Ekvoral kaps. soft 50 mg No. 50

Pharmacological properties

Pharmacodynamics. immunodepressive effect of cyclosporine consists in its ability to block early activation of T lymphocytes and to inhibit synthesis of cytokines, especially interleukin (silt)-2 or activation of their genes at the level of a transcription. as a result of a research of the mechanism of action it is proved that cyclosporine works as the inactive predecessor of medicine. connecting to the intracellular connecting protein (tsiklofilliny), it forms the complex connecting and inhibiting activity of intracellular phosphatase (kaltsineyrin) which is necessary for activation of a cytoplasmatic subunit of a nuclear factor of the activated T lymphocytes (nfat). not activated cellular component of nfat cannot get to a cell kernel therefore maturing nfat and a transcription of a gene for silt-2 are blocked.

Ekvoral — the powerful immunosuppressive tool specific in relation to T lymphocytes. Ekvoral inhibits immune responses on allograft, delayed-type hypersensitivity reactions, the reaction a transplant against the owner (RTAO) and also antibody formation, dependent on T-cages. Cyclosporine affects lymphocytes is specific and is reversible. Unlike cytostatic means, it does not make negative impact on a hematopoiesis and function of phagocytes. The patients receiving therapy by cyclosporine are less inclined to infections in comparison with the patients receiving other immunosuppressive medicines.

Ekvoral promotes sewing of transplantirovanny fabrics, especially skin, hearts, kidneys, a pancreas, marrow and lungs.

Efficiency of therapy was proved to

also at treatment of various states having the proved or expected autoimmune origin.

Pharmacokinetics. Cyclosporine after oral administration is absorbed in a duodenal and small intestine then there is an absorption in an ileal and large intestine. The average bioavailability at healthy volunteers was about 30%. Concentration of cyclosporine in blood plasma after intake reaches a maximum in 1–6 h. At some patients can note a curve with two peaks which arises in connection with the accelerated absorption after meal or as a result of enterogepatichesky circulation. Presence of RMS cytochrome 3A at a wall of a gut causes decrease in a bidostupnost owing to presistemny metabolism of cyclosporine. Absorption of cyclosporine decreases owing to diarrhea and increases at increase in speed of gastric emptying. Cyclosporine absorption is influenced substantially by length of a small intestine. To children reduce the dose necessary for maintenance of therapeutic concentration as with age their small intestine is extended. Absorption of cyclosporine decreases owing to dysfunction of intestines at a toshchepodvzdoshny anastomosis, Crohn's disease, insufficient biliary secretion, the enteritis caused khimio- and radiation therapy of intestines at RTPH. Level of the absorbed cyclosporine is lower at representatives of negroid race (about 30%) in comparison with representatives of Caucasian race (about 39%). At the increased TG level in blood plasma the bioavailability increases, and at the increased hemoglobin level — decreases. Food with the high content of fat promotes induction of a lipase of a liver owing to what concentration of cyclosporine in blood increases. At children the bioavailability of medicine at intake considerably increases at simultaneous application about alpha tocopheryl-polyethyleneglycol 100 (TRGS) — a water-soluble form of vitamin E.

About 33-37% of cyclosporine contains in blood plasma, from them about 90% are connected with plasmatic proteins, first of all with lipoproteins. 4–9% of cyclosporine contain in lymphocytes, 5–12% — in granulocytes and 41–58% — in erythrocytes. Cyclosporine belongs to lipophilic substances therefore it collects in fats. In a liver, a pancreas and kidneys reveal bigger amount of cyclosporine, than in blood plasma. Cyclosporine contains also in reticuloendothelial and endocrine systems, is distributed in many bodies and tissues of the person and gets into breast milk. The maximum concentration of cyclosporine is defined in fatty tissue and a pancreas, its large number contains also in kidneys, a liver, a spleen, marrow, heart, an aorta, skin, tissues of an eye and in synovial fluid. The volume of distribution fluctuates in the range of 3.5-13 l/kg of body weight. At women the volume of distribution is slightly higher, than at men, owing to the bigger content of fat in a body. At patients after transplantation of a kidney the volume of distribution is 4.5 l/kg, patients with diseases of a liver have 3.9 l/kg and children with heart failure have 0.9 l/kg. Distribution volume at children with diabetes high — about 15 l/kg. The volume of distribution of cyclosporine at patients after bone marrow transplantation changes in the course of treatment. At the beginning of therapy its average size is 27.2 l/kg, after 3 weeks of treatment its decrease to 21.8 l/kg is noted.

