Khlorambutsil
When ATH:
L01AA02
Characteristic
Aromatic derivatives from the group of nitrogen-containing mustard, bifunctional alkylating-type, tsiklonespetsificheskogo action. Hydrolysis in water. White or white with slightly pink or creamy white crystalline powder. Practically insoluble in water, easily soluble in alcohol.
Pharmacological action
Antitumor, alkylating, cytostatic, immunosuppressive.
Application
Limfogranulematoz, non-Hodgkin's lymphoma (lymph- and reticulosarcoma), chronic lymphocytic leukemia, volosatokletochnыy leukemia, multiple myeloma, Waldenstrom's macroglobulinemia, polycythemia vera, Letterer's disease - Gray, ovarian cancer, eggs, Breast, horionepitelioma uterus, nephrotic syndrome.
Contraindications
Hypersensitivity, incl. other alkylating agents, bone marrow hypoplasia (expressed leukopenia, thrombocytopenia), epilepsy, renal failure, severe liver.
Restrictions apply
Assessment of the risk-benefit ratio is needed in the appointment of the following cases: enable vetryanaya, herpes zoster and other systemic infections, suppression of bone marrow function, bone marrow infiltration of tumor cells, prior cytotoxic or radiation therapy (the interval should be 4-6 weeks), gout, urolithiasis disease, hyperuricemia, the liver and kidneys, head injury, convulsive disorders (incl. history), children and old age.
Pregnancy and breast-feeding
Contraindicated in pregnancy.
Category actions result in FDA - D. (There is evidence of the risk of adverse effects of drugs on the human fetus, obtained in research or practice, However, the potential benefits, associated with drugs in pregnant, may justify its use, in spite of the possible risk, if the drug is needed in life-threatening situations or severe disease, when safer agents should not be used or are ineffective.)
At the time of treatment should stop breastfeeding.
Side effects
From the digestive tract: gastrointestinal bleeding, thrush, nausea, vomiting, diarrhea, abnormal liver function (necrosis, cirrhosis), jaundice.
Cardio-vascular system and blood (hematopoiesis, hemostasis): myelodepression — leukopenia, thrombocytopenia, anemia, lymphopenia, Acute leukemia, bleeding and hemorrhage.
From the respiratory system: cough, breathlessness, fibrosis, interstitial pneumonia.
With the genitourinary system: painful, strangury, hematuria, hyperuricemia, aseptic cystitis, swelling, amenorrhea, azoospermia.
From the nervous system and sensory organs: tremor, muscle tremors, excitation, disturbance of consciousness, ataxia, peripheral neuropathy, vyalыe paralysis, hallucinations, partial and / or systemic seizures (neurotoxic effects).
For the skin: erythema multiforme, toxic epidermal necrosis, Syndrome Stevens - Johnson, rash, dermatitis and other skin allergic reactions.
Other: pain syndrome (backache, joints), the development of infections, fever, chills, secondary malignancy.
Cooperation
By increasing the concentration of uric acid, reduces the effect of drugs protivopodagricakih (allopurinola, colchicine, probenecid or sulfinpirazona) in the treatment of hyperuricemia and gout (last dose adjustment is necessary). Uricosuric agents increase the risk of nephropathy. In patients receiving tricyclic antidepressants, haloperidol, Maprotiline, MAO inhibitors (including furazolidone, procarbazine, selegiline), phenothiazines or thioxanthenes increases the risk of seizures (reduce the seizure threshold). Weakens the effectiveness of immunization inactivated vaccines; using vaccines, containing live viruses, enhances viral replication and side effects of vaccination. At simultaneous application with other immunosuppressants (azathioprine, glucocorticoids, kortykotropyn, cyclophosphamide, cyclosporine, cytarabine, and others.) increased risk of infections and secondary tumors. In an application with lovastatin (Heart transplantation) increased risk of rhabdomyolysis and acute renal failure. Other myelotoxicity drugs, Radiation therapy may potentiate the development myelodepression (neutropenia, thrombocytopenia). Compatible with other cytotoxic drugs in combination chemotherapy (methotrexate, ftoruracil), and prednisone.
