Instructions for use SANDIMMUN NEORAL® capsules

Sandimmun Neoral soft capsules are prescribed for the following indications:

Indications for transplantations

• Solid organ transplantation: preventing rejection of solid organ transplants;
• treatment of transplant rejection in patients previously treated with other immunosuppressive drugs.

Indications not related to transplantation

• Endogenous uveitis: active middle or posterior uveitis, threatening vision loss, of non-infectious etiology in cases where alternative treatment has proven ineffective or unacceptable due to adverse reactions;
• uveitis in Behcet's disease with repeated exacerbations of inflammation involving the retina without neurological symptoms.

Compound

Active ingredient: ciclosporin;

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

Excipients: castor oil polyethoxyvane, hydrogenated mono- and di-triglycerides of corn oil; ethanol; propylene glycol; α-tocopherol;

Capsule shell: gelatin, propylene glycol, glycerin (85%), residual solvents, titanium dioxide (E 171), black iron oxide (E172) - only for capsules 25 mg and 100 mg;

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

Contraindications

Hypersensitivity to cyclosporine or to any of the excipients of the drug. Concomitant use with medicinal products containing Hypericum perforatum (St. John's wort) due to the risk of reducing the concentration of cyclosporine in the blood and, thus, reducing the therapeutic effect.

Concomitant use with drugs that are substrates of the multidrug efflux transporter P-glycoprotein (Pgp) or organic anion transport proteins (OATP), an increase in plasma concentrations of which is associated with the development of serious adverse reactions and/or life-threatening adverse reactions, for example with bosentan , dabigatran etexilate and aliskiren.

The following contraindications are also possible:

• Renal failure, with the exception of patients with nephrotic syndrome and moderately elevated initial creatinine concentrations up to a maximum of 200 µmol/L in adults and 140 µmol/L in children. In case of nephrotic syndrome, careful treatment is allowed using doses not exceeding 2.5 mg/kg/day, only if the use of cyclosporine helps to normalize creatinine levels increased as a result of the disease.
• Insufficiently controlled hypertension.
• Poorly controlled infection.

A history of known or diagnosed malignant neoplasms of any kind, with the exception of precancerous conditions or malignant skin lesions after treatment.

Instructions for use SANDIMMUN NEORAL® capsules

Sandimmune Neoral® should be prescribed only by physicians who have experience in immunosuppressive therapy and are able to provide adequate monitoring of the patient, including regular complete physical examination, measurement of blood pressure and monitoring of laboratory safety indicators, in particular monitoring of serum creatinine concentrations. Monitoring of patients who have undergone transplantation and received the drug should be carried out only in those institutions that are provided with special medical personnel, adequate laboratory and other resources. The doctor responsible for maintenance therapy must receive complete information on the patient's treatment.

Like other immunosuppressants, cyclosporine increases the risk of developing lymphomas and other neoplasms, especially of the skin. The increased risk of developing this complication is related more to the intensity and duration of immunosuppression than to the use of a specific drug. Therefore, caution should be exercised when using combination immunosuppressive regimens, keeping in mind the potential for the development of lymphoproliferative diseases and solid organ tumors, which are sometimes fatal. Due to the increased risk of developing skin cancer, patients taking Sandimmune Neoral® should be warned to avoid prolonged exposure to ultraviolet radiation.

Cyclosporine can cause the development of various bacterial, fungal and viral infections, often involving opportunistic pathogens. Because this can be fatal, appropriate therapeutic strategies should be used in patients with long-term immunosuppression, especially in cases of long-term use of combination immunosuppressive therapy.

During the first few weeks of treatment with Sandimmune Neoral, a common and potentially dangerous complication that may occur is an increase in serum creatinine and urea levels. These functional changes are reversible and depend on the dosage regimen. As a rule, reducing the dose leads to a marked improvement in well-being. With long-term treatment, some patients may develop structural changes in the kidneys (for example, arteriolar hyalinosis, tubular atrophy and interstitial fibrosis), which in patients with renal transplants should be differentiated from changes in chronic rejection. Sandimmune Neoral® may also cause a dose-dependent, reversible increase in serum bilirubin and, less commonly, liver enzymes. It is necessary to regularly monitor relevant indicators of liver and kidney function; if necessary, the dose should be reduced if these indicators deviate from the norm. It is also necessary to especially carefully monitor renal function in elderly patients.

