Leukeranum

General characteristics. Structure:

Tablets, coated brown color, round, biconvex, on one party an engraving of "L", on another - "GX EG3".

Active ingredient: hlorambutsit 2 mg

Excipients: lactose anhydrous, cellulose microcrystallic, silicon colloid anhydrous, stearic acid.

Structure of a cover: Opadry brown YS-1-16655A (gipromelloza, titanium dioxide, macrogoal, ferrous oxide yellow, ferrous oxide red).

Pharmacological properties:

Hlorambutsil treats aromatic derivatives of nitrogenous yperite and acts as the bifunctional alkylating drug. Alkylation happens by means of education of highly active radicals of an etilenimonium. Possibly, there is a cross linkng of radicals of an etilenimoiium with a spiral of DNA and the subsequent disturbance of process of DNA replication.

Pharmacokinetics. Drug is well soaked up from a GIT. Cmax (492±160 ng/ml) are reached in 0.25 - 2 h after reception. T1/2 averages 1.3 ±0.5 h. Communication with proteins of plasma - 99%.

After intake of a hlorambutsil, marked 14C, the maximum radioactivity of plasma is noted in 40-70 min. Hlorambutsil is brought from a blood plasma on average in 1.5 h.

It is quickly and completely metabolized in a liver (metabolism is connected with S - oxidation of a side chain of butyric acid) to pharmacological active metabolite of alpha-toluic yperite (bis 2-Aether chloratus-2 (4 aminophenyl) - acetsilt acid). It is removed by kidneys - 15-60%. T1/2 averages 1.8±0.4 h AUC bis 2-Aether chloratus-2 (4 aminophenyl) - acetsilt acid approximately at 1:33 time exceeds AUC of a hlorambutsil that confirms the alkylating activity of a metabolite.

Does not get through GEB. Passes through a placental barrier.

Indications to use:

— lymphogranulomatosis (Hodzhkin's disease);

— malignant lymphoma (including lymphosarcoma);

— chronic lymphoid leukosis;

— Valdenstrem's macroglobulinemias.

Route of administration and doses:

Leukeranum usually is one of components of a combination therapy in this connection at the choice of doses and the mode of administration of drug it is necessary to address special literature. Leikeran is accepted inside. Tablets should not be divided into parts.

Hodzhkin's disease

In the form of monotherapy Leikeran apply usually in a dose 0.2 mg/kg of mass of a body / within 4-8 weeks.

Nekhodzhkinsky lymphoma

In the form of monotherapy Leikeran usually apply originally in a dose 0.1-0.2 mg/kg of mass of a body / within 4-8 weeks; then carry out a maintenance therapy or in a smaller daily dose, or discontinuous courses.

Chronic lymphoid leukosis

The initial dose of Leukeranum makes 0.15 mg/kg of mass of a body / until total number of leukocytes of blood does not decrease to 10000/mkl. In 4 weeks after the termination of the first course of therapy treatment it is possible to renew in a maintenance dose 0.1 mg/kg of mass of a body /

Valdenstrem's macroglobulinemia

Leukeranum is choice drug. The initial dose makes 6-12 mg / daily, and after development of a leukopenia it is recommended to pass to a maintenance therapy in a dose 2-8 mg / ки daily during an uncertain span.

Children: Leukeranum can be applied to treatment of a disease of Hodzhkin and nekhodzhkinsky lymphoma at children, using the same schemes, as at adults.

At lymphocytic infiltration of marrow or in case of a marrow hypoplasia the daily dose of Leukeranum should not exceed 0.1 mg/kg of body weight.

Features of use:

Leukeranum is cytotoxic means which should be applied only under control of the doctor having experience of use of similar drugs.

At the unimpaired outside cover contact of tablets of Leukeranum with skin is harmless. Division of tablets is forbidden. When using tablets of Leukeranum it is necessary to implement recommendations about use of cytotoxic drugs.

As Leukeranum can cause irreversible oppression of function of marrow, during treatment it is necessary systematically (not less than 2-3 weekly) to make the general blood test with calculation of uniform elements of peripheral blood.

At use in therapeutic doses Leukeranum oppresses development of lymphocytes and to a lesser extent influences quantity of neutrophils and thrombocytes, and also hemoglobin level.

There is no need to stop reception of Leukeranum at the first signs of decrease in quantity of neutrophils, however it is necessary to remember that decrease in quantity of neutrophils can continue within 10 and more days after reception of the last dose.

To the patients who were earlier treated by cytostatic drugs or being exposed to radiation therapy, Leykerai appoint not earlier than in 1.5-2 months after the end of the previous treatment, on condition of lack of the expressed leukopenia, thrombocytopenia and anemia.

Children with a nephritic syndrome, the patients receiving high-dose pulse therapy Leukeranum and also patients with convulsive attacks have to be in the anamnesis under careful observation of the doctor during a course of treatment Leukeranum as at them the risk of development of spasms can be increased.

Patients with disturbances of secretory function of kidneys have to is under careful observation since at them more expressed miyelosupressiya connected with an azotemia can develop.

