MELPHALAN

MELPHALAN
(mel'fa-lan)
Alkeran
Classifications: antineoplastic; alkylating agent;
Therapeutic:antineoplastic; alkylating agent

Prototype: Cyclophosphamide
Pregnancy Category: D

Availability

2 mg tablets; 50 mg/vial injection

Action

Forms a highly reactive carbonium ion which causes cross-linking and abnormal base-pairing in DNA, thereby interfering with DNA as well as RNA replication and protein synthesis.

Therapeutic Effect

Strong immunosuppressive and myelosuppressive effects.

Uses

Chiefly for palliative treatment of multiple myeloma. Also many other neoplasms, including Hodgkin's disease and carcinomas of breast and ovary.

Unlabeled Uses

Polycythemia vera.

Contraindications

Severe bone marrow suppression; hepatic disease; renal impairment, renal failure; severe electrolyte imbalance; lactation; pregnancy (category D); men and women of childbearing age.

Cautious Use

Recent treatment with other chemotherapeutic agents; concurrent administration with radiation therapy; severe anemia, neutropenia, or thrombocytopenia.

Route & Dosage

Multiple Myeloma
Adult: PO 6 mg/d for 2–3 wk, drug then withdrawn for 4–5 wk,  restart at 2 mg/d when WBC and platelet counts start to rise IV 16 mg/m2 over 15 min q2wk for 4 doses

Epithelial Ovarian Cancer
Adult: PO 0.2 mg/kg/d for 5 d as single course, may repeat course q4–5wk

Administration

Oral
  • Give with meals to reduce nausea and vomiting. An antiemetic may be ordered.
Intravenous

PREPARE: IV Infusion: Reconstitute melphalan powder by RAPIDLY injecting 10 mL of the provided diluent into the vial to yield 5 mg/mL. Shake vigorously until clear. Immediately dilute further with NS to a concentration of 0.45 mg/mL or less. Note: 45 mg in 100 mL yields 0.45 mg/mL. Do not refrigerate reconstituted solution prior to infusion.  

ADMINISTER: IV Infusion: Give over ≥15 min. Administration MUST be completed within 60 min of reconstitution of drug because both reconstituted and diluted solutions are unstable.  

INCOMPATIBILITIES Solution/Additive: D5W, Ringer's lactate. Y-site: Amphotericin B, chlorpromazine.

  • Store at 15°–30° C (59°–86° F) in light-resistant, airtight containers.

Adverse Effects (≥1%)

Hematologic: Leukopenia, agranulocytosis, thrombocytopenia, anemia, acute nonlymphatic leukemia. Body as a Whole: Uremia, angioneurotic peripheral edema. GI: Nausea, vomiting, stomatitis. Skin: Temporary alopecia. Respiratory: Pulmonary fibrosis.

Interactions

Drug: Increases risk of nephrotoxicity with cyclosporine, cimetidine may decrease efficacy. Food: Food decreases absorption.

Pharmacokinetics

Absorption: Incompletely and variably absorbed from GI tract. Peak: 2 h. Distribution: Widely distributed to all tissues. Metabolism: By spontaneous hydrolysis in plasma. Elimination: 25–50% in feces; 25–30% in urine. Half-Life: 1.5 h.

Nursing Implications

Assessment & Drug Effects

  • Lab tests: Monitor WBC and platelet counts 2–3 times/wk during dosage adjustment period; determine WBC each week for 6–8 wk during maintenance therapy. Monitor serum uric acid levels.
  • Monitor laboratory reports to anticipate leukopenic and thrombocytopenic periods.
  • A degree of myelosuppression is maintained during therapy so as to keep leukocyte count in range of 3000–3500/mm3.
  • Assess for flank and joint pains that may signal onset of hyperuricemia.

Patient & Family Education

  • Be alert to onset of fever, profound weakness, chills, tachycardia, cough, sore throat, changes in kidney function, or prolonged infections and report to physician.
  • Understand that reversible hair loss is an expected adverse effect.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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