Regular monitoring of cyclosporine blood levels is an important safety measure in transplant patients.

To monitor blood levels of cyclosporine, it is preferable to use specific monoclonal antibodies (measurement of the amount of unchanged drug). An HPLC (high-pressure liquid chromatography) method can be used, which also measures the concentration of unchanged substance. If plasma or serum is used, standard separation procedures (time and temperature) should be followed. For initial monitoring of cyclosporine concentrations in liver transplant patients, both specific monoclonal antibodies and parallel determinations using specific and nonspecific monoclonal antibodies can be used to achieve a dose that provides adequate immunosuppression. During treatment with cyclosporine, blood pressure should be regularly monitored; if it increases, appropriate antihypertensive therapy should be prescribed. Preference should be given to an antihypertensive agent that does not affect the pharmacokinetics of cyclosporine, for example, isradipine.

Since there are isolated reports of cases of slight reversible increases in blood lipid levels during therapy with Sandimmune Neoral, it is recommended to determine the concentration of lipids in the blood before starting treatment and 1 month after it starts. In this case, you need to prescribe the patient a diet with limited fat and reduce the dose of cyclosporine.

Because the drug in some cases increases the risk of hyperkalemia, especially in patients with impaired renal function, or increases pre-existing hyperkalemia, it is recommended to monitor serum potassium levels. Patients receiving Sandimmune Neoral® should avoid excessive intake of potassium from food and should not use potassium-containing or potassium-sparing drugs:

• potassium-sparing diuretics, ACE inhibitors, angiotensin II receptor antagonists, taking into account serum potassium levels.

Cyclosporine increases the clearance of magnesium, which can lead to symptomatic hypomagnesemia, especially during the peritransplantation period. Monitoring magnesium levels is recommended during the peritransplant period, especially if neurological signs/symptoms occur. If necessary, magnesium supplements should be prescribed.

Caution should be exercised when treating patients with hyperuricemia. It is recommended to monitor serum uric acid concentrations, especially in patients with previous hyperuricemia.

During treatment with Sandimmune Neoral, vaccination may be less effective, and the use of live attenuated vaccines should be avoided.

Additional safety precautions must be taken when cyclosporine and lercanidipine are co-administered.

The ethanol content should be taken into account when prescribing the drug to pregnant or breastfeeding women, patients with liver disease or epilepsy, alcoholics or if Sandimmune Neoral® is prescribed to a child.

Precautions for non-transplant indications

Cyclosporine should not be prescribed to patients with impaired renal function (except for patients with nephrotic syndrome), uncontrolled arterial hypertension, infectious diseases that cannot be adequately treated, or malignant neoplasms.

Endogenous uveitis

Since Sandimmun Neoral® can cause renal dysfunction, treatment can only be prescribed if renal function is initially normal. During treatment, renal function should be monitored frequently. If serum creatinine remains elevated by more than 30% of the initial values ​​(before treatment with Sandimmune Neoral) in more than one measurement, then a dose reduction of 25-50% is required. It is recommended to consider further dose reduction if serum creatinine increases by more than 50%. These recommendations should be followed even if creatinine concentrations remain within the laboratory normal range.

Sandimmune Neoral® should be used with caution in patients with neurological Behçet's syndrome. The neurological condition of such patients should be carefully monitored.

Experience with the use of Sandimmune Neoral in children with endogenous uveitis is currently limited.

Nephrotic syndrome

Since Sandimmune Neoral® can cause renal dysfunction, frequent monitoring of renal function is necessary during treatment. If serum creatinine remains elevated by more than 30% of the initial values ​​(before treatment with Sandimmune Neoral) in more than one measurement, then a dose reduction of 25-50% is required. It is recommended to consider further dose reduction if serum creatinine increases by more than 50%. For patients with initially impaired renal function, the initial dose should be 2.5 mg/kg/day. It is necessary to ensure careful monitoring of the condition of these patients.

Due to impaired renal function caused by nephrotic syndrome, in some patients it may be difficult to detect impaired renal function caused by the action of Sandimmune Neoral. This explains the fact that in some cases, structural changes in the kidneys associated with Sandimmune Neoral were observed without an increase in serum creatinine. Kidney biopsy is indicated for patients with steroid-dependent minimal change nephropathy who have received maintenance therapy with Sandimmune Neoral for more than a year.

