melphalan Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
1678 148-82-3

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • melphalan hydrochloride
  • melphalan
  • alkeran
  • levofalan
  • levofolan
  • levopholan
  • melfalan
  • phenylalanine mustard
  • sarcoclorin
  • melphalan HCl
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.
  • Molecular weight: 305.20
  • Formula: C13H18Cl2N2O2
  • CLOGP: -0.21
  • LIPINSKI: 0
  • HAC: 4
  • HDO: 2
  • TPSA: 66.56
  • ALOGS: -2.93
  • ROTB: 8

  • Status: OFP

  • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Benet LZ, Broccatelli F, Oprea TI
S (Water solubility) 0.10 mg/mL Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 12 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.33 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 71 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 0.48 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 7 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.14 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 1 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Jan. 17, 1964 FDA GLAXOSMITHKLINE

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Febrile neutropenia 672.85 66.18 186 2823 10696 2344380
Mucosal inflammation 593.28 66.18 145 2864 5079 2349997
Neutropenia 492.74 66.18 172 2837 21376 2333700
Venoocclusive liver disease 443.92 66.18 79 2930 529 2354547
Myelodysplastic syndrome 436.96 66.18 99 2910 2461 2352615
Pyrexia 419.88 66.18 198 2811 53510 2301566
Cytomegalovirus infection 393.93 66.18 92 2917 2621 2352455
Sepsis 393.11 66.18 140 2869 18348 2336728
Thrombocytopenia 351.07 66.18 130 2879 19001 2336075
Diarrhoea 326.67 66.18 194 2815 83370 2271706
Graft versus host disease 322.87 66.18 65 2944 894 2354182
Adenovirus infection 307.69 66.18 53 2956 284 2354792
Pancytopenia 301.99 66.18 102 2907 11350 2343726
Thrombotic microangiopathy 295.23 66.18 64 2945 1283 2353793
Acute graft versus host disease 289.49 66.18 55 2954 547 2354529
Acute myeloid leukaemia 250.72 66.18 64 2945 2646 2352430
Off label use 246.15 66.18 155 2854 73443 2281633
Acute kidney injury 241.12 66.18 111 2898 28011 2327065
Bone marrow failure 212.20 66.18 66 2943 5620 2349456
Pneumonia 206.04 66.18 120 2889 49176 2305900
Infection 205.46 66.18 87 2922 17942 2337134
Plasma cell myeloma 196.73 66.18 68 2941 8065 2347011
Venoocclusive disease 196.59 66.18 35 2974 233 2354843
Stomatitis 170.25 66.18 64 2945 9646 2345430
Renal failure 159.42 66.18 72 2937 17277 2337799
Viraemia 156.28 66.18 26 2983 108 2354968
Haemophagocytic lymphohistiocytosis 154.42 66.18 38 2971 1345 2353731
Product use in unapproved indication 147.50 66.18 60 2949 11140 2343936
BK virus infection 147.30 66.18 28 2981 278 2354798
Multiple organ dysfunction syndrome 147.23 66.18 54 2955 7587 2347489
Vomiting 146.98 66.18 112 2897 71490 2283586
Respiratory failure 146.38 66.18 63 2946 13465 2341611
Vitreous haemorrhage 142.03 66.18 29 2980 427 2354649
Mucosal disorder 141.78 66.18 29 2980 431 2354645
