Sandimmun Neoral (cyclosporin) soft capsules 100 mg. №50

Description

Sandimmun Neoral (cyclosporin) soft capsules 100 mg. №50

Composition

active substance: ciclosporin;

1 capsule contains 10 or 25, or 50, or 100 mg of cyclosporine microemulsion;

auxiliary substances: polyethoxylated castor oil, hydrogenated; mono- and di-triglycerides of corn oil; anhydrous ethanol; propylene glycol; α-tocopherol;

capsule shell: gelatin, propylene glycol, glycerin (85%), residual solvents, titanium dioxide (E 171), iron oxide black (E 172) – only for capsules 25 mg and 100 mg;

red food ink: carminic acid (E 120), aluminum chloride hexahydrate, sodium hydroxide, propylene glycol, hypromellose, isopropyl alcohol, purified water.

Medicinal form

Capsules are soft.

The main physical and chemical properties:

• capsules 10 mg – oval soft gelatin capsules of yellow-white color with the inscription NVR 10 in red;
• capsules 25 mg – oval soft gelatin capsules of gray-blue color with the inscription NVR 25 mg in red;
• capsules 50 mg – oblong soft gelatin capsules of yellow-white color with the inscription NVR 50 mg in red;
• capsules 100 mg – oblong soft gelatin capsules of gray-blue color with the inscription NVR 100 mg in red.

Contents of capsules: clear, yellow to pale yellow or brownish yellow to pale brownish yellow liquid.

The liquid contains oily components of natural origin that can harden at low temperatures. Gel-like formations can be observed at temperatures below 20 °C, which disappear at temperatures above 30 °C. Slight flakes or light sediment may still be observed. This does not affect the quality of the capsules.

Pharmacotherapeutic group

Antineoplastic and immunomodulatory agents. Immunosuppressants. Calcineurin inhibitors. Cyclosporine.
ATX code L04A D01.

Pharmacological properties

It is an immunosuppressive (suppressive immune response) agent. Suppresses cellular-type reactions, incl. allograft rejection, allergic encephalomyelitis, delayed-type allergic reaction, arthritis caused by Freund’s adjuvant, T-lymphocyte-dependent antibody formation, graft versus host reaction. Blocks resting lymphocytes at the cellular level (in phases G0, G1) and inhibits the production and release of lymphokines, induced by the antigen.

Indications

In transplantation is used:

• for the prevention of rejection reaction after transplantation of solid (whole) organs: liver, heart, kidney, cardiopulmonary transplant, lungs, pancreas;
• to prevent graft rejection after bone marrow transplantation;
• for the treatment of a graft rejection reaction in individuals who have previously received other immunosuppressants;
• for the prevention / treatment of graft versus host disease.

For autoimmune diseases:

• with nephrotic syndrome caused by damage to the vascular glomerulus (membranous glomerulonephritis, nephropathy of minimal changes, segmental / focal glomerulosclerosis) – for the induction of remission, its maintenance;
• with endogenous uveitis (active, vision-threatening uveitis of the middle / posterior area of ​​the eye of a non-infectious nature, if standard therapy is ineffective or causes severe adverse reactions; Behcet’s uveitis with a recurrent course affecting the retina);
• in severe rheumatoid arthritis (when the use of standard therapy is impossible or ineffective);
• in psoriasis with severe psoriasis (when the use of standard therapy is impossible or ineffective);
  with severe atopic dermatitis, when systemic therapy is indicated.

Contraindications

Do not use in case of intolerance to the active / auxiliary components.
Patients are contraindicated:

• with impaired renal function;
• with uncontrolled arterial hypertension;
• with an acute infectious disease;
• with a malignant neoplasm.

Application during pregnancy and lactation

The drug is not used during these periods.

Method of administration and dosage

The given oral dose ranges should be considered as recommendations only. The daily dose of Sandimmun Neoral soft capsules should always be divided into 2 doses with equal time intervals between doses. It is recommended to use Sandimmun Neoral soft capsules according to a clear schedule, taking into account the time of day and diet. If the prescribed dosage regimen cannot be provided with the help of capsules, in particular for patients with low body weight, it is recommended to use an oral solution.

Sandimmun Neoral soft capsules can be prescribed only by a doctor who has experience in immunosuppressive therapy and/or organ transplantation.

Indications for transplantation

Regular monitoring of cyclosporine levels in the blood using a radioimmunoassay using monoclonal antibodies is necessary. The obtained results are the basis for determining the dose necessary to achieve the target concentrations.

Transplantation of solid organs

The initial dose is 10–15 mg/kg of body weight, which is divided into 2 doses and applied a maximum of 12 hours before transplantation. During 1–2 weeks after the operation, the drug is used daily in the same dose, after which the dose is gradually reduced under the control of the cyclosporine concentration in the blood according to the local protocol of immunosuppressive therapy until a maintenance dose of 2–6 mg/kg/day is reached (in 2 doses). .

