Melphalan Injection

— THERAPEUTIC CATEGORIES —
  • Leukemias, lymphomas, and other hematologic cancers
PAGE CONTENTS
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  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Melphalan Injection Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Melphalan HCl 50mg/vial; pwd for IV infusion after reconstitution and dilution.

    Pharmacological Class

    Alkylating agent.

    See Also

    How Supplied

    Contact supplier

    Manufacturer

    Various generic manufacturers

    Melphalan Injection Indications

    Indications

    Palliative treatment of multiple myeloma when oral therapy is not appropriate.

    Melphalan Injection Dosage and Administration

    Adult

    Give by IV infusion over 15–20 minutes. 16mg/m2 every 2 weeks for a total of 4 doses, then at 4-week intervals. Continue treatment as hematological recovery permits. Renal insufficiency (BUN≥30mg/dL): consider reducing dose by 50%.

    Adult

    • Usual IV dose: 16mg/m2 as a single infusion over 15–20 minutes. Administer every 2 weeks for 4 doses, then after adequate recovery from toxicity, administer at 4-week intervals. Consider reducing dose by up to 50% in patients with renal insufficiency (BUN ≥30mg/dL).

    • Based on evidence with oral melphalan, 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. Consider adjusting dose based on blood cell counts at the nadir and day of treatment.

    Children

    Not recommended.

    Melphalan Injection Contraindications

    Contraindications

    Prior resistance to melphalan.

    Melphalan Injection Boxed Warnings

    Boxed Warning

    Should be administered under the supervision of an experienced physician in cancer chemotherapeutic agents. May cause severe bone marrow suppression with resulting infection or bleeding. Intravenous (IV) form may be more myelosuppressive than oral form. Leukemogenic in humans. Potentially mutagenic.

    Melphalan Injection Warnings/Precautions

    Warnings/Precautions

    Prior irradiation or chemotherapy. Bone marrow suppression. Azotemia. Monitor platelets, hemoglobin, WBC and differential at start of therapy and prior to each course; discontinue if WBC <3,000cells/µL or platelets <100,000cells/µL. Moderate to severe renal impairment. Elderly. Pregnancy (Cat.D), nursing mothers: not recommended.

    Warnings/Precautions

    • Melphalan hydrochloride for injection may cause local tissue damage should extravasation occur. Do not administer by direct injection into a peripheral vein.

    • Melphalan hydrochloride for injection is recommended to be administered by injecting slowly into a fast-running IV infusion via an injection port, or via a central venous line.

    • Administer melphalan under the supervision of an experienced physician in cancer chemotherapeutic agents. 

    • Monitor platelets, hemoglobin, WBC and differential at start of therapy and prior to each course. Withhold further therapy if thrombocytopenia and/or leukopenia occur until the blood counts have sufficiently recovered.

    • Consider adjusting dose on the basis of blood counts at the nadir and day of treatment.

    • Do not readminister oral or IV melphalan if hypersensitivity reactions occur, including anaphylaxis.

    • Secondary malignancies (e.g., acute nonlymphocytic leukemia, myeloproliferative syndrome, carcinoma) have been reported in patients with cancer treated with alkylating agents, including melphalan. The potential benefits and risks from melphalan therapy must be weighed on an individual basis.

    • Use 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.

    • Avoid administration of live vaccines to immunocompromised patients.

    • Suppression of ovarian function in premenopausal women may occur with melphalan resulting in amenorrhea.

    • Laboratory Tests: Obtain periodic CBCs with differentials during treatment. Obtain at least 1 determination prior to each treatment course. Monitor patients closely for consequences of bone marrow suppression, including severe infections, bleeding, and symptomatic anemia.

    Pregnancy Considerations

    Pregnancy Category D

    • May cause fetal harm. Melphalan was embryo-lethal and teratogenic in rats.

    • There are no adequate and well-controlled studies in pregnant women.

    • Women of childbearing potential should avoid becoming pregnant.

    Nursing Mother Considerations

    Not known whether melphalan is excreted in human milk. Do not administer to nursing mothers.

    Pediatric Considerations

    Safety and effectiveness of melphalan tablets in pediatric patients have not been established.

    Geriatric Considerations

    In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. 

    Melphalan Injection Pharmacokinetics

    Absorption

    Mean (±SD) peak melphalan plasma concentrations in myeloma patients given IV melphalan at doses of 10 or 20 mg/m2 were 1.2 ± 0.4 and 2.8 ± 1.9 mcg/mL, respectively. 

    Distribution

    The steady-state volume of distribution of melphalan is 0.5 L/kg. The average melphalan binding to plasma proteins is highly variable (range: 53% to 92%). 

    Elimination

    Following injection, the terminal elimination phase half-life was approximately 75 minutes.

    Melphalan Injection Interactions

    Interactions

    Radiotherapy potentiates antineoplastic effect. For IV: caution with cyclosporine, cisplatin, BCNU, nalidixic acid.

    Melphalan Injection Adverse Reactions

    Adverse Reactions

    Bone marrow suppression, GI upset, hepatic dysfunction, anemia, blood dyscrasias, secondary malignancies (eg, nonlymphocytic leukemia), rash, alopecia, pulmonary fibrosis, interstitial pneumonitis, gonadal toxicity (amenorrhea, infertility); hypersensitivity reactions, cardiac arrest (rare).

    Adverse Reactions

    • Hematologic: Bone marrow suppression leading to leukopenia, thrombocytopenia, and anemia. Irreversible bone marrow failure has been reported.

    • Gastrointestinal: Nausea, vomiting, diarrhea, oral ulceration. Hepatic disorders ranging from abnormal liver function tests to hepatitis and jaundice have been reported. Hepatic veno-occlusive disease has been reported.

    • Miscellaneous: Other reported adverse reactions include pulmonary fibrosis (including fatal outcomes) and interstitial pneumonitis, skin hypersensitivity, maculopapular rashes, vasculitis, alopecia, and hemolytic anemia. Allergic reactions have occurred.

    Melphalan Injection Clinical Trials

    Clinical Trials

    • In a randomized clinical trial, prednisone plus IV melphalan was compared to prednisone plus oral melphalan for the treatment of myeloma. All patients received oral prednisone starting at 0.8 mg/kg/day with doses tapered over 6 weeks. 

    • For the melphalan treatment arms, patients were randomly assigned to receive either oral melphalan 0.15 mg/kg/day x 7 followed by 0.05 mg/kg/day when WBC began to rise; or IV melphalan 16 mg/m2 every 2 weeks x 4 (over 6 weeks) followed by the same dose every 4 weeks.

    • The overall response rates were similar at week 22 between oral and IV melphalan (44% vs 38%, respectively). There were more patients who had a poor-risk classification (58% vs 44%) and high tumor load (51% vs 34%) in the oral arm compared to the IV arm (P <.04).

    • The IV melphalan arm had a higher incidence of severe myelotoxicity (WBC ≤1,000 and/or platelets ≤25,000) vs the oral melphalan arm (28% vs 11%, respectively).

    Melphalan Injection Note

    Notes

    Formerly known under the brand name Alkeran.

    Melphalan Injection Patient Counseling

    Patient Counseling

    Advise patients that major toxicities of melphalan are related to bone marrow suppression, hypersensitivity reactions, gastrointestinal toxicity, and pulmonary toxicity.

    Advise patients that the major long-term toxicities are related to infertility and secondary malignancies.

    Advise patients to consult their health care provider if they experience skin rash, vasculitis, bleeding, fever, persistent cough, nausea, vomiting, amenorrhea, weight loss, or unusual lumps/masses.

    Advise women of childbearing potential to avoid becoming pregnant.

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