Contents

Search

melphalan (Alkeran, L-PAM, L-sarcolysin phenylalanine mustard, melphalan flufenamide, Pepaxto)

Tradename: Alkeran. Indications: - palliative treatment of multiple myeloma - palliative treatment of non-resectable epithelial ovarian carcinoma - neuroblastoma - rhabdomyosarcoma - thyroid carcinoma - testicular carcinoma - breast cancer - diffuse large B-cell lymphoma [4] - stem cell transplantation [4] Contraindications: - melphalan flufenamide (Pepaxto) does not improve progression-free or overall survival; may lose FDA accelerated approval granted in Feb 2021 [5] Dosage: 1) 0.25 mg/kg/day PO for 4 days every 6 weeks 2) maximum: 6 mg/day Tabs: 2 mg (preferred route of administration is oral) Powder for injection: 50 mg (10 mL) Do: 1) protect from light 2) do not refrigerate reconstituted solution 3) complete administration within 1 hour of reconstitution Pharmacokinetics: 1) erratic oral absorption (25-90%) 2) 90% protein bound 3) metabolized spontaneously in blood 4) cleared mostly by non-renal routes 5) 1/2life 1.5-4 hours Adverse effects: 1) common (> 10%) - myelosuppression - onset 7 days - nadir 8-10 days & 27-32 days - recovery 6-7 weeks - secondary malignancies - SIADH - pulmonary fibrosis - interstitial pneumonitis - hemolytic anemia - pruritus & rash - sterility (permanent) & amenorrhea - hypersensitivity - alopecia 2) less common (1-10%) - vasculitis, alopecia, rash, pruritus, leukopenia, thrombocytopenia, anemia, agranulocytosis, hemolytic anemia, vesiculation of skin, bladder irritation, hemorrhagic cystitis, pulmonary fibrosis, nausea/vomiting, stomatitis, diarrhea 3) other [2]: - mild to moderate nausea - anaphylaxis Drug interactions: 1) cyclosporine increases the risk of nephrotoxicity 2) cimetidine decreases oral absorption of melphalan Test interactions: - false positive Coomb's test (direct) Mechanism of action: 1) alkylating agent 2) interferes with DNA & RNA synthesis

Interactions

drug adverse effects of alkylating agents

General

alkylating agent nitrogen mustard

Properties

MISC-INFO: elimination route PLASMA 1/2life 1.5-4 HOURS

Database Correlations

PUBCHEM correlations

References

  1. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  2. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  3. Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 529
  4. Deprecated Reference
  5. Young KD Follow-up Trial of Myeloma Drug 'Flopped,' Says FDA Panel. Medscape. September 23, 2022 https://www.medscape.com/viewarticle/981343

Component-of

melphalan/prednisone/thalidomide (ThaMP) recombinant parathyroid hormone (1-84) (Natpara)