Cyclosporine in a human body is completely metabolized by the fermental system of monooxygenases which is catalyzed by CYP cytochrome 3A with formation of a large number of primary metabolites. The enzymes which are taking part in cyclosporine biotransformation contain mainly in an endoplasmic reticulum of cells of a liver and also in a digestive tract. The immunosuppressive activity of metabolites of cyclosporine is much lower in comparison with the main substance. At the most active metabolite of AM1 10–20% of primary activity remain, at increase in polarity of metabolites their immunosuppressive activity respectively decreases. Distribution of metabolites of cyclosporine in fabrics uneven. In comparison with blood plasma higher concentrations note in fatty tissue and a pancreas (40 times higher), and the highest — in a liver and kidneys (190 times higher). Though toxicity of metabolites of cyclosporine which was revealed during the researches on animals, low, it defines gepato- and nephrotoxicity of cyclosporine.

Simultaneous use of the medicines interacting with the system of P450 cytochrome can influence cyclosporine metabolism. Inductors of P450 cytochrome reduce concentration of cyclosporine in blood plasma while inhibitors of P450 cytochrome raise it. Grapefruit juice also influences cyclosporine metabolism therefore its use is not recommended to patients.

Clearance of cyclosporine fluctuates in the range of 0.28-3 l/h/kg. Cyclosporine is removed generally with bile. A part of cyclosporine which is allocated with bile is repeatedly absorbed. Removal of cyclosporine from blood two-phase. Final the T _½ medicine Ekvoral fluctuates in the range of 8-18 h (on average 8.4 h).

Cyclosporine gets into breast milk. Concentration of cyclosporine in breast milk in the range of 16-263 ng/ml are revealed. A small amount of not changed cyclosporine is removed by kidneys (0.1-6% of a dose). At patients with heavy burns of T _½ 1–2 h make. Smaller by T _½ it is revealed at patients with violation of functions of a liver and kidneys, children, elderly people and at patients with diabetes. The hemodialysis considerably does not affect clearance of cyclosporine. In dialyzate less than 1% of a dose of cyclosporine are revealed. The plasma exchange has insignificant impact on clearance of cyclosporine.

Indication

Transplantation

Transplantation of parenchymatous bodies

Prevention and treatment of rejection of fabrics after transplantation of a kidney, a liver, heart, lungs, a pancreas or after the combined transplantation of heart and lungs.

Bone marrow transplantation

Prevention of rejection after bone marrow transplantation.

Prevention or treatment of the disease caused by RTPH.

Indication, not connected with transplantation

Endogenous uveitis

Active average or back uveitis of a non-infectious etiology menacing to sight in cases when traditional therapy is inefficient or exists risk of development of heavy side reactions. Bekhchet's uveitis with repeated inflammation of a retina.

Nephrotic syndrome

Resistant to steroids and a nephrotic syndrome, dependent on steroids, at adults and children as result of a glomerular nephropathy with the minimum changes, a focal and segmentary glomerulosclerosis or hymenoid glomerulonephritis.

can use the Drug Ekvoral for achievement and maintenance of remission and also for maintenance of the remission reached due to intake of steroids that allows to stop their reception.

Pseudorheumatism

Treatment of a heavy highly active pseudorheumatism at patients if traditional therapy by means of slowly operating antirheumatic medicines is inefficient or inexpedient.

Psoriasis

Treatment of patients with a severe form of psoriasis at whom traditional therapy was inefficient or inexpedient.

Atopic dermatitis

Short-term treatment (8 weeks) of patients with a severe form of atopic dermatitis which had an inefficient or inexpedient traditional therapy.

Use

should divide the Daily dose of an ekvoral into two separate doses which need to be accepted with an interval of 12 h (in the morning and in the evening). it is regularly necessary to control cyclosporine level in blood for definition of the optimum mode of dosing and achievement of necessary target concentration. considering differences in bioavailability of different forms of cyclosporine for oral administration, it is impossible to transfer patients from one form of medicine on another without appropriate control of level of cyclosporine and creatinine in blood plasma and hell.

Transplantation of parenchymatous bodies

needs to begin Ekvoral's Use with

not later than for 12 h before surgery; it is necessary to use medicament in the dose of 10-15 mg/kg/days divided into 2 receptions (in the morning and in the evening). The specified daily dose needs to be applied for 1–2 weeks from the moment of operation, then to gradually reduce it depending on cyclosporine level in blood to achievement of a maintenance dose of 2-6 mg/kg/days which also should be divided into 2 receptions (in the morning and in the evening). Dose adjustment should be carried out under control of level of cyclosporine to blood and function of kidneys.

