclosporin, the risk of developing local and generalized infections (viral, bacterial, fungal etiology) and parasitic infestations increases. It is also possible to exacerbate existing infectious diseases and reactivate poliomavirus infection leading to the development of polyomavirus-associated nephropathy (PVA) (especially associated with VC virus) or progressive multifocal leukoencephalopathy (PMLE) (associated with JC virus). It was reported on the development of severe infectious diseases, in some cases with a fatal outcome.

In patients receiving immunosuppressive treatment with cyclosporine or combination therapy, including ciclosporin, increases the risk of developing lymphomas, lymphoproliferative diseases and solid malignant tumors, especially the skin. The incidence of malignant neoplasms increases with increasing intensity and duration of immunosuppressive therapy.

The incidence of side effects is classified according to the recommendations of the World Health Organization: very often - at least 10%; often - not less than 1%, but less than 10%; infrequently - not less than 0,1%, but less than 1%; rarely - not less than 0.01%, but less than 0.1%; very rarely - 0.01%, including individual reports.

Infections: often - infection of the upper respiratory tract, infection of the lower respiratory tract, including bronchiolitis, urinary tract infection, cytomegalovirus infection; infrequently - sepsis, herpetic infection, candidiasis infection.

Neoplasms: rarely - skin papilloma, basal cell carcinoma, squamous cell carcinoma, Bowen's disease, lymphoproliferative diseases, including lymphoma; very rarely - seborrheic keratosis, melanoma.

From the side of the blood and lymphatic system: infrequently - anemia, thrombocytopenia; rarely - microangiopathic anemia, haemolytic syndrome.

From the nervous system: very often - tremor, headache, including migraines; often paresthesia; infrequently - encephalopathy, convulsions, confusion, disorientation, inhibition, psychomotor agitation, sleep disturbance, visual impairment, cortical blindness, coma, paresis, cerebellar ataxia; rarely - motor polyneuropathy; very rarely - edema of the optic disc, including edema of the nipple of the optic nerve secondary to benign intracranial hypertension.

From the cardiovascular system: very often - an increase in blood pressure (BP).

From the digestive system: often - anorexia, nausea, vomiting, abdominal pain, diarrhea, gingival hyperplasia; infrequently - a violation of the liver (increased activity of "liver" transaminases and bilirubin concentration in the blood serum); rarely - pancreatitis.

From the skin and subcutaneous tissue: often hypertrichosis; infrequently - an allergic skin rash.

From the side of the musculoskeletal and connective tissue: often - muscle spasms, myalgia; rarely - muscle weakness, myopathy.

From the urinary system: very often - a violation of kidney function.

From the genitourinary system: rarely - dysmenorrhea, gynecomastia.

Laboratory indicators: very often hyperlipidemia; often - hypercholesterolemia, hyperuricemia, hyperkalemia, hypomagnesemia; rarely - hyperglycemia.

Other: often fatigue; infrequently, weight gain, swelling.

Overdose:

Data on acute drug overdose are absent to date and there is limited experience with overdose with other cyclosporins.

Symptoms: disorders of kidney function, which are probably reversible and disappear when the drug is withdrawn.

Treatment: general supportive measures should be taken. The drug can be withdrawn from the body only with the help of nonspecific measures, including gastric lavage, because ciclosporin is practically not excreted in hemodialysis and hemoperfusion with the use of activated charcoal.

Interaction:

Listed below are medications for which interaction with cyclosporine is confirmed and clinically significant.

Various drugs can increase or decrease concentrations of cyclosporin in plasma or whole blood, usually by suppressing or inducing enzymes involved in the metabolism of cyclosporin, in particular the cytochrome P450 isoenzyme CYP3A4. Because the ciclosporin is an inhibitor of the isoenzyme CYP3A4 and the membrane carrier of P-glycoprotein molecules, while simultaneous application with cyclosporine, an increase in the concentration of preparations that are substrates of the CYP3A4 isoenzyme and / or the P-glycoprotein membrane transporter is possible.

Drugs that reduce the concentration of cyclosporine in the blood plasma by inhibiting the isoenzyme CYP3A4

Barbiturates, carbamazepine, oxcarbazepine, phenytoin, nafcillin, sulfadimidine for intravenous administration, rifampicin, octreotide, probucol, orlistat, preparations containing St. John's wort (Hypericum perforatum), ticlopidine, sulfinpyrazone, terbinafine, bosentan.

