melphalan (Rx)

Brand and Other Names:Alkeran, Evomela
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

injection, lyophilized powder for reconstitution

  • 50mg

tablet

  • 2mg
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Multiple Myeloma

Palliative treatment

  • Indicated for the palliative treatment of patients with MM
  • Oral
    • 6 mg PO qDay for 2-3 weeks, OR
    • 10 mg PO qDay for 7-10 days, OR
    • 0.15 mg/kg/day PO for 7 days, THEN
    • After adequate recovery from toxicity (monitor WBCs and platelets) give 1-3 mg or 0.05 mg/kg PO qDay
  • IV
    • If unable to take oral, may administer IV 16 mg/m² IV as a single infusion over 15-20 minutes q2wk for 4 doses, THEN
    • After adequate recovery from toxicity (monitor WBCs and platelets) administer q4wk

Conditioning treatment

  • Indicated for use as a high-dose conditioning treatment prior to hematopoietic progenitor (stem) cell transplantation
  • 100 mg/m²/day IV administered over 30 min for 2 consecutive days (Day -3 and Day -2) prior to autologous stem cell transplantation (ASCT, Day 0) 
  • Patients weighing >130% of their ideal body weight, body surface area should be calculated based on adjusted ideal body weight

Ovarian Cancer

0.2 mg/kg/day PO for 5 days; repeat q4-5Weeks 

Dosage Modifications

Renal impairment (BUN ≥30 mg/dL): Consider dosage reduction of up to 50%

Orphan Designations

Stem cell transplantation

  • High dose conditioning treatment prior to hematopoietic progenitor (stem) cell transplantation
  • Orphan sponsor: CyDex Pharmaceuticals, Inc; 10513 W. 84th Terrace; Lenexa, KS 66214

Cutaneous melanoma

  • Sponsor: Delcath Systems, Inc; 1301 Avenue of the Americas, 43rd Floor; New York, NY 10019

Hepatocellular cancer

  • Sponsor: Delcath Systems, Inc; 1301 Avenue of the Americas, 43rd Floor; New York, NY 10019

Ocular (uveal) melanoma

  • Sponsor: Delcath Systems, Inc; 1301 Avenue of the Americas, 43rd Floor; New York, NY 10019

Neuroendocrine tumors

  • Sponsor: Delcath Systems, Inc; 1301 Avenue of the Americas, 43rd Floor; New York, NY 10019

Retinoblastoma

  • Intraocular injection
  • Sponsor: Icon Bioscience, Inc; 1253 Reamwood Ave; Sunnyvale, CA 94089

Multiple myeloma (new dosage form)

  • Melphalan flufenamide hydrochloride
  • Orphan designation for this salt; results in intracellular trapping of melphalan in malignant cells to increase efficacy
  • Sponsor: Oncopeptides AB; Vastra Tradgardsgatan 15; 111 53 Stockholm, Sweden

Cholangiocarcinoma

  • Sponsor: Delcath Systems, Inc; 1301 Avenue of the Americas, 43rd Floor; New York, NY 10019

Other Indications & Uses

Off-label: Breast cancer, testicular cancer, melanoma

Safety and efficacy not established

Multiple Myeloma

Induction

6 mg PO qDay for 2-3 weeks, OR

10 mg PO qDay for 7-10 days, OR

0.15 mg/kg/day PO for 7 days, OR

16 mg/m² IV q2Weeks for 4 doses  

Maintenance

Wait until WBC and platelet counts rise

1-3 mg PO qDay, OR

0.05 mg/kg/day PO, OR

16 mg/m² IV q4Weeks  

Ovarian Cancer

0.2 mg/kg/day PO for 5 days; repeat q4-5Weeks

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Interactions

Interaction Checker

and melphalan

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10%

            Myelosuppression (30%)

            Frequency Not Defined

            Nausea

            Vomiting

            Interstitial pneumonia

            Pulmonary fibrosis

            Diarrhea

            Stomatitis

            Mucositis

            Secondary malignancy

            Hypersensitivity reaction

            Tissue necrosis

            Jaundice

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            Warnings

            Black Box Warnings

            The drug should be administered under the supervision of an experienced cancer chemotherapy physician

            Severe bone marrow suppression that may result in bleeding and infection may occur. Oral melphalan has been reported to be more myelosuppressive than the IV formulation

            Hypersensitivity reactions, including anaphylaxis, reported in patients receiving IV formulation

