SANDIMMUN-NEORAL CAPSULES 25MG

Packaging

50 pieces

Mechanism of action

Sandimmune NEORAL, an immunosuppressive drug, is a cyclic polypeptide consisting of 11 amino acids. Cyclosporin is a selective immunosuppressant that inhibits the activation of Calcium neuronal lymphocytes in the G0 or G1 phase of the cell cycle. Thus, the activation of T-lymphocytes and, at the cellular level, the antigen-dependent release of lymphokines, including interleukin 2 (T-lymphocyte growth factor), is prevented. Cyclosporin acts on lymphocytes specifically and reversibly. Unlike cytostatics, it does not suppress hematopoiesis and does not affect the function of phagocytes.

Cyclosporine increases the lifetime of allogeneic grafts of skin, heart, kidney, pancreas, bone marrow, small intestine, and lungs. Cyclosporin also inhibits the development of cellular reactions against allograft, skin reactions of delayed-type hypersensitivity, experimental allergic encephalomyelitis, arthritis caused by Freund's adjuvant, graft-versus-host disease (TTP) and antibody-dependent T-lymphocytes. Sandimmune was shown to be effective in transplanting bone marrow and solid organs in humans for the prevention and treatment of rejection and GVHD, as well as in treating various conditions that are autoimmune in nature or can be treated as such.

Dosage forms of the preparation Sandimmune Neoral (oral solution and soft capsules, which also contain the solution) have the following feature. The solution is a microemulsion preconcentrate that forms a microemulsion in the presence of a liquid (a liquid with which the solution is mixed for ingestion before ingestion or in the presence of liquids in the stomach while taking the drug in the form of capsules).This reduces the variability of pharmacokinetic parameters and provides a linear relationship between the dose and the effect of cyclosporine with a more uniform absorption profile and a lesser dependence on simultaneous food intake. When studying a microemulsion preconcentrate, it was shown that the correlation between the basal concentration of cyclosporine and its action is more pronounced with the use of Sandimmune Neoral, than Sandimmune.

Indications and usage

Transplantation

- Transplantation of solid organs: prevention of allograft rejection of the kidney, liver, heart, lung, pancreas, as well as a combined cardiopulmonary transplant; treatment of transplant rejection in patients previously treated with other immunosuppressants;

- bone marrow transplantation: prevention of transplant rejection after bone marrow transplantation; prevention and treatment of graft versus host disease.

Non-transplanted indications

- endogenous uveitis: an active, menacing or posterior uveitis of a non-infectious etiology that threatens eyesight in cases where traditional treatment had no effect or in cases of severe side effects; Behcet's uveitis with repeated bouts of inflammation with retinal involvement;

- nephrotic syndrome: steroid-dependent and steroid-resistant nephrotic syndrome in adults and children, due to glomerular pathology, such as minimal change nephropathy, focal and segmental glomerulosclerosis, membranous glomerulonephritis. Sandimmune Neoral can be used to induce and maintain remission and to maintain remission caused by glucocorticosteroids, which allows them to be canceled;

- treatment of severe forms of active rheumatoid arthritis;

- treatment of severe forms of psoriasis, when traditional therapy is ineffective or impossible;

- severe forms of atopic dermatitis, when systemic therapy is required.

Contraindications

Hypersensitivity to cyclosporine and other components of the drug.

Dosage and administration

The drug is prescribed by mouth, regardless of the meal.

The daily dose of Sandimmune Neoral should always be divided into 2 doses.

