The drug is used inside, regardless of food intake. The daily dose of the drug Sandimun Neoral should always be divided into 2 receptions: morning and evening.
The following ranges of oral doses should be considered only as recommendations. Conventional monitoring of the concentration of cyclosporin in the blood should be performed, with the possible use of a radioimmunoassay method based on the use of monoclonal antibodies. Based on the results obtained, determine the dose necessary to achieve the desired concentration of cyclosporine in blood plasma in different patients.
In case of ineffectiveness of Sandimmun Neoral therapy in capsule form in 2 divided doses in the morning and evening (especially in patients with low body weight) it is possible:
use of different doses of the drug in the morning and in the evening;
use of solution for oral administration.
In patients receiving ciclosporin for indications not related to transplantation, the control of the concentration of cyclosporine in the blood plasma is not significant.Exceptions are cases of recurrence of the disease on the background of cyclosporine therapy, which may be associated with a decrease in plasma concentration of cyclosporine as a result of violations of adherence to treatment in violation of absorption in the gastrointestinal tract or pharmacokinetic interaction.
Transplantation
Transplantation of solid organs
Treatment with the drug Sandimmun Neoral should be started 12 hours prior to transplantation at a dose of 10 to 15 mg / kg / day, divided into 2 divided doses. 13 for 1-2 weeks after the operation the preparation is applied daily at the same dosage, after which the dose was gradually reduced under the control of the concentration of cyclosporine in the blood to achieve the maintenance dose of 2-6 mg / kg / day, divided into 2 doses.
In the case of drug Sandimmun Neoral composed of circuits combined therapy with other immunosuppressants (e.g. with corticosteroids as part of a ternary or quaternary therapy), its dose can be reduced (e.g., 3-6 mg / kg / day in 2 divided doses).
Bone marrow transplantation
The initial dose should be taken on the day preceding the transplant.It is recommended to start therapy with a drug at a dose of 12.5-15 mg / kg / day in 2 divided doses. Supportive therapy is performed for at least 3 months (preferably 6 months), after which the dose is gradually reduced to complete discontinuation of the drug within 1 year after transplantation. Patients with diseases of the digestive system, accompanied by a decrease in absorption, may require higher doses of the drug Sandimmun Neoral or the use of cyclosporine in the form of intravenous infusions.
After the discontinuation of the use of the drug Sandimun Neoral, some patients may develop a "graft-versus-host disease" (GVHD), which usually regresses after the resumption of therapy. In such cases, the drug should be used at the initial loading dose of 10-12.5 mg / kg / day and further continue therapy with the drug in a maintenance dose previously regarded as satisfactory. To treat this condition with its chronic course in a mild form, use the drug Sandimmun Neoral in low doses.
Indications not related to transplantation
When using the drug Sandimmun Neoral for any of the indications not related to transplantation, the following general rules should be observed.
Before the start of therapy, it is necessary to determine at least twice the initial concentration of creatinine in the blood plasma, and also regularly monitor the kidney function.
The total daily dose should not exceed 5 mg / kg. with the exception of the total daily dose in patients with endogenous uveitis, threatening vision, and in children with nephrotic syndrome.
For maintenance therapy, the lowest effective and well tolerated dose of the drug should be individually selected.
In cases where during a certain period (depending on the indication) the drug fails to achieve clinical efficacy, or the achievement of an effective dose is not compatible with safety, treatment with the drug Sandimmun Neoral should be discontinued.
Endogenous uveitis
Achievement of remission
To achieve remission, the drug is used in an initial dose of 5 mg / kg / day, divided into 2 doses, until the signs of active inflammation disappear and visual acuity improvement. If the initial dose is not effective, therapy with the drug can be carried out at a dose of up to 7 mg / kg / sug. divided into 2 receptions for a short period.
To achieve a more rapid remission (to reduce the severity of inflammatory reactions) and / or when monotherapy with the drug Sandimmun Neoral is not effective enough, additional therapy with glucocorticosteroids, for example, prednisolone in a dose of 0.2-0.6 mg / kg / day or another glucocorticosteroid drug in an equivalent dose.
It is necessary to cancel therapy with the drug Sandimmun Neoral if there is no improvement in the patient's condition 3 months after the start of therapy.
