melphalan
melphalan [mel´fah-lan]
melphalan
lan´), n brand name: Alkeran;
drug class: antineoplastic;
action: responsible for cross-linking DNA strands, which leads to cell death;
uses: palliative treatment of multiple myeloma and nonresectable epithelial carcinoma of the ovary.
melphalan (L-PAM, L-phenylalanine mustard, L-sarcolysin) Warning - Hazardous drug!
Alkeran
Pharmacologic class: Alkylator
Therapeutic class: Antineoplastic
Pregnancy risk category D
FDA Boxed Warning
• Give under supervision of physician experienced in cancer chemotherapy, in facility with adequate diagnostic and treatment resources.
• Drug may cause severe bone marrow suppression leading to infection or bleeding. I.V. use causes greater myelosuppression than oral use, and also may lead to hypersensitivity reactions (including anaphylaxis).
• Drug may cause leukemia and is potentially mutagenic.
Action
Forms cross-links between strands of cellular DNA, disrupting DNA and RNA transcription and causing cell death
Availability
Powder for injection (melphalan hydrochloride): 50 mg
Tablets: 2 mg
⊘Indications and dosages
➣ Multiple myeloma
Adults: Initially, 6 mg P.O. daily for 2 to 3 weeks, then discontinue drug for up to 4 weeks or until white blood cell (WBC) and platelet counts increase; then give maintenance dosage of 2 mg/day or 0.15 mg/kg/day P.O. for 7 days or 0.25 mg/kg for 4 days, repeated q 4 to 6 weeks. For those who can't tolerate oral therapy, 16 mg/m2 by I.V. infusion over 15 to 20 minutes at 2-week intervals for four doses (usually with prednisone); I.V. dose can be repeated q 4 weeks after recovery from toxicity.
➣ Nonresectable advanced ovarian cancer
Adults: 0.2 mg/kg/day P.O. for 5 days q 4 to 5 weeks
Dosage adjustment
• Renal impairment
Contraindications
• Hypersensitivity to drug
• Patients whose disease has shown previous drug resistance
Precautions
Use cautiously in:
• bone marrow depression, infection, renal disease
• previous radiation therapy
• patients with childbearing potential
• pregnant or breastfeeding patients
• children (safety and efficacy not established).
Administration
• Before starting therapy, obtain CBC with white cell differential and platelet count. Repeat periodically before each course.
• For I.V. use, reconstitute by rapidly injecting 10 ml of supplied diluent into vial with lyophilized powder. Shake until solution is clear (yields a concentration of 5 mg/ml).
• Dilute desired dosage in 0.9% sodium chloride injection to a concentration no greater than 0.45 mg/ml. Administer over 15 minutes, being sure to give entire dose within 60 minutes of reconstitution.
☞ Minimize time between reconstitution, dilution, and administration, because solution is unstable.
| Route | Onset | Peak | Duration |
| P.O. | 5 days | 2-3 wk | 5-6 wk |
| I.V. | Unknown | Unknown | Unknown |
Adverse reactions
CV: hypotension, tachycardia, vasculitis
GI: nausea, vomiting, diarrhea, oral ulcers, stomatitis
GU: hyperuricemia, amenorrhea, gonadal suppression, infertility
Hematologic: anemia, purpura, bone marrow depression, leukopenia, thrombocytopenia
Hepatic: hepatotoxicity
Metabolic: hyperuricemia
Respiratory: dyspnea, interstitial pneumonitis, bronchospasm, fibrosis
Skin: rash, urticaria, pruritus, alopecia, sweating
Other: edema, extravasation at I.V. site, allergic reactions including anaphylaxis
Interactions
Drug-drug. Carmustine: increased pulmonary toxicity
Cimetidine: decreased GI absorption of melphalan
Cisplatin: increased risk of renal dysfunction, decreased melphalan clearance
Cyclosporine: increased risk of nephrotoxicity, severe renal failure
Interferon alfa: decreased melphalan blood level
Live-virus vaccines: decreased antibody response to vaccine
Myelosuppressants: additive toxicity
Nalidixic acid: increased risk of severe hemorrhagic necrotic enterocolitis (in children)
Drug-diagnostic tests. Hemoglobin, platelets, red blood cells, WBCs: decreased values
Nitrogenous compounds: increased levels
Drug-food. Any food: decreased absorption of oral melphalan
Patient monitoring
☞ Monitor patient for thrombocytopenia and leukopenia. If platelet count exceeds 100,000/mm3 or WBC count is below 3,000/mm3, discontinue drug until peripheral blood counts recover.
☞ Watch closely for indications of bone marrow depression, including infection, anemia, and bleeding.
☞ After multiple courses, watch for acute hypersensitivity reaction. If it occurs, discontinue drug and administer volume expanders, corticosteroids, or antihistamines, as prescribed.
• Watch for signs and symptoms of GI or pulmonary toxicity.
• Evaluate renal and hepatic function.
Patient teaching
• Tell patient to take oral tablets without food, because food may decrease drug absorption.
• Instruct patient to take entire daily oral dose at one time on empty stomach.
☞ Advise patient to immediately report unusual bleeding or bruising, fever, chills, sore throat, shortness of breath, yellowing of skin or eyes, persistent cough, flank or stomach pain, joint pain, black tarry stools, rash, or unusual lumps or masses.
• Tell patient to consult prescriber before using over-the-counter medications.
• Advise patient to use reliable contraception.
• Caution patient to avoid breastfeeding.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and foods mentioned above.
melphalan
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