Chemical: Drug
melphalan

PharmGKB contains no dosing guidelines for this . To report known genotype-based dosing guidelines, or if you are interested in developing guidelines, click here.



PharmGKB contains no Clinical Variants that meet the highest level of criteria.

To see more Clinical Variants with lower levels of criteria, click the button at the bottom of the page.

Disclaimer: The PharmGKB's clinical annotations reflect expert consensus based on clinical evidence and peer-reviewed literature available at the time they are written and are intended only to assist clinicians in decision-making and to identify questions for further research. New evidence may have emerged since the time an annotation was submitted to the PharmGKB. The annotations are limited in scope and are not applicable to interventions or diseases that are not specifically identified.

The annotations do not account for individual variations among patients, and cannot be considered inclusive of all proper methods of care or exclusive of other treatments. It remains the responsibility of the health-care provider to determine the best course of treatment for a patient. Adherence to any guideline is voluntary, with the ultimate determination regarding its application to be made solely by the clinician and the patient. PharmGKB assumes no responsibility for any injury or damage to persons or property arising out of or related to any use of the PharmGKB clinical annotations, or for any errors or omissions.

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The table below contains information about pharmacogenomic variants on PharmGKB. Please follow the link in the "Variant" column for more information about a particular variant. Each link in the "Variant" column leads to the corresponding PharmGKB Variant Page. The Variant Page contains summary data, including PharmGKB manually curated information about variant-drug pairs based on individual PubMed publications. The PMIDs for these PubMed publications can be found on the Variant Page.

The tags in the first column of the table indicate what type of information can be found on the corresponding Variant Page.

Links in the "Gene" column lead to PharmGKB Gene Pages.

List of all variant annotations for melphalan

Gene ? Variant?
(147)
Alternate Names ? Chemicals ? Alleles ?
(+ chr strand)
Function ? Amino Acid?
Translation
No VIP available CA VA
rs4240803 NC_000016.10:g.87855597G>A, NC_000016.9:g.87889203G>A, NM_003486.5:c.539-3748C>T, XM_006721286.2:c.20-3748C>T, XM_011523354.1:c.538+13288C>T, XM_011523355.1:c.8-3748C>T, rs57243996
G > A
SNP
No VIP available CA VA
rs4553808 NC_000002.11:g.204731005A>G, NC_000002.12:g.203866282A>G, NG_011502.1:g.3497A>G, NM_001037631.2:c.-1661A>G, NM_005214.4:c.-1661A>G, XR_241294.1:n.-1521A>G, rs61636940
A > G
SNP
No VIP available No Clinical Annotations available VA
rs4572514 NC_000019.10:g.45400508T>C, NC_000019.9:g.45903766T>C, NM_001142502.1:c.-21-2169A>G, NM_006663.3:c.-21-2169A>G, XM_005258424.1:c.190-2169A>G, rs35908066, rs60493644
T > C
SNP
No VIP available No Clinical Annotations available VA
rs967591 NC_000019.10:g.45406676G>A, NC_000019.9:g.45909934G>A, NG_015839.2:g.77153C>T, NM_001142502.1:c.-406C>T, NM_001297590.1:c.-21G>A, NM_006663.3:c.-1699C>T, NM_012099.1:c.-21G>A, XM_005258424.1:c.-196C>T, XM_005258425.1:c.-21G>A, rs35294695
G > A
SNP
Alleles, Functions, and Amino Acid Translations are all sourced from dbSNP 147

Overview

Generic Names
Trade Names
  • Alkeran
  • L-PAM
  • L-Phenylalanine mustard
  • L-Sarcolysin
  • L-Sarcolysine
  • L-Sarkolysin
  • Levofalan
  • Melfalan
  • Mephalan
  • Phenylalanine mustard
  • Phenylalanine nitrogen mustard
  • Sarcolysine
  • Sarkolysin
Brand Mixture Names

PharmGKB Accession Id

PA450354

Type(s):

Drug

Description

An alkylating nitrogen mustard that is used as an antineoplastic in the form of the levo isomer - melphalan, the racemic mixture - merphalan, and the dextro isomer - medphalan; toxic to bone marrow, but little vesicant action; potential carcinogen.

Source: Drug Bank

Indication

For the palliative treatment of multiple myeloma and for the palliation of non-resectable epithelial carcinoma of the ovary. Has also been used alone or as part of various chemotherapeutic regimens as an adjunct to surgery in the treatment of breast cancer, alone or in combination regimens for palliative treatment of locally recurrent or unresectable in-transit metastatic melanoma of the extremities, as well as for the treatment of amyloidosis with prednisone.

Source: Drug Bank

Other Vocabularies

Information pulled from DrugBank has not been reviewed by PharmGKB.

Pharmacology, Interactions, and Contraindications

Mechanism of Action

Alkylating agents work by three different mechanisms: 1) attachment of alkyl groups to DNA bases (primarily at the N-7 position of guanine and to a lesser extent, at the N-3 position of adenine), forming monoadducts and resulting in the DNA being fragmented by repair enzymes in their attempts to replace the alkylated bases, preventing DNA synthesis and RNA transcription from the affected DNA, 2) DNA damage via the formation of cross-links (bonds between atoms in the DNA) which prevents DNA from being separated for synthesis or transcription, and 3) the induction of mispairing of the nucleotides leading to mutations.

Source: Drug Bank

Pharmacology

Melphalan is an antineoplastic in the class of alkylating agents and is used to treat various forms of cancer. Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumor growth by cross-linking guanine bases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. In addition, these drugs add methyl or other alkyl groups onto molecules where they do not belong which in turn inhibits their correct utilization by base pairing and causes a miscoding of DNA. Alkylating agents are cell cycle-nonspecific. Alkylating agents work by three different mechanisms all of which achieve the same end result - disruption of DNA function and cell death.

