melphalan (Alkeran, L-PAM, L-sarcolysin phenylalanine mustard, melphalan flufenamide, Pepaxto)
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Introduction
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
Tabs: 2 mg (preferred route of administration is oral)
Powder for injection: 50 mg (10 mL)
Do:
- protect from light
- do not refrigerate reconstituted solution
- complete administration within 1 hour of reconstitution
Pharmacokinetics
- erratic oral absorption (25-90%)
- 90% protein bound
- metabolized spontaneously in blood
- cleared mostly by non-renal routes
- 1/2life 1.5-4 hours
elimination via plasma
1/2life = 1.5-4 hours
Adverse effects
- 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
- myelosuppression
- 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
- other[2]:
- mild to moderate nausea
- anaphylaxis
Drug interactions
- cyclosporine increases the risk of nephrotoxicity
- cimetidine decreases oral absorption of melphalan
Test interactions
- false positive Coomb's test (direct)
Mechanism of action
- alkylating agent
- interferes with DNA & RNA synthesis
More general terms
Component of
References
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ 2.0 2.1 Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
- ↑ Harrison's Principles of Internal Medicine, 14th ed. Fauci et al (eds), McGraw-Hill Inc. NY, 1998, pg 529
- ↑ 4.0 4.1 4.2 Deprecated Reference
- ↑ 5.0 5.1 Young KD Follow-up Trial of Myeloma Drug 'Flopped,' Says FDA Panel. Medscape. September 23, 2022 https://www.medscape.com/viewarticle/981343