Busulphan
Mechanism :
Busulfan is a bifunctional alkylating agent. Binding to DNA is believed to play a role in its mode of action, and di-guanyl derivatives have been isolated, but interstrand crosslinking has not been conclusively demonstrated. The basis for the uniquely selective effect of busulfan on granulocytopoiesis is not fully understood.
Indication :
- Chronic granulocytic (myelocytic, myeloid) leukemia (CML)
- Bone marrow transplantation
Contraindications :
Busulfan should not be given if neutrophil or platelet counts are depressed. Busulfan should not be used in patients whose disease has demonstrated resistance to busulfan. Busulfan should not be given to patients with previous hypersensitivity reaction to the drug or any of its components.
Dosing :
Safety and efficacy in pediatric population has not been established.
CML:
Initial Dose: ≤12 kg: 1.1 mg/kg/dose.
Initial Dose: >12 kg: 0.8 mg/kg/dose.
Doses are administered every 6 hours as 2 hour IV infusions over 4 days for a total of 16 doses. Therapeutic drug monitoring and dose adjustment following the first dose is recommended. Adjust subsequent doses to achieve the desired target AUC (1125 uM/min):
Adjusted Dose (mg) = Actual Dose (mg) x Target AUC (uM/min)/Actual AUC (uM/min)
Bone Marrow Transplant conditioning:
≤12 kg: 1.1 mg/kg IV 6 hourly on day -9,-8,-7,-6.
>12 kg: 0.8 mg/kg IV 6 hourly on day -9,-8,-7,-6.
Adverse Effect :
Bone marrow failure leading to severe pancytopenia, nausea, stomatitis, anorexia, diarrhea, fever, insomnia, hypomagnesemia, headache, hyperglycemia, abdominal pain, asthenia, hypocalcemia, chills, dyspepsia, tachycardia, pain, constipation, hypertension, hypersensitivity, edema, thrombosis, dry mouth, vasodilation, epistaxis, back pain, chest pain, injection site inflammation.
Interaction :
Itraconazole decreases busulfan clearance.
Phenytoin increases the clearance of busulfan by 15% or more, possibly due to the induction of glutathione-S-transferase.
Because busulfan is eliminated from the body via conjugation with glutathione, use of acetaminophen prior to (<72 hours) or concurrent with busulfan may result in reduced busulfan clearance based upon the known property of acetaminophen to decrease glutathione levels in the
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 20-50 | Dose as in normal renal function |
| 10-20 | Dose as in normal renal function |
| <10 | Dose as in normal renal function |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Unknown dialysability. Dose as in normal renal function |
| HD | Dialysed. Dose as in normal renal function |
| HDF/High flux | Dialysed. Dose as in normal renal function |
| CAV/VVHD | Unknown dialysability. Dose as in normal renal function |
Hepatic Dose :
No dosage adjustments are recommended.