Leykeran
Leukeran: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Drug interactions
- 10. Analogs
- 11. Terms and conditions of storage
- 12. Terms of dispensing from pharmacies
- 13. Reviews
- 14. Price in pharmacies
Latin name: Leukeran
ATX code: L01AA02
Active ingredient: Chlorambucil (Chlorambucil)
Producer: GlaxoSmithKline Trading (Glaxo Wellcome Operations), Germany
Description and photo update: 2018-27-07
Prices in pharmacies: from 3057 rubles.
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Leukeran is an antineoplastic drug; bifunctional alkylating compound.
Release form and composition
Dosage form Leukeran - coated tablets: biconvex, round, brown, engraved on one side "L", on the other - "GX EG3" (25 pcs. In dark glass bottles, 1 bottle in a cardboard box).
1 tablet contains:
- Active substance: chlorambucil - 2 mg;
- Auxiliary components: stearic acid, microcrystalline cellulose, anhydrous lactose, anhydrous colloidal silicon;
- Sheath: Opadry brown YS-1-16655A (titanium dioxide, hypromellose, macrogol, iron oxide red and yellow).
Pharmacological properties
Leukeran has antitumor and cytostatic effects.
Pharmacodynamics
Chlorambucil is an aromatic derivative of nitrogen mustard and exhibits the action characteristic of a bifunctional alkylating agent. The substance affects DNA replication and provokes cell apoptosis by accumulating the cytosolic protein p53 with further activation of the apoptosis promoter.
The cytotoxic effect of the active component of Leukeran is due to both chlorambucil itself and its main metabolite, phenylacetic acid mustard gas.
It has been proven that resistance to nitrogen mustards occurs due to disturbances in the transfer of these compounds and their derivatives associated with the action of various proteins that cause multiple resistance, disturbances in the kinetics of DNA cross-linking caused by these substances, changes in apoptosis processes and disturbances in DNA repair processes. Chlorambucil does not belong to the substrates of the multiple resistance protein BMP1 (ABCC1) and BMR2 (ABCC2).
Pharmacokinetics
Chlorambucil is well absorbed from the gastrointestinal tract by passive diffusion and for 15-30 minutes after oral administration it enters the systemic circulation. After a single dose of 10-200 mg chlorambucil inside, its bioavailability is 70-100%. The maximum concentration of the substance in plasma (492 ± 160 ng / ml) is recorded 0.25–2 hours after ingestion. The pharmacokinetic parameters of chlorambucil in plasma after oral administration of Leukeran in doses of 15–70 mg vary slightly depending on individual characteristics [2-fold variation in values in individual patients and 2–4-fold variation in AUC (area under the concentration-time pharmacokinetic curve) in most patients]. This is in line with the predicted rate and other parameters of the chlorambucil absorption process.
The rate of absorption of the active component of Leukeran decreases when it is taken after meals. Eating increases the average time to reach the maximum content of chlorambucil in the body by more than 100%, reduces the maximum concentration of this substance by more than 50% and reduces the average AUC by about 27%.
The volume of distribution of chlorambucil is approximately 0.14-0.24 L / kg. There is a covalent binding of the substance with erythrocytes and plasma proteins (mainly albumin), and the degree of binding reaches 98%.
Chlorambucil with a high degree of intensity is metabolized in the liver through beta-oxidation and monodichloroethylation, forming phenylacetic acid mustard (IPA) as the main metabolite characterized by alkylating activity. IPA and chlorambucil itself in vivo undergo destruction with the formation of mono- and dihydroxy derivatives. Chlorambucil also reacts with glutathione to form chlorambucil mono- and di-glutathione conjugates.
After oral administration of Leukeran at a dose of about 0.2 mg / kg in the plasma of some patients, IFC was detected already after 15 minutes, and its plasma level, adjusted in accordance with the average dose, was 306 ± 73 ng / ml and was recorded for 1– 3 hours.
In the terminal phase, the half-life is 1.3-1.5 hours for chlorambucil and approximately 1.8 hours for IFA. Chlorambucil and IPA are excreted through the kidneys to an insignificant extent: within 24 hours, less than 1% of the taken dose of each of these substances is excreted in the urine, and the rest of the dose is excreted mainly in the form of mono- and dihydroxy derivatives.
