Cyclosporine

When ATH:
L04AD01

Pharmacological action.
Immunosuppressive.

Application.

Kidney transplant, liver, hearts, light, pancreas (Prevention of transplant rejection, treatment response rejection), bone marrow (prevention of rejection reaction, prevention and treatment of graft versus host disease); acute non-infectious uveitis, vision-threatening, Behcet's uveitis with recurrent inflammation and retinal involvement, chronic glomerulonephritis, accompanied by the development of nephrotic syndrome, highly active rheumatoid arthritis, psoriasis, severe forms of atopic dermatitis.

Contraindications.

Hypersensitivity (incl. a polyoxyethylated castor oil), malignant neoplasms, serious infectious disease, impaired renal and / or liver function, arterial hypertension, hyperuricemia, hyperkalemia, pregnancy, lactation.

Pregnancy and breast-feeding.

Category actions result in FDA - C. (The study of reproduction in animals has revealed adverse effects on the fetus, and adequate and well-controlled studies in pregnant women have not held, However, the potential benefits, associated with drugs in pregnant, may justify its use, in spite of the possible risk.)

Side effects.

Acute and chronic renal failure, interstitial renal fibrosis, arterial hypertension, tremor, weakness, headache, paresthesia, seizures, myopathy, abnormal liver function, pancreatitis, nausea, vomiting, anorexia, abdominal pain, a feeling of heaviness in the epigastric region, diarrhea, giperplaziya right, fluid retention, reversible dysmenorrhea and amenorrhea, hypertryhoz, thrombocytopenia, anemia, hyperkalemia, hyperuricemia, increased susceptibility to infections.

Cooperation.

Melphalan increases toxicity, diltiazem, nikardipin, verapamil, beta-blockers, fluconazole, imidazole derivatives, glucocorticoids, macrolides - plasma level. Increases the risk of myopathy and rhabdomyolysis when prescribing lipid-lowering drugs (HMG-CoA reductase), renal dysfunction - against the background of aminoglycosides, amphotericin B, Trimethoprim, co-trimoxazole, ciprofloxacin, some cephalosporins, NSAIDs, propafenone. Phenytoin, Carbamazepine, barbiturates, benzodiazepines, aminoglutethimide, estrogen-progestational drugs, progesterone, rifampicin, Isoniazid, metamizole sodium weaken the effect - accelerate elimination. Enhances the action of quinidine, teofillina, sodium valproate, as well as potassium preparations and potassium-sparing diuretics (increased likelihood of hyperkalemia).

Overdose.

Symptoms: vomiting, drowsiness, headache, tachycardia, severe renal insufficiency.

Treatment: stimulation of vomiting and gastric lavage (in the first hours after oral administration), maintaining vital functions; dialysis and hemoperfusion with activated charcoal are ineffective.

Dosing and Administration.

Inside, I /. The daily dose is divided into 2 admission. The solution for intravenous infusion is prepared time, diluting the concentrate with isotonic sodium chloride solution or 5% glucose solution in the ratio 1:20–1:100; administered within 2-6 hours. The initial dose is 3-5 mg / kg per day. IV applications are considered optimal at the initial stage of treatment of patients with bone marrow transplant.. The oral solution can be diluted in a glass (but not plastic) a glass of cold chocolate drink, milk, fruit juice (excluding grapefruit), coca cola, mix well and drink immediately. The capsules should be swallowed whole. When transplanting organs - by mouth at a dose of 10-15 mg / kg 4-12 hours before the operation, once, and then in this daily dose for 1-2 weeks; in the future, the dose is gradually reduced to a maintenance (usually 2-6 mg / kg). For autoimmune diseases - by mouth in a daily dose of 2.5-5 mg / kg (excluding endogenous uveitis, in which for a short time it is possible to increase the daily dose to 7 mg / kg).

Precautions.