Graft versus host disease in skin 137.52 66.18 26 2983 250 2354826
Aspartate aminotransferase increased 137.31 66.18 59 2950 12553 2342523
Epstein-Barr virus infection 136.63 66.18 33 2976 1078 2353998
Cardiac failure 133.04 66.18 57 2952 12037 2343039
Herpes zoster 131.11 66.18 53 2956 9672 2345404
Anaemia 130.07 66.18 79 2930 34713 2320363
Cytomegalovirus viraemia 129.26 66.18 27 2982 447 2354629
Acute graft versus host disease in intestine 128.07 66.18 24 2985 219 2354857
Graft versus host disease in gastrointestinal tract 125.28 66.18 24 2985 249 2354827
Alanine aminotransferase increased 124.91 66.18 57 2952 13975 2341101
Varicella zoster virus infection 124.76 66.18 25 2984 333 2354743
Prothrombin level increased 122.25 66.18 20 2989 73 2355003
Human herpesvirus 6 infection 117.36 66.18 24 2985 356 2354720
Acute graft versus host disease in skin 115.72 66.18 24 2985 383 2354693
Posterior reversible encephalopathy syndrome 114.72 66.18 34 2975 2446 2352630
Septic shock 110.98 66.18 43 2966 7011 2348065
Chronic graft versus host disease 110.72 66.18 23 2986 370 2354706
Retinal pigment epitheliopathy 107.56 66.18 18 2991 78 2354998
Disease progression 105.38 66.18 54 2955 17041 2338035
Leukopenia 105.36 66.18 46 2963 10150 2344926
Atrial fibrillation 101.13 66.18 49 2960 13719 2341357
Second primary malignancy 99.04 66.18 25 2984 981 2354095
Premature menopause 97.26 66.18 19 2990 220 2354856
Neuropathy peripheral 97.17 66.18 45 2964 11387 2343689
Plasma cell myeloma recurrent 94.95 66.18 20 2989 345 2354731
Stem cell transplant 94.05 66.18 20 2989 362 2354714
Pneumonia fungal 93.74 66.18 20 2989 368 2354708
Nausea 93.17 66.18 106 2903 112083 2242993
Post transplant lymphoproliferative disorder 93.12 66.18 21 2988 504 2354572
Encephalitis viral 92.49 66.18 18 2991 204 2354872
Bronchospasm 91.64 66.18 30 2979 2994 2352082
Eyelid oedema 91.64 66.18 29 2980 2597 2352479
Epstein-Barr viraemia 88.51 66.18 16 2993 117 2354959
Pleural effusion 87.09 66.18 42 2967 11626 2343450
Enterococcal sepsis 86.06 66.18 16 2993 139 2354937
Ascites 83.92 66.18 33 2976 5587 2349489
Pericardial effusion 83.36 66.18 30 2979 3979 2351097
Malignant transformation 83.28 66.18 13 2996 32 2355044
Encephalopathy 83.23 66.18 31 2978 4530 2350546
Chorioretinal atrophy 83.00 66.18 13 2996 33 2355043
Pulmonary mycosis 81.03 66.18 15 2994 127 2354949
Iris atrophy 78.93 66.18 12 2997 23 2355053
Cystitis haemorrhagic 78.73 66.18 19 2990 617 2354459
Refractory cytopenia with multilineage dysplasia 77.03 66.18 12 2997 29 2355047
Platelet count decreased 75.05 66.18 42 2967 15771 2339305
Bacterial sepsis 73.03 66.18 17 2992 471 2354605
Toxicity to various agents 70.74 66.18 53 2956 32701 2322375
Gastrointestinal fungal infection 70.62 66.18 12 2997 58 2355018
Fungal infection 70.50 66.18 28 2981 4861 2350215
Nasal abscess 69.39 66.18 11 2998 31 2355045
Hypotension 68.96 66.18 52 2957 32384 2322692
Aplasia 67.80 66.18 16 2993 471 2354605
Basal cell carcinoma 66.90 66.18 23 2986 2664 2352412

