Ciclosporin Sandoz^® (Capsules, Solution) Instructions for Use

ATC Code

L04AD01 (Ciclosporin)

Active Substance

Ciclosporin (Rec.INN registered by WHO)

Clinical-Pharmacological Group

Immunosuppressive drug

Pharmacotherapeutic Group

Immunosuppressive agent

Pharmacological Action

Immunosuppressant. It is a cyclic polypeptide consisting of 11 amino acids. It has a selective effect on T-lymphocytes.

It suppresses the development of cellular and humoral immune reactions dependent on T-lymphocytes, including immunity to the allograft. It prevents lymphocyte activation by inhibiting the release of lymphokines.

It does not suppress hematopoiesis and does not affect the functioning of phagocytic cells.

Pharmacokinetics

Capsules and oral solution are bioequivalent.

Absorption

After oral administration of the drug in the form of a solution, C_max of ciclosporin in blood plasma is reached in the interval of 1.3±0.53 h, in the form of capsules – 1.35±0.42 h.

When the drug is taken orally, stable absorption and almost complete absence of the influence of food intake are noted, which ensures low variability of pharmacokinetics and a pronounced relationship between the drug’s effect and the dose taken.

Distribution

Ciclosporin is distributed mainly outside the bloodstream with a V_d of 3-5 l/kg. From 33% to 47% is determined in plasma, from 5% to 12% in granulocytes, from 4% to 9% in lymphocytes, and from 41% to 58% of the administered drug in erythrocytes. Binding to plasma proteins is about 90%.

Metabolism

Up to 15 metabolites are formed during biotransformation. The main pathways of metabolism are mono- and dihydroxylation in various parts of the molecule. None of the metabolites exceeds the original substance in activity by more than 10%.

Excretion

It is excreted from the body mainly with bile, only about 6% of the administered dose is excreted in the urine as metabolites and about 0.1% as unchanged substance. T_1/2 in healthy volunteers is about 6.3 h.

Pharmacokinetics in special clinical cases

The clearance of ciclosporin in children is approximately 2 times higher than in adults.

T_1/2 is characterized by significant fluctuations and is about 20.4 h in patients with severe liver diseases, about 11 h (from 2 to 25 h) in kidney transplantation.

Indications

Transplantation

• Immunosuppression and prophylaxis of rejection after kidney, liver, heart, combined cardiopulmonary, lung or pancreas transplantation;
• Prophylaxis of graft rejection after bone marrow transplantation;
• Prophylaxis and treatment of graft-versus-host disease reactions.

Other diseases

• Endogenous uveitis (after exclusion of infectious etiology): active, vision-threatening uveitis of the middle or posterior segment of the eye; Behçet’s uveitis with recurrent attacks of inflammation affecting the retina;
• Severe psoriasis (as a rule, in cases of resistance to previous therapy);
• Corticosteroid-dependent and corticosteroid-resistant nephrotic syndrome (impaired renal function with significant protein loss) caused by glomerular pathology (such diseases as minimal change nephropathy, focal and segmental glomerulonephritis);
• Severe forms of active rheumatoid arthritis (in cases where classical slow-acting antirheumatic drugs are ineffective or their use is impossible);
• Severe forms of atopic dermatitis when systemic therapy is indicated.

ICD codes

Dosage Regimen

Solution

Transplantation

For adults, Ciclosporin is usually prescribed together with other immunosuppressive agents. The initial dose is 10-14 mg/kg/day in 2 doses with a 12-hour interval for 1-2 weeks after the operation. Then the concentration of ciclosporin in the blood plasma is monitored and the dose is gradually reduced to 2-6 mg/kg/day, also in 2 doses. The therapeutic range of ciclosporin concentrations in blood plasma during subsequent use is from 100 to 400 ng/ml.

In kidney transplantation, when using ciclosporin in doses less than 3-4 mg/kg and with a ciclosporin concentration in blood plasma of about 100 ng/ml, there is a risk of developing rejection reactions.