At increase in concentration of uric acid in blood serum use of the means alkalinizing urine is recommended. Development of a nephropathy can be prevented by adequate consumption of liquid or purpose of Allopyrinolum if necessary.

Patients with heavy abnormal liver functions should appoint smaller doses.

As use of the alkylating means is associated with substantial increase of frequency of development of an acute leukosis, at purpose of a hlorambutsil it is necessary to compare risk of developing of an acute leukosis with potential therapeutic effect of this drug.

Patients of childbearing age should use reliable methods of contraception.

Side effects:

Determination of frequency: very often (> 1/10), it is frequent (from> 1/100 to <1/10), sometimes (from> 1/1000 to <1/100) it is rare (from> 1/10000 to <1/1000), is extremely rare (<1/10000).

From system of a hemopoiesis: very often - a leukopenia (it is reversible if administration of drug is stopped timely), thrombocytopenia, a lymphopenia, a neutropenia, decrease in a hemoglobin content; extremely seldom - irreversible oppression of function of marrow.

From digestive tract: often - nausea, vomiting, diarrhea, ulcerations of a mucous membrane of an oral cavity; seldom - a hepatotoxic action of toksiko-allergic genesis (гепатонекроз or cirrhosis, a cholestasia, jaundice).

From respiratory system: extremely seldom - an intersticial pneumosclerosis (at long reception of a hlorambutsil), intersticial pneumonia.

Allergic reactions: sometimes - skin rash; seldom - urtikaropodobny rash, a Quincke's disease; extremely seldom - a multiformny exudative erythema (Stephens-Johnson's syndrome), a toxic epidermal necrolysis (Lyell's disease).

From a nervous system: often - spasms at children with a nephrotic syndrome; seldom - local and/or generalized spasms at the children and adults receiving were hlorambutsit in therapeutic doses daily or courses high-dose by pulse therapy; extremely seldom - uncertainty when walking, a tremor, muscular twitchings, a peripheral neuropathy, paresis, excitement, confusion of consciousness, the expressed weakness, uneasiness, hallucinations.

From outside мочевыделительноп systems: extremely seldom - aseptic cystitis.

Others: the medicinal hyperthermia, a hyperuricemia or a nephropathy caused by the increased formation of uric acid (result of bystry disintegration of cells), disturbance of a menstrual cycle, a secondary amenorrhea, an azoospermism, a secondary malignancy.

Interaction with other medicines:

At simultaneous use with the medicines oppressing a hemopoiesis strengthening of a miyelotoksichnost is possible.

At simultaneous use with antigouty means correction of doses of the last is required (hlorambutsit can increase concentration of uric acid in blood).

Tricyclic aitidepressant, and also a haloperidol, Maprotilinum, inhibitors of a monoaminooxidase, fenotiazina, thioxanthenes can reduce a threshold of convulsive activity and increase risk of developing of convulsive attacks.

The drugs which are intensively contacting proteins of plasma increase toxicity of a hlorambutsil (the competition at the level of communication with protein).

With inaktivirovaniy virus vaccines - decrease in development of antibodies in response to introduction of a vaccine; with live virus vaccines - an intensification of process of replication of a vaccinal virus, strengthening of its side/adverse effects and/or decrease in development of antibodies.

Contraindications:

— pregnancy;

— feeding period breast;

— hypersensitivity to any component of this drug.

With care (it is necessary to compare risk and advantage) - oppression of function of marrow (the expressed leukopenia, thrombocytopenia and anemia); chicken pox (now or recently postponed), the surrounding herpes, acute infectious diseases of the virus, fungal and bacterial nature, infiltration of marrow tumor cells, gout (in the anamnesis), нефроуролитиаз uratny, a head injury (in the anamnesis), epilepsy (in the anamnesis), a serious illness of a liver and kidneys.

 

Use of the drug LEUKERANUM at pregnancy and feeding by a breast

Contraindicated: pregnancy, feeding period breast.

 

Use at abnormal liver functions

With care (it is necessary to compare risk and advantage) a serious illness of a liver.

 

Use at renal failures

With care (it is necessary to compare risk and advantage) - a serious illness of kidneys.

 

Use for children

Children: Leukeranum can be applied to treatment of a disease of Hodzhkin and nekhodzhkinsky lymphoma at children, using the same schemes, as at adults.

Overdose:

Symptoms: a reversible pancytopenia, a hyperexcitability, an ataxy, repeated epileptoidny attacks like grand mal. The specific antidote is not known.

Treatment: an immediate gastric lavage, monitoring and maintenance of the vital functions of an organism, careful control of blood tests and the general supporting actions, including hemotransfusion or its components according to indications. Dialysis is not effective.

Storage conditions:

List A. To store at a temperature of 2-8 °C in the place, unavailable to children. A period of validity - 3 years. Not to use drug after the expiry date specified on packaging.

Issue conditions:

According to the recipe

Packaging:

25 - bottles of dark glass (1) - a pack cardboard.