ALKERAN (melphalan) Tablets are indicated for the palliative treatment of multiple myeloma and for the palliation of non-resectable epithelial carcinoma of the ovary.
DOSAGE AND ADMINISTRATION
Multiple Myeloma: The usual oral dose is 6 mg (3 tablets) daily. The
entire daily dose may be given at one time. The dose is adjusted, as required,
on the basis of blood counts done at approximately weekly intervals. After 2
to 3 weeks of treatment, the drug should be discontinued for up to 4 weeks,
during which time the blood count should be followed carefully. When the white
blood cell and platelet counts are rising, a maintenance dose of 2 mg daily
may be instituted. Because of the patient-to-patient variation in melphalan
plasma levels following oral administration of the drug, several investigators
have recommended that the dosage of ALKERAN (melphalan) be cautiously escalated until some
myelosuppression is observed in order to assure that potentially therapeutic
levels of the drug have been reached.
Other dosage regimens have been used by various investigators. Osserman and
Takatsuki have used an initial course of 10 mg/day for 7 to 10 days. They report
that maximal suppression of the leukocyte and platelet counts occurs within
3 to 5 weeks and recovery within 4 to 8 weeks. Continuous maintenance therapy
with 2 mg/day is instituted when the white blood cell count is greater than
4,000 cells/mcL and the platelet count is greater than 100,000 cells/mcL. Dosage
is adjusted to between 1 and 3 mg/day depending upon the hematological response.
It is desirable to try to maintain a significant degree of bone marrow depression
so as to keep the leukocyte count in the range of 3,000 to 3,500 cells/mcL.
Hoogstraten et al have started treatment with 0.15 mg/kg/day for 7 days. This
is followed by a rest period of at least 14 days, but it may be as long as 5
to 6 weeks. Maintenance therapy is started when the white blood cell and platelet
counts are rising. The maintenance dose is 0.05 mg/kg/day or less and is adjusted
according to the blood count.
Available evidence suggests that about one third to one half of the patients
with multiple myeloma show a favorable response to oral administration of the
One study by Alexanian et al has shown that the use of ALKERAN (melphalan) in combination
with prednisone significantly improves the percentage of patients with multiple
myeloma who achieve palliation. One regimen has been to administer courses of
ALKERAN (melphalan) at 0.25 mg/kg/day for 4 consecutive days (or, 0.20 mg/kg/day for 5 consecutive
days) for a total dose of 1 mg/kg/course. These 4- to 5-day courses are then
repeated every 4 to 6 weeks if the granulocyte count and the platelet count
have returned to normal levels.
It is to be emphasized that response may be very gradual over many months;
it is important that repeated courses or continuous therapy be given since improvement
may continue slowly over many months, and the maximum benefit may be missed
if treatment is abandoned too soon.
In patients with moderate to severe renal impairment, currently available pharmacokinetic
data do not justify an absolute recommendation on dosage reduction to those
patients, but it may be prudent to use a reduced dose initially.
Epithelial Ovarian Cancer: One commonly employed regimen for the treatment
of ovarian carcinoma has been to administer ALKERAN (melphalan) at a dose of 0.2 mg/kg daily
for 5 days as a single course. Courses are repeated every 4 to 5 weeks depending
upon hematologic tolerance.
Administration Precautions: 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.
ALKERAN (melphalan) is supplied as white, film-coated, round, biconvex tablets containing
2 mg melphalan in amber glass bottles with child-resistant closures. One side
is engraved with "GX EH3" and the other side is engraved with an "A."
Bottle of 50 (NDC 59572-302-50).
Store in a refrigerator, 2° to 8° C (36° to 46° F). 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.
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. 1983;1:426-428.
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. 1983;33:258-263.
7. American Society of Hospital Pharmacists. ASHP technical assistance bulletin
on handling cytotoxic and hazardous drugs. Am J Hosp Pharm. 1990;47:1033-1049.
8. Controlling Occupational Exposure to Hazardous Drugs. (OSHA Work-Practice
Guidelines.) Am J Health-Syst Pharm. 1996;53:1669-1685.
GlaxoSmithKline, Research Triangle Park, NC 27709. Distributed
by Celgene Corporation Summit, NJ 07901. June 2007. FDA Rev date: 6/9/2005