Sandimmun Neoral - Instructions For Use, 100 Mg, 50 Mg, 25 Mg, 10 Mg

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Sandimmun Neoral

Sandimmun Neoral: instructions for use and reviews

1. 1. Release form and composition
2. 2. Pharmacological properties
3. 3. Indications for use
4. 4. Contraindications
5. 5. Method of application and dosage
6. 6. Side effects
7. 7. Overdose
8. 8. Special instructions
9. 9. Application during pregnancy and lactation
10. 10. In case of impaired renal function
11. 11. Use in the elderly
12. 12. Drug interactions
13. 13. Analogs
14. 14. Terms and conditions of storage
15. 15. Terms of dispensing from pharmacies
16. 16. Reviews
17. 17. Price in pharmacies

Latin name: Sandimmun Neoral

ATX code: L04AD01

Active ingredient: cyclosporin (ciclosporin)

Producer: Catalent Germany Eberbach GmbH (Germany), Delpharm Huningue SAS (France), RP Scherer GmbH & Co. KG (Germany)

Description and photo update: 2019-26-08

Prices in pharmacies: from 2375 rubles.

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Sandimmun Neoral is an immunosuppressive drug. A cyclic polypeptide of eleven amino acids.

Release form and composition

The drug is available in the following forms:

• soft gelatin capsules Sandimmun Neoral 10 mg: oval, yellowish-white, with red marking in the form of the manufacturer's logo (S in the triangle) and the code "10 mg" (10 pieces in a blister, six blisters in a cardboard box);
• soft gelatin capsules Sandimmun Neoral 25 mg: oval, gray-blue, with red marking in the form of the manufacturer's logo (S in the triangle) and the code "25 mg" (5 pieces in a blister, ten blisters in a cardboard box);
• soft gelatin capsules Sandimmun Neoral 50 mg: oblong, yellowish-white, with red marking in the form of the manufacturer's logo (S in the triangle) and the code "50 mg" (5 pieces in a blister, ten blisters in a cardboard box);
• soft gelatin capsules Sandimmun Neoral 100 mg: oblong, gray-blue, with red marking in the form of the manufacturer's logo (S in a triangle) and the code "100 mg" (5 pieces in a blister, ten blisters in a cardboard box);
• oral solution Sandimmun Neoral: transparent, from brownish-yellow to light brownish-yellow or from yellow to light yellow, with a specific smell of ethanol and oil (50 ml in dark glass vials, in a cardboard box one bottle in complete with a dosing set (measuring syringe and a tube for taking a solution)).

Each pack also contains instructions for the use of Sandimmune Neoral.

Composition of 1 capsule:

• active substance: cyclosporine - 10 mg, 25 mg, 50 mg or 100 mg;
• auxiliary components: propylene glycol, polyoxyl 40 of hydrogenated castor oil, D, L-α-tocopherol, mono-, di- and triglycerides of corn oil, ethanol;
• capsule shell: glycerol 85%, gelatin, titanium dioxide, propylene glycol, black iron oxide.

Composition of 1 ml solution:

• active substance: cyclosporine - 100 mg;
• auxiliary components: propylene glycol, polyoxyl 40 of hydrogenated castor oil, D, L-α-tocopherol, mono-, di- and triglycerides of corn oil, absolute ethanol.

Pharmacological properties

Pharmacodynamics

Sandimmun Neoral is an immunosuppressive drug.

The active substance is cyclosporin, a cyclic polypeptide consisting of 11 amino acids. It is a selective immunosuppressant that inhibits the activation of lymphocyte calcineurin in the G ₀ or G ₁ phases _{of the} cell cycle. This prevents the activation of T-lymphocytes. In addition, at the cellular level, antigen-dependent release of lymphokines, including interleukin-2 (a growth factor for T lymphocytes), is also prevented. Cyclosporin has a reversible and specific effect on lymphocytes. Cyclosporin differs from cytostatics in that it does not affect the function of phagocytes and does not suppress hematopoiesis.

