A drug used to treat chronic myelogenous leukemia (CML). It is also used with other medications to prepare CML patients for a stem cell transplant. It is also being studied in the treatment of other types of cancer . Busulfan binds to DNA in cells and may kill cancer cells. It is a type of renter.
Mechanism of action
Antineoplastic, bifunctional alkylating agent. It acts specifically during the S phase of the cell cycle. It reacts with nucleophilic atoms of the nucleic bases, forming inter and intra-chain bridges in the DNA double helix, causing important interferences in the transcription and DNA replication processes.
Comp .: Tto. Palliative of the chronic phase of chronic granulocytic leukemia . Polycythemia vera (get complete remission). Essential thrombocythemia and myelofibrosis . Conc. For infusion: – followed by cyclophosphamide as tto. of pre-transplantation conditioning of hematopoietic progenitor cells (TCPH) in ads., when the combination is considered to be the best available option. – followed by fludarabine as tto. of conditioning prior to TCPH in ads. candidates for a reduced intensity conditioning regimen. – followed by cyclophosphamide or melphalan as treatment. of conditioning prior to TCPH in pediatric patients.
Bifunctional alkylating agent with cytotoxic properties, which belongs to the group of alkylsulfonates. Busulfan, like other alkylating agents, is believed to enter the cell via active transport systems. Its general mechanism of action involves an intramolecular cyclization to form an ethylene oxide ion that can directly transfer or, through the formation of a carbonium ion, an alkyl group to a cellular component. In the DNA molecule, the main alkylation site is the 7-position of guanine; however, there is also alkylation of other bases, phosphate, and DNA-related proteins. These interactions occur in one or both DNA strands, as cross-linking, which determines the cytotoxic action, and in clinical terms, myelosuppression, since it interferes with the synthesis of RNA, DNA and proteins . Its action is not specific to the cell cycle; however, cells are more susceptible to alkylation in the final G1 and S phases of the cell cycle , and manifest blockage in the G2 phase. Busulfan interferes with mitosis and cell division in all rapidly growing tissues, although it also affects tissues with a low mitotic index, such as liver, kidney, and mature lymphocytes. Its only pharmacological action appears to be myelosuppression. In small doses it inhibits granulocytopoiesis and, to a lesser extent, thrombocytopoiesis ; has little effect on lymphocytes. With high doses it produces severe bone marrow depression. Due to its selective action, it is used in the control of chronic myeloid leukemia, where it produces symptomatic relief with a reduction in the size of the spleen and a general feeling of well-being. It does not induce true remission. Its therapeutic effect is appreciable after one or two weeks of treatment. It is rapidly and completely absorbed after oral administration. It undergoes rapid biotransformation in the liver, where methanesulfonic acid is formed, and is slowly eliminated in the urine.
Oral. Ads .: individualized dose. Administration in cycles or continuous. – Tto. palliative of the chronic phase of chronic granulocytic leukemia: Induction 0.06 mg / kg / day, max .: 4 mg / day in 1 single dose; increase dose only if response is not adequate after 3 weeks. Maintenance: 0.5-2 mg / day. – Polycythemia vera: 4-6 mg / day / 4-6 weeks. – Essential thrombocythemia and myelofibrosis: 2-4 mg / day. Discontinue if total leukocyte count <5 x 109 / l or platelets <500 x 109 / l. IV. – Combination with cyclophosphamide or melphalan: Ads .: 0.8 mg / kg, in perfus. 2 h IV every 6 h, 4 consecutive days, for a total of 16 doses, followed by 60 mg / kg / day of cyclophosphamide for 2 days. Children (0 to 17 years): recommended dose: <img width = ‘350’ height = ‘238’ src = > followed by 4 cycles of 50 mg / kg of cyclophosphamide or 140 mg / m2 of melphalan. It is administered in perfus. 2 h, every 6 h, 4 consecutive days, 16 doses, followed by cyclophosphamide or melphalan, before conventional transplantation. Do not start the treatment. cyclophosphamide or melphalan up to 24 h after the 16th dose of busulfan. – Combination with fludarabine: Ads .: fludarabine 30 mg / m2 / day (single dose) in infus. 1 h IV for 5 consecutive days or 40 mg / m2 for 4 consecutive days. Immediately after fludarabine, 3.2 mg / kg of busulfan will be infused. Single daily IV lasting 3 hours.
Contraindicated in cases of bone marrow depression, viral or bacterial infections, gout or hyperuricaemia, and hypersensitivity to busulfan, or the risk-benefit ratio should be carefully evaluated. It is contraindicated during pregnancy and lactation. The use of this drug should be restricted to patients in whom there is an indication to perform weekly blood tests or at more frequent intervals, because it can cause very severe bone marrow depression. Discontinue administration immediately if severe bone marrow depression or manifestations of pulmonary fibrosis occur . Increases the effects of other myelosuppressive agents and radiation therapy Therefore, under conditions of simultaneous administration, the dose should be reduced. Busulfan increases serum uric acid values .
Warnings and Cautions
IR, severe IH, children (<9 kg therapeutic monitoring), Fanconi anemia, history of seizures. Risk of sickness. Veno-occlusive liver disease, especially in those who have received radiotherapy, chemotherapy or previous transplantation of progenitor cells. Cases of acute respiratory distress syndrome have been reported. Risk of 2nd malignant tumor. Hepatic, renal, cardiac monitoring. Monitor complete blood counts. Risk of myelosuppression. Not recommended vaccine with live microorganisms. Chromosomal abnormalities have been reported. It can cause infertility. Use contraceptive method . It can produce menopausal symptoms and in preadolescents prevent the onset of puberty.
Caution in severe IH.
Caution. Periodic monitoring of kidney function.
See Prec. In addition: Metabolism reduced by: paracetamol. Risk of additive toxicity with other myelosuppressive agents. With thioguanine, it causes regenerative nodular hyperplasia , portal hypertension , and esophageal varices. At high doses of busulfan with phenytoin, it causes a decrease in the myeloablative effect.
Contraindicated. In preclinical studies it has caused embryo-fetal death and malformations.
To avoid. Contraindicated, it is unknown whether it is excreted in human milk.
Rhinitis, pharyngitis, viral infection, CMV reactivation, EBV reactivation, bacterial infection, invasive fungal infection; lung infection; neutropenia, thrombocytopenia, anemia, pancytopenia, febrile neutropenia; allergic reaction; anorexia, hyperglycemia, hypocalcemia, hypokalaemia, hypomagnesemia, hypophosphatemia, hypoalbuminemia, electrolyte disorder; anxiety, depression, insomnia; headache, vertigo; tachycardia; HT, hypotension, vasodilation, thrombosis; dyspnea, epistaxis, cough, hiccups; nausea, stomatitis, vomiting, anorexia, diarrhea, constipation, dyspepsia, anal discomfort; hepatomegaly, jaundice, enf. hepatic veno-occlusive; rash, pruritus, alopecia; back pain, myalgia, arthralgia; dysuria, oliguria, hemorrhagic cystitis; asthenia, chills, fever, chest pain, edema, general edema, pain, pain or inflammation at the injection site, mucositis; increased transaminases, increased bilirubin, increased GGT, increased alkaline phosphatase, weight gain, abnormal sound when breathing, elevated creatinine.