Busulfex (Page 5 of 5)

OVERDOSAGE

There is no known antidote to BUSULFEX other than hematopoietic progenitor cell transplantation. In the absence of hematopoietic progenitor cell transplantation, the recommended dosage for BUSULFEX would constitute an overdose of busulfan. The principal toxic effect is profound bone marrow hypoplasia/aplasia and pancytopenia, but the central nervous system, liver, lungs, and gastro intestinal tract may be affected. The hematologic status should be closely monitored and vigorous supportive measures instituted as medically indicated. Survival after a single 140 mg dose of Myleran® Tablets in an 18 kg, 4-year old child has been reported. Inadvertent administration of a greater than normal dose of oral busulfan (2.1 mg/kg; total dose of 23.3 mg/kg) occurred in a 2-year old child prior to a scheduled bone marrow transplant without sequelae. An acute dose of 2.4 g was fatal in a 10-year old boy. There is one report that busulfan is dialyzable, thus dialysis should be considered in the case of overdose. Busulfan is metabolized by conjugation with glutathione, thus administration of glutathione may be considered.

DOSAGE AND ADMINISTRATION

When BUSULFEX (busulfan) Injection is administered as a component of the BuCy conditioning regimen prior to bone marrow or peripheral blood progenitor cell replacement, the recommended doses are as follows:

Adults (BuCy2): The usual adult dose is 0.8 mg/kg of ideal body weight or actual body weight, whichever is lower, administered every six hours for four days (a total of 16 doses). For obese, or severely obese patients, BUSULFEX should be administered based on adjusted ideal body weight. Ideal body weight (IBW) should be calculated as follows (height in cm, and weight in kg): IBW (kg; men)= 50 + 0.91x (height in cm -152); IBW (kg; women)= 45 + 0.91x (height in cm — 152). Adjusted ideal body weight (AIBW) should be calculated as follows: AIBW= IBW + 0.25x (actual weight -IBW). Cyclophosphamide is given on each of two days as a one-hour infusion at a dose of 60 mg/kg beginning on BMT day –3, no sooner than six hours following the 16 th dose of BUSULFEX.

BUSULFEX clearance is best predicted when the BUSULFEX dose is administered based on adjusted ideal body weight. Dosing BUSULFEX based on actual body weight, ideal body weight or other factors can produce significant differences in BUSULFEX (busulfan) Injection clearance among lean, normal and obese patients.

BUSULFEX should be administered intravenously via a central venous catheter as a two-hour infusion every six hours for four consecutive days for a total of 16 doses. All patients should be premedicated with phenytoin as busulfan is known to cross the blood brain barrier and induce seizures. Phenytoin reduces busulfan plasma AUC by 15%. Use of other anticonvulsants may result in higher busulfan plasma AUCs, and an increased risk of VOD or seizures. In cases where other anticonvulsants must be used, plasma busulfan exposure should be monitored (See DRUG INTERACTIONS). Antiemetics should be administered prior to the first dose of BUSULFEX and continued on a fixed schedule through administration of BUSULFEX. Where available, pharmacokinetic monitoring may be considered to further optimize therapeutic targeting.

Pediatrics: The effectiveness of BUSULFEX in the treatment of CML has not been specifically studied in pediatric patients. For additional information see Special Populations -Pediatric section.

Preparation and Administration Precautions:

An administration set with minimal residual hold-up volume (2-5 cc) should be used for product administration.

As with other cytotoxic compounds, caution should be exercised in handling and preparing the solution of BUSULFEX. Skin reactions may occur with accidental exposure. The use of gloves is recommended. If BUSULFEX or diluted BUSULFEX solution contacts the skin or mucosa, wash the skin or mucosa thoroughly with water. BUSULFEX is a clear, colorless solution. Parenteral drug products should be visually inspected for particulate matter and discoloration prior to administration whenever the solution and container permit. If particulate matter is seen in the BUSULFEX ampoule the drug should not be used.

Preparation for Intravenous Administration:

BUSULFEX must be diluted prior to use with either 0.9% Sodium Chloride Injection, USP (normal saline) or 5% Dextrose Injection, USP (D5 W). The diluent quantity should be 10 times the volume of BUSULFEX, so that the final concentration of busulfan is approximately 0.5 mg/mL. Calculation of the dose for a 70 kg patient, would be performed as follows:

(70kg patient) x (0.8 mg/kg) ÷ (6 mg/mL) = 9.3 mL BUSULFEX (56 mg total dose).

