Brands, Medical Use, Clinical Data
Drug Category
- Antineoplastic Agents, Alkylating
- Myeloablative Agonists
Dosage Forms
- Tablet
- Solution (for injection)
Brands / Synonyms
Alkeran; Alkeran Injection; L-PAM; L-Phenylalanine mustard; L-Sarcolysin; L-Sarcolysine; L-Sarkolysin; Levofalan; Melfalan; Mephalan; Phenylalanine mustard; Phenylalanine nitrogen mustard; Sarcolysine; Sarkolysin
Indications
For the palliative treatment of multiple myeloma and for the palliation of non-resectable epithelial carcinoma of the ovary.
Pharmacology
Melphalan is an antineoplastic in the class of alkylating agents and is used to treat various forms of cancer. Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumor growth by cross-linking guanine bases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. In addition, these drugs add methyl or other alkyl groups onto molecules where they do not belong which in turn inhibits their correct utilization by base pairing and causes a miscoding of DNA. Alkylating agents are cell cycle-nonspecific. Alkylating agents work by three different mechanisms all of which achieve the same end result - disruption of DNA function and cell death.
Mechanism of Action
Alkylating agents work by three different mechanisms: 1) attachment of alkyl groups to DNA bases, resulting in the DNA being fragmented by repair enzymes in their attempts to replace the alkylated bases, preventing DNA synthesis and RNA transcription from the affected DNA, 2) DNA damage via the formation of cross-links (bonds between atoms in the DNA) which prevents DNA from being separated for synthesis or transcription, and 3) the induction of mispairing of the nucleotides leading to mutations.
Absorption
Incomplete, variable, 25-89% post oral dose
Toxicity
Vomiting, ulceration of the mouth, diarrhea, and hemorrhage of the gastrointestinal tract; The principal toxic effect is bone marrow suppression. LD50=11.2 mg/kg (orally in rat)
Biotrnasformation / Drug Metabolism
Melphalan is not actively metabolised, it spontaneously degrades to mono and dihydroxy products.
Contraindications
ALKERAN should not be used in patients whose disease has demonstrated a prior resistance to this
agent. Patients who have demonstrated hypersensitivity to melphalan should not be given the drug.
Drug Interactions
DRUG INTERACTIONS
There are no known drug/drug interactions with oral ALKERAN
Vaccinations with live organism vaccines are not recommended in immunocompromised
individuals
Nalidixic acid together with high-dose intravenous melphalan has caused deaths in
children due to haemorrhagic enterocolitis.
Impaired renal function has been described in bone marrow transplant patients who
were conditioned with high-dose intravenous melphalan and who subsequently received
cyclosporin to prevent graft-versus-host disease
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