Cyclosporine helps to increase the life span of allogeneic transplants of the lungs, pancreas, skin, kidneys, heart, small intestine, bone marrow. The substance also inhibits the development of cellular reactions in relation to allograft, experimental allergic encephalomyelitis, delayed-type hypersensitivity skin reactions, arthritis caused by Freund's adjuvant, GVHD (graft versus host disease) and the formation of antibodies dependent on T-lymphocytes. Cyclosporine is effective in solid organ and bone marrow transplants in humans, when used to prevent and treat rejection and GVHD, and in conditions that are or could be considered autoimmune in nature.

The dosage forms of Sandimmun Neoral (oral solution and soft capsules, which also contain a solution) have the following feature. The solution is a microemulsion preconcentrate that forms a microemulsion in the presence of liquid (liquid with which the solution is mixed for oral administration before use, or in the presence of liquids in the stomach when taking the drug in the form of capsules). This reduces the variability of pharmacokinetic parameters. This feature also provides a linear relationship between the dose of the drug and the effect of cyclosporine with a more uniform absorption profile and less dependence on simultaneous food intake. The study of the microemulsion preconcentrate showed that the correlation between the basal concentration of the substance and its effect when using Sandimmune Neoral is more pronounced,than with Sandimmune therapy.

Pharmacokinetics

When taking Sandimmun Neoral, there is a clearer linear dependence of the dose and effect of cyclosporine (AUC _B), a more constant absorption profile and less dependence on the daily rhythm and simultaneous food intake, which is characteristic of Sandimmun. Taken together, these properties are responsible for the low variability of the pharmacokinetic parameters of cyclosporine in the same patient and a more pronounced correlation between the basal concentration and bioavailability (AUC _B). Because of these additional benefits, there is no need to take food intake into account in the dosing regimen. Also, the use of Sandimmune Neoral provides a more uniform effect of cyclosporine both during the day and during the course of maintenance treatment.

Oral solution and soft gelatin capsules are bioequivalent.

The absolute bioavailability of cyclosporine varies between patient populations.

T _max (time to reach the maximum concentration of the substance) is in the range from 1.5 to 2 hours. The absorption of the substance occurs quickly, in comparison with Sandimmun, the average value of C _max (maximum concentration of the substance) in plasma and bioavailability is higher by 59 and 29%, respectively.

The distribution of cyclosporine occurs mainly outside the bloodstream. In the blood from 33 to 47% of the substance is in the plasma, in lymphocytes - 4–9%, in granulocytes - 5–12%, in erythrocytes - 41–58%. Plasma protein binding (mainly lipoproteins) is approximately 90%.

The substance undergoes biological transformation to a large extent by the CYP3A4 isoenzyme, is metabolized to a lesser extent in the gastrointestinal tract and kidneys, with the formation of approximately 15 metabolites. There is no single major metabolic pathway.

Excretion of cyclosporine occurs mainly in the bile. About 6% of the dose is excreted in the urine (of which 0.1% is unchanged).

The terminal T _1/2 (half-life) of cyclosporine has significant variability. With unchanged liver function, the final T _1/2 value is approximately 6.3 hours, in the presence of severe liver disease - about 20.4 hours.

Indications for use

• prevention of graft rejection after bone marrow transplantation, prevention and treatment of graft versus host disease;
• prevention of rejection of allografts of the heart, pancreas, liver, lung, kidney, as well as combined cardiopulmonary transplant; prevention of graft rejection in patients who have previously received other immunosuppressive drugs;
• steroid-resistant and steroid-dependent nephrotic syndrome in children and adults, caused by glomerular pathology (segmental and focal glomerulosclerosis, minimal change nephropathy, membranous glomerulonephritis);
• active vision-threatening posterior or secondary uveitis of non-infectious origin in the absence of the effect of traditional treatment or with the development of severe side effects; Behcet's uveitis with repeated bouts of inflammation involving the retina;
• treatment of severe forms of psoriasis when traditional therapy is ineffective or impossible;
• treatment of severe active rheumatoid arthritis;
• treatment of severe forms of atopic dermatitis if systemic therapy is necessary.

Contraindications

Sandimmun Neoral is contraindicated in case of hypersensitivity to the main or auxiliary components of the drug.