For some patients one month after transplantation, with simultaneous administration of corticosteroids, a dose of less than 5 mg/kg is recommended.

In bone marrow transplantation, short-term use of ciclosporin in combination with methotrexate is usually recommended. The dose of ciclosporin is selected individually (1-2 days before the operation, intravenous administration of ciclosporin at a dose of 2.5-5 mg/kg/day is recommended). After the operation, as soon as oral administration of the drug becomes possible, switch to oral administration at a dose of 12.5 mg/kg/day (in 2 doses) for 3-6 months. Then the dose is gradually reduced until the course of treatment is completely finished.

When conducting therapy for acute graft-versus-host disease, the initial dose of ciclosporin is 12.5-15 mg/kg/day in 2 doses. After 50 days, the dose begins to be reduced by 5% each time over a week and therapy is discontinued after about 20 weeks. If acute reaction recurs after discontinuation of ciclosporin, therapy should be started anew.

If transient gastrointestinal complaints are observed when taking ciclosporin during organ transplantation, bone marrow transplantation and in acute graft-versus-host disease, one third of the recommended daily dose can be administered once intravenously (in the appropriate dosage form).

The duration of use of ciclosporin in organ transplantation (except for therapy of acute graft-versus-host disease) is established individually.

Other diseases

For severe endogenous uveitis, the initial dose of ciclosporin is 5-10 mg/kg/day in 2 doses until inflammation decreases and visual acuity improves. In acute cases, prednisolone at a dose of 200-600 mcg/kg/day or another similar corticosteroid can be additionally prescribed.

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

The therapeutic level of ciclosporin concentration in the blood is from 100 to 150 ng/ml.

The duration of use is from 3 to 16 months.

For severe forms of psoriasis, the drug is recommended to be prescribed at a dose of 2.5 mg/kg/day in 2 doses. If no improvement in skin condition is observed after 1 month of therapy, the dose can be gradually increased by 1 mg/kg, up to a maximum of 5 mg/kg/day in 2 doses. When repeating the treatment, Ciclosporin should be used at the minimum effective dose.

If significant improvement does not occur after 6 weeks of using ciclosporin at a dose of 5 mg/kg/day, the drug should be discontinued.

The duration of use is usually 12 weeks.

For nephrotic syndrome with normal renal function, it is recommended to prescribe the drug to adults at a daily dose of no more than 5 mg/kg, to children – no more than 6 mg/kg, in 2 doses.

For patients with impaired renal function, the initial dose of ciclosporin should not exceed 2.5 mg/kg. With serum creatinine levels in adults above 200 µmol/L and in children – above 140 µmol/L, the use of ciclosporin is contraindicated.

In case of severe liver dysfunction, the initial dose of ciclosporin should be reduced by 25-50%.

For patients with corticosteroid-resistant nephrotic syndrome, in case of insufficient effectiveness of ciclosporin alone, its combination with low doses of corticosteroids is recommended.

If symptoms of nephrotic syndrome persist after 3 months of treatment with ciclosporin, the drug should be discontinued.

For severe rheumatoid arthritis, during the first 6 weeks of therapy, the recommended daily dose of ciclosporin is 2.5 mg/kg in 2 doses. If the drug is poorly tolerated, the dose can be reduced. Further, the dose is set individually, depending on the clinical manifestations of the disease and tolerance; the drug should be used at the minimum effective dose. The daily dose of 4 mg/kg should not be exceeded. In emergency cases, it is possible to increase the dose of ciclosporin to 5 mg/kg/day.

Ciclosporin can be prescribed in combination with low doses of corticosteroids and/or NSAIDs.

If there is no therapeutic effect after 3 months of treatment, the drug should be discontinued.