Drugs that increase the concentration of cyclosporine in the blood plasma by inhibiting the isoenzyme CYP3A4

Antibiotics macrolides (mainly erythromycin, azithromycin and clarithromycin), ketoconazole, fluconazole, itraconazole, voriconazole, diltiazem, nicardipine, verapamil, metoclopramide, oral contraceptives, danazol, methylprednisolone (high doses), allopurinol, amiodarone, cholic acid and its derivatives, HIV protease inhibitors, imatinib, colchicine, nefazodone.

Other drug interactions

Caution should be exercised when using simultaneously with drugs that increase the risk of developing nephrotoxic effects, including those with aminoglycosides (gentamicin, tobramycin), amphotericin B, ciprofloxacin, vancomycin, trimethoprim (+ sulfamethoxazole), nonsteroidal anti-inflammatory drugs (NSAIDs) (diclofenac, naproxen, sulindac), melphalan, H2-histamine receptors with blockers (cimetidine, ranitidine), methotrexate.

Simultaneous application with tacrolimus should be avoided due to an increased risk of developing nephrotoxicity.

In the case of simultaneous use with drugs that have a nephrotoxic effect, it is necessary to carefully monitor the indicators of kidney function (in particular, regularly determine the concentration of creatinine in the blood serum).If there is a pronounced impairment of kidney function, the dose of this drug should be reduced or considered the possibility of alternative treatment.

There are some reports of the development of a significant but reversible renal dysfunction (with a corresponding increase in creatinine concentration) in patients undergoing transplantation, while using cyclosporine with fibrolic acid derivatives (for example, bezafibrate, fenofibrate). Therefore, in this category of patients, renal function should be monitored. In the case of development of severe renal dysfunction, simultaneous use of the above medicines should be discontinued.

Simultaneous use with nifedipine may lead to more pronounced gingival hyperplasia than with cyclosporine monotherapy. In patients with gingival hyperplasia on the background of cyclosporine therapy, simultaneous use of nifedipine should be avoided.

With simultaneous application with lercanidipine, an increase in the area under the concentration-time curve (AUC) of lercanidipine is 3-fold and AUC of cyclosporine is 21%. Care should be taken when using lercanidipine simultaneously.

Cyclosporine is a highly active inhibitor of the P-glycoprotein and can increase the concentration in the blood plasma of drugs that are a substrate of the glycoprotein, such as aliskiren. After simultaneous application of cyclosporine and aliskiren, the maximum concentration of aliskiren increases approximately by 2.5 times, and the AUC by 5 times. The pharmacokinetic profile of cyclosporine does not change significantly. It was found that simultaneous application with diclofenac can significantly increase the bioavailability of diclofenac, with the possible development of reversible renal dysfunction. An increase in the bioavailability of diclofenac is most likely due to a decrease in its metabolism in the "first pass" through the liver. When used simultaneously with NSAIDs with a less pronounced "first pass" effect (for example, acetylsalicylic acid) increase in their bioavailability is not expected. NSAIDs with pronounced "first pass" effect through the liver (including diclofenac) should be used in smaller doses than in patients who do not receive ciclosporin.

Cyclosporine can reduce the clearance of digoxin, colchicine, prednisolone, inhibitors of HMG-CoA reductase (statins) and etoposide.Several cases of severe glycoside intoxication were reported within a few days after starting treatment with cyclosporine in patients receiving digoxin. There are also reports that ciclosporin can enhance the toxic effects of colchicine, including the development of myopathy or neuropathy, especially in patients with impaired renal function. With the simultaneous use of cyclosporine with digoxin or colchicine, careful clinical observation is necessary to timely detect the toxic effects of these drugs and to address the issue of dose reduction or withdrawal of treatment.

In literature, the cases of muscle toxicity are described, including muscle pain, weakness, myositis and rhabdomyolysis while the use of cyclosporine with lovastatin, simvastatin, atorvastatin, pravastatin and, in rare cases, fluvastatin, observed in post-marketing period. If you need to use the above drugs simultaneously with cyclosporine, you need to reduce their dose. Therapy with statins should be temporarily discontinued or canceled entirely in patients with symptoms of myopathy,as well as in patients with predisposing factors to severe impairment of renal function, including renal failure secondary to rhabdomyolysis.

