Description of the active substance:
This information is a reference and it is not enough that the drug has been prescribed by a doctor ..
PHARMACHOLOGIC EFFECT
Immunosuppressive agent, cyclic undecapeptide. Has a selective effect on T-lymphocytes. Inhibits the activation of calcium luminescent lymphocytes in the phase G 0or G 1 of the cell cycle. Thus, activation of T-lymphocytes is prevented and, at the cellular level, antigen-dependent release of lymphokines, including interleukin-2 (growth factor of T-lymphocytes). Cyclosporine acts on lymphocytes specifically and reversibly. Unlike cytostatics, it does not inhibit hemopoiesis and does not affect the function of phagocytes.
At the predicted oppression of lacrimal fluid production in patients with dry keratoconjunctivitis, it is considered that cyclosporine, when applied topically (in the form of an emulsion) acts as an immunomodulator in part. The exact mechanism of action is not established. A statistically significant increase in the functional parameters of the lacrimal gland is indicated. There was no increase in the severity of inflammatory eye diseases of the bacterial or fungal nature with topical application of cyclosporine.
PHARMACOKINETICS
In systemic administration, cyclosporine is distributed primarily outside the bloodstream. In blood, the active substance is present in the plasma - from 33% to 47%, in lymphocytes - from 4% to 9%, in granulocytes - from 5% to 12% and in erythrocytes - from 41% to 58%. Binding to plasma proteins, mainly with lipoproteins, is 90%. Metabolized with the formation of about 15 metabolites. It is excreted mainly with bile; 6% is excreted by the kidneys mainly in the form of metabolites and only 0.1% - in unchanged form. T 1/2 from the body is approximately 19 hours, regardless of dose and route of administration.
The concentration of cyclosporine in all selected blood samples after topical application in adults at a concentration of 500 Ојg / ml 2 times / day for up to 12 months was below the detectable level of 0.1 ng / ml. There was no cumulation of cyclosporine in the blood during treatment for 12 months by topical application in the form of an eye emulsion.
INDICATIONS
For systemic use: the need to suppress immunity after the transplantation of the kidneys, bone marrow, solid organs; Rheumatoid arthritis with a high degree of activity with resistance to basic therapy; severe forms of psoriasis and atopic dermatitis with ineffective standard therapy; nephrotic syndrome caused by the pathology of the vascular glomerulus (nephropathy of minimal changes, focal and segmental glomerulosclerosis, membranous glomerulonephritis).
For topical application: to increase the production of lacrimal fluid in patients with a predicted decrease in the production of tear fluid due to inflammatory eye damage associated with dry keratoconjunctivitis.
DOSING MODE
The treatment regimen depends on the indications and is set individually. The choice of the initial dose, as well as the correction of the dosing regimen during the treatment, are carried out taking into account the clinical and laboratory parameters, as well as the values ​​of the concentration of cyclosporine in the blood plasma, determined daily. The daily intake for oral administration is 3.5-6 mg / kg.
In a conjunctival sac, 1 drop of eye emulsion is instilled 2 times / day with an interval of 12 hours.
SIDE EFFECT
From the digestive system: a feeling of heaviness in the epigastric region, loss of appetite, nausea (especially at the beginning of treatment), vomiting, diarrhea, pancreatitis, swelling of the gums, impaired liver function.
From the central nervous system and peripheral nervous system: headache, paresthesia, convulsions are possible.
From the cardiovascular system: increased blood pressure.
From the side of the urinary system: renal dysfunction.
From the side of metabolism: increased concentration of potassium and uric acid in the body.
On the part of the endocrine system: excessive hair, reversible dysmenorrhea and amenorrhea.
From the musculoskeletal system: rarely - muscle spasms, muscle weakness, myopathy.
On the part of the hematopoiesis system: minor anemia; rarely - thrombocytopenia.
Local reactions: very often - a burning sensation in the affected eye; often - congestion hyperemia, discharge from the eyes, pain, foreign body sensation, itching, visual impairment (most often - blurred vision); often - allergic reactions.
CONTRAINDICATIONS
Uncontrolled arterial hypertension, acute infectious diseases, malignant tumors (except for malignant skin tumors in patients with psoriasis and atopic dermatitis), renal dysfunction (except for patients with nephrotic syndrome).
PREGNANCY AND LACTATION
Experience with cyclosporine in pregnancy is limited. Data obtained for patients with transplanted organs show that, in comparison with traditional methods of treatment, cyclosporine does not increase the risk of adverse effects on the course and outcome of pregnancy.
Cyclosporine excreted in breast milk. If necessary, use during lactation should stop breastfeeding.
In experimental studies it was shown that cyclosporine does not have a teratogenic effect.
APPLICATION FOR FUNCTIONS OF THE LIVER
Contraindicated in disorders of kidney function (except for patients with nephrotic syndrome). In patients with impaired renal function, local use of cyclosporine in ophthalmology has not been studied.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
In patients with impaired liver function, local application of cyclosporine in ophthalmology has not been studied.
SPECIAL INSTRUCTIONS
During the treatment with cyclosporin, systematic monitoring of the functional state of the kidneys and liver, control of blood pressure, determination of potassium concentration in plasma (especially in patients with impaired renal function), as well as serum lipids (before and after the first month of treatment) are shown. If the increase in the concentration of urea, creatinine, bilirubin, liver enzymes in the blood is persistent, the dose of cyclosporine should be reduced. In the case of hypertension, antihypertensive treatment should be initiated. When serum lipid levels are increased, consideration should be given to reducing the dose of cyclosporine and / or using a special diet.