Treatment should be carried out in a specialized hospital by doctors, with sufficient experience in immunosuppressive therapy. It will be appreciated, that against the background of cyclosporine, the predisposition to lymphoproliferative malignant neoplasms increases, therefore, before its appointment, it is necessary to decide, how much the expected beneficial effect justifies the risk of undesirable effects. Use during pregnancy is permissible only under strict indications.. Since there is a possibility of developing anaphylactoid reactions with intravenous administration, prophylactic intake of antihistamines is advisable, and the fastest possible transfer of the patient to oral medications. It is recommended to select the dose depending on the content in the blood.. After kidney transplantation, the plasma level is determined within the first 2 weeks. 2 times a week, for 3-6 weeks - 1 once a week, with outpatient supervision - 1 once every 2-3 months. Regular monitoring of plasma creatinine concentration is necessary - an increase may indicate a rejection reaction, or about nephrotoxicity and require (in the latter case) dose reduction: on 25% with an increase in creatinine by more than 30% starting from, and 50%, if its level doubles; when the dose is reduced during 4 weeks does not lead to a decrease in creatinine, cyclosporine is canceled. Blood pressure monitoring is recommended, blood potassium, Uric acid, bilirubin, transaminases, lipid profile, during the treatment period, immunization with live attenuated vaccines is contraindicated. In the treatment of autoimmune diseases, the lack of adequate positive results through 3 month indicates the need to stop treatment.

Cautions.

It is advisable to use glass containers for the preparation of the infusion solution..

