Look Up > Drugs > Melphalan
Melphalan
Pronunciation
U.S. Brand Names
Generic Available
Synonyms
Pharmacological Index
Use
Pregnancy Risk Factor
Contraindications
Warnings/Precautions
Adverse Reactions
Overdosage/Toxicology
Drug Interactions
Stability
Mechanism of Action
Pharmacodynamics/Kinetics
Usual Dosage
Dietary Considerations
Monitoring Parameters
Test Interactions
Mental Health: Effects on Mental Status
Mental Health: Effects on Psychiatric Treatment
Dental Health: Local Anesthetic/Vasoconstrictor Precautions
Dental Health: Effects on Dental Treatment
Patient Information
Nursing Implications
Dosage Forms
References

Pronunciation
(MEL fa lan)

U.S. Brand Names
Alkeran®

Generic Available

No


Synonyms
L-PAM; L-Sarcolysin; Phenylalanine Mustard

Pharmacological Index

Antineoplastic Agent, Alkylating Agent


Use

Palliative treatment of multiple myeloma and nonresectable epithelial ovarian carcinoma; neuroblastoma, rhabdomyosarcoma, breast cancer


Pregnancy Risk Factor

D


Contraindications

Hypersensitivity to melphalan or any component; severe bone marrow suppression; patients whose disease was resistant to prior therapy


Warnings/Precautions

The U.S. Food and Drug Administration (FDA) currently recommends that procedures for proper handling and disposal for antineoplastic agents be considered. Is potentially mutagenic, carcinogenic, and teratogenic; produces amenorrhea. Reduce dosage or discontinue therapy if leukocyte count <3000/mm3 or platelet count <100,000/mm3; use with caution in patients with bone marrow suppression, impaired renal function, or who have received prior chemotherapy or irradiation; will cause amenorrhea. Toxicity to immunosuppressives is increased in elderly. Start with lowest recommended adult doses. Signs of infection, such as fever and WBC rise, may not occur. Lethargy and confusion may be more prominent signs of infection.


Adverse Reactions

>10%:

Hematologic: Myelosuppressive: Leukopenia and thrombocytopenia are the most common effects of melphalan. Irreversible bone marrow failure has been reported.

WBC: Moderate

Platelets: Moderate

Onset (days): 7

Nadir (days): 8-10 and 27-32

Recovery (days): 42-50

Second malignancies: Reported are melphalan more frequently

1% to 10%:

Cardiovascular: Vasculitis

Dermatologic: Vesiculation of skin, alopecia, pruritus, rash

Endocrine & metabolic: SIADH, sterility and amenorrhea

Gastrointestinal: Nausea and vomiting are mild; stomatitis and diarrhea are infrequent

Genitourinary: Bladder irritation, hemorrhagic cystitis

Hematologic: Anemia, agranulocytosis, hemolytic anemia

Respiratory: Pulmonary fibrosis, interstitial pneumonitis

Miscellaneous: Hypersensitivity


Overdosage/Toxicology

Symptoms of overdose include hypocalcemia, pulmonary fibrosis, nausea and vomiting, bone marrow suppression


Drug Interactions

Decreased effect: Cimetidine and other H2-antagonists: The reduction in gastric pH has been reported to decrease bioavailability of melphalan by 30%

Increased toxicity: Cyclosporine: Increased incidence of nephrotoxicity


Stability

Tablets/injection: Protect from light, store at room temperature (15°C to 30°C)

The time between reconstitution/dilution and administration of parenteral melphalan must be kept to a minimum (<60 minutes) because reconstituted and diluted solutions are unstable

Injection: Preparation:

Dissolve powder initially with 10 mL of diluent to a concentration of 5 mg/mL. This solution is chemically and physically stable for at least 90 minutes when stored at 25°C (77°F).

Immediately dilute dose in 0.9% sodium chloride to a concentration of 0.1-0.45 mg/mL. This solution is physically and chemically stable for at least 60 minutes at 25°C (77°F). HIGHLY UNSTABLE SOLUTION - administration should occur within one hour of dissolution. Do not refrigerate solution - precipitation occurs.

Standard I.V. dilution:

Dose/250-500 mL NS (concentration of 0.1-0.45 mg/mL)

MUST BE PREPARED FRESH - solution is stable for 1 hour after dilution and must be administered within that time period


Mechanism of Action

Alkylating agent which is a derivative of mechlorethamine that inhibits DNA and RNA synthesis via formation of carbonium ions; cross-links strands of DNA


Pharmacodynamics/Kinetics

Absorption: Oral: Variable and incomplete from the GI tract; food interferes with absorption

Distribution: Vd: 0.5-0.6 L/kg throughout total body water

Bioavailability: Unpredictable, decreasing from 85% to 58% with repeated doses

Half-life, terminal: 1.5 hours

Time to peak serum concentration: Reportedly within 2 hours

Elimination: 10% to 30% of a dose excreted unchanged in the urine; 20% to 50% excreted in the stool after oral administration


Usual Dosage

Oral (refer to individual protocols); dose should always be adjusted to patient response and weekly blood counts:

