melphalan

High Alert

IV: High-dose conditioning treatment prior to hematopoietic stem cell transplantation (Evomela only).
IV: Palliative treatment of multiple myeloma.
IA: Uveal melanoma in patients 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).

Contraind./Precautions ⬆ ⬇

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 ≤2000 cells/mm³ (Hepzato only);
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Active infections;
↓bone marrow reserve;
Renal impairment (↓ dose ↓ for palliative treatment only if BUN ≥30 mg/dL);
Abnormal hepatic vascular or biliary anatomy or gastric acid hypersecretion syndromes (↑ risk of periprocedural complications with intra-arterial administration);
Rep: Women of reproductive potential and men with female 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.

Adv. Reactions/Side Effects ⬆ ⬇

CV: hypotension (Hepzato only), peripheral edema

Derm: alopecia, DEEP VEIN THROMBOSIS (DVT) (HEPZATO ONLY), pruritus, rash

Endo: menstrual irregularities

F and E: hypokalemia, hypophosphatemia

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

GU: infertility

Hemat: ↑aPTT, ↑INR, anemia, leukopenia, neutropenia, thrombocytopenia, HEMORRHAGE (HEPZATO ONLY)

Metab: hyperuricemia

MS: ↑troponin I, pain

Neuro: dizziness, fatigue, headache, lethargy

Resp: cough, dyspnea, PULMONARY EMBOLISM (PE) (HEPZATO ONLY)

Misc: fever, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS), SECONDARY MALIGNANCY

Interactions ⬆ ⬇

Drug-drug:

↑bone marrow depression with other antineoplastics or radiation therapy.
May ↓ antibody response to live-virus vaccines and ↑ risk of adverse reactions.
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.
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.

Availability ⬆ ⬇

(Generic available)

Powder for injection: 50 mg/vial
Solution for injection: 90 mg/mL

Route/Dosage ⬆ ⬇

Multiple Myeloma (Palliative Treatment)

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

Renal Impairment

IV (Adults ): BUN ≥30 mg/dL:↓ dose by up to 50%.

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

US Brand Names ⬆ ⬇

~~Alkeran,~~ Evomela, Hepzato, Ivra

Action ⬆ ⬇

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

Therapeutic effects:

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

Classifications ⬆ ⬇

Therapeutic Classification: antineoplastics

Pharmacologic Classification: alkylating agents

Pharmacokinetics ⬆ ⬇

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.

Time/Action Profile ⬆ ⬇

(effects on blood counts)

ROUTE	ONSET	PEAK	DURATION
IV	unknown	2–3 wk	4–5 wk
Intra-arterial	unknown	10–13 days	2–3 wk

Patient/Family Teaching ⬆ ⬇

Explain purpose of melphalan to patient. If an appointment is missed, contact health care provider as soon as possible to reschedule. Advise patient to read Medication Guide before starting and periodically during therapy in case of changes.
Emphasize need for periodic lab tests to monitor for side effects.
Advise patient to notify health care provider 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 provider 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 provider if pain interferes with eating. Stomatitis pain may require treatment with opioid analgesics.
Advise patient to notify health care provider 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 light-headed or dizzy; blurry vision; swelling of face, tongue, or throat) occur.
Instruct patient not to receive any vaccinations without advice of health care provider.
Inform patient that melphalan may cause new cancers.
Rep: May cause fetal harm. Advise women of reproductive potential to use effective contraception during therapy and for 6 mo after last dose and to avoid breastfeeding during therapy and for 1 wk after last dose. Advise men with a female partner of reproductive potential to use effective contraception during therapy and for 3 mo after last dose. May cause female and male infertility.

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Indications ⬇