In rare cases, the appearance of malignant tumors (including Hodgkin's lymphoma) has been observed in patients suffering from nephrotic syndrome who received immunosuppressants (including Sandimmune Neoral®).

Rheumatoid arthritis

Since Sandimmune Neoral® may impair renal function, a reliable baseline serum creatinine level should be established in at least two measurements prior to treatment. Creatinine levels should be monitored at 2-week intervals during the first 3 months of therapy and then once a month. After 6 months of therapy, serum creatinine should be determined every 4-8 weeks depending on the stability of the underlying disease, the presence of concomitant therapy and concomitant diseases. More frequent monitoring is necessary when increasing the dose of Sandimmune Neoral, when prescribing concomitant NSAID therapy or increasing their dose. If serum creatinine remains elevated by more than 30% of baseline (pre-treatment) values ​​in more than one measurement, then the dose should be reduced. If serum creatinine increases by more than 50%, then the dose should be reduced by 50%. These recommendations should be followed even if creatinine concentrations continue to remain within the laboratory normal range. If dose reduction does not lead to a decrease in creatinine levels within 1 month, then treatment with Sandimmune Neoral should be discontinued. Discontinuation of treatment is also necessary if uncontrolled arterial hypertension occurs during treatment with Sandimmune Neoral.

As with long-term use of other immunosuppressants, one should be aware of the increased risk of lymphoproliferative disorders. Particular caution should be exercised when using Sandimmune Neoral in combination with methotrexate.

Psoriasis

Since Sandimmune Neoral® may impair renal function, a reliable baseline serum creatinine level should be established in at least two measurements prior to treatment. Serum creatinine levels should be monitored at 2-week intervals during the first 3 months of therapy. In the future, if the creatinine level remains stable, measurements should be taken at intervals of 1 month. If serum creatinine remains elevated by more than 30% of baseline (pre-treatment) values ​​in more than one measurement, then the dose should be reduced by 25-50%. It is recommended to consider further dose reduction if serum creatinine increases by more than 50%. These recommendations should be followed even if creatinine concentrations continue to remain within the laboratory normal range. If dose reduction does not lead to a decrease in creatinine levels within one month, then treatment with Sandimmune Neoral should be discontinued. Discontinuation of treatment is also necessary if uncontrolled arterial hypertension occurs during treatment with Sandimmune Neoral.

Prescription of Sandimmune Neoral to elderly patients is possible only in cases of disabling psoriasis, and careful monitoring of renal function is necessary.

Experience with the use of Sandimmune Neoral in children with psoriasis is currently limited.

In patients with psoriasis receiving treatment with Sandimmune Neoral, as with the use of other immunosuppressants for a long time, the occurrence of malignant neoplasms, especially of the skin, has been reported. If there are skin lesions that are not typical for psoriasis and if they are suspected of being malignant or a precancerous condition, a biopsy should be performed before starting treatment with Sandimmune Neoral. Treatment of patients with malignant or precancerous lesions with Sandimmune Neoral is possible only after appropriate treatment of these lesions and in the absence of alternative effective therapy.

Lymphoproliferative diseases were observed in several patients with psoriasis treated with Sandimmune Neoral. In these cases, immediate discontinuation of the drug made it possible to stop the processes of tissue proliferation. Patients being treated with Sandimmune Neoral should not simultaneously receive ultraviolet B radiation or PUVA therapy.

Atopic dermatitis

Since Sandimmune Neoral® may impair renal function, baseline serum creatinine should be accurately determined in at least two measurements prior to treatment. Creatinine levels should be monitored at 2-week intervals during the first 3 months of therapy. In the future, if the creatinine level remains stable, measurements should be taken at intervals of 1 month.

If serum creatinine remains elevated by more than 30% of baseline (pre-treatment) values ​​in more than one measurement, then the dose should be reduced by 25-50%. It is recommended to consider further dose reduction if serum creatinine increases by more than 50%. These recommendations should be followed even if serum creatinine concentrations remain within the normal range. If the dose reduction does not lead to a decrease in creatinine levels within one month, then treatment with Sandimmune Neoral should be discontinued. Discontinuation of treatment is also necessary if uncontrolled arterial hypertension occurs during treatment with Sandimmune Neoral.

