Melphalan (melphalan HCl)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Melphalan, a nitrogen mustard-derivative alkylating agent, is an antineoplastic agent.
Melphalan is an alkylating agent that exhibits cytotoxic effects due to the extent of its interstrand cross-linking with DNA, probably by binding at the N7 position of guanine. Similar to other bifunctional alkylating agents, melphalan is active against both resting and rapidly dividing tumor cells.
Following oral administration, absorption of melphalan is extremely variable with respect to both time to initial appearance in plasma (range: 0- 6 hours) and maximum serum concentration. The mean absolute bioavailability of oral melphalan is also highly variable (range: 56% to 93%). This inconsistency may be due to incomplete intestinal absorption, variable ''first pass'' hepatic metabolism, or rapid hydrolysis.
Administration of oral melphalan with a high fat meal may decrease exposure by 36-54%. Following IV administration, serum melphalan concentrations decrease rapidly in a biexponential manner and the drug is distributed in whole body water. Melphalan distributes into CSF in low concentrations.
The drug is reportedly variably bound to plasma proteins (range: 53- 92%), mainly albumin, and to a lesser extent (about 20%) to alpha1-acid glycoprotein (alpha1-AGP). About 30% of melphalan is irreversibly bound to plasma proteins. Interactions of melphalan with immunoglobulins have been found to be negligible.
Following administration of a single oral dose, the terminal plasma half-life of melphalan was 1.5 hours. Following IV administration of melphalan hydrochloride in adult patients, the half-life of melphalan was about 10 minutes in the initial distribution phase (t1/2alpha) and about 75 minutes in the terminal elimination phase (t1/2beta). Melphalan is apparently eliminated from plasma mainly by spontaneous hydrolysis, forming the monohydroxy and dihydroxy derivatives of the drug; no other metabolites have been identified in humans.
Following IV administration of melphalan hydrochloride, total body clearance of the drug averages 7-9 mL/minute per kg in adult patients, although considerable interindividual variation in body clearance exists. In adult patients, total body clearance of melphalan may be decreased following multiple IV doses (e.g., 0.5 mg/kg every 6 weeks). Approximately 10% of a single oral dose of melphalan is excreted in urine unchanged within 24 hours.
Although renal elimination of melphalan appears to be low, results of a pharmacokinetic study indicate that there may be a direct correlation between renal function and theelimination rate constant of the drug, while a negative correlation may exist between AUC of the drug and renal function.
USES: This medication is used to treat certain types of cancer (such as multiple myeloma, ovarian). Melphalan is also used as a pretreatment for people who are undergoing a stem cell transplant for multiple myeloma. Melphalan belongs to a class of drugs known as alkylating agents.
It works by slowing or stopping the growth of cancer cells.
Generic name: melphalan HCl
Pronunciation: (MEL-fa-lan)
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Melphalan
Indications
The following indications are listed for Melphalan:
- Multiple Myeloma
Also known as: Plasma Cell Myeloma.
Dosing
Dosage of melphalan hydrochloride is expressed in terms of melphalan.
Dosage of melphalan must be adjusted carefully according to the clinical and hematologic response and tolerance of the patient in order to obtain optimum therapeutic results with minimum adverse effects.
If adverse effects occur during melphalan therapy, temporary interruption of therapy, dosage reduction, and/or permanent discontinuance of the drug may be necessary.
For oral melphalan tablets, discontinue therapy if the leukocyte count falls below 3000/mm3 or the platelet count falls below 100,000/mm3. May restart therapy after blood cell counts have recovered. Consider dose adjustment on the basis of blood counts at the nadir and day of treatment.
For IV melphalan hydrochloride, in some controlled clinical studies in patients with multiple myeloma, dosage reductions of 25% were employed when platelet counts were 75,000-99,999/mm3 or leukocyte counts were 3000-3999/mm3 and dosage reductions of 50% were used when platelet counts were 50,000-74,999/mm3 or leukocyte counts were 2000-2999/mm3; IV melphalan was discontinued when platelet or leukocyte counts fell below 50,000/mm3 or 2000/mm3, respectively.
Do not readminister oral or IV melphalan if a hypersensitivity reaction occurs.
Administer melphalan orally or by IV infusion. Melphalan also has been administered intraperitoneally+ and by regional isolated perfusion or infusion+(e.g., for melanoma).
Various preparations and formulations of melphalan are commercially available; dosage recommendations differ between the different preparations.
Store melphalan tablets in a refrigerator (2-8degreesC) protected from light.
Store melphalan hydrochloride powder for injection at controlled room temperature (20-25degreesC) protected from light.
Store melphalan hydrochloride for injection (Evomela(R)) at room temperature (25degreesC) protected from light. Excursions are permitted to 15-30degreesC.
Inspect parenteral drug products visually for particulate matter and discoloration prior to administration whenever solution and container permit.
No dosing information is available for this tab.
No dosing information is available for this tab.
Drug interactions
Drug interaction information involving melphalan is limited since degradation of the drug does not involve hepatic metabolism.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*History of serious hypersensitivity reaction to melphalan.
*Use in patients whose disease has demonstrated prior resistance to treatment.
There are no contraindication contraindications for this drug.
There are no severe contraindications for this drug.
There are no moderate contraindications for this drug.
Adverse reactions
Adverse effects reported in patients receiving oral melphalan include bone marrow suppression, nausea, vomiting, diarrhea, oral ulceration, hepatic disorders, pulmonary fibrosis, interstitial pneumonitis, rash, vasculitis, alopecia, hemolytic anemia, and allergic reactions.
Adverse effects reported in at least 50% of patients receiving IV melphalan (Evomela(R)) include decreased neutrophil, white blood cell, lymphocyte, and platelet counts, diarrhea, nausea, fatigue, hypokalemia, anemia, and vomiting.
There are no severe adverse reactions for this drug.
There are no less severe adverse reactions for this drug.
Precautions
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Safety and efficacy of melphalan have not been established in pediatric patients.
Melphalan may cause fetal harm if administered to pregnant women based on its mechanism of action and results of animal studies.
It is not known whether melphalan is distributed into milk in humans. Because of the potential for adverse reactions to melphalan in breast-fed infants, breastfeeding is not recommended.
The manufacturers make no specific dosage recommendations for geriatric patients. In general, dosage selection for geriatric patients should usually start at the low end of the dosing range.
Studies of oral melphalan did not include a sufficient number of patients 65 years and older to determine whether they respond differently from younger subjects. In the single-arm pivotal study of IV melphalan (Evomela(R)), 30% of patients were 65 years of age and older; no differences in safety or effectiveness were observed between these geriatric patients and younger adults. However, an increased incidence of engraftment syndrome was observed in older versus younger patients.
ICD codes
No ICD codes are available for this drug.
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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