An increase in creatinine concentration was observed in clinical studies in which simultaneous use of everolimus or sirolimus with high doses of cyclosporin in the form of a microemulsion was studied. This effect is often reversible after lowering the dose of cyclosporine. Everolimus and sirolimus have little effect on the pharmacokinetic parameters of cyclosporine. Simultaneous use of cyclosporine with everolimus or sirolimus leads to a significant increase in the concentration of the latter in the blood plasma. Caution should be exercised when using cyclosporine with potassium-sparing drugs (potassium-sparing diuretics, angiotensin-converting enzyme (ACE) inhibitors, angiotensin II receptor antagonists) or potassium preparations to prevent the possible development of severe hyperkalemia. Cyclosporin can increase the concentration of repaglinide and increase the risk of developing hypoglycemia.

In patients who undergone transplantation, while using drugs that reduce or increase the bioavailability of cyclosporine should regularly determine the concentration of cyclosporine and, if necessary, adjust the dose of cyclosporine, especially at the initial stage of combined treatment or during the period of its withdrawal.

In patients without graft the observation of the concentration of cyclosporine is not so important, since for these patients the relationship between plasma concentration and clinical effects has not been proven with complete certainty. With the simultaneous use of cyclosporine and drugs that increase its concentration, frequent monitoring of kidney function and monitoring of side effects of cyclosporine are more important than determining the concentration of cyclosporine in the plasma.

Food interaction

The use of cyclosporine against the background of the use of grapefruit juice and fatty foods can be accompanied by an increase in its bioavailability.

During treatment with cyclosporine, vaccination should not be given due to the fact that the effectiveness of live attenuated vaccines can be reduced.

Special instructions:

The preparation of Ecoral® can be used only by a doctor who has experience of carrying out immunosuppressive therapy and has the opportunity to organize appropriate monitoring of the patient, including regular full physical examination, measurement of blood pressure and monitoring of serum creatinine concentration. Monitoring of patients who undergo transplantation and receiving the drug should be carried out only in those facilities that are provided with trained medical personnel and appropriate laboratory resources.

It should be borne in mind that when using cyclosporine, as well as other immunosuppressive drugs, the risk of developing lymphomas and other malignant tumors, especially the skin, increases. The increased risk of these complications depends more on the degree and duration of immunosuppression than on the specific drug. Therefore, care should be taken when using combined regimens of immunosuppressive therapy, remembering the likelihood of developing lymphoproliferative diseases and solid malignant tumors, sometimes leading to death.

Given the potential risk of developing malignant skin tumors, patients treated with cyclosporine should avoid excessive exposure to direct sunlight, exposure to ultraviolet (ultraviolet B (UVB)), PUVA therapy (photochemotherapy).

The use of cyclosporine, like other immunosuppressive drugs, predisposes to the development of various bacterial, fungal, parasitic and viral infections, often with the involvement of opportunistic pathogens. Reactivation of polyomavirus from the latent state can lead to the development of PVAN or PMELEP. Such conditions are often associated with a high degree of immunosuppression and should be considered in differential diagnosis of the causes of impaired renal and nervous system function in patients receiving immunosuppressive therapy. Given the potential risk of these infections for the life of the patient, an effective system of preventive and curative interventions should be applied, especially in cases of prolonged use of combined immunosuppressive treatment.

During the first few weeks of therapy with the preparation of Ecoral®, a frequent and potentially dangerous complication may arise - an increase in the concentration of creatinine and urea in the blood serum. These functional changes are reversible and dose-dependent, as a rule, normalized with a decrease in dose. With prolonged treatment, some patients may develop structural changes in the kidney (eg, interstitial fibrosis), which in patients with renal transplants should be differentiated with changes in chronic rejection. The drug Ecoral® can also cause a dose-dependent reversible increase in bilirubin concentration and, rarely, an increase in the activity of "liver" transaminases. In the course of clinical practice, reports of hepatotoxicity of cyclosporine were received, which was manifested by the development of cholestasis, hepatic jaundice, and liver failure. In most cases, the condition of patients was burdened by concomitant diseases and other aggravating factors (infectious complications and simultaneous use of drugs with a hepatotoxic effect).In these cases, careful monitoring of kidney and liver function is required. In case of deviations of these parameters from the norm, a decrease in the dose of cyclosporine may be required.

In elderly patients, monitoring of kidney function should be particularly careful.

When using EcoRAL® in patients after transplantation, it is necessary to determine the concentration of cyclosporin in the blood plasma.

To control the concentration of cyclosporine in the blood, it is preferable to use specific monoclonal antibodies (measurement of the amount of unchanged drug). You can use the high-performance liquid chromatography method, which also measures the concentration of unchanged substance. If plasma or serum is used, the standard separation procedure (time and temperature) should be followed. To determine the initial concentration of cyclosporin in patients with liver transplants, specific monoclonal antibodies should be used. Parallel determinations using specific and non-specific monoclonal antibodies are also possible to achieve a dose that provides adequate immunosuppression.

