Alkeran - General Information
An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - melphalan, the racemic mixture - merphalan, and the dextro isomer - medphalan; toxic to bone marrow, but little vesicant action; potential carcinogen.
Pharmacology of Alkeran
Alkeran 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.
Alkeran 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
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.
There are no known drug/drug interactions with oral ALKERAN
Vaccinations with live organism vaccines are not recommended in immunocompromised
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
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.
Additional information about Alkeran
Alkeran Indication: For the palliative treatment of multiple myeloma and for the palliation of non-resectable epithelial carcinoma of the ovary.
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.
Drug Interactions: Cyclosporine Alkeran increases toxicity of cyclosporine
Food Interactions: Take on an empty stomach. Food decreases bioavailabilty. Increase liquid intake.
Generic Name: Melphalan
Synonyms: Not Available
Drug Category: Antineoplastic Agents, Alkylating; Myeloablative Agonists
Drug Type: Small Molecule; Approved
Other Brand Names containing Melphalan: Alkeran; L-PAM; L-Phenylalanine mustard; L-Sarcolysin; L-Sarcolysine; L-Sarkolysin; Levofalan; Melfalan; Mephalan; Phenylalanine mustard; Phenylalanine nitrogen mustard; Sarcolysine; Sarkolysin;
Absorption: Incomplete, variable, 25-89% post oral dose
Toxicity (Overdose): 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)
Protein Binding: Moderate to high (60 to 90%), primarily to albumin and alpha 1-acid glycoprotein, while 30% is irreversibly bound to plasma proteins.
Biotransformation: Melphalan is not actively metabolised, it spontaneously degrades to mono and dihydroxy products.
Half Life: 1.5 (±0.83) hours
Dosage Forms of Alkeran: Tablet Oral
Chemical IUPAC Name: 2-amino-3-[4-[bis(2-chloroethyl)amino]phenyl]propanoic acid
Chemical Formula: C13H18Cl2N2O2
Melphalan on Wikipedia: http://en.wikipedia.org/wiki/Melphalan
Organisms Affected: Humans and other mammals