MELPHALAN HYDROCHLORIDE- melphalan injection, powder, lyophilized, for solution
Par Pharmaceutical, Inc.
PRESCRIBING INFORMATION
WARNING
Melphalan hydrochloride for injection should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. Severe bone marrow suppression with resulting infection or bleeding may occur. Controlled trials comparing intravenous (IV) to oral melphalan have shown more myelosuppression with the IV formulation. Hypersensitivity reactions, including anaphylaxis, have occurred in approximately 2% of patients who received the IV formulation. Melphalan hydrochloride for injection is leukemogenic in humans. Melphalan hydrochloride for injection produces chromosomal aberrations in vitro and in vivo and, therefore, should be considered potentially mutagenic in humans.
DESCRIPTION
Melphalan, also known as L-phenylalanine mustard, phenylalanine mustard, L-PAM, or L-sarcolysin, is a phenylalanine derivative of nitrogen mustard. Melphalan is a bifunctional alkylating agent that is active against selected human neoplastic diseases. It is known chemically as 4-[bis(2-chloroethyl)amino]-L- phenylalanine. The molecular formula is C13 H18 Cl2 N2 O2 and the molecular weight is 305.20 Melphalan is the active L-isomer of the compound and was first synthesized in 1953 by Bergel and Stock; the D-isomer, known as medphalan, is less active against certain animal tumors, and the dose needed to produce effects on chromosomes is larger than that required with the L-isomer. The racemic (DL-) form is known as merphalan or sarcolysin.
Melphalan is practically insoluble in water and has a pKa1 of ~2.5.
Melphalan hydrochloride for injection is supplied as a sterile, nonpyrogenic, freeze-dried powder. Each single-use vial contains melphalan hydrochloride equivalent to 50 mg melphalan and 20 mg povidone. Melphalan hydrochloride for injection is reconstituted using the sterile diluent provided. Each vial of sterile diluent contains sodium citrate 0.2 g, propylene glycol 6.0 mL, ethanol (96%) 0.52 mL, and Water for Injection to a total of 10 mL. Melphalan hydrochloride for injection is administered intravenously.
CLINICAL PHARMACOLOGY
Melphalan is an alkylating agent of the bischloroethylamine type. As a result, its cytotoxicity appears to be related to the extent of its interstrand cross-linking with DNA, probably by binding at the N7 position of guanine. Like other bifunctional alkylating agents, it is active against both resting and rapidly dividing tumor cells. INDICATIONS AND USAGE
Melphalan hydrochloride for injection is indicated for the palliative treatment of patients with multiple myeloma for whom oral therapy is not appropriate.