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Pronunciation: MEL-fa-lan
Class: Nitrogen mustard

Trade Names

- Tablets 2 mg
- Injection, lyophilized powder for reconstitution 50 mg


Melphalan is a bifunctional, alkylating agent of the bischloroethylamine type. Its cytotoxicity appears to be related to the extent of its interstrand cross-linking with DNA. Like other bifunctional alkylating agents, it is active against resting and rapidly dividing tumor cells.

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C max is 70 to 4,000 ng/mL (oral); may vary depending on absorption or metabolism. T max is 0 to 7 h (oral).


Vd ss is 0.5 L/kg; protein binding is 60% to 90% (approximately 30% irreversibly bound). CSF penetration is low.


Melphalan undergoes hydrolysis to form monohydroxy and dihydroxy melphalan.


The t ½ is approximately 75 min for IV and approximately 90 min for oral.

Indications and Usage

Palliative therapy of multiple myeloma (oral and IV) and nonresectable epithelial carcinoma of the ovary (oral).

Unlabeled Uses

Breast carcinoma, testicular carcinoma, bone marrow transplantation.


Prior resistance or hypersensitivity to the product.

Dosage and Administration

Multiple Myeloma

PO Start with 6 mg daily. Adjust dose based on blood cell counts done at approximately weekly intervals. After 2 to 3 wk of treatment, stop the drug for up to 4 wk, during which time the blood cell count should be followed carefully. When the WBC and platelet counts are rising, a maintenance dose of 2 mg/day may be instituted. Response may be very gradual over many months; therefore, it is important that repeated courses or continuous therapy be given since improvement may continue slowly over many months, and the maximum benefit may be missed if treatment is abandoned too soon.


IV infusion 16 mg/m 2 over 15 to 20 min every 2 wk for 4 doses, then as tolerated every 4 wk. Decrease the dose by 50% in patients with BUN at least 30 mg/dL (or serum creatinine at least 1.5 mg/dL).

Epithelial Ovarian Cancer

PO 0.2 mg/kg daily for 5 days as a single course. Courses are repeated every 4 to 5 wk, depending on hematologic tolerance.

Dosage Adjustments

PO/IV Adjust all doses based on hematological parameters at nadir.

General Advice

  • Inject 10 mL of the supplied diluent directly into the vial of lyophilized powder using a 20-gauge or larger needle and syringe. Immediately shake vigorously until a clear solution is obtained. This provides 5 mg/mL of melphalan.
  • Immediately dilute dose to be administered in sodium chloride 0.9% injection to a concentration of no more than 0.45 mg/mL.
  • Complete administration within 60 min of reconstitution.
  • Administer by injecting slowly into a fast-running IV infusion via an injection port of central venous line.
  • Do not administer by direct injection into a peripheral vein.


Store tablets in refrigerator (36° to 46°F) in glass bottles. Protect from light. Store powder for oral injection at controlled room temperature (59° to 86°F). Protect from light. Do not refrigerate reconstituted solution.

Drug Interactions


Melphalan may increase the likelihood of carmustine pulmonary toxicity.

Cimetidine and interferon alfa

May decrease serum concentrations of melphalan.


May alter melphalan Cl, resulting in renal function impairment.


Bone marrow transplant patients receiving melphalan followed by cyclosporine had a high frequency of severe renal function impairment in one study.


Avoid administration of live vaccines to immunocompromised patients.

Laboratory Test Interactions

None well documented.

Adverse Reactions


Cardiac arrest.


Alopecia, maculopapular rash, skin hypersensitivity, skin necrosis, urticaria.


Diarrhea, hepatic veno-occlusive disease, mucositis, nausea, oral ulceration, vomiting.


Ovarian and testicular suppression.


Bone marrow suppression, nadir at 2 to 3 wk leading to leukopenia, thrombocytopenia, and anemia; irreversible bone marrow failure.


Hemolytic anemia; vasculitis.


Abnormal LFTs, hepatitis, jaundice.


Anaphylactoid reaction (2.4%).


Skin ulceration at injection site.


Pulmonary fibrosis, interstitial pneumonitis.


Allergic reactions; elevated BUN; edema.



Administer under supervision of a qualified health care provider experienced in the use of cancer chemotherapy. Severe bone marrow suppression with resulting infection or bleeding may occur. Hypersensitivity reactions, including anaphylaxis, have occurred in 2% of patients who received IV melphalan. Melphalan is leukemogenic in humans. This has been demonstrated in vitro and in vivo; therefore, consider melphalan to be potentially mutagenic.


Monitor platelet count, hemoglobin, whole blood cell count, and differential at the start of therapy and prior to each subsequent course of therapy. Obtain at least 1 CBC determination prior to each treatment course. Observe patients closely for consequences of bone marrow suppression, including severe infections, bleeding, and symptomatic anemia.


Category D .




Safety and efficacy in children have not been established.


Use with caution, usually starting at the low end of the dosage range, because of the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapy.

Renal Function

Consider dose reduction in patients with renal function impairment.


Suppression of ovarian function may occur in premenopausal women, resulting in amenorrhea.


IV melphalan is a vesicant; extravasation can cause severe local necrosis.

Prior radiation and chemotherapy

Use with extreme caution in patients whose bone marrow reserve may have been compromised by prior irradiation or chemotherapy or whose marrow function is recovering from previous cytotoxic therapy.



Adult respiratory distress syndrome, cholinomimetic effects, colitis, convulsions, decreased consciousness, diarrhea, elevated liver enzymes, hemorrhage of the GI tract, muscular paralysis, nephrotoxicity, veno-occlusive disease, severe mucositis, severe nausea and vomiting, significant hyponatremia, stomatitis.

Patient Information

  • Inform patients that major toxicities are related to myelosuppression, hypersensitivity, GI toxicity, pulmonary toxicity, infertility, and non-lymphocytic leukemia, and not to take without close medical supervision.
  • Notify health care provider of amenorrhea; black, tarry stools; chills; fever; flank or stomach pain; joint pain; mouth sores; nausea; persistent cough; shortness of breath; skin rash; sore throat; unusual bleeding or bruising; unusual lumps or masses; vasculitis; vomiting; weight loss; or yellow discoloration of skin or eyes.
  • Contraceptive measures are recommended during therapy.
  • Advise lactating women not to breast-feed.

Copyright © 2009 Wolters Kluwer Health.