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.