It should be remembered that the concentration of cyclosporine in the blood, plasma or serum is only one of many factors characterizing the clinical state of the patient. The results of the determination of the concentration of cyclosporine are only one of the factors determining the dosage regimen and are considered in conjunction with various clinical and laboratory indicators.

In the course of treatment with the preparation of Ecoral®, it is necessary to regularly monitor blood pressure. With an increase in blood pressure, adequate antihypertensive therapy should be used. Preference should be given to such antihypertensive drugs that do not affect the pharmacokinetics of cyclosporine.

Since in rare cases, the preparation of Ecoral® causes insignificant reversible hyperlipidemia, it is recommended to determine the concentration of lipids in the blood plasma before treatment and a month after the start of therapy. With an increase in lipid concentration, consideration should be given to restricting the consumption of fats with food and, if necessary, reducing the dose of Ecoral®. The use of Ecoral® may increase the risk of hyperkalemia, especially in patients with impaired renal function.Caution should also be exercised while using cyclosporine with potassium-sparing diuretics, ACE inhibitors, angiotensin II receptors with antagonists and potassium-containing drugs, and in cases of a diet enriched with potassium. In these cases it is recommended to control the concentration of potassium in the blood plasma.

Cyclosporine increases the excretion of magnesium from the body, which can lead to clinically significant hypomagnesemia, especially in the peri-transplant period. In this regard, in the peri-transplant period it is recommended to monitor the concentration of magnesium in the blood plasma, especially when neurologic symptoms appear. If necessary, magnesium preparations are used. It is recommended to monitor the concentration of uric acid in the blood serum, especially in patients with previous hyperuricemia.

For the prevention of anaphylactoid reactions, administration of antihistamines (H1-histamine receptor blockers) can be used before using Ecoral®.

Additional precautions for indications not related to transplantation

Do not use ciclosporin in patients with impaired renal function (with the exception of patients with nephrotic syndrome and the permissible degree of these disorders), uncontrolled hypertension, infectious diseases that can not be adequately treated, malignant neoplasms.

Since the preparation of Ecoral® can cause renal dysfunction, a significant initial serum creatinine concentration must be established in at least 2 measurements prior to treatment. The concentration of creatinine should be monitored at 2-week intervals during the first 3 months of therapy and in the future - monthly. After 6 months of therapy, the creatinine concentration should be determined every 4-8 weeks, depending on the stability of the underlying disease, the type of concomitant therapy and concomitant diseases. More frequent monitoring is necessary with an increase in the dose of Ecoral®, with concomitant therapy with NSAIDs or an increase in their dose. Additional precautions for endogenous uveitis

If the serum creatinine concentration remains elevated by more than 30% compared to the baseline concentration (before starting treatment with Ecoral®) in more than one measurement, then a dose reduction of 25-50% is required.These recommendations should be followed even if the creatinine concentration continues to be within the laboratory standard.

The experience of using Ecoral® in children with endogenous uveitis is limited.

Additional precautions for nephrotic syndrome

If the creatinine concentration remains elevated by more than 30% compared to the baseline (before starting treatment with Ecoral®) in more than one measurement, a dose reduction of 25-50% is required. In patients with initially impaired renal function, the initial dose should be 2.5 mg / kg / day. Careful monitoring of the condition of these patients is necessary.

Due to changes in renal function due to nephrotic syndrome, it may be difficult for some patients to detect renal impairment caused by immunosuppressive drugs. This explains the fact that in a number of cases, associated with the use of an immunosuppressive drug, structural changes in the kidneys were not accompanied by an increase in the concentration of creatinine. A kidney biopsy was shown to patients with a minimal change in steroid-dependent nephropathy who received supportive therapy with Ecoral® for more than 1 year.In rare cases, patients with nephrotic syndrome who were treated with immunosuppressive drugs, noted the appearance of malignant tumors, including Hodgkin's lymphoma.

Additional precautions for rheumatoid arthritis

If the creatinine concentration remains elevated by more than 30% of the baseline and more than one dimension, then a dose reduction is necessary. If the creatinine concentration increases by more than 50%, then it is necessary to reduce the dose by 50%. These recommendations should be followed even if the creatinine concentration continues to be within the laboratory standard. If dose reduction does not lead to a decrease in creatinine concentration within 1 month, treatment with Ecoral® should be discontinued.