The transition from Sandimmune to Sandimmune Neoral

Available data show that when switching from taking Sandimmune to taking Sandimmune Neoral while maintaining the 1: 1 dose ratio, basal concentrations of cyclosporine, as measured in whole blood, are comparable. In many patients, however, higher values ​​of maximum concentration and an increase in the duration of exposure (AUC) may be observed. In a small percentage of patients, these changes are more noticeable and may be clinically significant. Their magnitude depends largely on the individual differences in the absorption of cyclosporine from the originally used Sandimmune, whose bioavailability is characterized by high variability. In patients with variable values ​​of basal concentrations or receiving Sandimmune in very high doses (including in patients with cystic fibrosis, patients with transplanted liver with concomitant cholestasis or poor bile secretion, children or some patients with a transplanted kidney), cyclosporine absorption may to be low or inconsistent, however, when switching to Sandimmune Neoral, improvement in absorption is possible. As a result, in this patient population, after switching from Sandimmune to Sandimmune Neoral, while maintaining the 1: 1 dose ratio, an increase in the bioavailability of cyclosporine may be more pronounced than is usually observed. Given this, the dose of Sandimmune Neoral should be reduced by individual selection, depending on the range of basal concentrations and appropriate indications.

The absorption of cyclosporine from Sandimmune Neoral is less variable and the correlation between basal concentration and bioavailability (according to AUC values) is much more pronounced than with the use of Sandimmune. This makes the basal level of cyclosporine concentration in the blood a clearer and more reliable parameter for therapeutic control of the drug.

Since the transition from Sandimmune to Sandimmune Neoral can lead to an increase in drug exposure, the following rules should be observed.

In patients after transplantation, treatment with Sandimmune Neoral should be started with the same daily dose that was with the previous use of Sandimmune. The basal concentration of cyclosporine in whole blood should be monitored within 4-7 days after switching to Sandimmune Neoral.In addition, clinical safety parameters such as serum creatinine and blood pressure should be monitored during the first 2 months after the transition. If the basal concentration of cyclosporine in the blood is outside the therapeutic range and / or there is a deterioration in the clinical safety parameters, the dose should be adjusted accordingly.

In patients treated for indications not related to transplantation, treatment with Sandimmune Neoral should be started with the same dose that was used with Sandimmune. After 2, 4 and 8 weeks after the transition should be monitored concentration of creatinine in serum and blood pressure. If serum creatinine concentrations or blood pressure levels rise markedly compared to those before the transition, or if creatinine concentrations increased by more than 30% compared to the results before treatment with Sandimmune in more than one dimension, the dose should be reduced by 25-50 % If the serum concentration increases by more than 50%, then it is necessary to reduce the dose by 50%. In the case of the development of a toxic effect or when the drug is ineffective, the basal concentrations of cyclosporine in the blood should also be monitored.

The following dose ranges for oral administration should be considered only as recommendations. The generally accepted monitoring of the concentration of cyclosporine in the blood should be carried out, for which a radio-immunological method based on the use of monoclonal antibodies can be applied. On the basis of the obtained results, determine the dose required to achieve the desired concentration of cyclosporin in different patients.

Transplantation

With a solid organ transplant, treatment with Sandimmune Neoral should be started 12 hours before the operation at a dose of 10 to 15 mg / kg body weight, divided into 2 doses. Within 1-2 weeks after surgery, the drug is prescribed daily in the same dose, after which the dose is gradually reduced (under the control of cyclosporine concentration in the blood) until a maintenance dose of 2-6 mg / kg / day is reached (in 2 doses).

Sandimmune Neoral is prescribed in combination with other immunosuppressants, including with glucocorticoids, as well as as part of a combined three-component (Sandimmun Neoral + glucocorticoid + azathioprine) or four-component (Sandimmun Neoral + glucocorticoid + azathioprine + mono or polyclonal antibody preparations) therapy. The four-part scheme is used in patients with a high risk of developing rejection.If Sandimmune Neoral is used as part of a combination therapy regimen, its dose may be reduced already at the initial stage of therapy (3–6 mg / kg / day in 2 divided doses) or adjusted during the treatment, taking into account the concentration of cyclosporine in the blood plasma and the dynamics of safety indicators ( concentration of urea, serum creatinine, blood pressure).