For indications that are not related to transplantation, there are additional contraindications:

• uncontrolled arterial hypertension;
• infectious diseases that do not respond to adequate treatment;
• malignant tumors;
• impaired renal function (the exception is nephrotic syndrome with an acceptable degree of such disorders).

Sandimmun Neoral is prescribed with caution to elderly patients.

Use Sandimmun Neoral during pregnancy with caution; therapy is contraindicated during breastfeeding.

Sandimmun Neoral, instructions for use: method and dosage

Sandimmun Neoral capsules and solution are intended for oral administration before, during or after meals. The daily dose is divided into 2 doses.

When switching to Sandimmun Neoral from Sandimmun, the following rules must be observed:

• after transplantation, treatment begins with the same daily dose as with the previous use of Sandimmun. During the first 4-7 days, you should monitor the basal concentration of cyclosporine in the blood. Blood pressure and serum creatinine should also be monitored for 2 months after the transition. In case of deviations from the norm, the dose of cyclosporine is adjusted;
• when treating for indications not related to transplantation, therapy is also started with the daily dose that was used in the previous treatment with Sandimmun. Blood pressure and cyclosporine concentrations are monitored 2, 4 and 8 weeks after switching to Sandimmun Neoral.

Recommended doses and duration of treatment for indications related to transplantation:

• bone marrow transplantation: in the first 2 weeks after bone marrow transplantation, intravenous administration of the drug Sandimmun is used (according to the instructions). Then the patient is transferred to Sandimmun Neoral and a maintenance dose of about 12.5 mg / kg per day is prescribed in two divided doses. Reception continues for at least 3, and preferably 6 months. Then, within a year after the transplant, the dose is gradually reduced until it is completely canceled. When prescribing the oral form of the drug at the initial stage of treatment, the recommended dose is 12.5–15 mg / kg per day in two divided doses (starting from the day preceding the transplantation);
• transplantation of solid organs: 10-15 mg / kg of body weight per day in two divided doses. Treatment begins 12 hours before surgery. In the future, the drug is taken in the same dose for 1-2 weeks after transplantation, then the dose is gradually reduced to a maintenance dose equal to 2-6 mg / kg per day in two divided doses. If Sandimmun Neoral is prescribed as part of a combined three- or four-component therapy, already at the initial stage of treatment it is possible to reduce its dose to 3–6 mg / kg per day in two doses.

In diseases of the gastrointestinal tract, leading to a decrease in absorption, sometimes higher doses of Sandimmune Neoral are required, and in some cases intravenous administration of cyclosporine.

With the development of GVHD (graft-versus-host disease), Sandimmun Neoral is used in low doses.

Recommended doses and duration of treatment for indications not related to transplantation:

• endogenous uveitis (for the induction of remission): 5 mg / kg per day in two doses until the signs of inflammation disappear and vision improves. In severe cases, it is possible to increase the dose to 7 mg / kg per day for a short time. During maintenance treatment, the dose is gradually reduced to the lowest effective dose, which is no more than 5 mg / kg per day during remission;
• nephrotic syndrome (for the induction of remission): 5 mg / kg per day for adults and 6 mg / kg per day for children (in two divided doses). In case of impaired renal function, the initial dose of cyclosporine is not more than 2.5 mg / kg per day. In the future, the dose is reduced to a maintenance one, which is the minimum effective;
• rheumatoid arthritis: 3 mg / kg per day in two divided doses for the first six weeks. With insufficient effectiveness, a gradual increase in the dose is possible, but not more than 5 mg / kg per day. The duration of use in the initial dose is up to 12 weeks. The maintenance dose is selected individually and depends on the tolerance of Sandimmune Neoral;
• psoriasis: for the induction of remission, cyclosporine is prescribed at an initial dose of 2.5 mg / kg per day in two divided doses. If there is no improvement after one month of therapy, a gradual increase in the dose is possible, but not more than 5 mg / kg per day. In the absence of a satisfactory response after 6 weeks of therapy at a dose of 5 mg / kg, the drug should be discontinued. When a positive effect is achieved, Sandimmun Neoral is canceled. Subsequent relapse is treated by re-administering the drug at the previous effective dose. Sometimes maintenance therapy is required, the dose for which is selected individually and is the minimum effective (no more than 5 mg / kg per day);
• atopic dermatitis: 2.5–5 mg / kg per day in two divided doses. If a satisfactory response is not achieved within two weeks of treatment, it is possible to increase the daily dose to a maximum of 5 mg / kg per day. In severe cases, the maximum daily dose is used at the beginning of therapy. When a positive response is reached, the dose is gradually reduced, and if possible, Sandimmune Neoral is completely canceled. In case of relapses of the disease, a second course is prescribed. Sometimes for complete cleansing of the integument of the skin, 8 weeks of treatment is enough, but long-term therapy (up to one year) is more effective.