Maintaining remission
In the course of maintenance therapy, the dose of the drug should be slowly reduced to the lowest effective dose, which during the remission period of the disease should not exceed 5 mg / kg / day. divided into 2 receptions.
Psoriasis
Achievement of remission
Therapy of psoriasis should be of an individual nature in connection with various variants of the course of the disease. To achieve remission, the recommended initial dose is 2.5 mg / kg / day, divided into 2 doses. If there is no improvement after 1 month of therapy, the daily dose can be gradually increased by 0.5-1 mg / kg per month, but should not exceed 5 mg / kg / day, divided into 2 doses.Treatment with the drug Sandimmun Neoral should be discontinued if after 6 weeks of applying the maximum dose of 5 mg / kg / day, divided into 2 doses, there is no sufficient clinical effect or if the effective dose of the drug does not meet the established safety parameters.
Maintaining remission
For maintenance therapy, the drug is used in the minimum effective dose, but not more than 5 mg / kg / day.
After 6 months of maintenance therapy, it is necessary to gradually reduce the dose of the drug Sandimmun Neoral up to its complete cancellation.
Atopic dermatitis
Achievement of remission
In connection with various variants of the course of the disease, therapy should be individualized. The recommended dose is 2.5-5 mg / kg / day, divided into 2 divided doses. In case, after 2 weeks of treatment at a starting dose of 2.5 mg / kg / day, a satisfactory response to treatment is not achieved, the dose can be increased to a maximum of 5 mg / kg / day. In the case of severe disease, faster and more adequate control is achieved with a starting dose of 5 mg / kg / day.
Maintaining remission
When a satisfactory response to therapy is achieved, the dose of the drug should be gradually reduced, to the extent possible, until it is completely eliminated.With the development of recurrence of the disease, repeated treatment with the drug following the course is possible. Despite the fact that a course of treatment of 8 weeks may be sufficient to cleanse the skin, it is shown that therapy with a duration of up to 1 year is effective and well tolerated, provided that all necessary indications are mandatory.
Treatment with the drug Sandimmun Neural should be discontinued if after 4 weeks of applying a maximum dose of 5 mg / kg / day, divided into 2 doses, there is no satisfactory clinical effect.
Rheumatoid arthritis
Achievement of remission
During the first six weeks of treatment, the recommended dose is 3 mg / kg / day, divided into 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 / day. To achieve a satisfactory clinical response, it may take up to 12 weeks of therapy with the drug Sandimmun Neoral.
Maintaining remission
For maintenance therapy, the dose should be selected individually depending on the tolerability of the drug, the dose of the drug for maintenance therapy should be minimal effective.
The drug Sandimmun® Neural can be used in combination with low doses of glucocorticosteroids and / or non-steroidal anti-inflammatory drugs. The drug Sandimmun® Neoral can also be combined with a weekly course of methotrexate in low doses in patients with an unsatisfactory response to methotrexate ion therapy. The initial dose of the drug Sandimmun Neoral in this case is 2.5 mg / kg / day, divided into 2 doses, while the dose can be increased to a level limited by tolerability.
Nephrotic syndrome
Achievement of remission
To achieve remission, the recommended dose is up to 6 mg / kg / day, divided into 2 doses, for children and up to 5 mg / kg / day, divided into 2 doses for adult patients with normal kidney function, excluding proteinuria. In patients with impaired renal function of moderate severity (creatinine concentration in blood plasma is not more than 200 μmol / l for adults and 140 μmol / l for children), the initial dose should not exceed 2.5 mg / kg / day, divided into 2 divided doses. The dose should be selected individually, taking into account the efficacy (proteinuria) and safety (creatinine concentration in the blood plasma), but should not exceed 5 mg / kg / day, divided into 2 doses for adults and 6 mg / kg /divided into 2 receptions for children.
Maintaining remission
For maintenance therapy, the dose should be gradually reduced to a minimum effective dose.
Since patients of this category with the use of the drug Sandimmun Neural can develop or progress the violation of kidney function, with the use of the drug should closely monitor kidney function. When the concentration of creatinine in the blood plasma increases by more than 30% compared with the initial values, the dose of the drug Sandimmun Neoral should be reduced by 25-50%. It is necessary to ensure careful monitoring of the condition of these patients.