If Ekvoral is applied combined with other immunodepressants (for example with GKS or other combinations), it is possible to accept in an initiation of treatment Ekvoral in lower doses (3–6 mg/kg/days divided into 2 receptions (in the morning and in the evening)).

Bone marrow transplantation

In most cases prefer as

in/in cyclosporine infusion; the recommended dose makes 3–5 mg/kg/days. The specified dose is applied directly after transplantation for 2 weeks, and only after that it is necessary to begin reception of an oral maintenance dose, component about 12.5 mg/kg/days. At violations from a GIT which can cause decrease in absorption the oral administration in higher doses or in/in cyclosporine introduction is shown.

If the medicament is taken in an initiation of treatment orally, the recommended Ekvoral's dose makes 12.5-15 mg/kg/days; reception is begun in 1 day prior to transplantation and continues to be accepted in a maintenance dose for 3–6 months. After that gradually reduce a dose during 1 year from the moment of transplantation and only after that stop administration of drug.

some patients after the termination of reception of Ekvoral have RTPH. Reaction of an organism to repeated continuation of treatment usually positive. For treatment of the moderate chronic disease caused by RTPH use medicine in low doses.

Endogenous uveitis

Recommended initial dose makes 5 mg/kg/days which distribute on 2 receptions and apply before achievement of remission of an active uveitis and increase in visual acuity. In refractory cases the dose can be temporarily raised to maximum — 7 mg/kg/days

If for achievement of remission or elimination of acute inflammatory process of monotherapy by cyclosporine insufficiently, it is in addition possible to apply system corticosteroids, for example, Prednisonum in a daily dose of 0.2-0.6 mg/kg of body weight.

For the supporting treatment should lower a dose of medicine to minimum effective, not exceeding 5 mg/kg/days and to apply before achievement of remission.

Nephrotic syndrome

If function of kidneys of the patient, excepting presence of a proteinuria, normal, for achievement of remission to adult patients and children is more senior than 6 years it is recommended to apply in a dose 5 and 6 mg/kg/days respectively. In a renal failure the initial dose should not exceed 2.5 mg/kg/days. In case of insufficient efficiency of monotherapy by cyclosporine, first of all at the patients resistant to steroids, it is recommended to use medicament along with oral GKS in low doses. If in 3 months of treatment it was not reached satisfactory therapeutic effect at patients with a glomerulonephritis with the minimum changes and a focal segmentary glomerulosclerosis, treatment by cyclosporine should be stopped.

Dose of per os needs to be selected individually for each patient depending on efficiency of medicine (control of a proteinuria) and its safety (first of all depending on creatinine level in blood plasma) for the purpose of definition of the minimum effective maintenance dose. However the dose should not exceed 5 and 6 mg/kg/days at adult patients and children respectively.

Pseudorheumatism

Is recommended to

by

that initial therapy lasted 12 weeks. The dose of 2.5 mg/kg/days distributed on 2 receptions (in the morning and in the evening), is recommended to apply during the first 6 weeks. If the clinical effect of treatment is insufficient, the daily dose can be raised gradually according to individual sensitivity of the patient; however the dose should not exceed 4 mg/kg/days. The dose for the supporting treatment should be defined individually, depending on tolerance of medicine.

Psoriasis

is recommended to

For achievement of remission by

initial dose of 2.5 mg/kg/days distributed on 2 receptions (in the morning and in the evening). If as a result of treatment for 1 month of improvement of a condition of the patient it is noted, the daily dose can be raised gradually; however the dose should not exceed 5 mg/kg/days. At patients without signs of clinical improvement for 6 weeks of therapy at reception in a dose of 5 mg/kg/days the treatment by Ekvoral should be stopped. At patients whose condition demands fast improvement it is necessary to apply as initial a dose of 5 mg/kg/days. At achievement of satisfactory therapeutic effect the medicament treatment can be stopped.

needs to begin with

in case of a recurrence of a disease treatment by Ekvoral using already certain effective dose.

