Busulfan
When ATH:
L01AB01
Characteristic.
The white crystalline powder. Poorly soluble in water and alcohol.
Pharmacological action.
Antitumor, alkylating, cytostatic, immunosuppressive.
Application.
Chronic myelogenous leukemia, polycythemia vera, essential thrombocythemia, myelofibrosis, preparation for bone marrow transplantation.
Contraindications.
Hypersensitivity, bone marrow hypoplasia, Acute leukemia and podostryj, chronic lymphocytic leukemia, blastnыy crisis.
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, gout, urolithiasis disease, prior cytotoxic or radiation therapy, traumatic brain injury, convulsions (incl. history), childhood.
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: anorexia, gastrointestinal bleeding, stomatitis, dryness of the oral mucosa, diarrhea, nausea, vomiting, cholestatic jaundice, weight loss, abnormal liver function, dysplastic changes in the cells of the pancreas, liver.
From the nervous system and sensory organs: dizziness, weakness, fatigue, Cataract.
Cardio-vascular system and blood (hematopoiesis, hemostasis): edema of the lower extremities, gipotenziya, cardiac tamponade, endokardialinyi fibrosis, mielodeprescia (leukopenia, thrombocytopenia, anemia), bleeding and hemorrhage.
From the side of respiratory system: bronchopulmonary dysplasia, to the development of pulmonary fibrosis (cough, breathlessness).
With the genitourinary system: painful, strangury, hematuria, nephropathy, dysplastic changes in the cells of the bladder, amenorrhea, dysplasia cervical cells, inhibition of ovarian function, azoospermia, testicular atrophy, sterility.
For the skin: dermatomelasma (5–10%), erythema multiforme, alopecia, urticaria, "Allopurinolovaya rash", xerosis (to complete agidroza), при высоких дозах — фиброз с атрофией и некрозом кожи.
Metabolism: hyperuricemia, giperurikozurija, reduction in clearance 17 gidroksikortikosteroidov, syndrome, resembling adrenal insufficiency.
Other: pain syndrome (backache, by, joints); the development of infections; temperature rise, chills; gynecomastia; myasthenia gravis; dysplastic changes in the cells of the breast, lymph nodes, Thyroid.
Cooperation.
Weakens the effectiveness of immunization inactivated vaccines; using vaccines, containing live viruses, enhances viral replication and side effects of vaccination. Other myelotoxicity drugs, Radiation therapy may potentiate the neutropenia, thrombocytopenia. 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. Thioguanine increases the likelihood of liver nodular regenerative hyperplasia, portal hypertension, esophageal varices.
Overdose.
Symptoms: nausea, vomiting, dizziness, severe bone marrow depression, fever, bleeding.
Treatment: induction of vomiting, gastric lavage followed by activated carbon; hospitalization, monitoring vital functions; simptomaticheskaya therapy; if necessary - transfusion of blood components, the appointment of broad-spectrum antibiotics.
Dosing and Administration.
Inside (do not chew the tablets), single, at the same time of the day. Dose picked individually, corrected based on the clinical effect and the degree of suppression of bone marrow function.
In chronic myelogenous leukemia: взрослым из расчета 0,06 mg / kg / day (до снижения уровня лейкоцитов ниже 15·109/l), при резко выраженной спленомегалии и большом количестве лейкоцитов — 8–10 мг, при уменьшении количества лейкоцитов до 40·109/л−50·109/л доза не должна превышать 4 mg. The maximum daily dose - 10 mg; поддерживающая — 1–3 мг/сут, Treatment continued at least the duration of remission 3 Months. Treatment was resumed at the stage of remission, если ежемесячно определяется число лейкоцитов 50·109/l.
When myelofibrosis and essential thrombocythemia: 2–4 мг/сут (под контролем тромбоцитов — не ниже 500·109/л или лейкоцитов 5·109/l).
When polycythemia vera: 4–6 мг/сут в течение 4–6 нед.
Babies при хроническом миелолейкозе начальная доза — 0,06–0,12 мг/кг/сут или 1,8–4,6 мг/м2 /d. The dose is selected so, чтобы снизить число лейкоцитов и поддерживать их уровень около 20·109/l.
Precautions.
Use only under medical supervision, with experience of chemotherapy. Prior to and during treatment (at short intervals) you must determine the level of hemoglobin, or hematocrit, the number of leukocytes (overall, differential), Platelet, ALT activity, Alkaline phosphatase, bilirubin, Uric acid, continuous monitoring of renal function and light. If the following symptoms: chills, fever, cough or hoarseness, pain in the lower back or side, painful or difficult urination, bleeding or hemorrhage, black chair, blood in the urine or feces should immediately consult a doctor. Leukopenia develops from 10-15 days after initiation of therapy (before it is marked transient increase in the number of leukocytes), the lowest possible level observed at 11-30 days of treatment (may be reduced for 1 months after drug withdrawal), level leukocytes recovered over the next 12-20 weeks (when expressed myelodepression treatment should be discontinued until symptoms resolve gematotoksichnosti). When myelodepression (pantsitopenii) after the abolition of busulfan recovery of formed elements to the level of standards occurs within 1 Months - 2 years. If you experience nausea and vomiting should continue receiving busulfan, at the first sign of interstitial pulmonary fibrosis treatment should be discontinued. Bronchopulmonary dysplasia with pulmonary fibrosis development, accompanied by a decrease in lung function and vital elasticity of the lung tissue, may develop over 8 Months - 10 years (an average of 4 year) after treatment, during 6 months after diagnosis possible death. 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, to conduct dental procedures; 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. In order to prevent nephropathy, due to increased production of uric acid (It occurs most frequently in the initial stage of treatment), must be sufficient liquid intake, diuresis, use of allopurinol (in some cases) and the use of funds, causing urine alkalinization. In patients with increased seizure activity should be treated under the guise of anticonvulsants. If the reception was missed, dose not filled, and the following is not doubled. Should defer vaccination schedule (carried out not earlier than 3 Months before 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.). It should refrain from the use in pediatric practice, because the safety and efficacy of its use in children is not identified. During treatment should use appropriate contraceptive measures. In case of contact with skin or mucous membranes must be thorough washing with water (mucosa) or soap and water (skin).