Sandimmun Neoral soft capsules can be used in combination with other immunosuppressants/corticosteroids, as well as as part of combined three-component or four-component therapy. At the beginning of treatment, lower doses can be used (for example, an oral dose of 3–6 mg/kg per day, divided into 2 doses).

Bone marrow transplantation/ prevention and treatment of graft-versus-host disease

At the beginning of therapy, the recommended dose should be used 1 day before transplantation.

Sandimun, a concentrate for preparation of a solution for infusion, is usually preferred at the beginning of therapy. The recommended dose for intravenous administration is 3–5 mg/kg per day. Infusion administration at this dose should be continued during the early post-transplantation period for up to 2 weeks, after which switch to oral maintenance therapy with Sandimmun Neoral soft capsules at a daily dose of approximately 12.5 mg/kg divided into 2 doses.

The maintenance dose should be used for 3–6 (preferably 6) months. The dose is gradually reduced to zero within a year after transplantation. If the drug Sandimmun Neoral soft capsules is used at the beginning of therapy, the recommended dose is 12.5–15 mg/kg per day in 2 doses, starting from the day before transplantation.

In the presence of diseases of the gastrointestinal tract, which lead to a decrease in absorption, higher doses of capsules or concentrate for intravenous infusion (Sandimun) may be required.

In some patients, after discontinuation of Sandimmun Neoral soft capsules, a graft-versus-host reaction (GVHD) may occur, which usually resolves after resuming therapy. In such cases, an initial oral loading dose of 10–12.5 mg/kg should be prescribed, followed by oral maintenance therapy at the dose effective during previous treatment. Sandimmun Neoral soft capsules should be used in low doses for the treatment of this condition in its chronic course in a weakly expressed form.

Non-transplant indications

When using Sandimmun Neoral soft capsules for any approved indication not related to transplantation, the following general rules should be followed.

Before starting treatment, an objective baseline of renal function should be established based on the results of at least two measurements. Estimated glomerular filtration rate (GFR), determined by the MDRD formula, can be used to assess kidney function in adults. The appropriate formula should be used to estimate GFR in children. Due to the fact that Sandimmun Neoral soft capsules can impair kidney function, it is necessary to evaluate it frequently. If the eGFR decreases by more than 25% compared to the initial level in more than one measurement, the dose of Sandimmun Neoral soft capsules should be reduced by 25-50%. If the decrease in GFR compared to the initial level exceeds 35%, a further reduction in the dose of Sandimmun Neoral soft capsules should be considered. These recommendations are valid even if the values ​​obtained fall within the range of normal laboratory values. If dose reduction does not lead to recovery of GFR within 1 month, Sandimmun Neoral soft capsules therapy should be discontinued.

Constant blood pressure monitoring is necessary.

Before starting therapy, bilirubin concentration and other liver function assessment parameters should be determined. Careful monitoring of these indicators is recommended during treatment.

The concentration of serum lipids, potassium, magnesium and uric acid is recommended to be determined before starting therapy and periodically during treatment.

Periodic monitoring of the concentration of cyclosporine in the blood may be appropriate when used for indications not related to transplantation, for example, when Sandimmun Neoral soft capsules is prescribed concomitantly with drugs that can affect the pharmacokinetics of cyclosporine, or in cases of unusual clinical response ( for example, insufficient effectiveness or increased sensitivity to the drug, expressed in impaired kidney function).

The normal route of drug administration is oral. When using a concentrate for a solution for infusion, careful calculations should be made to select an adequate dose for intravenous administration that would correspond to the oral dose. Consultation with a physician experienced in the use of cyclosporine is recommended.

The total daily dose should not exceed 5 mg/kg, except in patients with vision-threatening endogenous uveitis and children with nephrotic syndrome.

For maintenance therapy, the lowest effective and tolerable dose should be used individually.

Sandimmun Neoral soft capsules therapy should be discontinued in patients who fail to respond adequately to treatment within the prescribed time period (see below for details) or whose effective dose does not meet established safety guidelines.

Endogenous uveitis

To promote remission, the recommended starting dose is 5 mg/kg/day orally in 2 divided doses until remission of active uveal inflammation and improvement of visual acuity. In refractory cases, the dose can be increased to 7 mg/kg per day for a short period.

To achieve an initial remission or counteract the exacerbation of eye inflammation, when sufficient control of the situation with Sandimmun Neoral soft capsules monotherapy is not possible, simultaneous use with a systemic corticosteroid, for example with prednisone at a dose of 0.2–0.6 mg/kg or an equivalent drug, is possible. After 3 months of treatment, the corticosteroid dose can be reduced to the lowest effective dose.

Sandimmun Neoral soft capsules should be discontinued if no improvement is observed after three months of treatment.

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

Before using immunosuppressive drugs, an infectious cause of uveitis should be ruled out.

The daily dose should be reduced by 25-50% if the concentration of creatinine in the blood plasma exceeds the baseline level by more than 30% in more than one measurement, even if this concentration is within the normal range.

