Expiration date: 03/2025
Pharmacological action
SANDIMMUN NEORAL is an immunosuppressive drug, is a cyclic polypeptide consisting of 11 amino acids. Ciclosporin is a selective immunosuppressant that inhibits the activation of calcineurin lymphocytes in phase G0 or G1 of the cell cycle. This prevents activation of T-lymphocytes and, at the cellular level, antigen-dependent release of lymphokines, including interleukin-2 (growth factor of T lymphocytes). Cyclosporine acts on lymphocytes specific and reversible. Unlike cytostatic agents it does not suppress haematopoiesis and does not affect the function of phagocytes.
Cyclosporine increases the lifetime of allogeneic transplants of skin, heart, kidney, pancreas, bone marrow, small intestine, lungs. Cyclosporine also inhibits the development of cellular responses against allograft, skin reactions of delayed hypersensitivity, experimental allergic encephalomyelitis, arthritis caused by Freund adjuvant, the disease “graft versus host” (BTP) and dependent T-lymphocytes formation of antibodies. Was shown the effectiveness of applying Sandimmuna bone marrow transplant and solid organs in humans for the prevention and treatment of rejection and BTP, as well as in the treatment of various conditions, which by their nature are autoimmune or can be treated as such.
The dosage form of the preparation Sandimmun Neoral (oral solution and soft capsules, which also concluded the solution) have the following feature. The solution is a microemulsion, preconcentrate, which forms a microemulsion in the presence of fluids (liquids, with which is mixed a solution for the reception inside in front of reception or in the presence of liquids in the stomach when taking the drug in capsule form). This reduces the variability of pharmacokinetic parameters and provides a linear relationship between dose and effect of cyclosporine with a more uniform absorption profile and less dependent on concurrent food intake. In the study of microemulsion preconcentrate it was shown that the correlation between basal concentration of cyclosporine and its effect is more pronounced with the application of Sandimmun Neoral than Sandimmun.
Testimony
Transplantation of solid organs (kidney, liver, heart, heart-lung complex, lung, pancreas) and bone marrow; endogenous uveitis, nephrotic syndrome, distinct forms of rheumatoid arthritis in active phase, severe psoriasis and atopic dermatitis.
Contraindications
Hypersensitivity (including to polioksietilirovannogo castor oil for pharmaceutical forms containing it); malignant neoplasms, precancerous lesions of the skin; children's age (up to 1 year), lactation, children age (to be used for the treatment of psoriasis and rheumatoid arthritis).
C caution. Varicella (currently or recently migrated, including the recent contact with sick), Varicella zoster (risk of generalization), etc. virus diseases, renal and/or hepatic insufficiency, hyperkalemia, hypertension, infections, malabsorption syndrome.
Application of pregnancy and breastfeeding
Experience of application Sandimmun Neoral in pregnant women is limited. In pregnant women, undergoing organ transplantation and treatment with immunosuppressive drugs, increases the risk of premature birth. There are a limited number of observations for children (up to the age of 7 years) exposed to cyclosporine in utero. Renal function and BP in these children were normal. However, adequate and well-controlled studies in pregnant women have not been conducted, so do not use Sandimmun Neoral during pregnancy, except in those cases where the expected benefit to the mother justifies the potential risk to the fetus.
The pilot studies have shown the toxic effect of the drug on the reproductive function.
Cyclosporine passes into breast milk. Mothers receiving Sandimmun Neoral should stop breastfeeding.
Special instructions
Sandimmun Neoral should only be used by physicians with experience in the use of immunosuppressive therapy and have the ability to provide adequate monitoring of the patient, including regular full physical examination, measurement of blood pressure and control the concentration of creatinine in serum . Monitoring of patients undergoing transplantation and receiving medication should only be undertaken in those institutions, which are provided by trained medical personnel, adequate laboratory and other resources.
It should be borne in mind that when using cyclosporine and other immunosuppressants, increased risk of developing lymphomas and other malignancies, often of the skin. An increased risk of developing this complication is associated more with the degree and duration of immunosuppression than with the use of a specific preparation. Thus, caution must be exercised in the application of combination regimens of immunosuppressive therapy, bearing in mind the likelihood of developing lymphoproliferative disorders and solid organ tumors, sometimes leading to fatal outcomes.
