Ekoral

• Structure
• Release form
• Pharmacological action
• Pharmacodynamics and pharmacokinetics
• Indications to use
• Contraindications
• Side effects
• Ekoral, application instruction (Way and dosage)
• Overdose
• Interaction
• Terms of sale
• Storage conditions
• Period of validity
• Analogs
• Responses

Structure

In 1 capsule of cyclosporine 25, 50 or 100 of mg. Alcohol, a macrogoal glyceryl, D, L - alpha tocopherol, polyglyceryl oleate as excipients.

Release form

Capsules of 100, 50 and 25 mg.

Solution of 100 mg / 1 ml, in bottles on 50 ml.

Pharmacological action

Immunodepressive.

Pharmacodynamics and pharmacokinetics

Pharmacodynamics

Active ingredient cyclosporine A represents polypeptide from 11 amino acids. Its action consists suppression of formation of lymphokines. Blocks the lymphocytes which are at rest (phase G0) or in the phase G1. Also suppresses release of lymphokines T lymphocytes. At the same time cyclosporine it is specific and reversibly affects lymphocytes, the hemogenesis also does not oppress.

Pharmacokinetics

At intake of Cmax in plasma is defined in 1 — 6 hours. Bioavailability makes 30% and at increase of a dose increases. Also direct dependence of bioavailability is noted also from reception duration. Absorption decreases after transplantation of a liver, at her diseases, and also at diarrhea or vomiting. Active ingredient contacts proteins (mainly with lipoproteins to 90%) and uniform elements of blood. It is distributed as follows: to 47% in plasma, to 12% in granulocytes, 4-9% in lymphocytes and 42-58% in erythrocytes. It is metabolized in a liver by system  of P450 3A cytochrome with formation of metabolites. Also only 6% of a dose — kidneys are removed with bile. T1/2 at adults about 19 hours at children — 7 hours.

Indications to use

At transplantation:

• for the purpose of the prevention of rejection of an allogenic transplant — a kidney, heart, a liver, a lung, heart lung, a pancreas;
• for the purpose of the prevention of graft rejection of marrow.

The diseases which are not connected with transplantation:

• heavy current of a pseudorheumatism;
• the uveitis menacing to sight;
• Bekhchet's uveitis;
• steroidozavisimy form of a nephrotic syndrome;
• severe forms of psoriasis;
• atopic dermatitis.

Contraindications

• hypersensitivity;
• malignant new growths of skin;
• shingles;
• heavy liver failure;
• sprue;
• hyperpotassemia;
• acute infectious diseases;
• the arterial hypertension which is not giving in to correction.

Side effects

• burning sensation of extremities (at the beginning of reception);
• the increased growth of hair;
• hypertrophy of gums;
• tremor;
• renal failure and liver;
• vomiting, anorexia, nausea, increase of level of bilirubin, creatinine and urea;
• arterial hypertension (at transplantation of heart);
• disorders of a gastrointestinal tract, a hypertrichosis, a face edema, children have spasms (at a bone marrow transplantation).

Side reactions often disappear at a dose decline.

Ekoral, application instruction (Way and dosage)

Capsules are washed down with water and swallowed without chewing. Grapefruit juice cannot be used for 1 h before administration of drug. The dose is divided into 2 receptions. The recommended doses are included below — a basis is appointment of the doctor after control in blood of the concentration of cyclosporine necessary for achievement of effect.

At an organ transplantation treatment is begun for 12 h before operation, appoint a daily dose of 10-15 mg/kg, having divided into 2 receptions. Depending on the weight of the patient apply more rational dosages Ekoral of 100 mg or Ekoral of 25 mg. Then 2 weeks constantly control concentration of cyclosporine, usually maintenance dose from 2 to 6 mg/kg a day.

If Ekoral is applied combinations with GKS, then the dose decreases even in an initiation of treatment — 3-6 mg/kg a day.

At transplantation of marrow — 12,5 mg/kg a day, also divided into 2 receptions. Till 3-6 months carry out a maintenance therapy, then reduce a dose during 1 year.

At a uveitis — 5 mg/kg a day for 2 receptions, accept before disappearance of an inflammation. In hard cases the dose is increased to 7 mg/kg a day and fix a long time. Sometimes for increase of efficiency add system GKS.

The maintenance dose is reduced to minimum effective (during remission to 5 mg/kg a day).

