It is an alkylating agent from the group of methanesulfonates, which is not related to nitrogen mustard. Mechanism of action: it is an electrophilic agent (multifunctional alkylating agent) that reacts with the nucleic bases of DNA to form interchain and intrachain bridges on it, destabilizing the DNA double helix and causing interference in the transcription and replication processes of cellular DNA . Pharmacokinetic absorption is highly variable (20-99%), but generally rapid and complete, with a significant first-pass effect. It reaches the maximum serum concentration between 2 and 4 h after administration. Its binding to plasma proteins is 32% and to red blood cells is 47%. It has a large volume of distribution. It crosses the placental barrier and the blood-brain barrier. Metabolism is largely hepatic through the cytochrome P450 system (it can increase with multiple doses). Glutathione conjugation occurs, followed by oxidation. It is mainly eliminated in the urine (10-50% as metabolites) within the first 24 h (2% of the drug unchanged). The elimination half-life is 2-3 h.
Chronic myeloid [leukemia]. Other uses: polycythemia vera, essential thrombocythemia, and myelofibrosis. Conditioning regimens for bone marrow transplantation.
Known hypersensitivity to busulfan. Patients with bone marrow depression , gouty disease, severe kidney dysfunction, urate [kidney stones], and recent viral infections such as chickenpox or shingles.
Women of childbearing age will be advised to avoid pregnancy during treatment. Amenorrhea and azoospermia can occur. LM: must be completed before starting treatment. Carcinogenicity: risk group 1. Busulfan should be discontinued if pulmonary toxicity develops. It should not be given at the same time or immediately after the patient is undergoing radiation therapy. Busulfan is ineffective once blast transformation has occurred. If anesthesia is required in patients with possible pulmonary toxicity, the inspired oxygen concentration should be kept as low as possible in terms of safety, as well as paying special attention to respiratory control during the postoperative period. If patients have hyperuricaemia and / or hyperuricosuria, this should be corrected before starting treatment. Likewise, both hyperuricemia and the risk of neuropathy should be prevented. Particular attention will be paid to monitoring the blood count throughout treatment to avoid as much as possible excessive myelosuppression and the risk of irreversible bone marrow aplasia.
Common: leukopenia and thrombocytopenia. They are used as indicators of the effectiveness of the medication. Hyperpigmentation of the skin (very similar to Addison’s disease and usually responds with cessation of treatment); irregularity in the menstrual cycle. Occasional: confusion, diarrhea , dizziness, anorexia, nausea, vomiting, [asthenia], arthralgia, lower limb edema, chills and sore throat. Rare: type 1 anaphylactoid reaction, aplasia anemia, endocardial fibrosis, cholestatic hepatitis with jaundice and pulmonary dysplasia with fibrosis. Pulmonary toxicity is rare in patients who receive a dose lower than 500 mg, although higher doses than this, and very fundamentally above 3 g and previous chest radiation, increases the probability of this toxicity. Subject to intensive surveillance yes
Inducers of CYP3A4 can decrease the levels and effects of acrolein (the active metabolite of cyclophosphamide): aminoglutethimide, carbamazepine, nevirapine, nafcillin, phenobarbital, phenytoin, and rifampin. CYP3A4 inhibitors (itraconazole, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazocodone, nicardipine, propofol, protease inhibitors, quinidine, verapamil): may increase the levels and effects of busulfan. Metronidazole can increase busulfan plasma levels. The pulmonary toxicity of other cytotoxic agents can be additive. Avoid ethanol, as it increases gastrointestinal irritation. Avoid the use of St. John’s wort, as it can decrease busulfan levels. May increase uric acid levels, therefore, the dosage of allopurinol, colchicine or probenecid should be adjusted. Administration of phenytoin usually results in a decrease in the myeloablative effect of busulfan. Concomitant systemic administration of itraconazole or [acetaminophen] with busulfan increases the levels of the latter.
In induction: 2-3 mg / m2 or 0.065 mg to 0.1 mg / kg / day until the leukocyte count falls below 15,000 cells / mm3. Maintenance: 2 mg, 2 times a week at 4 mg / day. Pediatric dose: 0.06-0.12 mg / kg / day. The specialist must make the modifications to the dose of the drug in relation to liver and kidney toxicity. Treatment of Acute Overdose and Serious Adverse Effects The main toxic effect of a chronic overdose is bone marrow depression and pancytopenia. There is no antidote. In some cases, toxic concentrations have been reduced with hemofiltration and hemodialysis methods. Gastric lavage and activated charcoal may be helpful. If high doses of busulfan are prescribed, prophylactic anticonvulsant therapy should be administered simultaneously, a benzodiazepine is preferred over a phenytoin. Appropriate supportive treatment should be administered while haematological toxicities are manifested. Basic information for the patient to avoid immunizations, unless the doctor approves them. Maintain adequate hydration (not less than 3 L / day) to preserve adequate kidney function and help the excretion of uric acid. Avoid contact with people who have an active infection. Patients should be instructed to notify the physician if they develop signs of fever, unusual bleeding, pain, or signs suggestive of anemia due to the possibility of infection or bleeding complications secondary to myelosuppression. From this derives the importance of carrying out periodic hematological controls. It should also be informed of the infrequent, but fatal pulmonary complication (diffuse fibrosis), for this reason you should be instructed to report the presence of any of these symptoms: dyspnea, persistent cough or congestion. Gonadal suppression (amenorrhea and azoospermia) can occur. It is recommended to avoid the use of busulfan during the first trimester of pregnancy, due to the mutagenic and teratogenic potential. Its use is not recommended during the lactation period.
Exclusive use of hospitals (Special Program Medication) Regulation of prescription medication for Special Cancer Program.