However some patients need continuous therapy. For maintenance therapy it is necessary to define a dose individually, adhering to the lowest effective dose which should not exceed 5 mg/kg/days

Atopic dermatitis

Is recommended to use medicament in the daily dose of 2.5-5 mg/kg/days distributed on 2 receptions for 8 weeks. If after application in an initial dose of 2.5 mg/kg/days the positive clinical effect is not noted for 2 weeks, the dose can be raised quickly to maximum — 5 mg/kg/days. In especially hard cases it is possible to reach fast therapeutic effect, having begun treatment with application in a dose of 5 mg/kg/days. After achievement of positive clinical effect the dose of medicine should be reduced gradually and depending on a condition of the patient completely to stop Ekvoral's application. At a probable recurrence it is necessary to conduct a new course of treatment.

Children

Dose for children correspond to doses for adult patients. Children can use capsules aged 6 years are more senior.

Patients of advanced age

At patients of advanced age note high probability of increase in the ABP and level of creatinine in blood plasma more than at 50% of initial size after treatment for 3–4 months. Therefore it is necessary to adhere to care when dispensing and to control the level of creatinine and cyclosporine in blood.

Patients who are on dialysis

Dose of medicine should not be korrigirovat in time and after dialysis.

to

Dose at some morbid conditions

to

to Patients with a cystiform pneumosclerosis and diabetes needs use of medicine in higher doses. Cyclosporine causes neurotoxic effect in patients with a hypochilesterinemia. Therefore such patients are recommended to use medicament in reduced doses (the dose should be lowered by 50% in case of 50% of decrease in level XC in blood plasma). Patients with excess body weight should apply in a dose, proceeding from ideal body weight, but not real.

needs to swallow of

Capsule whole, not to chew, wash down with enough water; the medicament needs to be taken regularly, each 12 h, adhering to one scheme (to food or between meals).

does not recommend to drink

for 1 h before use of medicine grapefruit juice.

Control of level of cyclosporine in blood

For control of level of cyclosporine in whole blood prefer as methods using specific monoclones though it is possible to use a method of highly effective liquid chromatography also. Initial observation at patients directly after transplantation can be made by means of specific monoclones or by simultaneous assessment by both specific, and nonspecific monoclones for the purpose of ensuring the dosing guaranteeing the corresponding immunosuppression. In practice usually determine concentration of cyclosporine by method of RIA in tests of whole blood at most its low level, that is before application of the following dose. Determine by method of RIA with use of nonspecific monoclones concentration of cyclosporine and its metabolites. Therapeutic range of level is definitely not established, standard range is determined by the manufacturing plant which delivers sets of instruments for diagnosis. Levels of cyclosporine define for the first 2 weeks after transplantation 2 times a day, for 3–6 weeks — once a week, during outpatient observation of the patient — 1 times in 2–3 months. At change of a dose the control is carried out not earlier than in 2 days. Therapeutic range at patients with autoimmune diseases not unified, and individual. Concentration of cyclosporine in blood is only one of many factors defining a clinical condition of the patient by which are guided at selection and dose adjustment of medicine.

Contraindication

Hypersensitivity to cyclosporine or other components of medicine; children under 6 years.

in case of the indications which are not connected with transplantation, use of medicine is contraindicated at patients with heavy renal failures (except for a nephrotic syndrome) or a liver, at patients with AG at which reveal mild reaction to the corresponding treatment, at patients with uncontrollable infections (generally shingles with risk of generalization of a disease and chicken pox) and also at patients with malignant tumors. In case of a pseudorheumatism, patients should not appoint medicine aged up to 18 years.

Simultaneous treatment by the medicines containing takrolimus.

Side effects

Side effects, as a rule, depend on a dose, at its decrease note reduction of their expressiveness. most often reveal a hypertrichosis, a tremor, a renal failure, ag (especially at patients is after transplantation of heart), an abnormal liver function, fatigue, a hypertrophy of gums, violations from a GIT (lack of appetite, nausea, vomiting, an abdominal pain, diarrhea), an acute pain in extremities (for the first week of treatment).

Nephrotoxicity of cyclosporine can be various degrees of severity. Usually it develops in 2–3 months after transplantation and disappears after a dose decline. More expressed nephrotoxicity with fast increase in level of urea and creatinine in blood which needs to be distinguished from fabric rejection can be noted through rather short time after transplantation. Only at some patients at the same time can note nephrotoxicity and rejection which are also eliminated by a dose decline. Throughout treatment by cyclosporine development of the chronic progressing nephrotoxicity which is shown a considerable renal failure and their morphological changes is possible (interstitial fibrosis with a simultaneous atrophy of tubules). Sometimes reveal also toxic tubulopatiya, peritubulyarny capillary stagnation, an arteriolopatiya and focal interstitial fibrosis with a simultaneous atrophy of tubules. Symptoms of chronic nephrotoxicity arise owing to long use of medicine in high doses and also in case of preservation of high level of cyclosporine in blood throughout a long time; and symptoms of nephrotoxicity can become irreversible.