For severe forms of atopic dermatitis, to relieve acute symptoms of the disease, the drug is used at a daily dose of 2.5 mg/kg in 2 doses. If no significant improvement is observed after 2 weeks of treatment, it is necessary to increase the dose of ciclosporin to a maximum of 5 mg/kg/day.

In isolated, most severe cases, the use of ciclosporin at an initial dose of 5 mg/kg is required. Upon improvement, the daily dose should be gradually reduced.

If no significant improvement is observed after 6 weeks of treatment or effective doses do not correspond to those recommended above, the drug must be discontinued.

As a rule, therapy for 6-8 weeks is sufficient for the disappearance of clinical symptoms of the disease.

Capsules

The daily dose of Ciclosporin HEXAL should always be divided into 2 doses.

Transplantation

For adults, Ciclosporin is usually prescribed together with other immunosuppressive agents. The initial dose is 10-14 mg/kg/day in 2 doses with a 12-hour interval for 1-2 weeks after the operation. Then the concentration of ciclosporin in the blood plasma is monitored and the dose is gradually reduced to 2-6 mg/kg/day, also in 2 doses. The therapeutic range of drug concentrations in blood plasma during subsequent use is from 100 to 400 ng/ml.

It has been shown that in kidney transplantation, the use of the drug in doses corresponding to the lower limit of the recommended range (i.e., less than 3-4 mg/kg) and with a ciclosporin concentration in blood plasma of about 100 ng/ml, there is a risk of developing rejection reactions.

For some patients one month after transplantation, with simultaneous administration of corticosteroids, a dose of less than 5 mg/kg is recommended.

In bone marrow transplantation, short-term use of ciclosporin in combination with methotrexate is usually recommended. The dose of ciclosporin is selected individually (1-2 days before the operation, intravenous administration of ciclosporin at a dose of 2.5-5 mg/kg/day is recommended). After the operation, as soon as oral administration of the drug becomes possible, switch to taking capsules at a dose of 12.5 mg/kg/day (in 2 doses) for 3-6 months. Then the dose is gradually reduced until the course of treatment is completely finished.

When conducting therapy for acute graft-versus-host disease, the initial dose of ciclosporin is 12.5-15 mg/kg/day in 2 doses. After 50 days, the dose begins to be reduced by 5% each time over a week and therapy is discontinued after about 20 weeks. If acute reaction recurs after discontinuation of ciclosporin, therapy should be started anew.

If transient gastrointestinal complaints are observed when taking Ciclosporin HEXAL during organ transplantation, bone marrow transplantation and in acute graft-versus-host disease, one third of the recommended daily dose of the drug can be administered once intravenously (other dosage forms).

The duration of use of Ciclosporin HEXAL in organ transplantation (except for therapy of acute graft-versus-host disease) is established individually.

Other diseases

For severe endogenous uveitis, the initial dose of ciclosporin is 5-10 mg/kg/day in 2 doses until inflammation decreases and visual acuity improves. In acute cases, prednisolone at a dose of 200-600 mcg/kg/day or another similar corticosteroid can be additionally prescribed.

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

The therapeutic level of ciclosporin concentration in the blood is from 100 to 150 ng/ml.

The duration of use is from 3 to 16 months.

For severe forms of psoriasis, the drug is recommended to be prescribed at a dose of 2.5 mg/kg/day in 2 doses. If no improvement in skin condition is observed after 1 month of therapy, the dose can be gradually increased by 1 mg/kg, up to a maximum of 5 mg/kg/day in 2 doses. When repeating the treatment, the drug should be used at the minimum effective dose.

If significant improvement does not occur after 6 weeks of using ciclosporin at a dose of 5 mg/kg/day, the drug should be discontinued.

The duration of use is usually 12 weeks.

For nephrotic syndrome with normal renal function, it is recommended to prescribe the drug to adults at a daily dose of no more than 5 mg/kg, to children – no more than 6 mg/kg, in 2 doses.