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Febrile neutropenia 870.10 55.79 274 3847 10826 1731834
Mucosal inflammation 769.54 55.79 201 3920 3968 1738692
Venoocclusive liver disease 765.25 55.79 152 3969 781 1741879
Myelodysplastic syndrome 716.29 55.79 181 3940 3108 1739552
Pyrexia 547.32 55.79 294 3827 46106 1696554
Acute myeloid leukaemia 538.12 55.79 142 3979 2899 1739761
Off label use 478.07 55.79 253 3868 38318 1704342
Sepsis 391.32 55.79 178 3943 19260 1723400
Pneumonia 367.16 55.79 227 3894 45955 1696705
Neutropenia 366.72 55.79 167 3954 18093 1724567
Graft versus host disease 364.79 55.79 91 4030 1462 1741198
Diarrhoea 354.62 55.79 235 3886 53617 1689043
Cytomegalovirus infection 339.99 55.79 101 4020 3200 1739460
Acute graft versus host disease 331.30 55.79 75 4046 772 1741888
Multiple organ dysfunction syndrome 272.16 55.79 111 4010 9131 1733529
Thrombocytopenia 263.38 55.79 140 3981 21109 1721551
Pancytopenia 259.83 55.79 114 4007 11243 1731417
Stomatitis 252.82 55.79 91 4030 5313 1737347
Venoocclusive disease 213.83 55.79 45 4076 317 1742343
Second primary malignancy 208.78 55.79 54 4067 1005 1741655
Plasma cell myeloma 204.81 55.79 93 4028 9921 1732739
Thrombotic microangiopathy 198.00 55.79 54 4067 1241 1741419
Product use in unapproved indication 197.40 55.79 89 4032 9333 1733327
Basal cell carcinoma 196.00 55.79 62 4059 2421 1740239
Human herpesvirus 6 infection 188.27 55.79 41 4080 346 1742314
Malignant transformation 186.12 55.79 31 4090 40 1742620
Septic shock 174.27 55.79 78 4043 8031 1734629
Respiratory failure 158.24 55.79 88 4033 14417 1728243
Acute kidney injury 153.79 55.79 120 4001 34824 1707836
Cytomegalovirus viraemia 151.72 55.79 37 4084 535 1742125
Anaemia 146.82 55.79 109 4012 29348 1713312
Acute graft versus host disease in skin 146.63 55.79 36 4085 536 1742124
Chorioretinal atrophy 143.21 55.79 24 4097 33 1742627
Plasma cell myeloma recurrent 142.05 55.79 34 4087 452 1742208
Aspergillus infection 141.08 55.79 42 4079 1331 1741329
Renal failure 139.36 55.79 91 4030 19926 1722734
Mucosal disorder 138.97 55.79 31 4090 295 1742365
Infection 134.77 55.79 75 4046 12285 1730375
Platelet count decreased 117.09 55.79 76 4045 16447 1726213
Bronchopulmonary aspergillosis 114.84 55.79 37 4084 1529 1741131
Adenovirus infection 113.03 55.79 28 4093 433 1742227
Nausea 112.48 55.79 119 4002 51077 1691583
Herpes zoster 111.10 55.79 48 4073 4525 1738135
Cytopenia 110.96 55.79 32 4089 904 1741756
Alanine aminotransferase increased 108.48 55.79 65 4056 12213 1730447
Aspartate aminotransferase increased 108.35 55.79 62 4059 10694 1731966
Refractory anaemia with an excess of blasts 107.78 55.79 21 4100 94 1742566
Chronic graft versus host disease 107.72 55.79 28 4093 530 1742130
Parainfluenzae virus infection 105.79 55.79 23 4098 192 1742468
C-reactive protein increased 105.62 55.79 50 4071 5835 1736825
Haemophagocytic lymphohistiocytosis 100.97 55.79 33 4088 1427 1741233
Neutropenic sepsis 100.27 55.79 33 4088 1459 1741201
Choroidal dystrophy 99.72 55.79 15 4106 3 1742657
Retinal pigment epitheliopathy 98.26 55.79 19 4102 81 1742579
Haematotoxicity 97.07 55.79 29 4092 929 1741731
Cardiac failure 96.74 55.79 61 4060 12541 1730119
Bacterial infection 96.22 55.79 34 4087 1868 1740792
Graft versus host disease in gastrointestinal tract 95.82 55.79 24 4097 389 1742271