Indications for use
- Hodgkin's lymphoma (malignant granuloma, lymphogranulomatosis);
- Malignant lymphomas (lymphosarcoma inclusive);
- Waldenstrom's macroglobulinemia;
- Chronic lymphocytic leukemia.
Contraindications
Absolute:
- Pregnancy period;
- Lactation (breastfeeding);
- Hypersensitivity to any of the components.
Relative (Leukeran is used with caution due to the increased likelihood of side effects, after a comprehensive assessment of the risk / benefit ratio):
- Oppression of bone marrow hematopoiesis (severe anemia, thrombocytopenia and leukopenia);
- Chickenpox (current or recent illness);
- Shingles;
- Acute infectious pathologies of bacterial, viral and fungal etiology;
- Infiltration of bone marrow tumor cells;
- Urolithiasis disease;
- Diseases of the kidneys and liver, severe;
- History of gout, head trauma, epilepsy.
Instructions for the use of Leukeran: method and dosage
Leukeran tablets are taken orally, swallowing whole, they should not be chewed or divided into parts.
Mostly the drug is used as part of complex therapy, therefore, for the correct choice of the dosage regimen, it is necessary to study the special literature and annotations to the drugs used in combination with Leukeran.
The recommended dosage regimen of Leukeran, depending on the condition / disease:
- Hodgkin's lymphoma (monotherapy): 0.2 mg / kg body weight per day for 4-8 weeks;
- Non-Hodgkin's lymphomas (monotherapy): initial dose - 0.1-0.2 mg / kg of body weight per day for 4-8 weeks; further maintenance treatment is carried out with intermittent courses or at a lower daily dosage;
- Chronic lymphocytic leukemia: initial dose - 0.15 mg / kg of body weight per day until the total number of blood leukocytes decreases to 10,000 / μl; 4 weeks after the end of the first course, it is allowed to resume treatment at a maintenance dose of 0.1 mg / kg of body weight per day;
- Waldenstrom's macroglobulinemia (as the drug of choice): initial dose - 6-12 mg per day daily; after the development of leukopenia, one should switch to a maintenance dose of 2-8 mg per day daily for an indefinite period.
In children, Leukeran is used to treat non-Hodgkin's lymphomas and Hodgkin's disease using the same regimens as for adult patients.
In the case of lymphocytic infiltration or bone marrow hypoplasia, the daily dose of the drug should not exceed 0.1 mg / kg of body weight.
Side effects
- Hematopoietic system: very often - thrombocytopenia, leukopenia (reversible with timely discontinuation of the drug), lymphopenia, decreased hemoglobin content, neutropenia; extremely rarely - depression of bone marrow function (irreversible);
- Gastrointestinal tract: often - ulceration of the oral mucosa, nausea, vomiting, diarrhea; rarely - toxic-allergic hepatotoxic effect (cirrhosis or hepatonecrosis, jaundice, cholestasis);
- Respiratory system: extremely rarely - interstitial pneumonia, and in the case of prolonged use of the drug, interstitial pulmonary fibrosis may develop;
- Allergic responses: sometimes - skin rash; rarely - angioedema, urticarial rash; extremely rarely - Stevens-Johnson syndrome (malignant exudative erythema), Lyell's syndrome (toxic or acute epidermal necrolysis);
- Nervous system: often - convulsions with nephrotic syndrome in children; rarely - generalized and / or local convulsions in adults and children receiving chlorambucil daily at therapeutic doses, or with high-dose pulse therapy; extremely rarely - tremor, uncertainty when walking, muscle twitching, paresis, peripheral neuropathy, agitation, severe weakness, confusion, anxiety, hallucinations;
- Urinary system: extremely rare - aseptic cystitis;
- Others: hyperuricemia, drug hyperthermia or nephropathy due to increased production of uric acid (as a result of rapid cell decay), secondary amenorrhea, menstrual irregularities, secondary malignancy, azoospermia.
Overdose symptoms are ataxia, hyperexcitability, reversible pancytopenia, repeated epileptoid seizures of the grand mal type. There is no specific antidote.
