ALKERAN for Injection is indicated for the palliative treatment of patients
with multiple myeloma for whom oral therapy is not appropriate.
DOSAGE AND ADMINISTRATION
The usual IV dose is 16 mg/m². Dosage reduction of up to 50% should be
considered in patients with renal insufficiency (BUN ≥ 30 mg/dL) (see PRECAUTIONS:
General). The drug is administered as a single infusion over 15 to 20
minutes. Melphalan is administered at 2-week intervals for 4 doses, then, after
adequate recovery from toxicity, at 4-week intervals. Available evidence suggests
about one third to one half of the patients with multiple myeloma show a favorable
response to the drug. Experience with oral melphalan suggests that repeated
courses should be given since improvement may continue slowly over many months,
and the maximum benefit may be missed if treatment is abandoned prematurely.
Dose adjustment on the basis of blood cell counts at the nadir and day of treatment
should be considered.
Administration Precautions: As with other toxic compounds, caution should
be exercised in handling and preparing the solution of ALKERAN. Skin reactions
associated with accidental exposure may occur. The use of gloves is recommended.
If the solution of ALKERAN contacts the skin or mucosa, immediately wash the
skin or mucosa thoroughly with soap and water.
Procedures for proper handling and disposal of anticancer drugs should be considered.
Several guidelines on this subject have been published.1-8 There
is no general agreement that all of the procedures recommended in the guidelines
are necessary or appropriate.
Parenteral drug products should be visually inspected for particulate matter
and discoloration prior to administration whenever solution and container permit.
If either occurs, do not use this product.
Care should be taken to avoid possible extravasation of melphalan and in cases
of poor peripheral venous access, consideration should be given to use of a
central venous line (see WARNINGS).
Preparation for Administration/Stability
- ALKERAN for Injection must be reconstituted by rapidly injecting 10 mL of
the supplied diluent directly into the vial of lyophilized powder using a
sterile needle (20-gauge or larger needle diameter) and syringe. Immediately
shake vial vigorously until a clear solution is obtained. This provides a
5-mg/mL solution of melphalan. Rapid addition of the diluent followed by immediate
vigorous shaking is important for proper dissolution.
- Immediately dilute the dose to be administered in 0.9% Sodium Chloride
Injection, USP, to a concentration not greater than 0.45 mg/mL.
- Administer the diluted product over a minimum of 15 minutes.
- Complete administration within 60 minutes of reconstitution.
The time between reconstitution/dilution and administration of ALKERAN should
be kept to a minimum because reconstituted and diluted solutions of ALKERAN
are unstable. Over as short a time as 30 minutes, a citrate derivative of
melphalan has been detected in reconstituted material from the reaction of ALKERAN
with Sterile Diluent for ALKERAN. Upon further dilution with saline, nearly
1% label strength of melphalan hydrolyzes every 10 minutes.
A precipitate forms if the reconstituted solution is stored at 5° C. DO
NOT REFRIGERATE THE RECONSTITUTED PRODUCT.
ALKERAN for Injection is supplied in a carton containing one single-use clear
glass vial of freeze-dried melphalan hydrochloride equivalent to 50 mg melphalan
and one 10-mL clear glass vial of sterile diluent (NDC 59572-301-01).
Store at controlled room temperature 15° to 30° C (59° to 86°
F) and protect from light.
1. ONS Clinical Practice Committee. Cancer Chemotherapy Guidelines
and Recommendations for Practice. Pittsburgh, PA: Oncology Nursing Society;1999:32-41.
2. Recommendations for the safe handling of parenteral antineoplastic
drugs. Washington, DC: Division of Safety, Clinical Center Pharmacy Department
and Cancer Nursing Services, National Institutes of Health; 1992. US Dept of
Health and Human Services. Public Health Service publication NIH 92-2621.
3. AMA Council on Scientific Affairs. Guidelines for handling
parenteral antineoplastics. JAMA. 1985;253:1590-1591.
4. 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 Longwood Avenue, Boston, MA 02115.
5. Clinical Oncological Society of Australia. Guidelines and
recommendations for safe handling of antineoplastic agents. Med J Australia.
6. 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.
7. American Society of Hospital Pharmacists. ASHP technical
assistance bulletin on handling cytotoxic and hazardous drugs. Am J Hosp
8. Controlling Occupational Exposure to Hazardous Drugs. (OSHA
Work-Practice Guidelines.) Am J Health-Syst Pharm. 1996;53:1669-1685.
ALKERAN and Diluent manufactured by GlaxoSmithKline, Research
Triangle Park, NC 27709. Distributed by : Celgene Corporation, Summit, NJ 07901.
March 2008. FDA revision date: 6/14/2005