Since the experience of using Sandimmune Neoral in children with atopic dermatitis is currently limited, the use of the drug in this category of patients is not recommended.

Prescription of Sandimmune Neoral to elderly patients is possible only in cases of disabling atopic dermatitis, and careful monitoring of renal function is necessary.

Benign lymphadenopathy is usually associated with hot flashes in atopic dermatitis and invariably resolves on its own or with general improvement in the disease. Lymphadenopathy that appears during treatment with cyclosporine should be regularly monitored. Lymphadenopathy that persists despite decreased disease activity should be biopsied to rule out the presence of lymphoma.

Cases of active herpes simplex should be cured before starting treatment with Sandimmune Neoral, but the appearance of herpes simplex is not a reason to discontinue the drug if treatment has already been started, except in severe cases.

Skin infections caused by Staphylococcus aureus,

are not an absolute contraindication for therapy with Sandimmune Neoral, provided that appropriate antibacterial drugs are prescribed.

Oral erythromycin should be avoided as it has the potential to increase cyclosporine blood concentrations, but unless alternative therapy is available, careful monitoring of cyclosporine blood concentrations, renal function, and cyclosporine side effects is recommended.

Due to the potential risk of developing malignant skin tumors, when treated with Sandimmune Neoral, patients should be warned to avoid direct exposure to sunlight and ultraviolet B radiation or PUVA therapy.

Use in pediatrics

Experience with the use of Sandimmune Neoral for the treatment of children is limited, however, when prescribing the recommended doses to children over the age of 1 year

There are no particular problems, so the drug is prescribed in the same doses as for adults. There is experience in treating children with higher doses of the drug compared to doses for adults.

Impact on the ability to drive vehicles and operate machinery

No data. Drivers and operators of complex machinery should be aware of the possibility of side effects from the nervous and musculoskeletal systems, which may reduce attention and reaction speed.

Overdose

Symptoms. Data on acute overdose of cyclosporine are limited. Oral doses of up to 10 g (approximately 150 mg/kg) resulted in relatively minor clinical effects such as vomiting, drowsiness, headache, tachycardia, and in some patients, relatively large renal impairment. However, accidental parenteral overdose in premature infants has resulted in severe toxicity.

Treatment. In all cases of overdose, symptomatic treatment and general supportive measures should be carried out. In the first hours after an overdose, it may be useful to induce vomiting and perform gastric lavage. The drug is practically not excreted during hemodialysis and is insufficiently excreted during hemoperfusion using activated carbon.

Sandimmun® neoral®

The drug is prescribed orally, regardless of food intake.

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

Switching from Sandimmune® to Sandimmune® Neoral®

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

Absorption of cyclosporine from Sandimmune Neoral is less variable and the correlation between basal concentration and bioavailability (as measured by AUC values) is much greater than with Sandimmune. This makes the basal blood concentration of cyclosporine a clearer and more reliable parameter for therapeutic drug monitoring.

Because switching from Sandimmune to Sandimmune® Neoral® may 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 as with the previous use of Sandimmune. The basal concentration of cyclosporine in whole blood should be monitored for 4-7 days after switching to Sandimmun® Neoral®. In addition, clinical safety parameters such as serum creatinine and blood pressure should be monitored during the first 2 months after switching. If the basal blood concentration of cyclosporine is outside the therapeutic range and/or deterioration in clinical safety parameters is observed, the dose should be adjusted accordingly.

In patients treated for non-transplant indications,

treatment with Sandimmune Neoral should be started with the same dose as when using Sandimmune. Serum creatinine concentrations and blood pressure should be monitored at 2, 4, and 8 weeks after transition. If serum creatinine concentrations or blood pressure levels increase markedly compared to those before switching, or if creatinine concentrations increase by more than 30% compared to pre-Sandimmun treatment values ​​in more than one dimension, then the dose should be reduced by 25-50 %. If serum concentration increases by more than 50%, then reduce the dose by 50%. In case of toxic effects or if the drug is ineffective, basal concentrations of cyclosporine in the blood should also be monitored.

The following oral dosage ranges should be considered guidelines only. Conventional monitoring of the concentration of cyclosporine in the blood should be carried out, for which a radioimmunological method based on the use of monoclonal antibodies can be used. Based on the results obtained, the dose required to achieve the desired concentration of cyclosporine in various patients is determined.

