Leukeranum

Leukeranum – antineoplastic drug; the bifunctional alkylating connection.

Form of release and structure

Dosage form of Leukeranum – a tablet, coated: biconvex, round, brown color, on one of the parties an engraving of "L", on another – "GX EG3" (on 25 pieces in bottles of dark glass, 1 bottle in a cardboard pack).

Contain in 1 tablet:

• Active agent: hlorambutsit – 2 mg;
• Auxiliary components: acid stearin, microcrystallic cellulose, lactose anhydrous, silicon colloid anhydrous;
• Cover: Opadry brown YS-1-16655A (titanium dioxide, gipromelloz, macrogoal, ferrous oxide red and yellow).

Indications to use

• Hodzhkin's lymphoma (malignant granuloma, lymphogranulomatosis);
• Malignant lymphoma (lymphosarcoma inclusive);
• Valdenstrem's macroglobulinemia;
• Chronic lymphoid leukosis.

Contraindications

Absolute:

• Pregnancy period;
• Lactation (breastfeeding);
• Hypersensitivity to any of components.

Relative (drug is used with care owing to the increased probability of side effects, after comprehensive assessment of a ratio risk/advantage):

• Oppression of a marrowy hemopoiesis (the expressed anemia, thrombocytopenia and leukopenia);
• Chicken pox (the current disease or postponed recently);
• Shingles;
• Acute infectious pathologies of a bacterial, virus and fungal etiology;
• Infiltration by tumor cells of marrow;
• Urolithiasis;
• Diseases of kidneys and liver of heavy degree;
• Data in the anamnesis on gout, injuries of the head, epilepsy.

Route of administration and dosage

Pill is taken inside, swallowing of whole, it is not necessary to chew or divide them into parts.

Preferential drug is used as a part of complex therapy therefore for a right choice of the mode of dosing it is necessary to study special literature and summaries to the medicines used in a combination with Leukeranum.

The recommended dosing mode depending on a state/disease:

• Hodzhkin's (monotherapy) lymphoma: 0,2 mg/kg of body weight a day for 4-8 weeks;
• Nekhodzhkinsky lymphoma (monotherapy): an initial dose – 0,1-0,2 mg/kg of body weight a day for 4-8 weeks; further carry out the supporting treatment by discontinuous courses or in a smaller daily dosage;
• Chronic lymphoid leukosis: an initial dose – 0,15 mg/kg of body weight a day before decrease in total number of leukocytes of blood to 10 000/mkl; 4 weeks later upon termination of the first course it is allowed to resume treatment in a maintenance dose – 0,1 mg/kg of body weight a day;
• Valdenstrem's macroglobulinemia (as choice drug): an initial dose – 6-12 mg a day daily; after development of a leukopenia it is necessary to pass to a maintenance dose – 2-8 mg a day daily throughout the uncertain period.

At children Leukeranum is applied to treatment of nekhodzhkinsky lymphoma and Hodzhkin's disease with use of the same schemes, as to adult patients.

In case of lymphocytic infiltration or a hypoplasia of marrow the daily dose of drug should not exceed 0,1 mg/kg of body weight.

Side effects

• System of a hemopoiesis: very often – thrombocytopenia, a leukopenia (reversible at the timely termination of administration of drug), a lymphopenia, decrease in a hemoglobin content, a neutropenia; extremely seldom – oppression of function of marrow (irreversible);
• Digestive tract: often – ulcerations of a mucous oral cavity, nausea, vomiting, diarrhea; seldom – a toksiko-allergic hepatotoxic action (cirrhosis or гепатонекроз, jaundice, a cholestasia);
• Respiratory system: extremely seldom – intersticial pneumonia, and in case of long administration of drug can develop an intersticial pneumosclerosis;
• Allergic answers: sometimes – rash on skin; seldom – a Quincke's disease, urtikaropodobny rash; extremely seldom – Stephens-Johnson's syndrome (a malignant exudative erythema), a Lyell's disease (a toxic or acute epidermal necrolysis);
• Nervous system: often – spasms at a nephrotic syndrome at children; seldom – generalized and/or local spasms at the adults and children receiving hlorambutsit daily in therapeutic doses, or at high-dose pulse therapy; extremely seldom – a tremor, uncertainty when walking, muscular twitchings, paresis, a peripheral neuropathy, excitement, the expressed weakness, confusion of consciousness, uneasiness, hallucinations;
• Urinary system: extremely seldom – aseptic cystitis;
• Another: a hyperuricemia, a medicinal hyperthermia or a nephropathy owing to the increased formation of uric acid (as result of bystry disintegration of cells), a secondary amenorrhea, disturbance of a menstrual cycle, a secondary malignancy, an azoospermism.

