melphalan

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

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);
Rep: 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.

Adv. Reactions/Side Effects ⬆ ⬇

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, 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.
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.

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

Availability ⬆ ⬇

(Generic available)

Powder for injection: 50 mg/vial

Assessment ⬆ ⬇

Assess for signs of infection (fever, chills, sore throat, cough, hoarseness, lower back or side pain, difficult or painful urination). Notify health care professional if these symptoms occur.
Assess for bleeding (bleeding gums, bruising, petechiae, guaiac stools, urine, and emesis). Avoid IM injections and taking rectal temperatures. Apply pressure to venipuncture sites for 10 min.
May cause nausea and vomiting. Monitor intake and output, appetite, and nutritional intake. Prophylactic antiemetics may be used. Adjust diet as tolerated.
Monitor for symptoms of gout (increased uric acid, joint pain, edema). Encourage patient to drink at least 2 L of fluid per day. Allopurinol may be given to decrease uric acid levels.
Anemia may occur. Monitor for increased fatigue and dyspnea.
Assess patient for allergy to chlorambucil. Patients may have cross-sensitivity.
Evomela: For patients receiving Evomela as part of a conditioning regimen, nausea, vomiting, mucositis, and diarrhea may occur in over 50% of patients. Use prophylactic antiemetic medication and provide supportive care. Provide nutritional support and analgesics for patients with severe mucositis

Lab Test Considerations:

Monitor CBC and differential weekly during therapy. The nadir of leukopenia occurs in 2–3 wk. Notify health care professional if leukocyte count is <3000/mm³. The nadir of thrombocytopenia occurs in 2–3 wk. Notify health care professional if platelet count is <100,000/mm³. Recovery of leukopenia and thrombocytopenia occurs in 5–6 wk.
- Monitor liver function studies (AST, ALT, LDH, bilirubin) and renal function studies (BUN, serum creatinine) prior to and periodically during therapy to detect hepatotoxicity and nephrotoxicity.
- May cause ↑ uric acid. Monitor periodically during therapy.
- May cause ↑ 5-hydroxyindoleacetic acid concentrations as a result of tumor breakdown.
- Intra-hepatic Hepzato can only be used in patients with Hgb ≥10 g/dL, platelets ≥100,000/mm³, and neutrophils >2000/mm³ who weigh ≥35 kg.

Implementation ⬆ ⬇

Hepzato: REMS: Hepzato is part of the Hepzato Kit Hepatic Delivery System [HDS], which is only available through the Hepzato Kit Hepatic Delivery System REMS. Health care professionals must complete required Hepzato Kit REMS training before administering Hepzato Kit, and health care facilities must be certified to offer the program. Oral anticoagulation, drugs affecting platelet function, ACE inhibitors, calcium channel blockers, and alpha-1-adrenergic blockers must be discontinued before the procedure.
Assess for latex allergies. The double balloon catheter component of the HDS contains natural rubber latex, which may cause allergic reactions.
If Grade 4 neutropenia of >5 days duration despite growth factor support or associated with neutropenic fever OR Grade 4 thrombocytopenia of >5 days duration or associated with a hemorrhage that required a transfusion occurs, a dose reduction to 2 mg/kg is recommended for subsequent treatments. Discontinue Hepzato if patients have life-threatening or Hepzato-related persistent toxicity that has not resolved to Grade ≤ 2 by 8 wk following treatment.
IA: Rapidly (in ≤5 seconds) inject 10 mL of the supplied sterile diluent into the Hepzato 50 mg vial using a sterile needle (≥20-gauge) and syringe. Resulting solution will contain melphalan 5 mg/mL. Immediately shake vial vigorously until a clear solution is obtained. No >5 seconds should elapse between discharge of the syringe and shaking. Immediately further dilute the required dose with the provided 0.9% NaCl, to a concentration <0.45 mg/mL. For Hepzato doses <110 mg: dilute in 250 mL of 0.9% NaCl. For Hepzato doses 111 mg–220 mg: divide total dose equally into 2 and dilute each in 250 mL of 0.9% NaCl. Solution is clear; do not administer solutions that are discolored or contain particulate matter. Administer diluted Hepzato intra-arterially with the Hepzato kit hepatic delivery system. Complete infusion within 30 min, followed by a 30-min washout period. Reconstituted and diluted solutions of Hepzato are unstable. No more than 60 min should elapse from reconstitution and completion of the intra-hepatic infusion of the diluted Hepzato solution. Do not refrigerate Hepzato once reconstituted.
Administration of Hepzato requires general anesthesia and extracorporeal bypass of circulation. Ensure patient is euvolemic, but do not overhydrate. Monitor for hemorrhage, hepatocellular injury, and thromboembolic events during the procedure and for at least 72 hr following the procedure. Closely monitor blood pressure during procedure; patients may require fluid support and vasopressors.