For the purpose of therapy, you should immediately flush the stomach, observe work and maintain vital body functions, carefully monitor blood tests and carry out general supportive measures, including transfusion of blood or its components (if indicated). Dialysis is not effective.
Overdose
Signs of an acute overdose of Leukeran include ataxia, reversible pancytopenia, hyperexcitability, and repeated grand mal seizures. No specific antidote has been identified.
As a treatment, the stomach is immediately washed, the vital functions of the body are monitored and maintained, and blood tests are performed regularly and general supportive measures are taken, including transfusion of blood or its components as indicated. The effectiveness of dialysis in this case is minimal.
special instructions
Leukeran is a cytotoxic agent that is recommended to be used exclusively under the supervision of a specialist who has experience in using such drugs.
Taking Leukeran tablets, you must follow all recommendations for the use of cytotoxic drugs. When the outer shell of the tablets is not damaged, their contact with the skin is harmless, therefore it is forbidden to crush the tablets.
Since chlorambucil is capable of irreversibly inhibiting the function of the bone marrow, during therapy, a general blood test should be done systematically (at least 2-3 times a week) with counting of peripheral blood cells.
In therapeutic doses, the drug inhibits the production of lymphocytes and, to a lesser extent, affects the level of hemoglobin, as well as the number of platelets and neutrophils.
The first signs of a decrease in the number of neutrophils are not an indicator for stopping the administration of Leukeran, but it must be remembered that the number of neutrophils can decrease for 10 days or more after taking the last dose of the drug.
After completion of radiotherapy or treatment with cytostatic agents are acceptable Leykeran not earlier than after 1 1 / 2 2 months, provided that there are no signs of severe leucopenia, anemia and thrombocytopenia.
Due to the increased risk of seizures throughout the course of treatment, the following groups of patients should be under close medical supervision: those receiving high-dose pulse therapy with Leukeran, children with nephritic syndrome and patients with a history of seizures.
Careful monitoring is required in patients with impaired renal excretory function, since due to azotemia, they may develop more pronounced myelosuppression.
In case of an increase in the concentration of uric acid in the blood serum, urine alkalizing agents should be used. The development of nephropathy can be prevented by fluid intake in the required amounts and / or the appointment of allopurinol as needed.
According to the instructions, Leukeran should be prescribed in smaller doses for severe liver dysfunction.
Since the use of alkylating agents is associated with a significant increase in the risk of developing acute leukemia, the potential therapeutic effect of this drug should be compared with the likelihood of acute leukemia due to chlorambucil administration.
Patients of reproductive age need to use reliable methods of contraception for protection during sexual intercourse.
Drug interactions
- Medicines that inhibit hematopoiesis: may increase myelotoxicity;
- Anti-gout drugs: Dose adjustments are necessary because chlorambucil can increase the concentration of uric acid in the blood;
- Tricyclic antidepressants, monoamine oxidase inhibitors, maprotiline, haloperidol, thioxanthenes, phenothiazines: can lower the seizure threshold, which increases the likelihood of seizures;
- Substances that intensively bind to plasma proteins: as a result of competition at the level of protein binding, they increase the toxic effect of chlorambucil;
- Inactivated viral vaccines: decreased production of antibodies in response to vaccination;
- Live viral vaccines: the replication of the vaccine virus is intensified, its side / adverse effects are enhanced and / or antibody production is reduced.
Analogs
Leukeran's analogs are: Chlorambucil, Chlorbutin.
Terms and conditions of storage
Store out of the reach of children at a temperature of 2 to 8 ° C.
The shelf life is 3 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Leykeran
According to reviews, Leykeran is a highly effective drug, but it is quite difficult to find it on sale. Some patients have to order it in Germany on their own. It is also worth noting that the drug has a high cost, so its counterfeits are quite common. For Leukeran treatment to be successful, it is recommended that you purchase it only from trusted specialized points of sale.
Price for Leykeran in pharmacies
The average price for Leykeran is approximately 3202–3353 rubles (for a pack containing 25 tablets).
Leykeran: prices in online pharmacies
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Drug name Price Pharmacy |
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Leukeran 2 mg film-coated tablets 25 pcs. 3057 RUB Buy |
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