            Melphalan is leukemogenic and potentially mutagenic (carcinogenic) in humans

            Contraindications

            Hypersensitivity to melphalan or chlorambucil

            Prior resistance to melphalan

            Cautions

            Renal impairment, leukopenia, thrombocytopenia, anemia, CLL

            Possibility of delayed myelosuppression that can last 4-6 wk

            Avoid pregnancy

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            Pregnancy & Lactation

            Pregnancy Category: D

            Lactation: not known if excreted in breast milk

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

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            Pharmacology

            Mechanism of Action

            Mechorethamine derivative that inhibits DNA & RNA synthesis via formation of carbonium ions; cross links DNA strands (interstrand and intrastrand crosslinking) causing miscoding breakage and subsequently DNA replication failure

            Pharmacokinetics

            Peak plasma time: 2 hr

            Concentration: 280 ng/mL

            Half-Life: 60-120 min (oral), 75 min (IV)

            Bioavailability: 60-90%

            Vd: 0.5 L/kg

            Clearance: 7-9 mL/min/kg

            Excretion: Feces (20-50%); urine (10% as unchanged drug)

            Dialyzable: No

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            Administration

            IV Incompatibilities

            Solution: D5W, LR, NS (NS can be used in short time period)

            Y-site: amphotericin B, chlorpromazine

            IV Compatibilities

            Y-site (partial list): acyclovir, bleomycin, most cephalosporins, cisplatin, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daunorubicin, diphenhydramine, doxorubicin, floxuridine, fluconazole, fludarabine, fluorouracil, furosemide, granisetron, heparin, idarubicin, imipenem-cilastatin, lorazepam, methotrexate, metoclopramide, mitomycin, morphine SO4, ondansetron, KCl, prochlorperazine, promethazine, NaHCO3, teniposide, thiotepa, vancomycin, vinblastine, vincristine, vinorelbine, zidovudine

            IV Preparation

            Use chemotherapy precautions for handling, preparation, administration, and disposal

            Alkeran

            • Reconstitute lyophilized powder
              • Rapidly inject 10 mL of the supplied diluent directly into the vial containing lyophilized powder using a needle ≥20-gauge
              • Immediately shake vial vigorously until a clear solution is obtained
              • Dissolve powder initially with 10 mL of provided diluent to 5 mg/mL
              • This results in a 5-mg/mL solution
              • Rapid addition of the diluent followed by immediate vigorous shaking is important for proper dissolution
            • Immediately dilute further
              • Immediately dilute solution in 0.9% NaCl to concentration <0.45 mg/mL
              • Keep to a minimum (<60 min) time between reconstitution/dilution & administration
              • Do not refrigerate solution; precipitation occurs
              • Standard dilution: dose/250-500 mL 0.9% NaCl (concentration <0.45 mg/mL); must be prepared fresh

            Evomela

            • Reconstitute lyophilized powder
              • Captisol-enabled; propylene glycol-free product
              • Use 8.6 mL 0.9% NaCl to reconstitute vial contents (yields 50 mg/10 mL [5 mg/ mL] solution)
              • The normal saline used to reconstitute each vial should appear to be assisted or pulled into the vial by the negative pressure (partial vacuum) present in the vial; discard any vial (and replace with another vial) if there is no vacuum present when reconstituting the vial with normal saline
              • Reconstituted solution is stable for 24 hr refrigerated (5°C)without any precipitation due to the high solubility or for 1 hr at room temperature
            • Dilute further
              • Calculate the required volume of reconstituted solution needed for the dose and withdraw that volume from the vial(s)
              • Add the required dosage volume to the appropriate volume of 0.9% NaCl to a final concentration of 0.45 mg/mL
              • Admixture solution is stable for 4 hr at room temperature in addition to the 1 hr following reconstitution

            IV Administration

            Alkeran

            • IV infusion
              • FDA approved for administration as a single infusion over a minimum of 15-20 min
              • Complete administration within 60 min of reconstituting the lyophilized powder
              • Avoid skin contact with IV formulation
            • IV bolus
              • May be administered via central line and via peripheral vein as a rapid IV bolus
              • Central line: IV bolus doses of 17-200 mg/² reconstituted and not diluted) have been given over 2-20 min
              • Peripheral line: IV bolus doses of 2-23 mg/² reconstituted and not diluted) have been given over 1-4 min

            Evomela

            • Administer prophylactic antiemetic agents
            • Palliative: Infuse IV over 15-20 minutes via an injection port or central venous catheter
            • Conditioning: Infuse IV over 30 minutes via an injection port or central venous catheter

            Oral Administration

            Take on empty stomach; oral administration with a high fat meal may reduce melphalan systemic exposure

            Storage

            Protect from light

            Store at room temp (15-30°C)

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            Formulary

            FormularyPatient Discounts

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            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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