Melphalan

Melphalan is an alkylating agent of the bischloroethylamine type. Its cytotoxic effect seems to depend on how far it forms interstrand cross-links with DNA, most likely by binding at the N 7 position of guanine. Like other bifunctional alkylating agents, melphalan is active against tumor cells that are resting as well as those that are dividing rapidly.

Melphalan can harm an unborn baby when it is given to a pregnant woman, because of how it works. This includes birth defects (teratogenicity) and loss of the baby (embryo-fetal lethality). Melphalan is a genotoxic drug, and it can cause chromatid or chromosome damage in humans. In animal studies, melphalan caused embryo death and birth defects in rats at doses below the recommended clinical doses. A pregnant woman should be told about the possible risk to her baby.

The background risk of major birth defects and miscarriage in the populations this medicine is used for is unknown. For comparison, in the U.S. general population the background risk of major birth defects is 2-4% and of miscarriage is 15-20% of clinically recognized pregnancies.

It isn't known whether melphalan passes into human milk. Many drugs do pass into milk, and melphalan could cause serious adverse reactions in a nursing child, so breastfeeding is not recommended during treatment with Melphalan and for 1 week after the last dose.

Pediatric Use: Children were not included in the clinical trials of Melphalan, so its safety and effectiveness in pediatric patients have not been established.

Geriatric Use: In the single-arm pivotal study of Melphalan, 30% of the subjects were 65 and over, and none were 75 and over. No overall differences in safety or effectiveness were seen between these subjects and the younger ones. Engraftment syndrome did occur more often in the older patients, though: 7% (3 of 43) of patients younger than 65 years old had it, against 28% (5 of 18) of patients 65 years old and over.

Overdoses of Melphalan have caused deaths. At doses up to 290 mg/m2, people have had severe nausea and vomiting, decreased consciousness, convulsions, muscular paralysis and cholinomimetic effects. At high doses (>100 mg/m2), severe mucositis, stomatitis, colitis, diarrhea and bleeding from the gastrointestinal tract occur. Raised liver enzymes and veno-occlusive disease happen infrequently. Significant hyponatremia has been seen, caused by an associated inappropriate secretion of ADH syndrome. Nephrotoxicity and adult respiratory distress syndrome have been reported rarely.

The main toxic effect is bone marrow suppression, which leads to leucopenia, thrombocytopenia and anemia. Blood counts should be followed closely for 3 to 6 weeks. One uncontrolled study suggests that giving autologous bone marrow or hematopoietic growth factors (such as sargramostim or filgrastim) may shorten the period of pancytopenia. General supportive measures should be started as the physician sees fit, together with suitable blood transfusions and antibiotics.

Hemodialysis and hemoperfusion do not remove Melphalan from plasma to any significant degree. A pediatric patient survived a 254 mg/m2 overdose after standard supportive care.

Keep Melphalan at room temperature, 25°C. Short periods between 15 and 30°C are permitted. Melphalan is sensitive to light, so leave it in its original carton until you need to use it. It is also a hazardous drug, so follow the special handling and disposal procedures that apply.