In the absence of improvement in the patient's condition after 3 months of treatment, the drug Sandimmun® Neoral should be discarded.
If monotherapy with the drug Sandimmun Neoral fails to achieve a satisfactory effect, especially in steroid-resistant patients, it is recommended that it be combined with low doses of glucocorticosteroids for oral administration.
In some cases, in patients with nephrotic syndrome receiving the drug Sandimmun® Neoral®, it was difficult to identify the causes of renal dysfunction (because the cause may be both treatment with the drug and the underlying disease).In rare cases, patients with nephrotic syndrome experienced changes in the structure of the kidney tissue caused by the drug, and not accompanied by a marked increase in the concentration of creatinine in the blood plasma. Thus, patients with a steroid-dependent form of nephropathy with minimal changes receiving treatment with the drug for longer than a year should consider the possibility of a kidney biopsy.
Use in patients of certain categories
Patients with impaired renal function
All indications
Ciclosporin is minimally excreted by the kidneys, and renal dysfunction does not affect its pharmacokinetics. However, taking into account the possible nephrotoxicity of the drug, careful monitoring of kidney function is recommended.
Indications not related to transplantation
The use of cyclosporine in patients with impaired renal function, with the exception of nephrotic syndrome, is contraindicated. In patients with nephrotic syndrome and impaired renal function, the initial dose of the drug should not exceed 2.5 mg / kg / day. When the concentration of creatinine in the blood plasma is increased by more than 50%, compared with the initial value, it is necessary to reduce the dose of cyclosporine by more than 50%.
Patients with impaired hepatic function
Dose reduction may be required in patients with severe liver dysfunction to maintain the plasma concentration of the drug in the recommended range.
Patients aged ≤ 18 years
The experience of using the drug Sandimmun Neoral in children under the age of 1 year is absent. When using the drug Sandimmun Neoral at recommended doses in children over the age of 1 year, the safety profile of the drug was similar to that of adult patients. In a number of studies, it has been established that in patients of this category, higher doses of the drug (based on body weight) may be used to achieve the desired concentration of cyclosporine in the blood plasma.
In children, the drug Sandimmun Neoral should not be used for indications other than transplantation, with the exception of nephrotic syndrome.
Patients ≥65 years of age
The experience of using the drug Sandimmun Neoral in patients of this category is limited, with the use of the drug in the recommended doses, there are no violations deserving special attention. In patients with rheumatoid arthritis aged ≥65 years with cyclosporine therapy for 3-4 monthssystolic hypertension and an increase in serum creatinine>> 50% higher than the baseline value.
It is necessary to carefully select a dose of cyclosporine for patients of this age category, starting with the lowest, due to a greater frequency of violations of the liver, kidney or heart, as well as the development of pathological conditions due to the presence of concomitant diseases and the simultaneous use of other medications.
Correction of the dosing regimen for the development of renal dysfunction in patients with endogenous uveitis, psoriasis, atopic dermatitis and rheumatoid arthritis
Since the use of the drug Sandimmun Neural possibly development of violations of kidney function, before starting the drug should determine the initial concentration of creatinine in the blood plasma, at least in two dimensions. The concentration of creatinine in the blood plasma should be determined at weekly intervals for 2 months after the initiation of therapy. In the future, if the creatinine concentration in the blood plasma remains stable, the determination should be made monthly.More frequent control is necessary with an increase in the dose of the drug Sandimmun Neoral and with the use of concomitant therapy with non-steroidal anti-inflammatory drugs or with an increase in their dose.
When the creatinine concentration in the blood plasma is increased by more than 30% compared to the baseline values for 2 or more measurements (even if the creatinine concentration remains within normal limits), the dose of the drug Sandimmun Neoral should be reduced by 25-50%. If the creatinine concentration is increased by more than 50% compared with the baseline value, further dose reduction should be considered.
If a decrease in the dose of the drug does not lead to a decrease in the concentration of creatinine in the blood plasma for one month, treatment with the drug Sandimmun Neoral should be discontinued.