Melphalan

Clinical summary

Indications and usage 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. Dosage and administration DOSAGE AND ADMINISTRATION: The usual IV dose is 16 mg/m 2 . Dosage reduction of up to 50% should be considered in patients with renal insufficiency (BUN ≥ 30 mg/dL) (see PRECAUTIONS , General ). The drug is administered as a single infusion over 15 to 20 minutes. Melphalan hydrochloride for injection is administered at 2-week intervals for 4 doses, then, after adequate recovery from toxicity, at 4‑week intervals. Available evidence suggests about one-third to one-half of the patients with multiple myeloma show a favorable response to the drug. Experience with oral melphalan suggests that repeated courses should be given since improvement may continue slowly over many months, and the maximum benefit may be missed if treatment is abandoned prematurely. Dose adjustment on the basis of blood cell counts at the nadir and day of treatment should be considered. Administration Precautions As with other toxic compounds, caution should be exercised in handling and preparing the solution of melphalan hydrochloride for injection. Skin reactions associated with accidental exposure may occur. The use of gloves is recommended. If the solution of melphalan hydrochloride contacts the skin or mucosa, immediately wash the skin or mucosa thoroughly with soap and water. Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published. 1-4 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate. Parenteral drug products should be visually inspected for particulate matter and discoloration prior to administration whenever solution and container permit. If either occurs, do not use this product. Care should be taken to avoid possible extravasation of melphalan and in cases of poor peripheral venous access, consideration should be given to use of a central venous line (see WARNINGS ). Preparation for Administration/Stability 1. Melphalan hydrochloride for injection must be reconstituted by rapidly injecting 10 mL of the supplied diluent directly into the vial of lyophilized powder using a sterile needle (20‑gauge or larger needle diameter) and syringe. Immediately shake vial vigorously until a clear solution is obtained. This provides a 5 mg/mL solution of melphalan. Rapid addition of the diluent followed by immediate vigorous shaking is important for proper dissolution. 2. Immediately dilute the dose to be administered in 0.9% Sodium Chloride Injection, USP, to a concentration not greater than 0.45 mg/mL. 3. Administer the diluted product over a minimum of 15 minutes. 4. Complete administration within 60 minutes of reconstitution. The time between reconstitution/dilution and administration of melphalan hydrochloride should be kept to a minimum because reconstituted and diluted solutions of melphalan hydrochloride are unstable. Over as short a time as 30 minutes, a citrate derivative of melphalan has been detected in reconstituted material from the reaction of melphalan hydrochloride with Sterile Diluent for melphalan hydrochloride. Upon further dilution with saline, nearly 1% label strength of melphalan hydrolyzes every 10 minutes. A precipitate forms if the reconstituted solution is stored at 5°C. DO NOT REFRIGERATE THE RECONSTITUTED PRODUCT. Warnings and cautions WARNINGS: Melphalan hydrochloride may cause local tissue damage should extravasation occur, and consequently it should not be administered by direct injection into a peripheral vein. It is recommended that melphalan hydrochloride for injection be administered by injecting slowly into a fast-running IV infusion via an injection port, or via a central venous line (see DOSAGE AND ADMINISTRATION , Administration Precautions ). Melphalan should be administered in carefully adjusted dosage by or under the supervision of experienced physicians who are familiar with the drug’s actions and the possible complications of its use. As with other nitrogen mustard drugs, excessive dosage will produce marked bone marrow suppression. Bone marrow suppression is the most significant toxicity associated with melphalan hydrochloride in most patients. Therefore, the following tests should be performed at the start of therapy and prior to each subsequent dose of melphalan hydrochloride: platelet count, hemoglobin, white blood cell count, and differential. Thrombocytopenia and/or leukopenia are indications to withhold further therapy until the blood counts have sufficiently recovered. Frequent blood counts are essential to determine optimal dosage and to avoid toxicity. Dose adjustment on the basis of blood counts at the nadir and day of treatment should be considered. Hypersensitivity reactions including anaphylaxis have occurred in a