Razvitiye AG (11.2-50%) depends on many factors: initial state of health of the patient (condition of function of kidneys, associated disease of heart), concomitant use of medicines (for example steroids, etc.). Therefore it is difficult to define a causal relationship between development of AG and therapy by cyclosporine. Increase in the ABP is noted approximately at 50% of patients after transplantation of a kidney and at most of patients after transplantation of heart.

Krom of nephrotoxicity and hypertensia, to the most frequent side effects are referred by a hypertrichosis and a tremor. The tremor and a hirsutism revealed at 21–55% of patients after transplantation of a kidney, a liver and heart.

Hyperplasia of gums is noted by

at 4–16% of patients after transplantation. After the treatment termination the regression or symptoms completely happened cyclosporine disappeared in 1–2 months

revealed Hepatotoxicity (4%) at use of cyclosporine in high doses. Tranzitorny increase in level of bilirubin in blood plasma for the first months of treatment was noted at 20% of patients after transplantation of a kidney. Increase in level of enzymes of a liver was defined not so often. Increase in level of bilirubin and enzymes of a liver noted at the concentration of cyclosporine exceeding 500 ng/ml, and oral doses it is higher than 17 mg/kg/days. The clinical importance of hepatotoxicity caused by cyclosporine is much less in comparison with the clinical importance of nephrotoxicity.

noted a headache, an acne, skin rash of allergic origin, an abnormal liver function (not symptomatic hepatotoxicity), a hyperpotassemia Less often (confusion, arrhythmia, violation of sensitivity and hypostases of extremities or a face (lips), the complicated breath, nervousness, weariness and weakness, heavy feeling in the lower extremities), a hyperuricemia, a hypomagnesiemia (spasms), violations from a GIT (lack of appetite, nausea, vomiting, rare excrements), increase in body weight, hypostases, pancreatitis and a malignancy (first of all skin). Arrhythmia happens, as a rule, the first symptom of a hyperpotassemia, it can be revealed by means of carrying out ECG inspection. The hyperpotassemia can be sometimes connected with a giperkhloremichesky metabolic acidosis. In some cases the leukopenia and thrombocytopenia can be connected with mikroangiopatichesky hemolytic anemia, a lipidemia, limfoproliferativny violations, encephalopathy symptoms (confusion, disorder of vision, hearing, mobility, decline in the ability to distinguish objects).

were Revealed also by existence of malignant new growths and limfoproliferativny violations (first of all lymphoma, 1–6%), however their frequency was similar that at the patients receiving traditional therapy. Besides, at treatment by cyclosporine fixed a large number of malignant new growths of skin, including bazaliy, epidermoid cancer, Kaposi sarcoma, keratoacanthomas and a malignant melanoma. At development of limfoproliferativny violations in patients with psoriasis noted quite fast elimination of therapy, their after the termination.

Special instructions

in case of intake of cyclosporine with food the concentration of cyclosporine in blood as a result of influence on absorption can change (decrease or increase). in certain cases absorption remains without changes. for ensuring constant level of absorption throughout use of cyclosporine it is necessary to take the drug, adhering to one scheme (to food, after a meal or between meals).

Food with the high content of fat promotes induction of a lipase of a liver therefore concentration of cyclosporine in blood increases.

Flavonovy substances which are contained in grapefruit juice affect with

CYP cytochrome 3A, in this regard it is not recommended to drink grapefruit juice for 1 h before administration of drug.

Use of a large number of alcoholic beverages can increase cyclosporine level in blood at patients after transplantation of a kidney.

Use during pregnancy or feeding by a breast. Adequate and well controlled researches concerning use of medicine during pregnancy were not conducted therefore pregnant women can use medicament only when the expected advantage of its application exceeds probable risk for a fruit.

Cyclosporine gets into breast milk therefore at its reception the feeding by a breast should be stopped.

Children. Drug is not recommended to be used at children under 6 years. To patients of this age category medicine is appointed in other dosage form.

Ability to influence speed of response at control of vehicles or work with other mechanisms. Does not influence.

Interaction

Drugs increasing nephrotoxicity of cyclosporine

Aminoglikozidny antibiotics, Amphotericinum B, ketokonazol, Trimethoprimum, Melphalanum, ciprofloxacin, colchicine, tsefalosporinovy antibiotics, NPVP, APF inhibitors, Cimetidinum, ranitidine, takrolimus.