Cooperation

Active substance	Description of interaction
Aztreonam	Do not change (mutually) Effects; combined permissible purpose.
Allopurinol	FKV. FMR. Inhibits CYP3A4, slows the biotransformation, It increases the blood concentration, the risk of developing toxic phenomena increases.
Amiodarone	FKV. May increase serum levels and cause nephrotoxicity; with a joint appointment, it is necessary to reduce the dose.
Ampicillin	It does not affect (mutually) on the effect; permissible use.
Amphotericin B	FMR. Strengthens (mutually) chance of kidney dysfunction.
Atsenokumarola	Against the background of cyclosporine, the effect may change unpredictably; with a joint appointment caution.
Aцetazolamid	FKV. FMR. Causes a marked increase in serum levels and may precipitate nephrotoxicity.
Acetylsalicylic acid	It does not affect (mutually) on the effect; combined use is permissible.
Acyclovir	May raise blood levels, increases (mutually) the risk of renal dysfunction.
Acitretin	FKV. The concentration 100 μmol inhibits the destruction of human liver microsomes and the production of primary metabolites (shows in vitro).
Basiliximab	FMR: synergism. Increases (mutually) effect.
Bromocriptine	FKV. Increases concentration of plasma.
Sodium valproate	FMR. Against the background of cyclosporine, the effect of.
Vancomycin	FMR. Increases (mutually) The risk of developing the GTR- and nephrotoxicity; with simultaneous and / or sequential use, periodic audiometry and monitoring of renal function may be required.
Warfarin	Against the background of cyclosporine, the effect may change unpredictably; with a joint appointment caution.
Verapamil	FKV. Inhibits CYP4503A, slows down biotransformation and increases tissue concentration; with a combined appointment, it is necessary to increase the dose.
Vynblastyn	Do not change (mutually) effect; combined use is permissible.
Vitamin E	FKV. Increases absorption.
Ganciclovir	FMR: synergism. Strengthens (mutually) the risk of kidney damage; with combined administration, constant monitoring of serum creatinine levels is required.
Gentamicin	FMR: synergism. Strengthens (mutually) kidney dysfunction.
Glibenclamide	FKV. Increases (mutually) free fraction level in blood (displaces - competition - from sites of communication on proteins).
Glipizide	FKV. FMR. Increases (mutually) free fraction level in blood (competes for binding sites on proteins); combined use can lead to hypoglycemia (monitoring of plasma glucose is required).
Daklizumaʙ	May exacerbate (mutually) effects, incl. side.
Danazol	FKV. FMR. Inhibits CYP4503A, slows the biotransformation, increases tissue concentration, increases the risk of hepatitis- and nephrotoxicity; with a joint appointment is necessary to reduce the dose.
Digoxin	FKV. FMR. Against the background of cyclosporine, clearance decreases, the apparent volume of distribution decreases, the risk of glycosidic intoxication increases.
Diclofenac potassium	FKV. FMR. Increases (mutually) The risk of developing nephrotoxicity. Against the background of cyclosporine, an increase in (in 2 times) blood level.
Diltiazem	FKV. FMR. Inhibits CYP4503A, slows the biotransformation, can increase the plasma concentration; combined use requires an increase in dose.
Doxycycline	FKV. Increases plasma concentration.
Doxorubicin	FKV. Against the background of cyclosporine (inhibits biotransformation and reduces clearance) increases the AUC, the severity and duration of manifestations of hematological toxicity increases, seizures and coma are also possible.
St. John's wort herb extract	FKV. FMR. Prolonged (within a few weeks) application reduces (much) serum level (may begin graft rejection).
Ibuprofen	FMR. Increases (mutually) the risk of kidney damage; when combined, it is necessary to monitor serum creatinine levels.
Isoniazid	FKV. FMR. Accelerates elimination, reduces tissue concentrations and weakens the effect.
Isotretinoin	FKV. The concentration 100 μmol inhibits the destruction of human liver microsomes and the production of primary metabolites (shows in vitro).
Indinavir sulfate	FKV. Suppresses CYP3A activity, slows the biotransformation, increases the concentration in the tissues; with a joint appointment caution.
Indomethacin	FMR. Increases (mutually) the likelihood of nephrotoxicity; combined use requires constant monitoring of serum creatinine levels.
Captopril	FMR. Strengthens (mutually) the probability of hyperkalemia; combined use requires caution and control of the level of potassium in the blood.
Carbamazepine	FKV. Induces CYP4503A, accelerates biotransformation, reduces plasma concentration; with a combined appointment, it is necessary to increase the dose.
Ketoconazole	FKV. FMR. Inhibits CYP3A, slows down biotransformation and can increase plasma concentration.
Ketoprofen	FMR. Increases (mutually) the risk of kidney damage; when used together, monitoring of serum creatinine is necessary.
Ketorolac	FMR. Increases (mutually) the risk of kidney damage; combined use requires monitoring of serum creatinine concentration.
Klindamiцin	FKV. May significantly reduce tissue levels; in case of joint administration, it is necessary to control the content of cyclosporine in the blood.
Clodronic acid	Does not affect efficiency; joint appointment is permissible.
Klonidin	FKV. May increase serum levels markedly; when used in combination, it is necessary to control the content of cyclosporine in the blood.
Co-trimoxazole [Sulfamethoxazole + Trimethoprim]	FMR. Increases (mutually) the risk of renal dysfunction.
Lovastatin	FKV. FMR. Increases (mutually) risk of developing myopathy. Against the background of cyclosporine, the content of active metabolites in plasma increases.
Melfalane	FMR: synergism. Increases (mutually) the likelihood of nephrotoxicity; with a joint appointment is necessary to monitor renal function.
Metamizole	FKV. FMR. Accelerates elimination, weakens the effect.
Methylprednisolone	FKV. FMR. Inhibits CYP4503A, slows (mutually) biotransformation, It increases the blood concentration.
Metoclopramide	FKV. Increases absorption and increases blood levels.