Cyclosporin, and other immunosuppressants, predisposes to the development of various bacterial, fungal, parasitic and viral infections, often involving opportunistic pathogens. Given the potential danger of these infections for the patient's life, should have an effective system of preventive and therapeutic measures, especially in cases of prolonged use of combined immunosuppressive treatment.
During the first few weeks of treatment Sandimmunom Neorala you may receive frequent and potentially dangerous complication - increased creatinine and urea in serum . These functional changes are reversible and dose-dependent, normalized at lower doses. Long-term treatment some patients may develop kidney structural changes (e.g., interstitial fibrosis), which in patients with renal transplants should be differentiated with changes in chronic rejection. Sandimmun Neoral may also cause dose-dependent reversible increase in serum bilirubin and, rarely, liver enzymes. In these cases, careful monitoring of indicators of function of kidneys and liver. In the case of deviations of these indicators from the norm may require dose reduction.
To control the concentration of cyclosporine in the blood, preferably using a specific monoclonal antibody (measurement of the amount of unchanged drug). You can use HPLC method, which also measured the concentration of unchanged substance. If you use plasma or serum, you should follow the standard technique of separation (time and temperature). For the initial determination of the concentration of cyclosporine in patients with liver grafts, use of specific monoclonal antibodies. We can also carry out parallel measurements with the use of specific and nonspecific monoclonal antibodies, to achieve a dose that provides adequate immunosuppression.
It should be remembered that the concentration of cyclosporine in blood, plasma or serum is only one of many factors characterizing the clinical condition of the patient. The results of determining the concentration of cyclosporine are only one of the factors that determine the dosage regimen, and are considered in relation with various clinical and laboratory parameters.
In the treatment of Sandimmunom Neorala requires regular monitoring AD. An increase in blood pressure must be assigned appropriate antihypertensive therapy.
Effects on ability to drive vehicles and management mechanisms
Currently, there are no data on the impact Sandimmun Neoral on the ability to drive and use machines.
Composition
1 capsule contains cyclosporine 25 mg;
excipients: D,L-?-tocopherol, ethanol, propylene glycol, mono-, di - and triglycerides of corn oil, polyoxyl 40 hydrogenated castor oil.
the composition of the shell capsules: iron oxide black, titanium dioxide, glycerol 85%, propylene glycol, gelatin.
Method of application and doses
The drug is prescribed inside, regardless of meals.
Sandimmun daily dose of Neoral should always be divided into 2 doses.
The transition from Sandimmun on Sandimmun Neoral
Available data show that in the transition from reception to reception Sandimmuna Sandimmun Neoral while maintaining the ratio of doses of 1:1 values of the basal concentration of cyclosporine determined in whole blood are comparable. Many patients, however, can be observed higher values of maximum concentration and increase the duration of exposure to drug (AUC). A small percentage of patients these changes are more visible and can be clinically significant. Their value depends to a large extent on individual differences in absorption of cyclosporine from the originally used Sandimmun, the bioavailability of which is characterized by high variability. In patients with variable values of basal concentrations or receiving Sandimmun in very high doses (incl. in patients with cystic fibrosis, patients with a transplanted liver with the concomitant cholestasis or poor bile secretion, children or some patients with the transplanted kidney) absorption of cyclosporine may be low or inconsistent, however, when you switch to Sandimmun Neoral is possible to improve absorption. Consequently, in this patient population after the transition of the reception Sandimmuna to the reception Sandimmun Neoral while maintaining the ratio of doses of 1:1 increase in bioavailability of cyclosporine may be more pronounced than is usually observed. Given this, Sandimmun the dose of Neoral should be reduced by individual selection depending on the range of basal concentrations and the relevant evidence.
Sandimmun absorption of cyclosporine from Neoral is less variable and the correlation between basal concentration and bioavailability (AUC values) is much more pronounced than in the application Sandimmun. This makes the basal concentration of cyclosporine in the blood a more precise and reliable parameter for therapeutic monitoring of the drug.
Because the transition from Sandimmun to Sandimmun Neoral may result in increased drug exposure, the following regulations must be observed.
In patients after transplantation treatment Sandimmunom Neorala should start with the same daily dose that was under the previous application Sandimmun. The basal concentration of cyclosporine in whole blood should be monitored for 4-7 days after the transition to Sandimmun Neoral. In addition, clinical safety parameters such as serum creatinine and BP should be monitored during the first 2 months after transfer. If basal concentration of cyclosporine in the blood is outside the therapeutic range and/or deterioration of the clinical safety parameters, the dose should be adjust accordingly.
