/mcL, or the platelet count below 100,000 cells/mcL, ALKERAN should be discontinued until the peripheral blood cell counts have recovered.
A recommendation as to whether or not dosage reduction should be made routinely in patients with renal insufficiency cannot be made because:
a) There is considerable inherent patient-to-patient variability in the systemic availability of melphalan in patients with normal renal function.
b) Only a small amount of the administered dose appears as parent drug in the urine of patients with normal renal function.
Patients with azotemia should be closely observed, however, in order to make dosage reductions, if required, at the earliest possible time.
Administration of live vaccines to immunocompromised patients should be avoided.
Information for Patients
Patients should be informed that the major toxicities of ALKERAN are related to bone marrow suppression, hypersensitivity reactions, gastrointestinal toxicity, and pulmonary toxicity. The major long-term toxicities are related to infertility and secondary malignancies. Patients should never be allowed to take the drug without close medical supervision and should be advised to consult their physician if they experience skin rash, vasculitis, bleeding, fever, persistent cough, nausea, vomiting, amenorrhea, weight loss, or unusual lumps/masses. Women of childbearing potential should be advised to avoid becoming pregnant.
Laboratory Tests
Periodic complete blood counts with differentials should be performed during the course of treatment with ALKERAN. At least one determination should be obtained prior to each treatment course. Patients should be observed closely for consequences of bone marrow suppression, which include severe infections, bleeding, and symptomatic anemia (see WARNINGS).
Drug Interactions
There are no known drug/drug interactions with oral ALKERAN.
Carcinogenesis, Mutagenesis, Impairment of Fertility
See WARNINGS section.
Pregnancy
Teratogenic Effects
Pregnancy Category D: See WARNINGS section.
Nursing Mothers
It is not known whether this drug is excreted in human milk. ALKERAN should not be given to nursing mothers.
Pediatric Use
The safety and effectiveness of ALKERAN in pediatric patients have not been established.
Geriatric Use
Clinical studies of ALKERAN Tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
ADVERSE REACTIONS
Hematologic
The most common side effect is bone marrow suppression leading to leukopenia, thrombocytopenia, and anemia. Although bone marrow suppression frequently occurs, it is usually reversible if melphalan is withdrawn early enough. However, irreversible bone marrow failure has been reported.
Gastrointestinal
Nausea, vomiting, diarrhea, and oral ulceration occur. Hepatic disorders ranging from abnormal liver function tests to clinical manifestations such as hepatitis and jaundice have been reported.
Miscellaneous
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