At a nephrotic syndrome appoint 5 mg/kg of weight a day the adult and 6 mg/kg of weight a day to children, the general dose is divided into 2 receptions. At a renal failure — to 2,5 mg/kg a day. Ekoral with peroral GKS is recommended to combine. If treatment within 3 months is not effective drug cancel.

At a pseudorheumatism the first 1,5 months a dose — 3 mg/kg a day, increase it if necessary to 5 mg/kg a day. For full effect the 3rd monthly administration of drug can be required. At this disease combinations with glucocorticoids and a methotrexate are justified.

At psoriasis for achievement of remission — 2,5 mg/kg / in the days divided into 2 receptions. If there is no effect in 1 month, the daily dose increases to 5 mg/kg a day. Treatment is stopped if at reception of this dose within 1,5 months the adequate answer is not reached. If treatment is effective, then drug is cancelled before the following recurrence of a disease. However some patients need the maintenance therapy which is carried out a long time.

At atopic dermatitis — from 2,5 to 5 mg/kg a day. Begin treatment with the minimum dose, increasing if necessary to maximum – 5 mg/kg. At a severe disease apply to fast control of symptoms initially 5 mg/kg a day, with a gradual dose decline. It is proved that treatment lasting 1 year is more effective, it is well transferred and it has to be recommended to patients with atopicheskimy dermatitis.

At all diseases in case of increase of the ABP or increase in level of creatinine by 30% undertake a drug dose decline for 25-50%.

Overdose

There are no data on acute overdose. Chronic overdose is shown by reversible renal failures. The general events, including a gastric lavage are held. It is necessary to consider that cyclosporine is almost not removed at hemoperfusion and a hemodialysis.

Interaction

Reduce concentration of active agent in blood barbiturates, carbamazepine, Sulfadimidunum, Phenytoinum, naftsillin, rifampicin, probucol, oktreotid, orlistat, troglitazon, drugs of the St. John's Wort which is made a hole.

Increase concentration in blood — erythromycin and klaritromitsin, flukonazol, ketokonazol, diltiazem, itrakonazol, nikardipin, verapamil, Methylprednisolonum, oral contraceptives, danazol, Allopyrinolum, cholic acid, Amiodaronum. In need of joint purpose of erythromycin it is inside recommended to control concentration of cyclosporine constantly.

Strengthening of nephrotoxic effects is noted at simultaneous use of gentamycin, Tobramycinum, ciprofloxacin, Amphotericinum In, Trimethoprimum, Vancomycinum, diclofenac, a sulindak, Naproxenum, Melphalanum. The combined use with diclofenac increases bioavailability of diclofenac that is connected with decrease in its metabolism.

The combined use with nifedipine leads to the expressed hyperplasia of gums. Cyclosporine reduces clearance of colchicine, digoxin, a lovastatin, Prednisolonum, a simvastatin, leading to strengthening of side effects (a miositis, muscular pains, rabdomioliz).

Carrying out vaccination live vaccines during Ekoral's reception do not recommend.

Terms of sale

According to the recipe.

Storage conditions

Temperature is up to 25 °C.

Period of validity

3 years.

Analogs

Konsupren, Panimun Bioral, Orgasporin, Restasis, Sandimmun, Tsiklopren, Cyclosporine.

About Ekorale

The patients who transferred transplantation have vital need for continuous use of the drugs interfering premature rejection of body. Implementation of cyclosporine A was an important step in creation of the drugs operating on subpopulation of lymphocytes.

Cyclosporine drugs quite strong immunosuppressors, but are not deprived of shortcomings — they are nefrotoksichna. Besides, shortcomings of pharmacokinetics of cyclosporine result in variability of its concentration in blood and attract not the constant level of immunosuppression. Microemulsion drug Sandimmun Neoral is deprived of shortcomings of usual cyclosporine. Ekoral is generic and many patients who were earlier accepting Sandimun Neoral reluctantly pass to new drug and connect with it the appeared nephrotoxicity. Patients differently transferred this drug that has reflection in responses.

• "… I accepted a long time Ekoral, by-effects were not, but recently transferred to Bioral — constant nausea developed".
• "… According to the program received and accepted all that give: Sandimmun did not shout, then 7 months this drug, later Panimun biorat. Everything was good. With analyses everything is OK".
• "… To the relative after transplantation of a kidney appointed this drug from which reception it had a severe nausea and vomiting".
• "… I worsened renal tests and began to swell".
• "… Read that at reception of this drug about 15% of ottorzheniye, and on Neorala only 4%".
• "… I had an acute nephrotoxicity from Ekoral who accepted from October to March".