Transplantation

For solid organ transplantation

treatment with Sandimmune Neoral should be started 12 hours before surgery at a dose of 10 to 15 mg/kg body weight, divided into 2 doses. For 1-2 weeks after surgery, the drug is prescribed daily at 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 is reached (in 2 doses).

Sandimmun® Neoral® is prescribed in combination with other immunosuppressants, incl. with GCS, as well as as part of a combined three-component (Sandimmune® Neoral® + GCS + azathioprine) or four-component (Sandimmune® Neoral® + GCS + azathioprine + mono- or polyclonal antibody preparations) therapy. The four-component regimen is used in patients at high risk of developing rejection. If Sandimmune Neoral is used as part of combination therapy regimens, its dose can be reduced already at the initial stage of therapy (3-6 mg/kg/day in 2 doses) or adjusted during 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 before transplantation. In most cases, IV administration is preferred; The recommended dose is 3-5 mg/kg/day. Infusion administration at the same dose is continued for 2 weeks after transplantation, then switched to oral maintenance therapy with Sandimmune Neoral at 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 also prescribed for the initial stage of therapy, then the recommended daily dose is 12.5-15 mg/kg (in 2 divided doses) starting from the day before the transplant.

In the presence of gastrointestinal diseases leading to decreased absorption, higher doses of Sandimmune Neoral or, in some cases, the use of intravenous infusions of Sandimmune may be required.

After discontinuation of Sandimmune, some patients may develop GVHD, which usually regresses after resumption of therapy. To treat this condition in its chronic, mild form, Sandimmune® Neoral® should be used in low doses.

Indications not related to transplantation

With endogenous uveitis

to
induce remission
, the drug is prescribed at 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 that are difficult to treat, the dose can be increased to 7 mg/kg/day for a short period.

If it is not possible to control the situation with Sandimmune Neoral alone, then to achieve initial remission or to stop an attack of inflammation, systemic corticosteroids can be added (prednisolone in a daily dose of 0.2-0.6 mg/kg or another glucocorticosteroid in an equivalent dose).

During maintenance therapy

the dose should be slowly reduced until the lowest effective dose is reached, which during the period of remission of the disease should not exceed 5 mg/kg/day.

For nephrotic syndrome

to
induce remission,
the recommended daily dose for
adults
is 5 mg/kg, for
children
- 6 mg/kg (in 2 divided doses) provided that renal function is normal, 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 alone fails to achieve a satisfactory effect, especially in steroid-resistant patients, then its combination with oral corticosteroids in low doses is recommended. If after 3 months of treatment no improvement has been achieved, Sandimmun® Neoral® should be discontinued.

Doses should be individualized, taking into account efficacy (proteinuria) and safety (serum creatinine concentration), but should not exceed a 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.

For 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 tolerated, but it should not exceed 5 mg/kg. It may take up to 12 weeks of treatment with Sandimmune Neoral to achieve full effectiveness.

For maintenance therapy

the dose should be selected individually depending on the tolerability of the drug.

Sandimmune® Neoral® can be prescribed in combination with low doses of GCS and/or NSAIDs. Sandimmun® Neoral® can also be combined with a weekly course of low-dose methotrexate in patients with an unsatisfactory response to methotrexate monotherapy. The initial dose of Sandimmune Neoral is 2.5 mg/kg/day (in 2 divided doses), and the dose can be increased to a level limited by tolerability.

For psoriasis

The dosage regimen 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 if a satisfactory response to psoriasis is not achieved after 6 weeks of treatment with a dose of 5 mg/kg/day or if the effective dose does not meet established safety parameters.

The use of a higher initial dose of 5 mg/kg/day may be justified in patients whose condition requires rapid improvement. If a satisfactory response is achieved, Sandimmun® Neoral® can be discontinued, and a subsequent relapse can be treated by re-prescribing Sandimmune Neoral at the previous effective dose. Some patients may require long-term maintenance therapy.

For maintenance therapy

Doses should be individualized to the minimum effective level and should not exceed 5 mg/kg/day.

For atopic dermatitis

The dosage regimen should be selected individually. 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 achieve a satisfactory response within 2 weeks, 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 using a dose of 5 mg/kg/day. When a satisfactory response is achieved, the dose should be gradually reduced and, if possible, Sandimmun® Neoral® should be discontinued. In case of relapse, a second course of Sandimmune Neoral may be administered.