Side effects

Many side effects associated with the use of Sandimmun Neoral are dose-dependent and reversible when it is reduced.

During treatment, undesirable effects are possible from the following systems and organs:

• digestive system: often - nausea or vomiting, diarrhea, anorexia, liver dysfunction, abdominal pain, gingival hyperplasia; rarely - pancreatitis;
• metabolism: very often - hyperlipidemia; often - hypomagnesemia, hyperkalemia, hyperuricemia; rarely - hyperglycemia;
• cardiovascular system: very often - increased blood pressure;
• hematopoietic system: sometimes - thrombocytopenia, anemia; rarely - hemolytic uremic syndrome, microangiopathic hemolytic anemia;
• central and peripheral nervous system: very often - headache, tremor; often - paresthesia; sometimes - lethargy, slow reactions, sleep disturbance, cortical blindness, paresis, convulsions, disorientation, agitation, coma, visual disturbances; very rarely - edema of the optic nerve head;
• urinary system: very often - impaired renal function;
• endocrine system: rarely - gynecomastia, disruptions in the menstrual cycle;
• musculoskeletal system: often - myalgia, muscle spasms; rarely - myopathy, muscle weakness;
• dermatological reactions: often - excessive hair growth; sometimes - an allergic rash;
• other reactions: often - increased fatigue; sometimes - weight gain, edema.

Overdose

Experience with Sandimmune Neoral overdose is limited.

Possible symptoms: impaired renal function (probably reversible); when used in a dose of up to 10 g - slightly pronounced clinical manifestations in the form of vomiting, dizziness, headache, tachycardia; in some cases - moderate reversible renal dysfunction.

There is information about severe toxic complications of parenteral overdose in premature infants in the neonatal period.

Therapy: symptomatic; during the first two hours, you can induce vomiting or flush the stomach.

During hemodialysis and hemoperfusion using activated carbon, the substance is practically not excreted. There is no specific antidote.

special instructions

Sandimmun Neoral should be used by professionals who have experience in immunosuppressive treatment and are able to ensure adequate patient control, including regular blood pressure measurement and determination of serum creatinine concentration.

Taking cyclosporine and other immunosuppressive drugs is associated with an increased risk of developing lymphomas and other malignant tumors, more often the skin.

Patients receiving Sandimmun Neoral should avoid exposure to photochemotherapy, ultraviolet radiation, and direct sunlight.

When using cyclosporine, the likelihood of various fungal, bacterial, viral and parasitic infections increases, and often with the participation of opportunistic microorganisms. Therefore, during treatment (especially long-term combined) with immunosuppressants, an effective system of preventive and therapeutic measures should be used.

Possible decrease in the effectiveness of vaccination; it is recommended that live attenuated vaccines be avoided.

Influence on the ability to drive vehicles and complex mechanisms

There is no data on the effect of Sandimmun Neoral on the ability to drive and perform other potentially hazardous work.

Application during pregnancy and lactation

• pregnancy: Sandimmun Neoral can be used only in cases where the expected benefit from therapy outweighs the possible harm. Adequate research has not been conducted, the experience of use is limited. Pregnant women who have undergone organ transplantation and received immunosuppressive treatment with cyclosporine or combination therapy, which included cyclosporine, are likely to have premature birth (before 37 weeks). Limited observation of the condition of children exposed to cyclosporine during intrauterine development did not reveal any violations;
• lactation period: therapy is contraindicated, since the substance passes into breast milk.