For patients with impaired renal function, the initial dose of ciclosporin should not exceed 2.5 mg/kg. With serum creatinine levels in adults above 200 µmol/L and in children – above 140 µmol/L, the use of ciclosporin is contraindicated.

The level of therapeutically effective concentrations of ciclosporin in the blood is from 60 to 160 ng/ml. Drug concentrations should be monitored initially, if possible, daily, and then every 2 weeks.

During the first 3 months of treatment, serum creatinine levels should be regularly monitored (with normal renal function – every 2 weeks, with impaired function – weekly). With a stable creatinine level, monitoring can be carried out at 2-month intervals.

In case of severe liver dysfunction, the initial dose of ciclosporin should be reduced by 25-50%.

For patients with corticosteroid-resistant nephrotic syndrome, in case of insufficient effectiveness of ciclosporin alone, its combination with low doses of corticosteroids is recommended.

If symptoms of nephrotic syndrome persist after 3 months of treatment with ciclosporin, the drug should be discontinued.

For severe rheumatoid arthritis, during the first 6 weeks of therapy, the recommended daily dose of ciclosporin is 2.5 mg/kg in 2 doses. If the drug is poorly tolerated, the dose can be reduced. Further, the dose is set individually, depending on the clinical manifestations of the disease and tolerance; the drug should be used at the minimum effective dose. The daily dose of 4 mg/kg should not be exceeded. In emergency cases, it is possible to increase the dose of ciclosporin to 5 mg/kg/day.

Ciclosporin can be prescribed in combination with low doses of corticosteroids and/or NSAIDs.

If there is no therapeutic effect after 3 months of treatment, the drug should be discontinued.

There is experience of clinical use of ciclosporin for 12 months.

For severe forms of atopic dermatitis, to relieve acute symptoms of the disease, the drug is used at a daily dose of 2.5 mg/kg in 2 doses. If no significant improvement is observed after 2 weeks of treatment, it is necessary to increase the dose of ciclosporin to a maximum of 5 mg/kg/day.

In isolated, most severe cases, the use of ciclosporin at an initial dose of 5 mg/kg is required. Upon improvement, the daily dose should be gradually reduced.

If no significant improvement is observed after 6 weeks of treatment or effective doses do not correspond to those recommended above, the drug must be discontinued.

As a rule, therapy for 6-8 weeks is sufficient for the disappearance of clinical symptoms of the disease.

Method of administration

The solution and capsules of Ciclosporin HEXAL should always be taken at the same time with meals. The daily dose is divided into 2 doses.

Capsules should be taken without chewing, with water.

The solution is recommended to be diluted with drinking water immediately before administration (but not in a plastic cup). To ensure the dose is taken completely, you can add liquid to the glass again and drink it.

The solution should be drawn up with the supplied measuring syringe with graduations from 0.5 to 4 ml at 0.1 ml intervals in the following order

• Remove the green cap, free the vial from the metal rim, pull out the black stopper from the vial and discard it;
• Tightly insert the rod with the hole into the dark glass vial (the rod will remain in the vial permanently);
• Insert the graduated syringe into the rod and draw the required amount of solution into the syringe; if there are many bubbles in the vial, the drawn contents should be poured back into the vial and the solution should be drawn again;
• Transfer the solution drawn into the syringe into a drinking glass (the syringe should not come into contact with the solution in the glass);
• Close the vial with the supplied screw cap.

To clean the syringe, wipe it with a dry napkin without rinsing.

Do not take the drug with grapefruit juice.

Adverse Reactions

The side effects of Ciclosporin HEXAL are dose-dependent.

From the kidneys most often (especially in the first weeks of treatment) – complications associated with an increase in the content of creatinine and urea in the blood serum (these phenomena are associated with functional changes in the kidneys, are dose-dependent and decrease when the dose is reduced).

From the hematopoietic system, anemia is possible; rarely – leukopenia; in isolated cases – thrombocytopenia and microangiopathic hemolytic anemia.

