Busulfan is a cytostatic drug with an alkylating effect. Derivative of methanesulfonic acid.
Content
Pharmacological action
It has a cytostatic effect on myeloid cells. At relatively low doses, granulocytopoiesis selectively inhibits.
Pharmacokinetics
After ingestion, it is completely absorbed from the digestive tract. Rapidly metabolized in the liver. T1 / 2 is about 2.5 hours. It is excreted by the kidneys, almost completely in the form of metabolites.
Indications
Chronic myeloid leukemia, erythremia / true polycythemia. Busulfan is used in some cases of essential thrombocythemia and myelofibrosis.
In high doses, busulfan is used as part of the conditioning regimen for bone marrow transplantation - in the mode of mini - transplantation - in combination with fludarabine phosphate , in the mode of full-scale transplantation - with cyclophosphamide or, less commonly, other cytostatics.
Dosage
Installed individually, depending on the indications and stage of the disease, the state of the hematopoietic system, anti-tumor therapy regimen.
Side effect
From the hemopoietic system: myelodepression (thrombocytopenia, leukopenia, less often - anemia); in some cases, irreversible bone marrow aplasia. From the respiratory system: in some cases - interstitial pulmonary fibrosis. From the digestive system: nausea, vomiting, diarrhea, stomatitis, loss of appetite; in some cases (with prolonged use as part of combination therapy) - hepatotoxic effect, the development of varicose veins of the esophagus, hepatic vein thrombosis. From the reproductive system: inhibition of ovarian function and amenorrhea (in patients in the period before menopause); in some cases, azoospermia and testicular atrophy in men. From the urinary system: nephropathy due to hyperuricemia. Other: in some cases - the occurrence of chromosomal aberrations, cardiac tamponade in patients with thalassemia, cataract (with prolonged use); very rarely - weakness.
Contraindications
Inhibition of bone marrow function, pregnancy, hypersensitivity to busulfan.
Pregnancy and lactation
Busulfan is contraindicated in pregnancy. If necessary, use during lactation should stop breastfeeding. Women of childbearing age should use reliable methods of contraception while taking busulfan.
Special instructions
It is not recommended for use in patients with chickenpox (including recently transferred or after contact with patients), herpes zoster, other acute infectious diseases, gout or nephrolithiasis (including a history). Use with caution in cases with a history of convulsive seizures, traumatic brain injury; during treatment with drugs that increase the risk of seizures; in patients previously treated with cytotoxic antitumor agents or radiation therapy. While taking busulfan, patients and their family members should not be vaccinated. Close monitoring of the picture of peripheral blood should be carried out 1 time per week during the induction of remission and at least 1 time in 4 weeks - with maintenance therapy. The use of busulfan should be discontinued in cases of a decrease in the number of leukocytes to 2000-2500 / ΞΌl or a decrease in the number of platelets to 100,000 / ΞΌl. Against the background of the use of busulfan, it is necessary to periodically monitor the activity of hepatic transaminases and alkaline phosphatase, as well as the level of bilirubin in blood plasma. In patients with hyperuricemia and / or hyperuricosuria, correction of these disorders is required before starting treatment with busulfan. In children, busulfan is used in very rare cases for strict indications. In experimental studies, the carcinogenic and mutagenic effects of busulfan have been established. Busulfan in the form of tablets is included in the List of Vital and Essential Drugs.
Drug Interactions
With simultaneous use with other drugs that have myelosuppressive properties, it is possible to increase the toxic effect of busulfan on hematopoiesis. With the simultaneous use of uricosuric antigout agents, an increased risk of developing nephropathy associated with increased formation of uric acid is possible, therefore, allopurinol is the preferred drug to prevent or eliminate hyperuricemia associated with busulfan therapy. With prolonged (more than 6 months) combined use of busulfan with thioguanine, cases of the development of varicose veins of the esophagus in combination with changes in laboratory parameters of liver function are described.