Melphalan
(L-PAML-Phenylalanine mustard, L-Sarcolysin)
Melphalan (Alkeran)
L-PAM (Alkeran)
L-Phenylalanine mustard (Alkeran)
L-Sarcolysin (Alkeran)
Melphalan
( MEL-fah-lan)
Pregnancy Category: D Alkeran (Abbreviation: MPL) (Rx)

Classification: Antineoplastic, alkylating agent

See Also: See also Antineoplastic Agents and Alkylating Agents .

Action/Kinetics: A bifunctional alkylating agent that forms an unstable ethylenimmonium ion that binds to or alkylates various intracellular substances including nucleic acids. It produces a cytotoxic effect by cross-linking of DNA and RNA strands as well as inhibition of protein synthesis. Absorption from GI tract is variable and incomplete. t 1/2 after PO: 90 min. Inactivated in tissues and body fluids although it will remain active in the blood for approximately 6 hr. Within 24 hr, 10% is excreted unchanged in the urine.

Uses: Multiple myeloma. Epithelial carcinoma of ovary (nonresectable). Use IV only when PO therapy is not appropriate. Investigational: Cancer of the breast and testes.

Contraindications: Lactation. Known resistance to drug.

Special Concerns: Safety and efficacy have not been determined in children less than 12 years of age. Use with extreme caution in those with compromised bone marrow function due to prior chemotherapy or radiation. Reduce IV dosage in impaired renal function.

Additional Side Effects: Severe bone marrow depression (especially after IV use) chromosomal aberrations (may be mutagenic), leukemia (acute, nonlymphatic) in clients with multiple myeloma. Also, hypersensitivity reactions including anaphylaxis, pulmonary fibrosis interstitial pneumonia, vasculitis, hemolytic anemia.

Laboratory Test Alterations: Uric acid and urinary 5-HIAA levels.

Overdose Management: Symptoms: Severe N&V;, decreased consciousness, seizures muscle paralysis, cholinomimetic symptoms, diarrhea, severe mucositis, stomatitis, colitis, hemorrhage of GI tract, bone marrow toxicity. Treatment: General supportive treatment, blood transfusions, antibiotics. Monitor hematology for up to 6 weeks. Use of filgrastim or sargramostim may decrease the period of pancytopenia.

Drug Interactions: Carmustine / Risk of lung toxicity Cisplatin / Drug-induced renal dysfunction melphalan excretion Cyclosporine / Risk of nephrotoxicity Interferon alfa / Levels of melphalan Nalidixic acid / Risk of severe hemorrhagic necrotic enterocolitis in pediatric clients

How Supplied: Powder for injection: 50 mg; Tablet: 2 mg

Dosage
?Tablets Multiple myeloma.
One of the following regimens may be used. (1) 6 mg given once daily for 2-3 weeks (adjust dose based on weekly blood counts). Drug is then discontinued for up to 4 weeks with blood count being monitored. When WBC and platelet counts are increasing, a maintenance dose of 2 mg/day can be started. (2) 10 mg/day for 7-10 days. Maximum leukocyte and platelet suppression occurs within 3-5 weeks with recovery within 4-8 weeks. When the WBC exceeds 4,000/mm ³ and the platelet count is greater than 100,000/mm ³, a maintenance dose of 2 mg/day can be started. Dose is then adjusted to 1-3 mg/day, depending on the hematologic response. Keep leukocytes in the range of 3,000-3,500 cells/mm ³. (3) 0.15 mg/kg/day for 7 days followed by a rest period of at least 2 weeks (up to 5 weeks may be needed). During the rest period, the leukocyte count will decrease; when WBC and platelet counts are increasing, a maintenance dose of 0.05 mg/kg/day may be given. (4) 0.25 mg/kg/day for 4 consecutive days (or 0.2 mg/kg/day for 5 consecutive days) for a total dose of 1 mg/kg/course of therapy. The 4- to 5-day courses can be repeated q 4-6 weeks if the granulocyte and platelet counts have returned to normal.
Epithelial ovarian cancer.
0.2 mg/kg/day for 5 days repeated q 4-5 weeks (as long as blood counts return to normal).
?IV Multiple myeloma.
Adults, usual: 16 mg/m ² as a single infusion over 15-20 min. Give this dose at 2-week intervals for a total of four doses. Reduce the dose up to 50% in clients with a BUN less than or equal to 30 mg/dL.