Methotrexate	FKV. FMR. Strengthens (mutually) effect, incl. risk of developing side. Serum levels rise moderately against cyclosporine.
Mycophenolic mofetil	FKV. FMR. May exacerbate (mutually) immunosuppression and the risk of side effects. Against the background of cyclosporine, the level in the blood decreases.
Minoksidil	FMR. Against the background of cyclosporine, the likelihood of developing hypertrichosis increases.
Morphine	FMR. Insomnia may develop on the background of cyclosporine, anxiety, amnesia, aphasia and severe confusion (described a single case).
Naproxen	FMR. Strengthens (mutually) The risk of developing nephrotoxicity; When combined requires monitoring of creatinine in serum.
Nelfinavir	FKV. Suppresses CYP3A activity, slows the biotransformation, increases the concentration in the tissues; with a joint appointment caution.
Nifedipine	FMR. Against the background of cyclosporine, the occurrence of gingival hyperplasia increases.
Octreotide	FKV. FMR. Induces CYP4503A, accelerates biotransformation, reduces tissue concentration, reduces the effect of (ie. may begin graft rejection).
Omeprazole	FKV. May increase serum levels (described 2- and 1.5x increase).
Orlistat	FKV. FMR. Reduces absorption and tissue concentration; when used together, it is possible to reduce the effect - the development of a reaction of acute graft rejection.
Paclitaxel	FKV. Against the background of cyclosporine, the plasma level rises.
Pantoprazole	Does not affect efficiency; combined use is permissible.
Paracetamol	FKV. Increases the likelihood of impaired renal function (slightly reduces creatinine clearance).
Perindopril	FMR: synergism. Increases (mutually) the risk of hyperkalemia; combined use requires caution and control of the level of potassium in the blood.
Pyrazinamide	FMR. May increase the likelihood of developing side effects (reported the occurrence of toxic myopathy).
Piroxicam	FMR. Increases (mutually) The risk of developing nephrotoxicity; when used together, it is necessary to monitor serum creatinine levels.
Prazosin	Against the background of cyclosporine, the (insignificantly) glomerular filtration rate in the transplanted kidney.
Prednisolone	FKV. May increase blood concentration in high doses. Against the background of cyclosporine, clearance decreases.
Probucol	FKV. Reduces blood levels; the combined appointment may need to increase the dose.
Progesterone	FKV. FMR. Accelerates elimination and weakens the effect.
Propafenone	FKV. FMR. Increases plasma concentration and increases the risk of impaired renal function.
Ranitidine	FMR: synergism. Increases the risk of kidney dysfunction, liver, deepens thrombocytopenia.
Ritonavir	FKV. Suppresses CYP3A activity, slows the biotransformation, increases the concentration in the tissues; with a joint appointment caution.
Rifabutin	FKV. Induces CYP4503A, enhances biotransformation and can reduce tissue content; combined use requires monitoring the concentration of cyclosporine in the blood.
Rifampicin	FKV. Induces CYP4503A, accelerates biotransformation and reduces tissue concentration; with a joint appointment, it is necessary to increase the dose.
Saquinavir	FKV. Suppresses CYP3A activity, slows the biotransformation, increases the concentration in the tissues; with a joint appointment caution.
Siʙutramin	Do not change (mutually) effect; sharing is acceptable.
Sirolimus	FMR: synergism. Strengthens (mutually) effect (immunosuppression), incl. side (manifestation of nephrotoxicity, decreased tolerance to infection, etc.). Against the background of cyclosporine, the level in the blood serum rises. Shared long-term use is not recommended.
Sulfadiazine	FKV. Decreases serum levels markedly.
Sulfamethoxazole	FMR: synergism. Increases (mutually) kidney dysfunction.
Sulfasalazine	One case reported of an increase in cyclosporine levels in a patient with a renal transplant after discontinuation of sulfasalazine.
Tacrolimus	FMR. Increases (mutually) risk of kidney damage.
Theophylline	FMR. Against the background of cyclosporine, the effect of.
Ticlopidine	FKV. Induces CYP4503A, accelerates biotransformation, may decrease tissue concentration.
Tobramycin	FMR: synergism. Strengthens (mutually) The risk of nephrotoxicity.
Trimetazidine	FMR. Does not affect the immunosuppressive effect, may reduce the risk of cytotoxicity manifestations .
Trimethoprim	FMR: synergism. Strengthens (mutually) kidney dysfunction.
Famotidin	FMR: synergism. Increases the risk of kidney dysfunction.
Phenylbutazone	FMR. Increases (mutually) the risk of kidney damage; combined use requires monitoring serum creatinine levels.
Phenytoin	FKV. Induces CYP4503A, accelerates biotransformation, reduces tissue concentration; combined use requires an increase in dose.
Phenobarbital	FKV. Induces CYP4503A, accelerates biotransformation, reduces tissue concentration; the combined appointment is necessary to increase the dose.
Fluconazole	FMR. Inhibits CYP3A, slows down biotransformation and can increase plasma concentration.
Flurbyprofen	FMR. Increases (mutually) the likelihood of nephrotoxicity; with a joint appointment necessary monitoring of serum creatinine.
Quinidine	FMR. Against the background of cyclosporine, the effect of.
Chloramphenicol	FKV. May increase serum levels.
Chloroquine	FKV. FMR. May raise serum levels and increase the risk of nephrotoxicity.
Celecoxib	FMR. Increases (mutually) the risk of kidney damage; combined use requires constant monitoring of serum creatinine levels.
Ceftazidime	FKV. FMR. May raise serum levels and increase the risk of nephrotoxicity.
Ceftriaxone	FKV. FMR. May raise serum levels and increase the risk of nephrotoxicity (mutually).
Ciprofloxacin	FMR. Increases (mutually) The risk of developing nephrotoxicity.
Enalapril	FMR. Increases (mutually) the risk of hyperkalemia; combined use requires caution and monitoring of plasma potassium.
Erythromycin	FKV. FMR. Slows biotransformation, increases plasma concentration, increases the risk of hepatitis- and nephrotoxicity; joint application requires caution.
Ethanol	There is a known case of a noticeable increase in the level of cyclosporine in the serum of a patient after drinking alcohol..