To prepare the final solution for infusion, add 9.3 mL of BUSULFEX to 93 mL of diluent (normal saline or D5 W) as calculated below:

(9.3 mL BUSULFEX)x(10)=93 mL of either diluent plus the 9.3 mL of BUSULFEX to yield a final concentration of busulfan of 0.54 mg/mL (9.3 mL x 6 mg/mL ÷ 102.3 mL = 0.54 mg/mL).

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

DO NOT put the BUSULFEX into an intravenous bag or large-volume syringe that does not contain normal saline or D5 W. Always add the BUSULFEX to the diluent, not the diluent to the BUSULFEX. Mix thoroughly by inverting several times. DO NOT USE POLYCARBONATE SYRINGES OR POLYCARBONATE FILTER NEEDLES WITH BUSULFEX.

Infusion pumps should be used to administer the diluted BUSULFEX solution. Set the flow rate of the pump to deliver the entire prescribed BUSULFEX dose over two hours. Prior to and following each infusion, flush the indwelling catheter line with approximately 5mL 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 BUSULFEX HAS NOT BEEN TESTED AND IS NOT RECOMMENDED.

STABILITY

Unopened vials of BUSULFEX are stable until the date indicated on the package when stored under refrigeration at 2°-8°C (36°-46°F).

BUSULFEX diluted in 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP is stable at room temperature (25°C) for up to 8 hours but the infusion must be completed within that time. BUSULFEX diluted in 0.9% Sodium Chloride Injection, USP is stable at refrigerated conditions (2°-8°C) for up to 12 hours but the infusion must be completed within that time.

HOW SUPPLIED

BUSULFEX is supplied as a sterile solution in 10 mL single-use clear glass vials each containing 60 mg of busulfan at a concentration of 6 mg/mL for intravenous use.

NDC 67286-0054-2 10mL (6mg/mL) in packages of eight vials.

Unopened vials of BUSULFEX must be stored under refrigerated conditions between 2°-8°C (36°-46°F).

HANDLING AND DISPOSAL

Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published.1,2,3,4,5,6 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.

Marketed by:

PDL BioPharma, Inc.

Redwood City, CA 94063

Manufactured by:

Ben Venue Labs, Inc.

Bedford OH 44146

United States Patent numbers are 5,430,057 and 5,559,148. Canadian Patent number is CA2171738. European Union Patent number is EP 0 725 637 B1.

Part No. 131401

Rev Date: April 2007

References

  1. Recommendations for the safe handling of parenteral antineoplastic drugs. Washington , DC: Division of Safety, National Institutes of Health; 1983. US Department of Health and Human Services, Public Health Service publication NIH 83-2621.
  2. AMA Council on Scientific Affairs. Guidelines for handling parenteral antineoplastics. JAMA 1985; 253:1590-1591.
  3. National Study Commission on Cytotoxic Exposure. Recommendations for handling cytotoxic agents. 1987. Available from Louis P. Jeffrey, Chairman, National Study Commission on Cytotoxic Exposure. Massachusetts College of Pharmacy and Allied Health Sciences, 179 Longhwood Avenue , Boston , MA 02115.
  4. Clinical Oncology Society of Australia. Guidelines and recommendations for safe handling of antineoplastic agents. Med J Australia 1983; 1:426-428.
  5. Jones RB, Frank R, Mass T. Safe handling of chemotherapeutic agents: a report from the Mount Sinai Medical Center. CA-A Cancer J for Clin 1983; 33:258-263.
  6. American Society of Hospital Pharmacists. ASHP technical assistance bulletin on handling cytotoxic and hazardous drugs. Am J Hosp Pharm 1990; 47:1033-1049.

For questions of medical nature call 1-866-437-7742 or 510-574-1444 (int’l)

BUSULFEX
busulfan injection
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:67286-0054
Route of Administration INTRAVENOUS DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
Busulfan (Busulfan) Busulfan 60 mg in 10 mL
Inactive Ingredients
Ingredient Name Strength
N,N-dimethylacetamide (DMA)
Polyethylene Glycol 400
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:67286-0054-2 8 AMPULE (8 AMPULE) in 1 PACKAGE contains a AMPULE
1 10 mL (10 MILLILITER) in 1 AMPULE This package is contained within the PACKAGE (67286-0054-2)
Labeler — ESP Pharma, Inc.

Revised: 05/2007 ESP Pharma, Inc.

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