Although a course of treatment of 8 weeks may be sufficient to clear the skin, therapy for up to 1 year has been shown to be effective and well tolerated, subject to mandatory monitoring of all necessary indicators.

Experience of using Sandimmune Neoral in elderly patients

limited.

In clinical studies of cyclosporine for the treatment of rheumatoid arthritis, the proportion of patients aged 65 years and older was 17.5%. These patients have been shown to be more likely to develop systolic hypertension and also more likely to have serum creatinine concentrations greater than 50% above baseline after 3 to 4 months of cyclosporine therapy.

The number of patients aged 65 years and older included in clinical trials of Sandimmune Neoral in transplant patients and in patients with psoriasis was not sufficient to determine whether the response to treatment in this category of patients differs from the response to treatment in older patients. young patients. Based on other available information on the use of cyclosporine in clinical practice, it can be concluded that the response to treatment does not differ between older and younger patients.

Dose selection in elderly patients should be done with caution; Usually, treatment is started at the lowest dose, taking into account the greater incidence of liver, kidney or cardiac dysfunction, as well as taking into account concomitant diseases or other concomitant therapy.

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

Since Sandimmun® Neoral® may impair renal function, a reliable baseline serum creatinine concentration should be established in at least two measurements prior to treatment. Creatinine concentrations should be monitored at 2-week intervals during the first three months of therapy. Thereafter, if the creatinine concentration remains stable, measurements should be performed monthly. If the serum creatinine concentration increases and remains elevated by more than 30% of baseline values ​​in more than one measurement, then the dose should be reduced by 25-50%. These recommendations should be followed even if creatinine concentrations continue to remain within the laboratory normal range. If 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 if an uncontrolled increase in blood pressure occurs during treatment with Sandimmune Neoral.

Additional dosing instructions for nephrotic syndrome

Since Sandimmune® Neoral® may cause renal dysfunction, it should be monitored frequently. If serum creatinine concentration remains elevated by more than 30% of baseline values ​​and in more than one dimension, then a dose reduction 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 careful monitoring of the condition of these patients.

Additional dosing guidelines for rheumatoid arthritis

Since Sandimmun® Neoral® may impair renal function, a reliable baseline serum creatinine concentration should be established in at least two measurements prior to treatment. Creatinine concentrations should be monitored at 2-week intervals during the first three months of therapy and monthly thereafter. After 6 months of therapy, serum creatinine concentrations should be determined every 4-8 weeks depending on the stability of the underlying disease, concurrent therapy and concomitant diseases. More frequent monitoring is necessary when increasing the dose of Sandimmune Neoral, when adding concomitant NSAID therapy or increasing their dose.

If the serum creatinine concentration remains elevated by more than 30% of 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 the dose should be reduced by 50%. These recommendations should be followed even if creatinine concentrations continue to remain within the laboratory normal range. If 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 if an uncontrolled increase in blood pressure occurs during treatment with Sandimmune Neoral.

Rules for the use and storage of the drug Sandimmune® Neoral®

Instructions for using the drug in the form of soft capsules

Softgels should be left in the blister pack until needed. After opening the blister pack, a characteristic odor is felt. This is normal.

Capsules should be swallowed whole.

Instructions for using the drug in the form of an oral solution

During initial use:

1. Remove the plastic cover.

2. Tear off the sealing ring completely.

3. Remove the black plug and discard it.

4. Push the tube with the white stopper firmly into the neck of the bottle.

5. Insert the measuring syringe into the white stopper.

6. Draw into a measuring syringe the volume of solution corresponding to the prescribed dose.

7. Expel any large bubbles by moving the plunger back and forth several times before separating the syringe containing the prescribed dose volume from the vial. The presence of a few very small bubbles is not significant and does not affect the dose in any way.

8. After use, wipe the outside of the measuring syringe only with a dry cloth and place it in the protective case. The white stopper and tube should remain in the bottle. Close the bottle with a lid.

When using the solution subsequently, you should start from step 5.