Patients, treated about testifying, not associated with transplantation, treatment with Sandimmunom Neorala should be started with the same dose which was in the application Sandimmun. After 2, 4 and 8 weeks after transition should monitor the concentration of creatinine in serum and AD. If the values of creatinine concentration in serum or the blood pressure is markedly increased compared with those before the transition, or if the values of creatinine concentration increased by more than 30% in comparison with indicators before treatment with Sandimmunom in more than one dimension, the dose should be reduced by 25-50%. If the concentration in the serum increases by more than 50%, it is necessary to reduce the dose by 50%. In the case of toxic action or the ineffectiveness of the drug should also control the basal concentration of cyclosporine in the blood.
The following dosage ranges for oral administration should be considered only as recommendations. Should be accepted to control the concentration of cyclosporine in the blood, which can be applied radioimmunoassay method based on the use of monoclonal antibodies. On the basis of the received results determine the size of the dose required to achieve the desired concentration of cyclosporine in different patients.
Transplantation
Transplantation of solid organs treatment Sandimmunom Neorala should be started 12 h before surgery at a dose of 10 to 15 mg/kg of body weight, divided into 2 doses. Within 1-2 weeks after the surgery the drug is administered daily at the same dose, then gradually reduce the dose (under the supervision of the concentration of cyclosporine in the blood) to achieve a maintenance dose of 2-6 mg/kg/day (2 admission).
Sandimmun Neoral is administered in combination with other immunosuppressants, including glucocorticoids, as well as in the combined three-component (Sandimmun Neoral + glucocorticoids + azathioprine) or four-component (Sandimmun Neoral + glucocorticoids + azathioprine + drugs mono - or polyclonal antibodies) therapy. A four-part scheme is used in patients with a high risk of rejection. In the case of Sandimmun Neoral as part of the scheme of combination therapy, its dose can be reduced already at the initial stage of therapy (3-6 mg/kg/day in 2 doses) or adjusted in the process of treatment taking into account the concentration of cyclosporine in the blood plasma and the dynamics of safety indicators (concentrations of urea, serum creatinine, BP).
When bone marrow transplantation the initial dose should be administered on the day prior to the transplant. In most cases, it is preferable in/in the introduction; the recommended dose is 3-5 mg/kg/day. Infusion the introduction of the same dose is continued for 2 weeks after transplanting, then move on to oral maintenance therapy with Sandimmun Neorala in a daily dose of about 12.5 mg/kg divided into 2 doses. Supportive therapy for at least 3 months (preferably 6 months), after which the dose is gradually reduced to zero within 1 year after transplantation. If Sandimmun Neoral is appointed and for the initial phase of therapy, the recommended daily dose is 12.5 to 15 mg/kg (2 admission) starting from one day before transplant.
Diseases of the gastrointestinal tract, leading to decreased absorption may require higher doses Sandimmun Neoral or in some cases, the application/infusion Sandimmun.
After cessation of Sandimmuna some patients can develop the disease "graft versus host", which usually regresses after resumption of therapy. To treat this condition in its chronic course in mild form, you should use Sandimmun Neoral at low doses.
Readings that are not associated with transplantation
Endogenous uveitis for inducing remission, the drug is administered in an initial daily dose of 5 mg/kg orally in 2 doses to the disappearance of signs of active inflammation and improving visual acuity. In cases that are difficult to treat, the dose may be increased to 7 mg/kg/day for a short period.
If you are unable to control the situation by using one Sandimmun Neoral, to achieve initial remission, or to heavily attack of inflammation can be attached systemic corticosteroids (prednisone at a daily dose of 0.2-0.6 mg/kg or other glucocorticosteroids in equivalent doses).
During maintenance therapy the dose should be slowly reduced to achieve the lowest effective dose, which in the period of remission should not exceed 5 mg/kg/day.
Nephrotic syndrome for inducing remission, the recommended daily dose for adults is 5 mg/kg, for children - 6 mg/kg (2 admission) under the condition of normal renal function, in addition to the proteinuria. In patients with impaired renal function initial dose should not exceed 2.5 mg/kg/day.
If when using one Sandimmun Neoral fails to achieve a satisfactory effect, especially in stroydormashtekhnika patients, it is recommended to combine it with oral corticosteroids in low doses. If after 3 months of treatment failed to achieve improvement, Sandimmun Neoral should be abolished.