According to studies, Sandimmun Neoral has a toxic effect on reproductive function.

With impaired renal function

In case of impaired renal function, cyclosporine is not recommended (for indications that are not associated with transplantation). These restrictions do not apply to patients with nephrotic syndrome with an acceptable degree of these disorders.

Use in the elderly

Therapy with Sandimmune Neoral in elderly patients should be carried out with caution under close monitoring of renal function.

Drug interactions

The concentration of cyclosporine is reduced when used simultaneously with the following drugs: phenytoin, rifampicin, orlistat, barbiturates, octreotide, ticlopidine, terbinafine, carbamazepine, bosentan, nafcillin, sulfinpyrazone, probucol, sulfadimidine (intravenous administration) and drugs for intravenous administration.

The concentration of cyclosporine increases with simultaneous use with drugs such as: fluconazole, nefazodone, ketoconazole, colchicine, macrolide antibiotics, imatinib, itraconazole, protease inhibitors, voriconazole, cholic acid and its derivatives, diltiazem, amiodarone, allopicardinipine, high doses of methylprednisolone, danazol, and oral contraceptives.

With caution, Sandimmun Neoral is used simultaneously with aminoglycosides, vancomycin, amphotericin B, diclofenac, sulindac, naproxen, ciprofloxacin, trimethoprim (+ sulfamethoxazole), histamine H ₂ receptor blockers, melphalan and methotrexate.

The question of the simultaneous use of Sandimmun Neoral with other drugs is decided by the doctor, since cyclosporine is highly active and enters into drug interactions with many drugs.

Analogs

Analogs of Sandimmune Neoral are: Cyclosporin Sandoz, Sandimmun, Orgasporin, Ekoral, Layfmun, Ekvoral, Sandimmun, Cyclosporin Alkaloid, Immunosporin, Panimun Bioral, Neolem, Restasis.

Terms and conditions of storage

Store at a temperature not exceeding 25 ° C (soft gelatin capsules) or 30 ° C (oral solution). Accidentally increasing the temperature to 30 ° C did not change the effectiveness of the capsules. Keep out of the reach of children. The shelf life is 3 years.

The opened bottle with oral solution must be stored at a temperature of 15-30 ° C and used within 2 months. When the solution is stored at temperatures below 20 ° C, the drug may become jelly-like. When the temperature rises to 30 ° C, the solution becomes liquid again, but small flakes or sediment may appear, which does not affect the safety, effectiveness and accuracy of dosing of the drug.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Sandimmun Neoral

Reviews about Sandimmun Neoral are mostly positive. The drug is highly effective, while there are indications of the development of side effects in the form of sleep disorders and skin reactions.

The price of Sandimmun Neoral in pharmacies

The price of Sandimmun Neoral depends on the form of release. The approximate cost is:

• oral solution Sandimmun Neoral 100 mg / ml (1 bottle of 50 ml) - 4743-4998 rubles,
• soft capsules Sandimmun Neoral 50 mg or 100 mg (50 pcs.) - 2476 or 4490 rubles,
• soft gelatin capsules Sandimmun Neoral 25 mg or 50 mg (50 pcs.) - 1255 or 2387 rubles.

Sandimmun Neoral: prices in online pharmacies

Drug name Price Pharmacy

Sandimmun Neoral 50 mg soft gelatin capsules 50 pcs. 2375 RUB Buy

Sandimmun Neoral 25 mg soft capsules 50 pcs. 2673 RUB Buy

Sandimmun Neoral 100 mg soft gelatin capsules 50 pcs. 4283 RUB Buy

Sandimmun neoral soft capsules 100mg 50pcs RUB 4595 Buy

Sandimmun Neoral solution for internal approx. 100mg / ml 50ml RUB 4810 Buy

Sandimmun Neoral 100 mg / ml oral solution 50 ml 1 pc. RUB 4810 Buy

Anna Kozlova Medical journalist About the author

Education: Rostov State Medical University, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!