Avoid excessive suppression of immunity.
During the therapy, vaccine should not be vaccinated with live attenuated vaccines against mumps, measles, rubella, poliomyelitis.
When used simultaneously with drugs that can change the concentration of cyclosporine in the blood plasma, careful monitoring of this concentration and appropriate correction of the dosing regimen are necessary.
It is not recommended simultaneous use of lipid-lowering drugs such as lovastatin and cytostatics such as melphalan.
Cyclosporine (in a special dosage form) can be applied topically in combination with preparations containing an artificial tear, between the injections should be observed interval of 15 minutes.
In patients with impaired renal function, liver, herpesviral keratitis, the local history of cyclosporine in ophthalmology has not been studied.
DRUG INTERACTION
With the simultaneous use of cyclosporine and potassium or potassium-sparing diuretics, the risk of developing hyperkalemia increases; with antibiotics of the aminoglycoside group, amphotericin B, ciprofloxacin, melphalan, colchicine, trimethoprim - the risk of developing nephrotoxicity increases; with NSAIDs - the risk of side effects from the kidneys; with lovastatin or colchicine - increases the risk of developing muscle pain and weakness.
Various drugs can increase or decrease the concentration of cyclosporine in the plasma by suppressing or induction of liver enzymes involved in the metabolism and elimination of cyclosporine. Drugs that increase the concentration of cyclosporine in plasma: erythromycin, clarithromycin, josamycin, doxycycline, chloramphenicol, roxithromycin, midecamycin, ketoconazole, fluconazole (apparently in high doses), itraconazole, diltiazem, nicardipine, verapamil, propafenone, amiodarone, carvedilol, metoclopramide ; oral contraceptives; danazol; methylprednisolone (high doses); allopurinol; amiodarone; cholic acid and its derivatives. Drugs that cause a decrease in the concentration of cyclosporin in the plasma: barbiturates, carbamazepine, phenytoin; metamizol, nafcillin, sulfadimidine with its iv introduction;rifampicin, griseofulvin, terbinafine, octreotide, probucol, orlistat, troglitazone, preparations containing St. John's wort (Hypericum perforatum).
It was noted that cyclosporine reduces the clearance of prednisolone, and treatment with high doses of prednisolone may increase the concentration of cyclosporine in the blood.
Glibenclamide can increase the concentration of cyclosporine in the blood plasma in an equilibrium state.
With the simultaneous use of cyclosporine with diuretics, the risk of kidney dysfunction increases; with doxorubicin - an increase in the concentration of doxorubicin in the blood plasma and an increase in its toxicity; with methotrexate - an increase in the concentration of cyclosporine in the blood plasma, an increase in the incidence of nephrotoxic action and arterial hypertension; with melphalan (with iv in the introduction in high doses) - it is possible to develop severe renal failure; with teniposide - a decrease in the clearance of teniposide, an increase in its T 1/2 , an increase in toxicity.
With simultaneous use with warfarin, there is a decrease in the effectiveness of cyclosporine and warfarin.
When cyclosporine is used with ACE inhibitors, potassium preparations, potassium-sparing diuretics, the risk of hyperkalemia increases.
With simultaneous application with enalapril may develop acute renal failure; with nifedipine - increased gingival hyperplasia.
In patients receiving cyclosporine, there is a significant increase in the bioavailability of diclofenac, with the possible development of reversible renal dysfunction.The increase in the bioavailability of diclofenac is associated, apparently, with the inhibition of its metabolism during the "first passage" through the liver.
With simultaneous use of cyclosporine reduces the clearance of prednisolone. When using prednisolone in high doses, an increase in the concentration of cyclosporine in the blood is possible. Methylprednisolone increases the concentration of cyclosporine in the blood.
When using cisapride in patients receiving cyclosporine, it is possible to increase its C max in blood plasma and the rate of absorption.
There may be a decrease in the clearance of digoxin, colchicine, lovastatin, pravastatin, simvastatin, prednisolone, which may lead to an increase in toxic effects: glycoside intoxication with digoxin and the manifestations of colchicine, lovastatin, pravastatin and simvastatin toxicity in muscles, in particular the appearance of muscle pain, weakness, Myositis and, in rare cases, rhabdomyolysis.
ACE inhibitors, antiviral drugs, antibiotics of the aminoglycoside group, cephalosporins, amphotericin B, trimethoprim, co-trimoxazole, ciprofloxacin, melphalan increase the nephrotoxicity of cyclosporine.
With the simultaneous use of cyclosporine and quinidine and its derivatives, theophylline and its derivatives, it is possible to enhance the effects of quinidine and its derivatives, theophylline and its derivatives.
When using imipenem in combination with cilastatin, an increase in the concentration of cyclosporine is possible, which can lead to the appearance of symptoms of neurotoxicity (trembling, increased excitability).
With the simultaneous use of cyclosporine with other immunosuppressants, the risk of infections and lymphoproliferative diseases increases.
Data on the interaction of cyclosporine in the form of an eye emulsion are absent. But with the application of eye emulsion, one can not exclude the interaction characteristic of cyclosporine in systemic application.