Doses should be selected individually, taking into account performance indicators (proteinuria) and safety (the concentration of serum creatinine), 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.
In rheumatoid arthritis during the first 6 weeks of treatment the recommended dose is 3 mg/kg/day in 2 admission. In case of insufficient effect the daily dose may be gradually increased if tolerance allows, but it should not exceed 5 mg/kg. To achieve full effectiveness may take up to 12 weeks of therapy with Sandimmunom Neorala.
For maintenance therapy the dose should be selected individually depending on tolerability.
Sandimmun Neoral can be administered in combination with low doses of corticosteroids and/or NSAIDs. Sandimmun Neoral can also be combined with a weekly course of methotrexate in low doses in patients with unsatisfactory response to monotherapy with methotrexate. Sandimmun initial dose of Neoral is 2.5 mg/kg/day (2 admission), while the dose can be increased to a level limited by the portability.
In psoriasis, the dosage regimen should be individualized. For the induction of remission recommended starting dose is 2.5 mg/kg/day in 2 admission. If no improvement after 1 month of therapy daily dose can be gradually increased but should not exceed 5 mg/kg. Treatment should be discontinued if you have not reached a satisfactory answer from the manifestations of psoriasis after 6 weeks of treatment with dose of 5 mg/kg/day or if effective dose does not meet the established security settings.
The use of higher initial doses of 5 mg/kg/day may be justified in patients whose condition requires immediate improvement. If a satisfactory response is achieved, Sandimmun Neoral can be canceled, and subsequent relapse to treat reappointment Sandimmun Neoral at the previous effective dose. Some patients may require prolonged maintenance therapy.
For maintenance therapy the dose should be adjusted individually to the minimum effective level and must not exceed 5 mg/kg/day.
In atopic dermatitis the dosage regimen should be individualized. The recommended starting dose is 2.5-5 mg/kg/day in 2 admission. If initial dose 2.5 mg/kg/day does not achieve a satisfactory response within 2 weeks, the daily dose can be rapidly increased to a maximum of 5 mg/kg. In very severe cases rapid and adequate control of the disease can be achieved using the original dose of 5 mg/kg/day. When you achieve a satisfactory response, the dose should be gradually reduced, and, if possible, Sandimmun Neoral should be abolished. In the case of relapse can be carried out repeated courses Sandimmun Neoral.
Despite the fact that treatment duration of 8 weeks may be sufficient to cleanse the skin, it has been shown that treatment duration up to 1 year is effective and well tolerated, with mandatory monitoring of all necessary parameters.
Experience of application Sandimmun Neoral in elderly patients is limited.
Additional guidance on the dosing regime with endogenous uveitis, psoriasis and atopic dermatitis
Since Sandimmun Neoral can impair the renal function, it should be reliable baseline concentration of serum creatinine in at least two dimensions, previous treatment. The creatinine concentration should be monitored with 2-week intervals during the first three months of therapy. Further, if the concentration of creatinine remains stable, measurements should be made on a monthly basis. If the concentration of serum creatinine increases and remains increased by more than 30% from the original values in more than one dimension, it is necessary to reduce the dose by 25-50%. These recommendations should be implemented, even if the values of creatinine concentration remain within laboratory norms. If reducing the dose does not reduce creatinine concentration within one month, the treatment Sandimmunom Neorala should be discontinued.
Discontinuation of treatment is necessary in case when during treatment Sandimmunom Neorala occurs uncontrolled increase in blood pressure.
Additional information on dosing regimen in nephrotic syndrome
Since Sandimmun Neoral can cause kidney problems, it is often necessary to control it. If the concentration of serum creatinine remains increased by more than 30% from the original values and in more than one dimension requires a reduction in the dose Sandimmun Neoral by 25-50%. For patients with initial impaired renal function the initial dose should be 2.5 mg/kg/day. It is necessary to ensure strict control of these patients.
Additional information on dosing regimen in rheumatoid arthritis
Since Sandimmun Neoral can impair the renal function, it should be reliable baseline concentration of serum creatinine in at least two measurements prior to treatment. The creatinine concentration should be monitored with 2-week intervals during the first three months of therapy and thereafter monthly. After 6 months of therapy the concentration of creatinine in the serum should be determined every 4-8 weeks depending on the stability of the underlying disease, at the same time applied therapy and comorbidities. More frequent monitoring is required if the dose Sandimmun Neoral, upon accession concomitant therapy non-steroidal anti-inflammatory drugs or increase their dose.
