• IV: High-dose conditioning treatment prior to hematopoietic stem cell transplantation (Evomela only).
• IV: Palliative treatment of multiple myeloma.
• IA: Patients with uveal melanoma with unresectable hepatic metastases affecting <50% of the liver and no extrahepatic disease or extrahepatic disease limited to the bone, lymph nodes, subcutaneous tissues, or lung that is amenable to resection or radiation (Hepzato only).

Contraindicated in:

• Hypersensitivity to melphalan
• History of allergy to natural rubber latex or heparin (Hepzato only)
• Heparin-induced thrombocytopenia (Hepzato only)
• History of severe allergic reaction to iodinated contrast not controlled by premedication with antihistamines and steroids (Hepzato only)
• Active intracranial metastases or brain lesion at risk for bleeding (Hepzato only)
• Liver failure, portal hypertension, or known varices at risk for bleeding (Hepzato only)
• Surgical or medical treatment of the liver in the past 4 wk (Hepzato only)
• Uncorrectable coagulopathy (Hepzato only)
• Unable to safely undergo general anesthesia, including active cardiac conditions (e.g., unstable coronary syndromes [unstable or severe angina or MI], worsening or new-onset HF, significant arrhythmias, or severe valvular disease) (Hepzato only)
• Platelets 100,000 cells/mm³ (Hepzato only)
• Hgb <10 g/dL (Hepzato only)
• Neutrophils 2,000 cells/mm³ (Hepzato only)
• OB: Pregnancy
• Lactation: Lactation.

Use Cautiously in:

• Active infections
• ↓bone marrow reserve
• Renal impairment (dose ↓ recommended for palliative treatment only if BUN 30 mg/dL)
• Abnormal hepatic vascular or biliary anatomy or gastric acid hypersecretion syndromes (↑ risk of peri-procedural complications with intra-arterial administration)
• Women of reproductive potential and men with female sexual partners of reproductive potential
• Pedi: Safety and effectiveness not established in children
• Geri: Begin at lower end of dosing range in older adults due to potential for age-related ↓ in renal, hepatic, or cardiac function.

CV: hypotension (Hepzato only), peripheral edema, THROMBOEMBOLIC EVENTS (HEPZATO ONLY).

Derm: alopecia, pruritus, rash.

Endo: menstrual irregularities.

F and E: hypokalemia, hypophosphatemia.

GI: ↓appetite, ↑liver enzymes (Hepzato Kit only), abdominal pain, constipation, diarrhea, hyperbilirubinemia, mucositis, nausea, vomiting, hepatotoxicity.

GU: infertility.

Hemat: ↑activated partial thromboplastin time, ↑international normalized ratio, anemia, leukopenia, neutropenia, thrombocytopenia, HEMORRHAGE (HEPZATO ONLY).

Metab: hyperuricemia.

MS: ↑troponin I, pain.

Neuro: dizziness, fatigue, headache, lethargy.

Resp: cough, dyspnea.
Misc: fever, (INCLUDING ANAPHYLAXIS)HYPERSENSITIVITY REACTIONS , SECONDARY MALIGNANCY.

Drug-Drug:

• ↑bone marrow depression with other antineoplastics or radiation therapy.
• May ↓ antibody response to live-virus vaccines and ↑ risk of adverse reactions.
• Concurrent use with cyclosporine may ↑ risk of renal failure.
• Apixaban, aspirin, clopidogrel, dabigatran, edoxaban, NSAIDs, prasugrel, rivaroxaban, ticagrelor, and warfarin may ↑ risk of bleeding during administration of intra-arterial infusion; discontinue prior to procedure.
• Use of ACE inhibitors, calcium channel blockers, or alpha-1 receptor blockers may ↑ risk of hypotension during administration of intra-arterial infusion; discontinue antihypertensives 5 half-lives before administration of intra-arterial infusion.

(Generic available)

• Powder for injection: 50 mg/vial;

Multiple Myeloma (Palliative Treatment)

• IV (Adults): 16 mg/m² every 2 wk for 4 doses, then every 4 wk.

Multiple Myeloma (Conditioning Treatment)

• IV (Adults): 100 mg/m²/day on Day 3 and Day 2 prior to autologous stem cell transplantation on Day 0.

Unresectable Hepatic Metastases in Patients with Uveal Melanoma

• IA (Adults): 3 mg/kg (based on ideal body weight) (max dose = 220 mg) every 6–8 wk for a total of 6 infusions.

Alkeran, Evomela, Hepzato

• Inhibits DNA and RNA synthesis by alkylation (cell-cycle phase–nonspecific).

• Death of rapidly replicating cells, particularly malignant ones.
• Also has immunosuppressive properties.

Therapeutic Classification: antineoplastics

Pharmacologic Classification: alkylating agents

Absorption: IV and intra-arterial administration results in complete bioavailability.

Distribution: Rapidly distributed to tissues.

Metabolism/Excretion: Rapidly metabolized in the bloodstream. Small amounts (10%) excreted unchanged by the kidneys.

Half-life: IV: 1.5 hr; Intra-arterial: 1.1 hr.

(effects on blood counts)

• Explain purpose of melphalan to patient.
• Advise patient to notify health care professional if fever; chills; dyspnea; persistent cough; sore throat; signs of infection; bleeding gums; bruising; petechiae; or blood in urine, stool, or emesis occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor. Caution patient not to drink alcoholic beverages or take products containing aspirin or other NSAIDs.
• Instruct patient to notify health care professional if skin rash, vasculitis, bleeding, fever, persistent cough, nausea, vomiting, amenorrhea, weight loss, or unusual lumps/masses occur.
• Instruct patient to inspect oral mucosa for redness and ulceration. If ulceration occurs, advise patient to use sponge brush and to rinse mouth with water after eating and drinking. Consult health care professional if pain interferes with eating. Stomatitis pain may require treatment with opioid analgesics.
• Advise patient to notify health care professional immediately if signs and symptoms of allergic reactions (skin reactions, including welts, rash, itching, and redness; fast heartbeat; shortness of breath or trouble breathing; feel lightheaded or dizzy; blurry vision; swelling of face, tongue, or throat) occur.
• Instruct patient not to receive any vaccinations without advice of health care professional.
• Inform patient that melphalan may cause new cancers.
• May cause fetal harm. Advise females of reproductive potential to use effective contraception during and for 6 mo after last dose of melphalan and avoid breastfeeding during and for 1 wk after last dose. Advise males with a female partner of reproductive potential to use effective contraception during and for 3 mo after last dose. May cause female and male infertility.
• Emphasize need for periodic lab tests to monitor for side effects.

MEL-fa-lan