Immediately before taking the solution, Sandimmune Neoral should be taken from the bottle using a measuring syringe (as indicated above), transferred to a glass or cup and mixed with orange or apple juice. You can also use other non-alcoholic drinks (according to individual taste). The added drink and solution should be mixed well. Grapefruit juice should not be used for dilution, given the possibility of its interaction with the P450-dependent enzyme system. Do not allow the measuring syringe to come into contact with the mixing drink. Do not rinse the syringe with water or any other liquid.

Sandimmun® Neoral® oral solution should be used within 2 months from the moment the bottle is opened and stored at a temperature of 15° to 30°C, preferably at a temperature of at least 20°C for long periods of storage, since the drug contains oil components of natural origin , which are prone to hardening at low temperatures. At temperatures below 20°C, a transition to a jelly-like state is possible, which again changes to liquid when the temperature rises to 30°C. This may leave a small sediment or flakes. These phenomena do not affect the effectiveness and safety of the drug and the accuracy of dosing using a measuring syringe.

Note!

Description of the drug Sandimmune Neoral caps. soft 50mg No. 50 on this page is a simplified author’s version of the apteka911 website, created on the basis of the instructions for use.
Before purchasing or using the drug, you should consult your doctor and read the manufacturer's original instructions (attached to each package of the drug). Information about the drug is provided for informational purposes only and should not be used as a guide to self-medication. Only a doctor can decide to prescribe the drug, as well as determine the dose and methods of its use.

Sandimmune Neoral caps 100 mg N50 (Novartis)

Sandimmune Neoral is taken orally: for adults undergoing solid organ transplantation, treatment should begin 12 hours before surgery at a dose of 10-15 mg/kg, divided into 2 doses. For 1-2 weeks after surgery - daily, at the same dose, after which the dose is gradually reduced (5%/week) until the maintenance level is reached - 2-6 mg/kg/day. When prescribed in combination with GCS or other immunosuppressants, smaller doses are used (3-6 mg/kg/day in the initial phase of treatment). In case of bone marrow transplantation - on the day preceding the transplantation, and during the transplantation period, for 2 weeks, at a daily dose of 12.5-15 mg/kg, then switch to maintenance therapy at a dose of about 12.5 mg/kg/day (if absorption is impaired, they may require higher oral doses or switch to IV administration). Maintenance treatment is continued for at least 3-6 months (preferably 6 months), after which the dose is gradually reduced so that treatment is stopped 1 year after transplantation. Some patients develop a rejection reaction after stopping treatment, in which case treatment should be resumed. For endogenous uveitis, to induce remission - in an initial daily dose of 5 mg/kg, in 1 or several doses, until inflammation subsides and visual acuity improves. In severe cases, the dose can be increased to 7 mg/kg/day for a limited period. During maintenance therapy, the dose should be slowly reduced until the lowest effective dose is reached, which during the period of remission of the disease should not exceed 5 mg/kg/day. For nephrotic syndrome, to induce remission - in a daily dose of 5 mg/kg for adults and 6 mg/kg for children (in 2 doses), provided that there is no decrease in renal function (except in cases of proteinuria). For patients with impaired renal function, the initial daily dose should not exceed 2.5 mg/kg. If monotherapy with cyclosporine fails to achieve the desired effect, combination with small doses of corticosteroids, orally, is possible. If after 3 months of treatment no positive effect is observed, therapy should be discontinued. For maintenance treatment, the dose should be slowly reduced to the minimum effective dose. For rheumatoid arthritis, during the first 6 weeks of treatment, the daily dose is 3 mg/kg in 2 doses. In case of insufficient effect, the daily dose can be gradually increased subject to satisfactory tolerability (not higher than 5 mg/kg/day). The course of treatment is up to 12 weeks. For maintenance therapy, the dose should be selected individually depending on tolerability (can be prescribed in combination with small doses of GCS and/or NSAIDs). For psoriasis, to induce remission, the daily dose is 2.5 mg/kg in 2 divided doses. In severe cases of the disease, when rapid achievement of an effect is required, the initial daily dose may be 5 mg/kg. If it is not possible to achieve an adequate effect when used at a daily dose of 5 mg/kg for 6 weeks, the drug should be discontinued. The dose for maintenance treatment of psoriasis should be minimally effective (should not exceed 5 mg/kg/day). For atopic dermatitis - the initial dose is 2.5 mg/kg/day. In severe cases, the dose may be increased to 5 mg/kg/day. If a positive result is achieved, the dose should be gradually reduced until completely discontinued.