Cycloral

Cycloral is a cyclic type polypeptide that contains 11 amino acids. It has an immunosuppressive effect.

The drug inhibits the development of cellular reactions, including the immune defense against the allograft and delayed epidermal intolerance, as well as the development of GVHD pathology, an allergic form of encephalomyelitis, arthritis associated with Freund's adjuvant, and with this the formation of antibodies, which depends on the activity of T-lymphocytes. [1]

Indications Cycloral

It is used in transplantology to prevent possible rejection after performing a transplant of solid organs (including the heart, lungs, kidneys, pancreas with liver, or complex cardiopulmonary transplant), and besides, after bone marrow transplantation . In addition, it is prescribed for the therapy of transplant rejection in persons who previously used other immunosuppressants.

Use for non-organ transplant disorders:

• uveitis endogenous type (dangerous for active type of uveitis, striking the back or the middle of the eye, non-infectious origin as the standard treatment is ineffective or causes severe adverse symptoms; Behcet disease affecting the retina, in which relapses inflammation);
• arising under the influence of GCS and resistant to them nephrotic syndrome associated with damage to the glomerulus of blood vessels (with the following pathologies - glomerulosclerosis of the segmental and focal type, BMI and the membranous form of glomerulonephritis), in order to induce and maintain remission, as well as to maintain remission caused by GCS, with their further cancellation;
• arthritis of the rheumatoid type in an active form in a severe degree (in situations where standard antirheumatic drugs with slow action do not have an effect or their use is impossible);
• psoriasis (in severe degree, when standard treatment does not work or its implementation is impossible);
• atopic form of severe dermatitis, when systemic treatment is required.

Release form

The release of a drug substance is realized in the form of capsules with a volume of 25, 50, 100 mg - 10 pieces each inside a cell pack (5 such packs inside a box). Also produced inside polyethylene bottles - 50 or 100 pieces inside the bottle.

Pharmacodynamics

The drug at the cell level blocks lymphocytes located in the Go or G1 stages of the cell cycle and inhibits the production and release of lymphokines (this includes IL-2, which are growth factors for T-lymphocytes), which are activated by T-lymphocytes, caused by the antigen.

It is believed that the effect of Cycloral on lymphocytes is reversible. The drug does not inhibit hematopoiesis and does not affect the activity of phagocytic cells, which distinguishes it from cytostatics.[2]

Pharmacokinetics

For oral administration, the plasma Cmax is noted after 17 ± 0.3 hours. There is a stable absorption and a low dependence on the use with food and the daily rhythm. Due to these properties, the severity of interpersonal differences in pharmacokinetic parameters decreases and a more uniform exposure relative to the drug in the daily period and on different days is noted.

Distribution takes place mainly outside the bloodstream; inside the plasma there is 33-47% of the drug, inside lymphocytes - 4-9%, inside granulocytes - 5-12%, inside erythrocytes - 41-58%.[3]

Inside the blood plasma, about 90% of the drug is involved in protein synthesis (mainly with lipoproteins). It takes part in biotransformation, which includes various reactions leading to the formation of about 15 metabolic elements.

Excretion is mainly in the form of metabolic components, together with bile; 6% of the portion is excreted through the kidneys. The half-life is 7-19 hours (in persons with severe hepatic pathologies).

Dosing and administration

The drug is administered orally, the dosage is selected and adjusted personally (laboratory and clinical indications are taken into account). The capsules are swallowed whole without chewing.

In the case of a solid organ transplantation procedure in an adult, therapy begins 12 hours before the operation: at a dosage of 10-15 mg / kg, which is divided into 2 doses. In the period of 1-2 weeks after the operation, the medicine is used every day in the indicated portion, and then it is gradually reduced by 5% per week to maintain 2-6 mg / kg per day in 2 uses (in this case, blood values need to be monitored cyclosporine).

In combination with GCS and other immunosuppressants, it can be used in lower dosages (3-6 mg / kg per day at the initial therapeutic stage).

Bone marrow transplantation.

On the day before transplantation, as well as during the post-transplant period (up to 14 days), intravenous cyclosporine should be administered. After that, the patient is transferred to maintenance treatment with Cycloral in portions of 12.5 mg / kg per day in 2 applications. The maintenance period lasts at least 3-6 months (six months are recommended), and then the dosage is gradually reduced to stop therapy 1 year after transplantation.

If GVHD develops, therapy should be resumed; with a mild degree of chronic disorder, low dosages of the drug are used.

For children from 2 years old, the medication is prescribed in adult portions. Dosages in excess of adults may also be used.

With maintenance treatment, the portion is reduced gradually until the minimum effective dose is obtained (in case of remission, it should be no more than 5 mg / kg per day).

Endogenous form of uveitis.

To induce remission, the drug is first used in a daily dose of 5 mg / kg for 2 uses - until visual acuity improves and the symptoms of active inflammation disappear. In intractable cases, the portion can be increased to 7 mg / kg per day for a short period.

Nephrotic syndrome.

To induce remission, it is necessary to apply 5 mg / kg per day (for an adult) and 6 mg / kg in 2 doses (for a child). Servings are for people with healthy kidney function, excluding proteinuria. Persons with renal dysfunction should use the drug in a dosage not exceeding 2.5 mg / kg per day.