If the concentration of serum creatinine remains increased by more than 30% from the original values and in more than one dimension, it is necessary to reduce the dose. If the concentration of serum creatinine increases by more than 50%, it is necessary to reduce the dose by 50%. These recommendations should be implemented, even if the values of creatinine concentration remain within laboratory norms. If reducing the dose does not reduce creatinine concentration within one month, the treatment Sandimmunom Neorala should be discontinued.
Discontinuation of treatment is necessary in case when during treatment Sandimmunom Neorala occurs uncontrolled increase in blood pressure.
Side effects
Many side effects associated with cyclosporin, dose dependent and reversible with dose reduction. The range of side effects in General the same for different indications, although the frequency and severity of side effects may vary. In patients undergoing transplantation because of the higher dose and longer duration of treatment side effects are more common and usually more pronounced than in patients with other indications.
The frequency of side effects: very common - ? 10%; often - ? 1% to < 10%; sometimes – from ? 0.1% to < 1%; rarely - ? 0.01% to < 0.1%; very rare < 0.01%.
From the urinary system:
Very often - violation of the kidney.
From the side of cardiovascular system:
Very often - the AD.
CNS and peripheral nervous system:
Very often - tremor, headache; often - Paresthesia ; sometimes - signs of encephalopathy, e.g. convulsion, confusion, disorientation, slowness of reactions, agitation, sleep disturbance, visual disturbances, cortical blindness, coma, paresis, cerebellar Ataxia ; rare - motor polyneuropathy; very rare - swelling of the optic nerve head (including the nipple of the optic nerve), secondary to benign intracranial hypertension.
From the digestive system:
Often - Anorexia , nausea, vomiting , abdominal pain, diarrhea, gum hyperplasia, liver dysfunction; rare - pancreatitis.
From the metabolic:
Very often, hyperlipidemia, and often hyperuricemia, hyperkalemia, hypomagnesemia; rare - hyperglycemia.
From the musculoskeletal system
Often - muscle spasms, Myalgia ; rare - muscle weakness, myopathy.
With the hematopoietic system:
Sometimes - anemia, thrombocytopenia; rarely - microangiopathic hemolytic anemia, hemolytic uremic syndrome.
Dermatological reactions:
Often, hypertrichosis; sometimes - allergic skin rash.
From the body as a whole:
Often - fatigue; sometimes - swelling, weight gain.
From the endocrine system:
Rarely - violation of the menstrual cycle, gynecomastia.
Drug interactions
Different drugs can increase or decrease the concentration of cyclosporine in plasma or blood by inhibition or induction of enzymes involved in the metabolism of cyclosporine, in particular isoenzymes of the cytochrome P-450 .
Drugs that reduce the concentration of cyclosporine: barbiturates, carbamazepine , phenytoin ; nafcillin, sulfadimidin when it is on/in the introduction; rifampicin ; octreotide ; probucol ; orlistat ; preparations containing St. John's wort (Hypericum perforatum); tiklopidin , sulfinpirazon , terbinafine .
Drugs that increase the concentration of cyclosporine, some antibiotics-macrolides (primarily erythromycin and clarithromycin ); ketoconazole , fluconazole , Itraconazole ; diltiazem , nicardipine, verapamil ; metoclopramide ; oral contraceptives; danazol ; methylprednisolone (high dose); allopurinol ; amiodarone ; haliewa acid and its derivatives; protease inhibitors, imatinib .
Should avoid prescribing erythromycin in, because he has the ability to increase the concentration of cyclosporine in the blood. If, due to the lack of alternative therapies, prescribed erythromycin it is recommended to carefully monitor the concentration of cyclosporine in the blood, kidney function and the presence of side effects of cyclosporine.
Caution should be exercised with simultaneous use of Sandimmun Neoral and drugs that have nephrotoxic effects, e.g. aminoglycosides (including gentamicin , tobramycin ), amphotericin b , ciprofloxacin , vancomycin , trimethoprim (+ sulfamethoxazole ); NSAIDs (including diclofenac , naproxen , sulindac); melphalan , histamine H 2 -receptors (e.g. cimetidine , ranitidine ).
Avoid joint application of cyclosporine with tacrolimus, since this can lead to increased risk of nephrotoxicity.