Drugs strengthening effect of cyclosporine

Quinidine and its derivatives, theophylline and its derivatives, Valproatum of sodium and its derivatives.

Drugs increasing concentration of cyclosporine in the blood at the expense of inhibition of enzymes (generally CYP cytochrome 3A) which are carrying out his metabolism and removal

Oral contraceptives, GKS, makrolidny antibiotics (erythromycin, klaritromitsin), imidazolovy and triazolovy antifungal means (metronidazole, flukonazol, itrakonazol, ketokonazol), antagonists of N ₂ - receptors (ranitidine, Cimetidinum), antagonists of calcium (diltiazem, nifedipine, nimodipin, nikardipin, verapamil), fluorokhinolon, pristinamitsin, doxycycline, propafenon, Allopyrinolum, Bromocriptinum, danazol, Metoclopramidum.

At simultaneous use of above-mentioned medicines and cyclosporine are noted by increase in frequency of side effects, first of all nephrotoxicity.

Drugs reducing concentration of cyclosporine in blood due to induction of enzymes, first of all CYP cytochrome 3A, which are carrying out metabolism and removal of cyclosporine

Antiepileptic means (not barbiturates — Phenytoinum, carbamazepine), barbiturates, benzodiazepines, phenyl propyl ketone and its derivatives, gestagena and estrogen, including their combinations, oktreotid, tiklopidin, aminoglutethimide, fenotiazin, rifampicin, an isoniazid, metamizol, Trimethoprimum and Sulfamidinum at in in introduction and also the medicines containing Hypericum perforatum (the St. John's wort which is made a hole).

Should apply with care cyclosporine along with above-mentioned medicines. At their application the thicket needs to control the level of cyclosporine and creatinine in blood plasma.

Drugs increasing risk of emergence of a myopathy at simultaneous application with cyclosporine

At a concomitant use of cyclosporine with colchicine and lovastatiny risk of development of a myopathy increases. If at application of a combination of above-mentioned medicines there are muscle pain or muscle weakness, it is necessary to determine the creatine kinase level as there is a risk of developing a rhabdomyolysis and OPN.

Taking into account that nifedipine can be the cause of a hypertrophy of gums, it it is not necessary to apply at patients at whom a gum were struck during treatment with cyclosporine.

At treatment by cyclosporine the efficiency of vaccination therefore at therapy by cyclosporine it is necessary to avoid use of live attenuated vaccines can decrease.

Considering that medicine can sometimes cause a hyperpotassemia or aggravation of already existing hyperpotassemia, it is necessary to control carefully use of the medicines containing potassium or promoting increase in level of potassium in blood plasma. In this regard it is recommended to control potassium level in blood plasma, especially at patients with a considerable renal failure.

At simultaneous use of medicines tsiklosporin/imipenem/tsilastatin needs to consider increase in concentration of cyclosporine that is the reason of symptoms of neurotoxicity (confusion, a tremor, excitement). Therefore the thicket needs to watch cyclosporine level in blood at application of the above-stated combination of medicines and also to observe the general condition of the patient for the purpose of prevention of possible violations from central nervous system.

At simultaneous use of cyclosporine and other immunodepressants the risk of developing infectious and limfoproliferativny diseases increases. Therefore it is not necessary to apply cyclosporine along with above-mentioned medicines, except for GKS (low doses of Prednisonum) and Azathioprinum. At a concomitant use of cyclosporine and above-mentioned medicines it is necessary to lower a cyclosporine dose respectively. In case of need applications of a combination of these medicines should be watched a condition of the patient taking into account above-mentioned risk.

Overdose

When exceeding a dose the renal failures having tranzitorny character and disappearing later medicament withdrawals can arise. considering slow absorption of cyclosporine from capsules, in case of overdose it is recommended to cause vomiting not later than in 2 h after administration of drug, to carry out symptomatic treatment.

By dialysis or hemoperfusion using activated carbon cyclosporine cannot be brought out of an organism. Symptoms of nephrotoxicity or hepatotoxicity in most cases disappear after a medicine dose decline.

Storage conditions

In original packing at a temperature up to 30 °C. not to freeze.

At a temperature above 40 °C the softening or deformation of the capsule are possible

. Relative humidity over 75% can cause softening, deformation of the capsule, etc., especially gelatin pollution by microorganisms.