IV Administration:

Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard IV equipment in specially designated container.
- If solution contacts skin or mucosa, immediately wash skin or mucosa with soap and water.
Intermittent Infusion: Reconstitution: Reconstitute with 10 mL of diluent supplied.Concentration: 5 mg/mL. Shake vigorously until solution is clear. Diluent: Dilute dose immediately with 0.9% NaCl.Concentration: Not to exceed 0.45 mg/mL. Administer within 60 min of reconstitution. Store at room temperature and protect from light; do not refrigerate reconstituted solution.
Rate: Administer over 15–30 min. Keep time between reconstitution/dilution and administration to a minimum; reconstituted and diluted solutions are unstable.
Evomela : Intermittent Infusion: For patients receiving Evomela as part of a conditioning regimen, myeloablation occurs in all patients. Do not begin the conditioning regimen if a stem cell product is not available for rescue.Reconstitution: Reconstitute with 8.6 mL 0.9% NaCl. Concentration: 5 mg/mL. Reconstituted solution is stable for 1 hr at room temperature and 24 hr if refrigerated. Solution is clear and colorless to light yellow; do not administer solutions that are discolored or contain particulate matter. Diluent: Dilute further in 0.9% NaCl.Concentration: 0.45 mg/mL. Diluted solution is stable for an additional 4 hr at room temperature.
Rate: Infuse over 30 min via injection port or central venous catheter; may cause local tissue damage if extravasation occurs. Do not administer IV push into a peripheral vein. Administer Evomela by injecting slowly into a fast-running IV infusion via a central venous access line.
Y-Site Compatibility:
- acyclovir
- alemtuzumab
- amikacin
- aminophylline
- amphotericin B lipid complex
- ampicillin
- anidulafungin
- argatroban
- arsenic trioxide
- aztreonam
- bivalirudin
- bleomycin
- bumetanide
- buprenorphine
- butorphanol
- calcium gluconate
- carboplatin
- carmustine
- caspofungin
- cefazolin
- cefepime
- cefotaxime
- cefotetan
- ceftazidime
- ceftriaxone
- cefuroxime
- cisplatin
- clindamycin
- cyclophosphamide
- cytarabine
- dacarbazine
- dactinomycin
- daptomycin
- daunorubicin hydrochloride
- dexamethasone
- dexrazoxane
- diltiazem
- diphenhydramine
- doxorubicin hydrochloride
- doxycycline
- droperidol
- enalaprilat
- ertapenem
- etoposide
- famotidine
- filgrastim
- floxuridine
- fluconazole
- fludarabine
- fluorouracil
- foscarnet
- fosphenytoin
- furosemide
- ganciclovir
- gemtuzumab ozogamicin
- gentamicin
- granisetron
- haloperidol
- heparin
- hetastarch
- hydrocortisone
- hydromorphone
- idarubicin
- ifosfamide
- imipenem/cilastatin
- leucovorin calcium
- linezolid
- lorazepam
- mannitol
- meperidine
- mesna
- methadone
- methotrexate
- methylprednisolone
- metoclopramide
- metronidazole
- milrinone
- mitomycin
- mitoxantrone
- morphine
- moxifloxacin
- nalbuphine
- octreotide
- ondansetron
- palonosetron
- pamidronate
- pentostatin
- piperacillin/tazobactam
- potassium acetate
- potassium chloride
- prochlorperazine
- promethazine
- sodium bicarbonate
- thiotepa
- tigecycline
- tirofiban
- tobramycin
- trimethoprim/sulfamethoxazole
- vancomycin
- vasopressin
- vecuronium
- vinblastine
- vincristine
- vinorelbine
- voriconazole
- zidovudine
- zoledronic acid
Y-Site Incompatibility:
- amiodarone
- chlorpromazine
- pantoprazole

Patient/Family Teaching ⬆ ⬇

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.
Rep: 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.

Evaluation/Desired Outcomes ⬆ ⬇

Decrease in size and spread of malignant tissue.