Source: Drug Bank

Food Interaction

Take on an empty stomach. Food decreases bioavailabilty by approximately 30%. Increase liquid intake.

Source: Drug Bank

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Melphalan is not actively metabolised, it spontaneously degrades to mono and dihydroxy products.

Source: Drug Bank

Protein Binding

Moderate to high (60 to 90%), primarily to albumin and, to a lesser extent, alpha 1-acid glycoprotein. 30% is irreversibly bound.

Source: Drug Bank

Absorption

Incomplete, variable, 25-89% post oral dose

Source: Drug Bank

Half-Life

1.5 (+/-0.83) hours

Source: Drug Bank

Toxicity

Vomiting, ulceration of the mouth, diarrhea, and hemorrhage of the gastrointestinal tract; The principal toxic effect is bone marrow suppression. LD 50=11.2 mg/kg (orally in rat)

Source: Drug Bank

Route of Elimination

The 24-hour urinary excretion of parent drug in these patients was 10% ± 4.5%, suggesting that renal clearance is not a major route of elimination of parent drug.

Source: Drug Bank

Volume of Distribution

  • 0.5 L/kg

Source: Drug Bank

Chemical Properties

Chemical Formula

C13H18Cl2N2O2

Source: Drug Bank

Isomeric SMILES

c1cc(ccc1C[C@@H](C(=O)O)N)N(CCCl)CCCl

Source: OpenEye

Canonical SMILES

N[C@@H](CC1=CC=C(C=C1)N(CCCl)CCCl)C(O)=O

Source: Drug Bank

Average Molecular Weight

305.2

Source: Drug Bank

Monoisotopic Molecular Weight

304.074533244

Source: Drug Bank

SMILES

N[C@@H](CC1=CC=C(C=C1)N(CCCl)CCCl)C(O)=O

Source: Drug Bank

InChI String

InChI=1S/C13H18Cl2N2O2/c14-5-7-17(8-6-15)11-3-1-10(2-4-11)9-12(16)13(18)19/h1-4,12H,5-9,16H2,(H,18,19)/t12-/m0/s1

Source: Drug Bank

Genes that are associated with this drug in PharmGKB's database based on (1) variant annotations, (2) literature review, (3) pathways or (4) information automatically retrieved from DrugBank, depending on the "evidence" and "source" listed below.

Curated Information ?

Drug Interactions

Interaction Description
cyclosporine - melphalan Melphalan increases toxicity of cyclosporine (source: Drug Bank )
cyclosporine - melphalan Melphalan increases toxicity of cyclosporine (source: Drug Bank )
melphalan - cyclosporine Melphalan increases toxicity of cyclosporine (source: Drug Bank )
melphalan - cyclosporine Melphalan increases toxicity of cyclosporine (source: Drug Bank )
trastuzumab - melphalan Trastuzumab may increase the risk of neutropenia and anemia. Monitor closely for signs and symptoms of adverse events. (source: Drug Bank )

Curated Information ?

Relationships from National Drug File - Reference Terminology (NDF-RT)

May Treat
Contraindicated With

Publications related to melphalan: 8

No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
A single nucleotide polymorphism in SLC7A5 is associated with gastrointestinal toxicity after high-dose melphalan and autologous stem cell transplantation for multiple myeloma. Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation. 2014. Giglia Jennifer L, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available VA No VIP available No VIP available
The importance of a sub-region on chromosome 19q13.3 for prognosis of multiple myeloma patients after high-dose treatment and stem cell support: a linkage disequilibrium mapping in RAI and CD3EAP. Annals of hematology. 2011. Vangsted Annette J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available VIP No VIP available
Very important pharmacogene summary: ABCB1 (MDR1, P-glycoprotein). Pharmacogenetics and genomics. 2011. Hodges Laura M, et al. PubMed
No Dosing Guideline available No Drug Label available CA VA No VIP available No VIP available
Genetic variation associated with bortezomib-induced peripheral neuropathy. Pharmacogenetics and genomics. 2011. Favis Reyna, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Population pharmacokinetics of melphalan and glutathione S-transferase polymorphisms in relation to side effects. Clinical pharmacology and therapeutics. 2008. Kühne A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Elevated plasma ferritin and busulfan pharmacodynamics during high-dose chemotherapy regimens in children with malignant solid tumors. Clinical pharmacology and therapeutics. 2007. Bouligand J, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Overexpression of glutathione-S-transferase, MGSTII, confers resistance to busulfan and melphalan. Cancer investigation. 2005. Harkey Michael A, et al. PubMed
No Dosing Guideline available No Drug Label available No Clinical Annotation available No Variant Annotation available No VIP available No VIP available
Polymorphic variation in GSTP1 modulates outcome following therapy for multiple myeloma. Blood. 2003. Dasgupta Ranjit K, et al. PubMed

LinkOuts

Web Resource:
Wikipedia
National Drug Code Directory:
0173-0045-35
DrugBank:
DB01042
ChEBI:
28876
KEGG Drug:
D00369
PubChem Compound:
4053
PubChem Substance:
7847435
Drugs Product Database (DPD):
4715
BindingDB:
50038356
Therapeutic Targets Database:
DAP000791

Clinical Trials

These are trials that mention melphalan and are related to either pharmacogenetics or pharmacogenomics.

No trials loaded.

NURSA Datasets

provided by nursa.org

No NURSA datasets available.

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Sources for PharmGKB drug information: DrugBank, PubChem.