The termination of treatment is also necessary when uncontrolled arterial hypertension occurs during the treatment with Ecoral®.

As with other long-term immunosuppressive treatment, one should remember about the increased risk of lymphoproliferative disorders. Particular care should be taken when using the product Ecoral® in combination with methotrexate.

Additional precautions for psoriasis

If the creatinine concentration rises and remains elevated by more than 30% of the baseline values and more than in one dimension, then a dose reduction of 25-50% is necessary. These recommendations should be followed even if the values of creatinine concentration continue to remain within the laboratory standard. If dose reduction does not lead to a decrease in creatinine concentration within 1 month, treatment with Ecoral® should be discontinued.

The termination of treatment is also necessary when uncontrolled arterial hypertension occurs during the treatment with Ecoral®.

The use of the drug Ecopal® in elderly patients is possible only in cases of disabling psoriasis, with careful monitoring of kidney function.

The experience of using the drug Ecoral® in children with psoriasis is limited.

It is known that in patients with psoriasis, treated with cyclosporine, as with other conventional immunosuppressive treatment, malignant neoplasms, especially the skin, may develop. If skin lesions are not typical of psoriasis, and if there is a suspicion of a malignant or precancerous disease, a biopsy should be performed before starting treatment with Ecoral®.Treatment with the preparation of Ecoral® patients with malignant or precancerous formations is possible only after appropriate treatment of these diseases and in the absence of alternative effective therapy. Patients with psoriasis who have been treated with cyclosporine may develop lymphoproliferative diseases. In these cases, it is necessary to immediately cancel the drug. Patients on treatment with Ecoral® should not simultaneously receive ultraviolet radiation of type B or PUVA therapy.

Additional precautions for atopic dermatitis

If the creatinine concentration rises and remains elevated by more than 30% of the baseline values in more than one measurement, then a dose reduction of 25-50% is necessary. These recommendations should be followed even if the creatinine concentration continues to be within the laboratory standard. If dose reduction does not lead to a decrease in creatinine concentration within one month, treatment with Ecoral® should be discontinued.

The termination of treatment is also necessary when uncontrolled arterial hypertension occurs during the treatment with Ecoral®.

Since the experience of using Ecoral® in children with atopic dermatitis is currently limited, it is not recommended to use the drug in this category of patients.

The use of the drug Ecopal® in elderly patients is possible only in cases of a disabling course of the disease, with careful monitoring of kidney function.

Benign lymphadenopathy is usually associated with sudden exacerbations of atopic dermatitis. It passes either alone or against a background of general improvement in the course of the disease. Lymphadenopathy, which appeared on the background of treatment with cyclosporine, should be regularly monitored.

Lymphadenopathy, which persists despite a decrease in the activity of the disease, should be biopsy to exclude lymphoma.

Cases of herpes simplex in the acute period should be cured before starting treatment with Ecoral®, but the appearance of herpes simplex is not a reason to discontinue the drug if the treatment has already begun, except in severe cases.

Skin infectious diseases caused by Staphylococcus aureus, are not an absolute contraindication for therapy with the drug Ecoral®, but should be controlled by the use of appropriate antibacterial drugs.

Due to the potential risk of skin cancer, when treating with Ecoral®, patients should be warned against direct exposure to sunlight and ultraviolet radiation of type B or PUVA therapy.

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

Care should be taken when driving vehicles and engaging in other potentially hazardous activities that require increased attention and speed of psychomotor reactions, given the potential for the development of adverse reactions from the nervous system, such as confusion, disorientation, inhibition, visual impairment.

Form release / dosage:

Capsules soft 25 mg, 50 mg and 100 mg.

Packaging:

10 capsules soft in a contour squeeze box (blister) made of a polyvinylchloride film and aluminum foil printed lacquered. 5 blisters in a carton box along with instructions for use.

Storage conditions:

Store at a temperature of no higher than 25 ° C, in a place protected from light. Do not store in the refrigerator.

Keep out of the reach of children.

Shelf life:2 years. Do not use after the expiration date.

Terms of leave from pharmacies:On prescription

Registration number:P N 015585/01

Date of registration:14.04.2009

The owner of the registration certificate:TEVA, LLC TEVA, LLC Russia

Manufacturer: & nbsp

Teva Czech Companies sr.o. Czech Republic

Information update date: & nbsp14.10.2015

Illustrated instructions

Instructions

Ecoral® (Equoral®)