BUSULFAN INJECTION Dosage and Administration

2.1 Initial Dosing Information

• Administer Busulfan Injection in combination with cyclophosphamide as a conditioning regimen prior to bone marrow or peripheral blood progenitor cell replacement. For patients weighing more than 12 kg, the recommended doses are:
  • Busulfan Injection 0.8 mg per kg (ideal body weight or actual body weight, whichever is lower) intravenously via a central venous catheter as a two-hour infusion every six hours for four consecutive days for a total of 16 doses (Days -7, -6, -5 and -4).
  • Cyclophosphamide 60 mg per kg intravenously as a one-hour infusion on each of two days beginning no sooner than six hours following the 16th dose of Busulfan Injection (Days -3 and -2).
  • Administer hematopoietic progenitor cells on Day 0.
• Premedicate patients with anticonvulsants (e.g., benzodiazepines, phenytoin, valproic acid or levetiracetam) to prevent seizures reported with the use of high dose Busulfan Injection. Administer anticonvulsants 12 hours prior to Busulfan Injection to 24 hours after the last dose of Busulfan Injection [see Warnings and Precautions (5.2)].
• Administer antiemetics prior to the first dose of Busulfan Injection and continue on a fixed schedule through Busulfan Injection administration.
• Busulfan Injection clearance is best predicted when the Busulfan Injection dose is administered based on adjusted ideal body weight. Dosing Busulfan Injection based on actual body weight, ideal body weight or other factors can produce significant differences in Busulfan Injection clearance among lean, normal and obese patients.
  • Calculate ideal body weight (IBW) as follows (height in cm, and weight in kg):

    Men:	IBW (kg)=50+0.91× (height in cm -152)
    Women:	IBW (kg)=45+0.91× (height in cm -152)

  • For obese or severely obese patients, base Busulfan Injection dosing on adjusted ideal body weight (AIBW):

     

    AIBW= IBW +0.25× (actual weight -IBW).

2.2 Preparation and Administration Precautions

Busulfan Injection is incompatible with polycarbonate. Do not use any infusion components (syringes, filter needles, intravenous tubing, etc.) containing polycarbonate with Busulfan Injection.

Use an administration set with minimal residual hold-up volume (2 mL to 5 mL) for product administration.

Busulfan Injection is a cytotoxic drug. Follow applicable special handling and disposal procedures. Skin reactions may occur with accidental exposure. Use gloves when preparing Busulfan Injection. If Busulfan Injection or diluted Busulfan Injection solution contacts the skin or mucosa, wash the skin or mucosa thoroughly with water.

Visually inspect parenteral drug products for particulate matter and discoloration prior to administration whenever the solution and container permit. Do not use if particulate matter is seen in the Busulfan Injection vial.

2.3 Preparation for Intravenous Administration

Busulfan Injection must be diluted prior to intravenous infusion with either 0.9% Sodium Chloride Injection, USP (normal saline) or 5% Dextrose Injection, USP (D5W). The diluent quantity should be 10 times the volume of Busulfan Injection, so that the final concentration of busulfan is approximately 0.5 mg per mL. Calculation of the dose for a 70 kg patient would be performed as follows:

To prepare the final solution for infusion, add 9.3 mL of Busulfan Injection to 93 mL of diluent (normal saline or D5W) as calculated below:

All transfer procedures require strict adherence to aseptic techniques, preferably employing a vertical laminar flow safety hood while wearing gloves and protective clothing.

Always add the Busulfan Injection to the diluent, not the diluent to the Busulfan Injection. Mix thoroughly by inverting several times. Discard unused portion.

Infusion pumps should be used to administer the diluted Busulfan Injection solution. Set the flow rate of the pump to deliver the entire prescribed Busulfan Injection dose over two hours. Prior to and following each infusion, flush the indwelling catheter line with approximately 5 mL of 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP. DO NOT infuse concomitantly with another intravenous solution of unknown compatibility. WARNING: RAPID INFUSION OF BUSULFAN INJECTION HAS NOT BEEN TESTED AND IS NOT RECOMMENDED.