Symptoms of overdose are the ataxy, a hyperexcitability, a reversible pancytopenia, repeated epileptoidny attacks like grandee маль (grand mal). There is no specific antidote.

For the purpose of therapy it is necessary to wash out immediately a stomach, to watch work and to support the vital functions of an organism, to carefully control blood tests and to hold the general supporting events, including hemotransfusion or its components (according to indications). Carrying out dialysis is not effective.

Special instructions

Leukeranum – cytotoxic means which is recommended to be applied only under control of the specialist having experience of use of similar drugs.

Taking the pill Leukeranum it is necessary to implement all recommendations about use of cytotoxic drugs. When the outside cover of tablets is not damaged, their contact with skin is harmless therefore it is forbidden to split up tablets.

As hlorambutsit it is capable it is irreversible to oppress functions of marrow, during therapy follows systematically (at least 2-3 weekly) to do the general blood test with calculation of uniform elements of peripheral blood.

In therapeutic doses drug oppresses development of lymphocytes and to a lesser extent exerts impact on hemoglobin level, and also on quantity of thrombocytes and neutrophils.

The first signs of decrease in quantity of neutrophils are not an indicator for the termination of reception of Leukeranum, but it is necessary to remember that the quantity of neutrophils can decrease for 10 days and more after reception of the last dose of drug.

After end of a course of radiation therapy or treatment by the cytostatic drugs Leukeranum it is admissible to accept not earlier than ^11/2-2 months later provided that there are no signs of the expressed leukopenia, anemia and thrombocytopenia.

Because of the increased risk of development of spasms throughout all course of treatment under careful medical control there have to be following groups of patients: receiving high-dose pulse therapy Leukeranum, children with a nephritic syndrome and patients with convulsive attacks in the anamnesis.

Careful monitoring is required to patients with disturbances of secretory function of kidneys as owing to an azotemia at them more expressed miyelosupressiya can develop.

In case of increase in blood serum of concentration of uric acid it is necessary to apply the means alkalinizing urine. Development of a nephropathy can be prevented consumption of liquid in required quantities and/or purpose of Allopyrinolum as necessary.

At heavy abnormal liver functions patients are recommended to appoint Leukeranum in smaller doses.

As use of the alkylating means is accompanied by essential increase in risk of development of an acute leukosis, it is necessary to compare potential therapeutic effect of this drug with probability of developing of an acute leukosis owing to reception of a hlorambutsil.

Patients of reproductive age for protection at sexual contacts need to use reliable ways of contraception.

Medicinal interaction

• The medicines oppressing a hemopoiesis: can strengthen a miyelotoksichnost;
• Antigouty drugs: it is necessary to adjust doses as hlorambutsit can increase concentration in blood of uric acid;
• Tricyclic antidepressants, monoamine oxidase inhibitors, Maprotilinum, haloperidol, thioxanthenes, fenotiazina: can lower a threshold of convulsive activity owing to what the probability of convulsive attacks increases;
• The substances which are intensively contacting proteins of plasma: as a result of the competition at the level of communication with protein strengthen toxic action of a hlorambutsil;
• The inactivated virus vaccines: development of antibodies in response to vaccination decreases;
• Live virus vaccines: process of replication of a vaccinal virus is intensified, its side/adverse effects amplify and/or development of antibodies decreases.

Terms and storage conditions

To store in the place unavailable to children, at a temperature from 2 to 8 °C.

Period of validity – 3 years.