Overdose
Symptoms: pancytopenia, CNS dysfunction (from inappropriate behavioral responses in the form of agitation to large epipripadkov), strengthening of other adverse symptoms.
Treatment: hospitalization, monitoring and maintenance of vital functions, gastric lavage, simptomaticheskaya therapy, the appointment of broad-spectrum antibiotics. Hemodialysis nyeeffyektivyen.
Dosing and Administration
Inside. Dose picked individually, corrected based on the clinical effect and, depending on the severity of haematological Actions.
If chlamydia - 0,2 mg / kg / day (for non-Hodgkin's lymphomas 0.1–0.2 mg/kg/day), single or divided doses, within 4-8 weeks; in chronic lymphocytic leukemia - 0,15 mg / kg / day (treatment should be continued, until the level of leukocytes reaches 10 109/l), further maintenance dose 0,1 mg/kg/day through 4 of the week.
When macroglobulinemia Waldenstrom 6–12 mg daily until leukopenia develops, then 2–8 mg daily.
When ovarian cancer - 0,2 mg/kg/day 4-6 weeks; maintenance dose 0,2 mg / kg / day 2-4 weeks with breaks of 2-6 weeks between each course.
When breast cancer - 0,2 mg/kg/day 4–6 weeks or 14–20 mg 4–6 weeks (in combination with prednisolone), or 5–7.5 mg/m2 /d (in combination with methotrexate, ftoruracilom, prednisolone).
Nephrotic syndrome 0,1–0.2 mg/kg/day once for 8–12 weeks.
The maximum recommended dose is 8.2–14 mg/kg, duration of treatment - 6-12 weeks.
Precautions
Use only under medical supervision, with experience of chemotherapy. Before the beginning, during and after treatment (no less 3 once a week) necessary to determine hemoglobin or hematocrit, the number of leukocytes (overall, differential), Platelet, IS aktivnosti, GOLD, LDH, Alkaline phosphatase, Uric acid.
With the development of toxic effects on the lungs or skin reactions expressed by the appearance of the drug should be discontinued. To prevent the development of irreversible myelosuppression is necessary to reduce the dose while reducing the number of white blood cells or platelets and to abolish the drug for more severe pancytopenia. When initially reduced level of white blood cells and platelets must be treated with low doses. After receiving a single high dose of the most low level of white blood cells and platelets available in 1-2 weeks of treatment, followed by recovery in 2-3 weeks; short-course mielodeprescia can not be celebrated (to 3 Sun).
In the event of thrombocytopenia advised extreme caution when performing invasive procedures, Regular inspection of places on / in the, skin and mucous membranes (for signs of bleeding), limit frequency troublesome and the rejection of the / m injection, control of blood in the urine, vomit, Kale. The patients must be carefully shave, manicure, brush your teeth, dentists use threads and toothpicks; should be the prevention of constipation, avoid falls and other injuries, as well as the intake of alcohol and acetylsalicylic acid, increase the risk of gastrointestinal bleeding.
Nausea and vomiting occur in single dose (inside in doses 20 mg and more), last less 24 h and become rarer with further treatment.
In children with nephrotic syndrome and patients, receiving large doses mode pulsterapii, high risk of generalized seizures. In order to prevent nephropathy, due to increased production of uric acid (most often it occurs in the initial period of treatment), must be sufficient liquid intake, the subsequent increased diuresis, use of allopurinol (in some cases) and the use of funds, causing urine alkalinization. It is important not to take more or less of the drug; if the reception has been missed, dose not filled, and the following is not doubled.
Should defer vaccination schedule (carried out not earlier than 3 Months, to 1 years after completion of the last cycle of chemotherapy) patient and other family members, residing with him (should abandon immunization oral polio vaccine). Avoid contact with infectious patients, or use non-event for the prevention of (face mask, etc.).
During treatment should use appropriate contraceptive measures. In case of contact of the drug with skin or mucous membranes, rinse thoroughly with water. (mucosa) or soap and water (skin).
Cautions
When working with the drug should be guided by the medical staff safety rules, adopted for toxic substances and skin-irritating.
