MELPHALAN

Chemistry - A nitrogen mustard derivative, melphalan occurs as an off-white to buff-coloredpowder that is practically insoluble in water. Melphalan is also known as L-PAM, L-Phenylalanine
Mustard, or L-Sarcolysin.

Storage, Stability, Compatibility

Store melphalan tablets in well-closed, light-resistant, glasscontainers at room temperature.

Pharmacology - MELPHALAN

Melphalan is a bifunctional alkylating agent and interferes with RNA transcription and DNA replication, thereby disrupting nucleic acid function. Because it is bifunctional, it hasaffect on both dividing and resting cells.

Uses, Indications

Melphalan may be useful in the treatment of a variety of neoplastic diseases, including ovarian carcinoma, multiple myeloma, lymphoreticular neoplasms, osteosarcoma, andmammary or pulmonary neoplasms.

Pharmacokinetics - MELPHALAN

Melphalan absorption is variable and often incomplete. It is distributedthroughout the body water, but it is unknown whether it crosses the placenta, blood brain barrier orenters maternal milk. Melphalan is eliminated principally by hydrolysis in the plasma. In humans, terminal half lives average about 90 minutes.

Contraindications, Precautions, Reproductive Safety

Melphalan should be used only when itspotential benefits outweigh its risks with the following conditions: anemia, bone marrow depression, current infection, impaired renal function, tumor cel infiltration of bone marrow, sensitivity tomelphalan or patients who have received previous chemotherapy or radiotherapy.
Safe use of melphalan during pregnancy has not been established and other alkylating agents areknown teratogens. Use only during pregnancy when the benefits to the mother outweigh the risksto the offspring. Melphalan can suppress gonadal function. While it is unknown whether melphalanenters maternal milk, nursing puppies or kittens should receive milk replacer when the bitch orqueen is receiving melphalan.

Adverse Effects, Warnings

Potential adverse effects include GI effects (anorexia, vomiting, diarrhea), and pulmonary infiltrates or fibrosis. The most serious adverse effect likely with melphalan is bone marrow depression (anemia, thrombocytopenia, leukopenia).
Overdosage, Acute Toxicity - Because of the toxic potential of this agent, overdoses must beavoided. Determine dosages carefully.

Drug Interactions

Use extreme caution when using concurrently with other drugs that are alsomyelosuppressive, including many of the other antineoplastics and other bone marrow depressant drugs (e.g., chloramphenicol, flucytosine, amphotericin B, or colchicine). Bonemarrow depression may be additive. Use with other immunosuppressant drugs (e.g., azathioprine, cyclophosphamide, corticosteroids) may increase the risk of infection. Live virus vaccines should be used with caution, if at all during therapy.
Anecdotal reports of melphalan causing increased nephrotoxicity associated with systemic cyclosporin use and severe hemorrhagic necrotic enterocolitis associated with nalidixic acid inhuman pediatric patients have been noted.
Laboratory Considerations - Melphalan may raise serum uric acid levels. Drugs such as allopurinol may be required to control hyperuricemia.