For bone marrow transplantation, the initial dose should be administered on the day preceding the transplant. In most cases, it is preferable to / in the introduction; The recommended dose is 3-5 mg / kg / day. Infusion administration at the same dose is continued for 2 weeks after transplantation, then transferred to oral maintenance therapy with Sandimmune Neoral in a daily dose of about 12.5 mg / kg, divided into 2 doses. Maintenance therapy is carried out for at least 3 months (preferably 6 months), after which the dose is gradually reduced to zero within 1 year after transplantation. If Sandimmune Neoral is prescribed for the initial stage of therapy, then the recommended daily dose is 12.5-15 mg / kg (in 2 doses) starting from the day before the transplant.

In the presence of gastrointestinal diseases, leading to a decrease in absorption, higher doses of Sandimmune Neoral may be required or, in some cases, IV dosage of Sandimmune.

After stopping the introduction of Sandimmune, graft versus host disease may develop in some patients, which usually regresses after resuming therapy. For the treatment of this condition in its chronic course in a weakly expressed form, Sandimmune Neoral should be used in low doses.

Non-transplanted indications

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

If you cannot control the situation with one Sandimmune Neoral, then to achieve initial remission or to relieve an attack of inflammation, you can attach systemic corticosteroids (prednisone at a daily dose of 0.2-0.6 mg / kg or another glucocorticosteroid at an equivalent dose).

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

With nephrotic syndrome for the induction of remission, the recommended daily dose for adults is 5 mg / kg, for children - 6 mg / kg (in 2 doses) provided normal kidney function, not counting proteinuria. In patients with impaired renal function, the initial dose should not exceed 2.5 mg / kg / day.

If the use of Sandimmune Neoral fails to achieve a satisfactory effect, especially in steroid-resistant patients, then it is recommended to combine it with oral GCS in low doses. If after 3 months of treatment no improvement was achieved, Sandimmune Neoral should be canceled.

Doses should be selected individually, taking into account the indicators of efficacy (proteinuria) and safety (serum creatinine concentration), but do not exceed the dose of 5 mg / kg / day for adults and 6 mg / kg / day for children.

For maintenance therapy, the dose should be gradually reduced to the minimum effective.

In rheumatoid arthritis during the first 6 weeks of treatment, the recommended dose is 3 mg / kg / day in 2 doses. In case of insufficient effect, the daily dose can be gradually increased, if tolerance allows, but it should not exceed 5 mg / kg. It may take up to 12 weeks of therapy with Sandimmune Neoral to achieve full effectiveness.

For maintenance therapy, the dose must be selected individually depending on the tolerance of the drug.

Sandimmune Neoral can be administered in combination with low doses of GCS and / or NSAIDs . Sandimmune Neoral 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 Sandimmune Neoral is 2.5 mg / kg / day (in 2 doses), while the dose can be increased to a level that is limited by tolerability.

In psoriasis, the dosing regimen should be selected individually. For induction of remission, the recommended initial dose is 2.5 mg / kg / day in 2 doses. In the absence of improvement after 1 month of therapy, the daily dose may be gradually increased, but should not exceed 5 mg / kg. Treatment should be discontinued if a satisfactory response from the manifestations of psoriasis after 6 weeks of treatment with a dose of 5 mg / kg / day or if the effective dose does not meet the established safety parameters.

The use of a higher initial dose of 5 mg / kg / day may be justified in patients whose condition requires early improvement. If a satisfactory answer is reached, then Sandimmune Neoral can be canceled, and the subsequent relapse can be treated by reappointment of Sandimmune Neoral in the previous effective dose. Some patients may require long-term maintenance therapy.

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

In atopic dermatitis, the dosing regimen should be selected individually. The recommended initial dose is 2.5-5 mg / kg / day in 2 doses. If the initial dose of 2.5 mg / kg / day does not allow to achieve a satisfactory response within 2 weeks, then the daily dose can be quickly increased to a maximum of 5 mg / kg. In very severe cases, rapid and adequate disease control 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, Sandimmune Neoral should be discontinued. In the event of a relapse, a repeated course of Sandimmune Neoral can be conducted.

Although the course of treatment for 8 weeks may be sufficient to cleanse the skin, it has been shown that therapy for up to 1 year is effective and well tolerated, provided that all necessary indicators are monitored.

