NAME OF DRUG
busulfan

Cytotoxic Agent- vesicant 
Alkylating Agent

ALTERNATE NAMES

BUSULFEX

INDICATIONS

• used in combination with cyclophosphamide as a conditioning regimen prior to allogenic hematopoietic stem cell transplantation

PHARMACOLOGY

• busulfan interferes with DNA replication and transcription of RNA, resulting in disruption of nucleic acid function.
• exhibits little immunosuppressive activity
• the serum half-life after IV administration is reported to be 3 hours
• busulfan is rapidly eliminated from the plasma and is extensively metabolised in the liver by glutathione conjugation and oxidation
• approximately 10-50% of a dose is excreted as metabolites in the urine within 24 hours

RECONSTITUTION AND STABILITY

• all cytotoxic agents are prepared in pharmacy and will be sent to the ward with a label indicating storage conditions and the expiry date. All cytotoxic waste including bags, sets, tubing, gloves, etc. must be properly disposed of in the cytotoxic waste containers on the nursing unit.
• diluted solutions in D5W or NS stable x 8 hours at room temperature inclusive of administration time; diluted solutions in NS stable x 12 hours in refrigerator inclusive of administration time

COMPATIBILITY

• compatible with NS, D5W
• incompatible with other drugs

ROUTES OF ADMINISTRATION

CENTRAL ROUTE

• IV infusion
  • dilute to 0.5mg/mL final concentration
  • administer 0.8mg/kg dose over 2 hours
  • administer 3.2mg/kg dose over 3 hours
  • flush tubing after administration to ensure all drug infused

VH & HSC ADMINISTRATION POLICY

A Parenteral Chemotherapy/Immunotherapy pre-printed order form (PPO # 45) must be used for prescribing if this cytotoxic agent
is not already on an existing PPO.

G - Cytotoxic Agents - see Drug Table G for specific administration guidelines.
H - The IV infusion rate must be controlled by an automated infusion control device.

DOSAGE

• 0.8 mg/kg IV Q6H X 4 consecutive days for a total of 16 doses
• 3.2 mg/kg IV daily X4 consecutive days for a total of 4 doses

POTENTIAL HAZARDS OF PARENTERAL ADMINISTRATION

• nausea, mucositis, vomiting, anorexia, diarrhea, abdominal pain, insomnia, anxiety, fever, headache, rash
• extravasation may lead to tissue necrosis (see appendix VII for extravasation protocol; follow procedures for carmustine)

IMPORTANT IMPLICATIONS

• major adverse effect is hematologic toxicity which is usually dose related and reversible after discontinuation of the drug
• profound myelosuppression in 100% of patients at the recommended dose and schedule; includes granulocytopenia, thrombocytopenia, anemia or a combined loss of formed elements of the blood.
• Seizure prophylaxis with phenytoin is recommended during busulfan administration and 24 hours after completion of the last dose
• Itraconazole decreases busulfan clearance by up to 25% and may produce higher AUC in some patients, thus, use an alternative agent if possible
• Premedicate with antiemetics to prevent nausea and vomiting
• Hyperbilirubinemia and hepatic veno-occlusive disease has occurred using the preconditioning regimen
• Fatal pulmonary effects (busulfan lung) have been reported in patients receiving long-term busulfan therapy, with onset of symptoms at an average of 4 years following initiation of therapy
• Mild or moderate tachycardia may occur as well as mild vasodilation manifested as flushing and hot flashes
• adverse nervous system effects include dizziness, blurred vision, loss of consciousness, myclonic and generalized tonic clonic (grand mal) seizures
• hyperuricemia may occur; in some patients uric acid nephropathy, renal stones and acute renal failure may result; minimze these effects with adequate hydration, alkinization of the urine and/or using xanthine oxidase inhibitor
• mild to moderate increase in serum creatinine concentration may occur
• Use of filters other than the specific type included with this drug is not recommended.

VGH Site only:
Notify security -84 immediately upon accidental spillage.
DO NOT ATTEMPT CLEAN-UP

Rev. May 2006