The combined use of nifedipine and cyclosporine can lead to more severe gingival hyperplasia than in monotherapy with cyclosporine.
Discovered that the combined use of diclofenac and cyclosporine can significantly increase the bioavailability of diclofenac, with the possible development of reversible renal dysfunction. The increase in the bioavailability of diclofenac is most likely associated with a reduction in its metabolism when "first pass" through the liver. When used in conjunction with cyclosporine NSAID with a less pronounced effect "first passage" (e.g., acetylsalicylic acid ) increase in their bioavailability is expected.
Cyclosporine may decrease the clearance of digoxin , colchicine , prednisolone and inhibitors of HMG - COA reductase inhibitor (statin). With simultaneous use of cyclosporine and digoxin or colchicine, careful clinical observation for early detection of toxic effects of these drugs and to address the issue of reducing the dose or eliminate the treatment.
The number of reported cases of severe glycoside intoxication within a few days after the start of treatment with cyclosporine in patients receiving digoxin. There are also reports that cyclosporine can exacerbate the toxic effects of colchicine, for example, the development of myopathy or neuropathy, especially in patients with impaired renal function.
When applying cyclosporine in clinical practice, as well as according to the literature, the reported cases of muscular toxicity, including muscle pain, weakness, myositis and rhabdomyolysis in the background of the simultaneous application of cyclosporine with lovastatin , simvastatin , atorvastatin , pravastatin and, in rare cases, fluvastatinom . If necessary, the use of such drugs concurrently with cyclosporine to reduce their dose. Statin therapy should be suspended or removed altogether in patients with symptoms of myopathy, and patients with factors predisposing to severe renal impairment, including renal failure, developed due to rhabdomyolysis.
The increase in creatinine concentration was observed in studies that have examined the combined use of everolimus or sirolimus with high doses of cyclosporine in the form of a microemulsion. This effect is often reversible after reducing the dose of cyclosporine. Everolimus and sirolimus have a minor impact on the pharmacokinetic parameters of cyclosporine. The combined use of cyclosporine with everolimus or sirolimus, leads to a significant increase in the concentration of the latter in the blood plasma.
The combination of cyclosporine with drugs that have nephrotoxic effects, requires careful monitoring of renal function (in particular, the concentration of creatinine in plasma). The detection of pronounced renal dysfunction the dose of these drugs should be reduced or consider alternative treatment.
There are isolated reports of the development of significant, but reversible renal dysfunction (with a corresponding increase in the concentration of creatinine) in patients undergoing transplantation with simultaneous use of cyclosporine derivative fibroevoy acid (for example, bezafibrat , fenofibrate ). Therefore, in this category of patients need to monitor kidney function. In the case of the expressed renal dysfunction concomitant use of such drugs should be discontinued.
The combination of cyclosporine with drugs that reduce or increase its bioavailability in patients undergoing transplantation requires frequent determination of the concentration of cyclosporine and, if necessary, change the dose of cyclosporine, especially in the initial phase of concomitant treatment or in the period of its abolition. In patients without graft surveillance of the concentration of cyclosporine has such a significant value, because for these patients the relationship of blood concentrations and clinical effects has not been proven with full evidence.
In combined administration of cyclosporine and drugs that increase its concentration, frequent monitoring of renal function and the monitoring of side effects of cyclosporine are more important than determining the concentration of cyclosporine in plasma.
Patients with gum hyperplasia during therapy with cyclosporine should be avoided combined use of nifedipine.
NSAIDs with a pronounced effect "first passage" through the liver (e.g., diclofenac) should be administered in smaller doses than patients not receiving cyclosporine.
With simultaneous use of cyclosporine and digoxin, colchicine or inhibitors of HMG-COA reductase (statins) careful clinical observation for early detection of toxic effects of these drugs and to address the issue of reducing the dose or eliminate the treatment.
Food interaction
There are reports that grapefruit juice increases the bioavailability of cyclosporine.
Overdose
Symptoms: the existing experience concerning overdose Sandimmun Neoral restricted. Perhaps the development of impaired renal function, which is probably reversible with drug discontinuation.
Treatment: symptomatic treatment, specific antidote exists. Cyclosporine is practically not displayed in hemodialysis and hemoperfusion using activated charcoal .
Storage conditions
The drug should be stored at temperatures not above 25°C.
Shelf life
3 years.