The experience of using Sandimmune Neoral in elderly patients is limited.

Additional guidance on dosing regimen for endogenous uveitis, psoriasis, and atopic dermatitis

Since Sandimmune Neoral can disrupt the function of the kidneys, a reliable initial concentration of serum creatinine should be established in at least two dimensions prior to treatment. Creatinine concentration should be monitored at 2-week intervals during the first three months of therapy. Further, if the creatinine concentration remains stable, measurements should be taken monthly. If the serum creatinine concentration increases and remains elevated by more than 30% from baseline values ​​in more than one dimension, then it is necessary to reduce the dose by 25-50%.These recommendations should be followed, even if the creatinine concentrations continue to be within the laboratory norm. If a dose reduction does not lead to a decrease in creatinine concentration within one month, then treatment with Sandimmune Neoral should be discontinued.

Discontinuation of treatment is also necessary when an uncontrolled increase in blood pressure occurs during the treatment with Sandimmune Neoral.

Additional guidance on dosing regimen for nephrotic syndrome

Since Sandimmune Neoral can cause renal dysfunction, it is often necessary to control it. If the serum creatinine concentration remains elevated by more than 30% from baseline values ​​and in more than one dimension, a reduction in the dose of Sandimmune Neoral by 25-50% is required. For patients with initially impaired renal function, the initial dose should be 2.5 mg / kg / day. It is necessary to ensure close monitoring of the condition of these patients.

Further guidance on dosing regimen for rheumatoid arthritis

Since Sandimmune Neoral can impair the function of the kidneys, a reliable initial serum creatinine concentration should be established in at least two dimensions prior to treatment. Creatinine concentration should be monitored at 2-week intervals during the first three months of therapy and then monthly. After 6 months of therapy, serum creatinine concentration should be determined every 4-8 weeks, depending on the stability of the underlying disease, simultaneously applied therapy and associated diseases. More frequent control is necessary with increasing doses of Sandimmune Neoral, with the addition of concomitant therapy with nonsteroidal anti-inflammatory drugs or increasing their dose.

If the serum creatinine concentration remains elevated by more than 30% from baseline values ​​and in more than one dimension, then the dose should be reduced. If the serum 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 concentrations continue to be within the laboratory norm. If a dose reduction does not lead to a decrease in creatinine concentration within one month, then treatment with Sandimmune Neoral should be discontinued.

Discontinuation of treatment is also necessary when an uncontrolled increase in blood pressure occurs during the treatment with Sandimmune Neoral.

On the part of the urinary system: very often - impaired renal function.

Since the cardiovascular system: very often - increased blood pressure.

From the side of the central nervous system and peripheral nervous system: very often - tremor, headache; often - paresthesias; sometimes signs of encephalopathy, such as convulsions, lethargy, disorientation, slow reactions, agitation, sleep disturbances, visual disturbances, cortical blindness, coma, paresis, cerebellar ataxia; rarely, motor polyneuropathy ; very rarely - swelling of the optic nerve head (including the nipple of the optic nerve), secondary to benign intracranial hypertension.

On the part of the digestive system: often - anorexia, nausea, vomiting, abdominal pain, diarrhea, gingival hyperplasia, abnormal liver function; rarely - pancreatitis.

On the part of metabolism: very often - hyperlipidemia; often - hyperuricemia, hyperkalemia, hypomagnesemia; rarely - hyperglycemia.

On the part of the musculoskeletal system: often - muscle spasms, myalgia; rarely - muscle weakness, myopathy.

From the hemopoietic system: sometimes - anemia, thrombocytopenia; rarely - microangiopathic hemolytic anemia, hemolytic uremic syndrome.

Dermatological reactions: often - hypertrichosis; sometimes an allergic rash.

On the part of the organism as a whole: often - fatigue; sometimes - swelling, weight gain.

On the part of the endocrine system: rarely - a violation of the menstrual cycle, gynecomastia.

3 years

Sandimmune neoral