Nephrotic syndrome

To promote remission, the recommended daily dose is 5 mg/kg for adults and 6 mg/kg for children, divided into 2 doses, provided that, with the exception of proteinuria, renal function is normal. For patients with impaired renal function, the initial dose of the drug should not exceed 2.5 mg/kg/day orally.

When Sandimmun Neoral soft capsules monotherapy is unsatisfactory, especially in steroid-resistant patients, a combination of Sandimmun Neoral soft capsules and low-dose oral corticosteroids may be useful.

Time to improvement is 3 to 6 months, depending on the type of glomerulopathy. If no improvement is observed during this period, Sandimmun Neoral soft capsules therapy should be discontinued.

Doses should be selected individually, taking into account efficacy (proteinuria) and safety, they should not exceed 5 mg/kg per day for adults and 6 mg/kg per day for children.

For maintenance therapy, the dose should be gradually reduced individually to the lowest effective level.

Rheumatoid arthritis

During the first 6 weeks of treatment, the recommended dose is 3 mg/kg per day orally, divided into 2 doses. In case of insufficient effect, the daily dose can be gradually increased, if tolerance allows, but not exceeding 5 mg/kg per day. To achieve maximum effectiveness, treatment with Sandimmun Neoral soft capsules can be continued for up to 12 weeks.

For maintenance therapy, the dose should be titrated individually to the lowest effective dose based on tolerability.

Sandimmun Neoral soft capsules can be prescribed in combination with low doses of corticosteroids and/or non-steroidal anti-inflammatory drugs (NSAIDs).

Sandimmun Neoral soft capsules can also be used in combination with low doses of methotrexate every week in case of ineffective monotherapy of the latter. In this case, Sandimun Neoral® is prescribed in an initial dose of 2.5 mg/kg/day, which is divided into 2 doses, with the possibility of increasing the dose within the limits of tolerance.

Psoriasis

Treatment with Sandimmun Neoral soft capsules should be started by a doctor with experience in the diagnosis and treatment of psoriasis. Given the variability of this disease, treatment should be individualized. For the induction of remission, the recommended initial dose is 2.5 mg/kg/day, divided into 2 doses; if no improvement is observed after 1 month of treatment, the dose is gradually increased to a maximum of 5 mg/kg/day. Treatment should be discontinued if an adequate response is not achieved within one month of daily administration of 5 mg/kg/day or if the effective dose is incompatible with established safety guidelines.

For patients whose condition requires particularly rapid improvement, an initial dose of 5 mg/kg/day is justified. There is a possibility of canceling Sandimun Neoral® treatment after achieving a satisfactory response and resuming it with the previous effective dose of Sandimun Neoral® in the event of a relapse. Some patients may require ongoing maintenance therapy.

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

The use of Sandimmun Neoral soft capsules should be gradually discontinued if the period of remission persists for more than 6 months. However, the risk of relapse after drug withdrawal is very high.

Atopic dermatitis

Treatment with Sandimmun Neoral soft capsules should be started by a doctor with experience in the diagnosis and treatment of atopic dermatitis. Given the variability of this disease, treatment should be individually selected. For adults and adolescents over 16 years of age, the recommended dose is 2.5–5 mg/kg/day, divided into 2 doses.

If after 2 weeks the response to the initial dose of 2.5 mg/kg/day is not satisfactory, the daily dose can be rapidly increased to a maximum dose of 5 mg/kg. In very severe cases, rapid and adequate disease control can be achieved with an initial dose of 5 mg/kg/day.

Treatment should be discontinued if patients with atopic dermatitis do not show sufficient improvement after one month of using Sandimmun Neoral soft capsules at a dose of 5 mg/kg/day.

Data available today on the use of Sandimmun Neoral soft capsules for the long-term treatment of atopic dermatitis are limited, so the recommended duration of individual treatment cycles is no more than 8 weeks.

Overdose

Possible impaired renal function. If indicated, appropriate treatment is carried out.

Side effects:

• Urinary disorders: increased concentration of creatinine, urea in the blood, interstitial fibrosis.
• Digestive disorders: anorexia, diarrhea, vomiting, abdominal pain, pancreatitis, dose-dependent increase in the level of bilirubin, the activity of liver enzymes.
• Cardiovascular disorders: arterial hypertension (especially after heart transplant).
• Neurological disorders: headache, convulsions, paresthesia, muscle spasm, myopathy, muscle weakness, tremor, encephalopathy, visual impairment, consciousness disorders, impaired motor function.
• Endocrine disorders: dysmenorrhea, amenorrhea.
• Hematological disorders: mild anemia, thrombocytopenia, hemolytic uremic syndrome.
• Allergic reactions: rash.
• Laboratory changes: hypomagnesemia, hyperkalemia, hyperuricemia.
• Others: weight gain, fatigue, hypertrichosis, gingival hypertrophy, edema, reversible hyperlipidemia, the development of malignant, lymphoproliferative diseases.