Keys to Success

• Patient's age, disease, and source of transplant
• Actual weight of patient; weight used for dosing, if different
• Date and exact start and stop time of infusion, including time for administration of hold-up volume of administration tubing
• Dose number (eg, dose 1)
• Exact timing of blood draws
• Total dose of IV BUSULFEX given
• Target AUC (if known and needed by laboratory); see Full Prescribing Information for more information
• Contact information for lab to call physician or designee with testing results

Dosing

• Critical collection = peak (or C_max) at end of the 2-hour infusion
• Use the same clock to ensure accuracy. Exact timing is critical to success. Minutes do make a difference in accuracy
• Do not collect PK samples during the 2-hour infusion if draws are through CVC line (sample could be contaminated with drug)
• Begin the infusion at 8 am each day to avoid circadian rhythmicity effect¹
• At least 3 blood samples are required for a valid PK profile¹
• For sampling times, see adult and pediatric examples at the end of this page.

How to Collect and Store Samples Prior to Processing²

• 1–3 mL in green top (Na heparin) tubes
• Place sample immediately in wet ice
• Centrifuge the samples immediately, at 4c within 1 hour. Send to your local lab where all of the specimens will be processed and shipped to the lab performing the PK testing

Troubleshooting PK Results

• If results are consistently high or low, or are outside of expected parameters, verify that drug administration and sampling procedures are accurate
• If IV BUSULFEX concentration level at 2 hours is extremely high, the drug may have been infusing (or not flushed from CVC) at lab draw, contaminating sample
• If PK levels are consistently low, verify that entire dose is being infused. Also verify that time recorded is actual stop time of the IV BUSULFEX infusion and actual blood draw time

AUC Calculation²

For the actual formula to calculate AUC, see IV BUSULFEX Full Prescribing Information.

Dosing Adjustments

For dosing adjustments, please see adult or pediatric dosing on the Dosing page or Full Prescribing Information.

Example: Adult PK Sampling*

Example: Pediatric PK Sampling*^‡

1. Hassan M, Öberg G, Bekassy AN, et al. Pharmacokinetics of high dose busulphan in relation to age and chronopharmacology. Cancer Chemother Pharmacol. 1991;28:130-134.
2. Prescribing Information for IV BUSULFEX.

* Example for "dose one only"—calculate timing based on amount of drug, tubing length, and number of samples required.

^†Next dose should not begin until after the +6 hour PK draw is complete.

^‡The effectiveness of IV BUSULFEX in the treatment of CML has not been specifically studied in pediatric patients. However, the product labeling includes information about available dosage and safety information based on a small, open-label, uncontrolled pharmacokinetic study in pediatric patients (n=24). In that study, all patients experienced neutropenia (absolute neutrophil count <0.5 x 10⁹/L) and thrombocytopenia (platelet transfusions or platelet count <20,000/mm³), and 79% of patients experienced lymphopenia (absolute lymphocyte count <0.1 x 10⁹/L). Four patients died during the trial.

For additional information, please see Special Populations – Pediatric section of Full Prescribing Information.

The only FDA-approved agent for use in combination with cyclophosphamide as a conditioning regimen prior to allogeneic hematopoietic progenitor cell transplantation for chronic myelogenous leukemia (CML)

Important Safety Information At the recommended dosage, IV BUSULFEX^® (busulfan) produced profound myelosuppression in all patients (ie, severe granulocytopenia, thrombocytopenia, anemia, or a combination thereof). Frequent complete blood counts should be monitored during treatment and until recovery. Hepatic veno-occlusive disease was diagnosed in 5/61 patients and was fatal in 2/5 cases. Anticonvulsant prophylactic therapy should be administered prior to treatment. Caution should be exercised in patients with a history of seizure disorder or head trauma or who are receiving other potentially epileptogenic drugs. Bronchopulmonary dysplasia with pulmonary fibrosis is a rare but serious condition following chronic busulfan therapy. Women of childbearing potential should be advised to avoid becoming pregnant as busulfan may cause fetal harm.

The most common nonhematologic adverse events were nausea (92% mild or moderate, 7% severe), stomatitis (71% grade 1-2, 26% grade 3-4), and vomiting (95% mild or moderate), anorexia (64% mild or moderate, 21% severe), diarrhea (75% mild or moderate, 5% grade 3-4), insomnia (83% mild or moderate, 1% severe), and fever (78% mild or moderate, 3% life-threatening).

Please see Full Prescribing Information.