Melphalan Hydrochloride Kit
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Questions & Answers
Side Effects & Adverse Reactions
Melphalan Hydrochloride for Injection 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 for Injection 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 approximately 2% of patients who received the IV formulation (see ADVERSE REACTIONS). These reactions usually occur after multiple courses of treatment. Treatment is symptomatic. The infusion should be terminated immediately, followed by the administration of volume expanders, pressor agents, corticosteroids, or antihistamines at the discretion of the physician. If a hypersensitivity reaction occurs, IV or oral melphalan should not be readministered since hypersensitivity reactions have also been reported with oral melphalan.
Secondary malignancies, including acute nonlymphocytic leukemia, myeloproliferative syndrome, and carcinoma, have been reported in patients with cancer treated with alkylating agents (including melphalan). Some patients also received other chemotherapeutic agents or radiation therapy. Precise quantitation of the risk of acute leukemia, myeloproliferative syndrome, or carcinoma is not possible. Published reports of leukemia in patients who have received melphalan (and other alkylating agents) suggest that the risk of leukemogenesis increases with chronicity of treatment and with cumulative dose. In one study, the 10-year cumulative risk of developing acute leukemia or myeloproliferative syndrome after oral melphalan therapy was 19.5% for cumulative doses ranging from 730 to 9,652 mg. In this same study, as well as in an additional study, the 10-year cumulative risk of developing acute leukemia or myeloproliferative syndrome after oral melphalan therapy was less than 2% for cumulative doses under 600 mg. This does not mean that there is a cumulative dose below which there is no risk of the induction of secondary malignancy. The potential benefits from melphalan therapy must be weighed on an individual basis against the possible risk of the induction of a second malignancy.
Adequate and well-controlled carcinogenicity studies have not been conducted in animals. However, intraperitoneal (IP) administration of melphalan in rats (5.4 to 10.8 mg/m2) and in mice (2.25 to 4.5 mg/m2) 3 times per week for 6 months followed by 12 months post-dose observation produced peritoneal sarcoma and lung tumors, respectively.
Melphalan has been shown to cause chromatid or chromosome damage in humans. Intramuscular administration of melphalan at 6 and 60 mg/m2 produced structural aberrations of the chromatid and chromosomes in bone marrow cells of Wistar rats.
Melphalan causes suppression of ovarian function in premenopausal women, resulting in amenorrhea in a significant number of patients. Reversible and irreversible testicular suppression have also been reported.
Melphalan may cause fetal harm when administered to a pregnant woman. While adequate animal studies have not been conducted with IV melphalan, oral (6 to 18 mg/m2/day for 10 days) and IP (18 mg/m2) administration in rats was embryolethal and teratogenic. Malformations resulting from melphalan included alterations of the brain (underdevelopment, deformation, meningocele, and encephalocele) and eye (anophthalmia and microphthalmos), reduction of the mandible and tail, as well as hepatocele (exomphaly). There are no adequate and well-controlled studies in pregnant women. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential should be advised to avoid becoming pregnant.
Legal Issues
There is currently no legal information available for this drug.
FDA Safety Alerts
There are currently no FDA safety alerts available for this drug.
Manufacturer Warnings
There is currently no manufacturer warning information available for this drug.
FDA Labeling Changes
There are currently no FDA labeling changes available for this drug.
Uses
Melphalan Hydrochloride for Injection is indicated for the palliative treatment of patients with multiple myeloma for whom oral therapy is not appropriate.
History
There is currently no drug history available for this drug.
Other Information
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 C13H18Cl2N2O2 and the molecular weight is 305.20. The structural formula is:
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 the inactive ingredient povidone 20 mg. 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.
Sources
Melphalan Hydrochloride Kit Manufacturers
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Mylan Institutional Llc
![Melphalan Hydrochloride Kit [Mylan Institutional Llc]](/wp-content/themes/bootstrap/assets/img/loading2.gif)
Melphalan Hydrochloride Kit | Mylan Institutional Llc
The usual IV dose is 16 mg/m2. 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 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 PrecautionsAs with other toxic compounds, caution should be exercised in handling and preparing the solution of Melphalan Hydrochloride. 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 for Injection should be kept to a minimum because reconstituted and diluted solutions of Melphalan Hydrochloride for Injection 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 for Injection. 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.
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Mylan Institutional Llc
Melphalan Hydrochloride Kit | Mylan Institutional Llc
The usual IV dose is 16 mg/m2. 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 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 PrecautionsAs with other toxic compounds, caution should be exercised in handling and preparing the solution of Melphalan Hydrochloride. 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 for Injection should be kept to a minimum because reconstituted and diluted solutions of Melphalan Hydrochloride for Injection 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 for Injection. 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.
![Melphalan Hydrochloride Kit [Mylan Institutional Llc]](http://dailymed.nlm.nih.gov/dailymed/image.cfm?setid=7349a5f7-0b8d-4055-98b2-3b4b2629dd1f&name=cf2e0ddb-dd86-4527-a31e-f34e7057f543-02.jpg)
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