Dermatological reactions often – excessive hair growth on the skin; rarely – rash, hair loss, allergic skin reactions, skin redness, itching.

From the cardiovascular system often – arterial hypertension; rarely – coronary artery disease.

From the immune system, malignant and lymphoproliferative disorders are possible. During psoriasis therapy, benign lymphoproliferative disorders, as well as B- and T-cell lymphomas, which may disappear upon discontinuation of the drug, are possible.

From the digestive system frequently – anorexia, nausea, vomiting, abdominal pain, diarrhea, gingival hyperplasia, impaired liver function (accompanied by an increase in bilirubin levels and activity of hepatic enzymes in the blood serum); rarely – pancreatitis.

From the musculoskeletal system rarely – muscle cramps, muscle pain, muscle weakness.

From the CNS and peripheral nervous system frequently – tremor, fatigue, paresthesia (mainly in the first weeks of therapy); rarely – motor polyneuropathy, signs of encephalopathy (seizures, lethargy, disorientation, psychomotor agitation, sleep disturbance, visual disturbances, cortical blindness, coma, paresis, cerebellar ataxia).

From metabolism frequently – slight reversible increase in serum lipid content; rarely – increased body weight, hyperglycemia, hyperuricemia, hyperkalemia, hypomagnesemia.

Contraindications

• Hypersensitivity to ciclosporin and other components of the drug.

Use in Pregnancy and Lactation

Use is possible in cases where the expected benefit of therapy for the mother outweighs the potential risk to the fetus.

Ciclosporin is excreted in breast milk, therefore, if it is necessary to use the drug during lactation, breastfeeding should be discontinued.

Use in Hepatic Impairment

In patients with impaired liver function, a significant change in the pharmacokinetics of ciclosporin is possible. In this case, the concentration of ciclosporin in the blood plasma should be constantly monitored and the dose of the drug should be adjusted if necessary. In severe liver function impairment, the initial dose of ciclosporin should be reduced by 25-50%.

Use in Renal Impairment

For patients with impaired renal function, the initial dose of ciclosporin should not exceed 2.5 mg/kg. In cases of serum creatinine levels in adults exceeding 200 µmol/L and in children – exceeding 140 µmol/L, the use of ciclosporin is contraindicated.

Pediatric Use

Experience with the use of ciclosporin in children under 1 year of age is limited. Children over 1 year of age are prescribed Ciclosporin in the average recommended doses. There is experience with the use of Ciclosporin HEXAL in children at higher doses than in adults. It has been shown that the clearance of ciclosporin is higher in children, therefore, to achieve the same plasma concentration, children require higher doses of the drug than adults.

Data on the use of the drug for severe endogenous uveitis in children under 5 years of age are not available. There are isolated reports on the use of ciclosporin in children over 5 years of age.

Geriatric Use

In elderly patients, data on the use of ciclosporin are insufficient. If it is necessary to use the drug in this category of patients, possible impairments of renal function associated with the aging process should be primarily considered, and an appropriate adjustment of the drug dose should be made.

Special Precautions

Ciclosporin HEXAL should be used by physicians experienced in immunosuppressive therapy and the treatment of patients after organ transplantation. The use of the drug is possible only in specialized medical institutions.

During treatment, constant monitoring of laboratory parameters, blood pressure, liver and kidney functions, as well as determination of serum lipid concentration (before the start of treatment and after the first month of treatment) is necessary. If blood pressure increases, antihypertensive therapy is recommended.

Ciclosporin may cause hyperkalemia or magnesium deficiency, therefore, especially in cases of severe renal impairment, it is necessary to monitor plasma potassium and magnesium levels and avoid excessive potassium intake (with food, potassium-sparing drugs).

When using ciclosporin simultaneously with other immunosuppressants, there is a risk of excessive immunosuppressive action, which can lead to the development of infection and the formation of lymphomas (predominantly Hodgkin’s lymphoma and reticular sarcoma). During drug administration, regular skin examination and histological control of suspicious areas are necessary.