Children: 4-20 mg/m2/day for 1-21 days

Adults:

Multiple myeloma: 6 mg/day initially adjusted as indicated or 0.15 mg/kg/day for 7 days or 0.25 mg/kg/day for 4 days; repeat at 4- to 6-week intervals

Ovarian carcinoma: 0.2 mg/kg/day for 5 days, repeat every 4-5 weeks

Intravenous (refer to individual protocols):

Children:

Pediatric rhabdomyosarcoma: 10-35 mg/m2/dose every 21-28 days

High-dose melphalan with bone marrow transplantation for neuroblastoma: 70-100 mg/m2/day on day 7 and 6 before BMT or 140-220 mg/m2 single dose before BMT or 50 mg/m2/day for 4 days or 70 mg/m 2/day for 3 days

Adults:

Multiple myeloma: 16 mg/m2 administered at 2-week intervals for 4 doses, then repeat monthly as per protocol for multiple myeloma

Dosing adjustment in renal impairment:

Clcr 10-50 mL/minute: Administer at 75% of normal dose

Clcr <10 mL/minute: Administer at 50% of normal dose

or

BUN >30 mg/dL: Reduce dose by 50%

Serum creatinine >1.5 mg/dL: Reduce dose by 50%

Hemodialysis: Unknown

CAPD effects: Unknown

CAVH effects: Unknown


Dietary Considerations

Food interferes with oral absorption


Monitoring Parameters

CBC with differential and platelet count, serum electrolytes, serum uric acid


Test Interactions

False-positive Coombs' test [direct]


Mental Health: Effects on Mental Status

None reported


Mental Health: Effects on Psychiatric Treatment

Myelosuppression is common; avoid concurrent use with clozapine and carbamazepine


Dental Health: Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions


Dental Health: Effects on Dental Treatment

No effects or complications reported


Patient Information

Infusion: Report promptly any pain, irritation, or redness at infusion site. Oral: Preferable to take on an empty stomach, 1 hour prior to or 2 hours after meals. Do not take alcohol, aspirin or aspirin-containing medications, and OTC medications without consulting prescriber. Inform prescriber of all prescription medication you are taking. Maintain adequate fluid balance (2-3 L/day of fluids unless instructed to restrict fluid intake). May cause hair loss (reversible); easy bleeding or bruising (use soft toothbrush or cotton swabs and frequent mouth care, use electric razor, avoid sharp knives or scissors); increased susceptibility to infection (avoid crowds or exposure to infection - do not have any vaccinations unless approved by prescriber). Report unusual bleeding or bruising or persistent fever or sore throat; blood in urine, stool, or vomitus; delayed healing of any wounds; skin rash; yellowing of skin or eyes; changes in color of urine or black stool; pain or burning on urination; respiratory difficulty; or other severe adverse reactions. Pregnancy/breast-feeding precautions: Inform prescriber if you are pregnant. Do not get pregnant during or for 1 month following therapy. Male: Do not cause a female to become pregnant. Male/female: Consult prescriber for instruction on appropriate barrier contraceptive measures. This drug may cause severe fetal defects. Breast-feeding is not recommended.


Nursing Implications

Avoid skin contact with I.V. formulation


Dosage Forms

Powder for injection: 50 mg

Tablet: 2 mg


References

Alberts DS, Chang SY, Chen HS, et al, "Oral Melphalan Kinetics," Clin Pharmacol Ther, 1979, 26(6):737-45.

Berg SL, Grisell DL, DeLaney TF, et al, "Principles of Treatment of Pediatric Solid Tumors," Pediatr Clin North Am, 1991, 38(2):249-67.

Coates TD, "Survival From Melphalan Overdose," Lancet, 1984, 2(8410):1048.

Hutchins LF and Lipschitz DA, "Cancer, Clinical Pharmacology, and Aging," Clin Geriatr Med, 1987, 3(3):483-503.

Jeffrey LP, Chairman, National Study Commission on Cytotoxic Exposure. Position Statement. "The Handling of Cytotoxic Agents by Women Who Are Pregnant, Attempting to Conceive, or Breast-Feeding," January 12, 1987.

Kaplan HG, "Use of Cancer Chemotherapy in the Elderly," Drug Treatment in the Elderly, Vestal RE, ed, Boston, MA: ADIS Health Science Press, 1984, 338-49.

Kellie SJ and Kingston JE, "Ovarian Failure After High-Dose Melphalan in Adolescents," Lancet, 1987, 1(8547):1425.

Pole JG, Casper J, Elfenbein G, et al, "High-Dose Chemoradiotherapy Supported by Marrow Infusions for Advanced Neuroblastoma: A Pediatric Oncology Group Study," J Clin Oncol, 1991, 9(1):152-8.

Schroeder H, Pinkerton CR, Powles RL, et al, "High-Dose Melphalan and Total Body Irradiation With Autologous Marrow Rescue in Childhood Acute Lymphoblastic Leukemia After Relapse," Bone Marrow Transplant, 1991, 7(1):11-15.


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