Portions are selected individually, taking into account the values of efficacy (proteinuria), as well as safety (serum creatinine), but it is forbidden to exceed the daily dosage of 5 mg / kg (adult) and 6 mg / kg (child).

With maintenance treatment, the dosage is gradually reduced to the lowest effective dose.

Rheumatoid arthritis.

During the first 1.5 months of therapy, it is required to apply 3 mg / kg per day in 2 doses. If the effect of the drug is not enough (provided that it is well tolerated), you can gradually increase the portion to a maximum of 5 mg / kg.

The treatment lasts up to 3 months. With supportive treatment, the portion is selected individually, taking into account the tolerance of the medication.

Psoriasis.

Serving size is determined personally. Induction of remission usually requires 2.5 mg / kg per day in 2 doses. If after 1 month of treatment there is no improvement, the daily portion is gradually increased (but not higher than 5 mg / kg). If there are no positive changes after 1.5 months of therapy using a daily dose of 5 mg / kg (or if the appropriate dosage does not meet the established safety limits), it is discontinued.

Maintenance dosages are selected personally (the lowest effective portion) and should be no more than 5 mg / kg per day.

Atopic dermatitis.

The dosage selection is done personally. First, it is recommended to use 2.5-5 mg / kg per day (for 2 doses). In the absence of positive changes when using the initial dosage of 2.5 mg / kg, over a period of 2 weeks, it can be increased to the maximum level (5 mg / kg). If the patient's case is extremely difficult, adequate and rapid control of the pathology can be achieved using immediately a portion of 5 mg / kg per day. After obtaining the required effect, the portion is gradually reduced, after which, if possible, the Cycloral must be canceled. If a relapse develops, a second cycle can be prescribed.

Although a treatment course lasting 2 months is sufficient to cleanse the epidermis, it has been established that treatment lasting up to 1 year is tolerated without complications and shows good efficacy (under conditions of constant monitoring of important vital signs).

Use Cycloral during pregnancy

It is forbidden to prescribe Cycloral during pregnancy (due to the lack of clinical information). For the period of therapy, it is necessary to abandon GV.

Contraindications

It is contraindicated to use in case of severe sensitivity to the medication.

Side effects Cycloral

The main side effects:

• disorders in the urogenital system: sometimes renal dysfunctions occur, in which there is an increase in serum levels of urea and creatinine (depending on the size of the dosage and is noted during the first weeks of therapy). Prolonged use may cause interstitial fibrosis (to be distinguished from changes associated with chronic rejection);
• liver and gastrointestinal tract damage: nausea, abdominal pain, anorexia, diarrhea, pancreatitis and vomiting; treatable hepatic dysfunctions may occur - an increase in bilirubin and transaminase levels (depending on the size of the dosage);
• problems with the work of the cardiovascular system and the blood system (hemostasis and hematopoiesis): blood pressure often rises (especially in people after heart transplantation). Occasionally, anemia and thrombopenia are observed, which occurs due to failure of the kidneys and the hemolytic form of anemia of the microangiopathic type (HUS);
• disorders of the sensory organs and NS: paresthesias, headaches and seizures may appear. Occasionally, muscle spasms and weakness, tremors and myopathy develop. People after liver transplantation develop symptoms of visual disturbances, impaired motor activity and consciousness, and encephalopathy;
• metabolic disorders: amenorrhea and treatable dysmenorrhea; hyperuricemia and -kalemia, as well as hypomagnesemia. Occasionally, a slight reversible increase in serum lipid values is observed;
• signs of allergies: epidermal rashes;
• others: fatigue, swelling, hypertrichosis, gingival hypertrophy, and weight gain. Lymphoproliferative and malignant pathologies may appear (also in persons with nephrotic syndrome). In psoriasis, malignant neoplasms (eg, epidermal) can occur.

Overdose

Signs of overdose include renal dysfunction.

Symptomatic and nonspecific actions are performed (start with gastric lavage). Hemoperfusion and hemodialysis procedures do not have the desired effect.

Interactions with other drugs

The drug reduces the rate of clearance of prednisolone.

When Cycloral is used together with potassium substances and potassium-sparing diuretics, the likelihood of hyperkalemia increases.

The combination with aminoglycosides, trimethoprim, NSAIDs, as well as ciprofloxacin, amphotericin B and colchicine increases the risk of nephrotoxicity.

Combination with lovastatin (or colchicine) increases the likelihood of developing weakness and myalgia.

The plasma level of the drug is increased by doxycycline, certain macrolides (among them josamycin with erythromycin), ketoconazole, propafenone, oral contraception, certain CCBs (this includes diltiazem and verapamil with nicardipine) and large doses of methylprednisolone.

Plasma values of drugs decrease when combined with phenytoin, barbiturates, metamizole Na, rifampicin and carbamazepine. A similar effect is exerted by trimethoprim with sulfadimezine (in the case of their intravenous administration).

Storage conditions

The cycloral must be kept in a dark place, out of the reach of children. Do not keep the medicine in the refrigerator. Temperature indicators - no more than 25 ° C.

Shelf life

Cycloral can be used for a 24-month term from the moment the therapeutic substance is sold.

Analogs

The analogs of the medication are Imusporin, Cellsept, Arava and Equoral with Panimun, and in addition to Mifortik and Lifemun.