Currently, data on the use of Ciclosporin HEXAL in organ transplantation in patients with impaired renal function are insufficient. However, taking into account the increase in serum creatinine levels or decrease in creatinine clearance, especially after kidney transplantation, as well as the possibility of developing rejection reactions, the dose is selected considering the risk factors and the benefit of therapy for the patient with full control of the disease course and mandatory determination of ciclosporin concentration in the blood plasma.

In patients with impaired liver function, a significant change in the pharmacokinetics of ciclosporin is possible. In this case, the concentration of ciclosporin in the blood plasma should be constantly monitored and the dose of the drug should be adjusted if necessary.

In elderly patients, data on the use of ciclosporin are insufficient. If it is necessary to use the drug in this category of patients, possible impairments of renal function associated with the aging process should be primarily considered, and an appropriate adjustment of the drug dose should be made.

The drug in the form of an oral solution contains 25.5% vol. ethanol. When the recommended dose is followed, up to 1.2 g of alcohol enters the body with each dose of ciclosporin. This should be taken into account when prescribing the drug in the form of an oral solution for liver diseases, alcoholism, epilepsy, brain lesions, pregnancy, and in young children. The effects of other medicinal products may be reduced or enhanced.

Control of laboratory parameters

Since Ciclosporin can affect kidney function, during treatment, at least two determinations of the baseline serum creatinine level should be performed. Measurements are repeated weekly for one month, and then for 3 months – at 2-week intervals. Then, with a stable creatinine level, measurements are performed monthly. More frequent monitoring of creatinine levels is required when it is necessary to increase the dose of ciclosporin or with simultaneous use of NSAIDs. If the creatinine level has increased by more than 30% from the baseline value (within normal limits), the dose of ciclosporin should be reduced by 25-50%. If the serum creatinine level has increased by more than 50%, it is necessary to reduce the dose of ciclosporin by at least 50%.

In endogenous uveitis, therapy should be carried out under constant ophthalmological control, as well as under the control of ciclosporin concentration in the blood plasma.

In nephrotic syndrome, it is necessary to determine baseline values and regularly monitor serum creatinine levels. The dose of the drug is adjusted in this case taking into account the dynamics of plasma creatinine concentration values. During treatment, systematic monitoring of creatinine levels is carried out at 2-week intervals during the first 3 months of therapy, and thereafter – once every 1-2 months. In case of long-term (more than 1 year) use of ciclosporin, a kidney biopsy is recommended. Patients should not receive Ciclosporin in case of uncontrolled increase in blood pressure. Worsening of renal function is possible in elderly patients.

In psoriasis, skin lesions atypical for psoriasis should be biopsied before starting treatment. Patients with cancerous or precancerous skin changes should receive treatment with the drug only after appropriate treatment of such changes in the absence of alternative forms of effective therapy. Prolonged sun exposure should be avoided.

Patients receiving Ciclosporin HEXAL should not be prescribed simultaneous ultraviolet B irradiation or PUVA therapy.

Before starting and during the first 3 months of treatment, it is necessary to monitor the level of uric acid in the blood and urine.

An increase in the activity of hepatic enzymes and bilirubin in the blood by a maximum of 2 times is allowed.

When treating rheumatoid arthritis, for the safety and efficacy of therapy, it is necessary to monitor the following parameters

• Regular monitoring of blood creatinine levels;
• Hematological profile (red blood cell, white blood cell, platelet count) – before starting treatment and every 4 weeks;
• Urinalysis – before starting treatment and every 4 weeks;
• Blood pressure measurement – before starting treatment and every 2 weeks for 3 months; thereafter – every 4 weeks;
• Blood potassium, lipid content – before starting treatment and every 4 weeks.