US Brand Names ⬆ ⬇

~~Alkeran,~~ Evomela, Hepzato

Code ⬆

NDC Code

25021- Sagent Pharmaceuticals
- 25021-221- Melphalan Hydrochloride
  - 25021-221-60- 1 KIT in 1 CARTON (25021-221-60) * 10 mL in 1 VIAL (25021-220-10) * 10 mL in 1 VIAL (25021-210-15)

42023- Par Pharmaceutical, Inc.
- 42023-149- Melphalan Hydrochloride
  - 42023-149-01- 10 mL in 1 VIAL (42023-149-01)

43598- Dr.Reddy's Laboratories Inc
- 43598-392- Melphalan Hydrochloride
  - 43598-392-48- 1 KIT in 1 CARTON (43598-392-48) * 10 mL in 1 VIAL, SINGLE-DOSE (43598-391-50) * 10 mL in 1 VIAL, SINGLE-USE (43598-393-35)

45963- Actavis Pharma, Inc.
- 45963-686- Melphalan Hydrochloride
  - 45963-686-02- 1 KIT in 1 PACKAGE, COMBINATION (45963-686-02) * 10 mL in 1 VIAL, SINGLE-DOSE (45963-687-49) * 10 mL in 1 VIAL, SINGLE-USE (45963-688-57)

52609- ApoPharma USA, Inc.
- 52609-0001- ALKERAN
  - 52609-0001-5- 50 TABLET, FILM COATED in 1 BOTTLE (52609-0001-5)

52609- ApoPharma USA, Inc.
- 52609-3001- ALKERAN
  - 52609-3001-0- 1 KIT in 1 CARTON (52609-3001-0) * 10 mL in 1 VIAL, SINGLE-DOSE (52609-3002-0) * 10 mL in 1 VIAL, SINGLE-USE (52609-3003-0)

63323- Fresenius Kabi USA, LLC
- 63323-760- Melphalan
  - 63323-760-20- 1 KIT in 1 CARTON (63323-760-20) * 10 mL in 1 VIAL, SINGLE-USE (63323-732-10) * 10 mL in 1 VIAL, SINGLE-DOSE (63323-761-20)

67457- Mylan Institutional LLC
- 67457-195- Melphalan Hydrochloride
  - 67457-195-01- 1 KIT in 1 CARTON (67457-195-01) * 10 mL in 1 VIAL, GLASS (67457-193-50) * 10 mL in 1 VIAL, GLASS (67457-194-10)

67457- Mylan Institutional LLC
- 67457-215- Melphalan Hydrochloride
  - 67457-215-01- 1 KIT in 1 CARTON (67457-215-01) * 10 mL in 1 VIAL, GLASS (67457-213-50) * 10 mL in 1 VIAL, GLASS (67457-214-10)

67457- Mylan Institutional LLC
- 67457-579- Melphalan Hydrochloride
  - 67457-579-01- 1 KIT in 1 CARTON (67457-579-01) * 10 mL in 1 VIAL, GLASS (67457-577-50) * 10 mL in 1 VIAL, GLASS (67457-578-10)

68083- Gland Pharma Limited
- 68083-259- Melphalan hydrochloride
  - 68083-259-01- 1 KIT in 1 CARTON (68083-259-01) * 10 mL in 1 VIAL, SINGLE-USE (68083-261-01) * 10 mL in 1 VIAL, SINGLE-DOSE (68083-260-01)

68152- Spectrum Pharmaceuticals, Inc.
- 68152-109- EVOMELA
  - 68152-109-00- 1 VIAL in 1 CARTON (68152-109-00) > 20 mL in 1 VIAL

70860- Athenex Pharmaceutical Division, LLC.
- 70860-214- Melphalan Hydrochloride
  - 70860-214-61- 1 KIT in 1 CARTON (70860-214-61) * 10 mL in 1 VIAL, SINGLE-DOSE (70860-212-10) * 10 mL in 1 VIAL, SINGLE-USE (70860-213-10)

71288- Meitheal Pharmaceuticals Inc.
- 71288-112- Melphalan hydrochloride
  - 71288-112-90- 1 KIT in 1 CARTON (71288-112-90) * 10 mL in 1 VIAL, SINGLE-USE (71288-110-10) * 10 mL in 1 VIAL, SINGLE-DOSE (71288-111-10)

72266- Fosun Pharma USA Inc
- 72266-128- Melphalan hydrochloride
  - 72266-128-01- 1 KIT in 1 CARTON (72266-128-01) * 10 mL in 1 VIAL, SINGLE-USE (72266-145-01) * 10 mL in 1 VIAL, SINGLE-DOSE (72266-144-01)

72893- Acrotech Biopharma LLC
- 72893-001- EVOMELA
  - 72893-001-01- 1 VIAL in 1 CARTON (72893-001-01) > 20 mL in 1 VIAL

section name header

Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