Use in pediatrics

Experience with the use of ciclosporin in children under 1 year of age is limited. Children over 1 year of age are prescribed Ciclosporin in the average recommended doses. There is experience with the use of Ciclosporin HEXAL in children at higher doses than in adults. It has been shown that the clearance of ciclosporin is higher in children, therefore, to achieve the same plasma concentration, children require higher doses of the drug than adults.

Data on the use of the drug for severe endogenous uveitis in children under 5 years of age are not available. There are isolated reports on the use of ciclosporin in children over 5 years of age.

Overdose

Symptoms possible impairment of consciousness, headache, tachycardia, reversible liver failure.

Treatment gastric lavage, symptomatic therapy. Ciclosporin is not eliminated from the body by hemodialysis and hemoperfusion using activated charcoal.

Drug Interactions

Ciclosporin in combination with potassium-sparing diuretics may cause hyperkalemia or magnesium deficiency (it is necessary to monitor potassium and magnesium content and avoid excessive potassium intake with food).

When Ciclosporin HEXAL is used simultaneously with other immunosuppressive agents, the risk of developing infections and lymphoproliferative diseases increases.

The risk of developing nephrotoxicity increases with the simultaneous administration of Ciclosporin HEXAL and antibiotics of the aminoglycoside group (gentamicin and tobramycin), amphotericin B, ciprofloxacin, melphalan, trimethoprim, vancomycin, NSAIDs (diclofenac, naproxen).

When taken simultaneously with nifedipine, gingival hyperplasia is possible.

In organ transplantation, when used simultaneously with fibrates (e.g., bezafibrate, fenofibrate), a more pronounced and persistent deterioration of renal function is sometimes observed.

Orlistat slows down the absorption of fats from food and thereby may change the bioavailability of Ciclosporin HEXAL.

Drugs that increase the concentration of ciclosporin in the blood : ketoconazole, fluconazole, itraconazole, some macrolide antibiotics (e.g., erythromycin, clarithromycin, josamycin, posinomycin and pristinamycin), doxycycline, oral contraceptives, propafenone, methylprednisolone (in high doses) metoclopramide, danazol, amiodarone, cholic acid and its derivatives, as well as calcium antagonists (e.g., diltiazem, nicardipine, verapamil, mibefradil).

Drugs that reduce the concentration of ciclosporin in the blood plasma barbiturates, carbamazepine, phenytoin, metamizole, rifampicin, octreotide, probucol, troglitazone, sulfadimidine and trimethoprim when administered intravenously, as well as St. John’s wort preparations.

If combined use cannot be avoided, careful individual dose selection of ciclosporin is necessary.

When used simultaneously with tacrolimus, the development of the nephrotoxic effect of ciclosporin is possible, as well as an increase in its half-life.

Ciclosporin reduces the clearance and increases the toxicity of digoxin, colchicine, lovastatin and prednisolone.

Due to the immunosuppressive effect of ciclosporin, the development of atypical potentially dangerous reactions during vaccination cannot be excluded, therefore, the use of live attenuated vaccines should be avoided during treatment.

Flavonoid substances contained in grapefruit juice affect cytochrome P₄₅₀ isoenzymes, in connection with this, an increase in the concentration of ciclosporin in the blood plasma is possible (it is not recommended to drink grapefruit juice within 1 hour before taking the drug).

Storage Conditions

The oral solution should be stored at a temperature not lower than 20°C (68°F) (not in the refrigerator!) and not higher than 30°C (86°F).

Shelf Life

The shelf life is 3 years. If stored at a temperature below 20°C (68°F), the solution may acquire a gelatinous consistency, which disappears when the temperature is raised to 30°C (86°F). In this case, a slight amount of flakes or slight sedimentation may remain. These phenomena do not affect the efficacy and safety of the drug and do not require dose adjustment.

Capsules should be stored at a temperature not exceeding 30°C (86°F). The shelf life is 3 years.

Dispensing Status

The drug is dispensed by prescription.

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.