Neuropathy peripheral 94.95 55.79 54 4067 9199 1733461
Blood bilirubin increased 94.10 55.79 47 4074 6163 1736497
Pleural effusion 93.43 55.79 57 4064 11053 1731607
Renal impairment 93.00 55.79 59 4062 12255 1730405
Respiratory distress 90.03 55.79 43 4078 5114 1737546
Acute respiratory distress syndrome 88.62 55.79 38 4083 3513 1739147
Epstein-Barr virus infection 88.31 55.79 28 4093 1097 1741563
Epstein-Barr viraemia 88.11 55.79 18 4103 107 1742553
Eyelid oedema 88.06 55.79 29 4092 1284 1741376
Stem cell transplant 88.04 55.79 23 4098 444 1742216
Vomiting 85.63 55.79 90 4031 38225 1704435
Bacteraemia 85.27 55.79 31 4090 1849 1740811
Pneumocystis jirovecii pneumonia 84.21 55.79 33 4088 2423 1740237
Hepatitis B 82.24 55.79 28 4093 1375 1741285
Choroidal infarction 82.02 55.79 14 4107 23 1742637
Squamous cell carcinoma of skin 81.56 55.79 27 4094 1215 1741445
Vitreous haemorrhage 80.86 55.79 22 4099 499 1742161
Apoptosis 77.56 55.79 15 4106 64 1742596
Post transplant lymphoproliferative disorder 77.26 55.79 23 4098 727 1741933
Cystitis haemorrhagic 75.51 55.79 22 4099 644 1742016
Atrial fibrillation 75.22 55.79 56 4065 15055 1727605
Extraocular muscle disorder 73.93 55.79 14 4107 52 1742608
Systemic candida 73.56 55.79 19 4102 350 1742310
Disease progression 72.86 55.79 58 4063 17205 1725455
Polyneuropathy 72.43 55.79 27 4094 1728 1740932
Staphylococcal infection 72.39 55.79 36 4085 4671 1737989
Device related infection 72.37 55.79 29 4092 2257 1740403
Lymphopenia 72.10 55.79 28 4093 2005 1740655
Malignant neoplasm progression 71.65 55.79 53 4068 14105 1728555
Abdominal pain 69.66 55.79 62 4059 21428 1721232
Aplasia 69.41 55.79 19 4102 441 1742219
Bone marrow failure 69.00 55.79 36 4085 5164 1737496
Bronchospasm 67.95 55.79 27 4094 2055 1740605
Staphylococcal bacteraemia 67.58 55.79 21 4100 769 1741891
Colitis 67.34 55.79 33 4088 4147 1738513
Acute graft versus host disease in intestine 67.10 55.79 17 4104 289 1742371
Prothrombin level increased 65.52 55.79 13 4108 65 1742595
Acute graft versus host disease in liver 65.25 55.79 15 4106 165 1742495
BK virus infection 64.11 55.79 18 4103 460 1742200
Diffuse large B-cell lymphoma 64.09 55.79 22 4099 1107 1741553
Ameloblastoma 63.60 55.79 10 4111 6 1742654
Pulmonary alveolar haemorrhage 63.41 55.79 22 4099 1143 1741517
Metastases to retroperitoneum 63.39 55.79 11 4110 21 1742639
Juvenile melanoma benign 62.42 55.79 10 4111 8 1742652
Hypoxia 61.66 55.79 35 4086 5928 1736732
Cytokine release syndrome 61.23 55.79 18 4103 544 1742116
Hyperbilirubinaemia 58.78 55.79 25 4096 2262 1740398
Bacterial sepsis 58.43 55.79 18 4103 640 1742020
Interstitial lung disease 57.52 55.79 40 4081 9656 1733004
Transplant failure 57.39 55.79 16 4105 398 1742262
Metastases to muscle 56.37 55.79 10 4111 23 1742637
Engraftment syndrome 56.08 55.79 12 4109 92 1742568
Adenocarcinoma of colon 55.97 55.79 16 4105 437 1742223

Pharmacologic Action:

SourceCodeDescription
ATC L01AA03 ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS
ANTINEOPLASTIC AGENTS
ALKYLATING AGENTS
Nitrogen mustard analogues
FDA MoA N0000000236 Alkylating Activity
FDA EPC N0000175558 Alkylating Drug
MeSH PA D000477 Alkylating Agents
CHEBI has role CHEBI:88188 drug allergen
CHEBI has role CHEBI:35610 antineoplastic agent
CHEBI has role CHEBI:35705 immunosuppressive agent
MeSH PA D000970 Antineoplastic Agents
MeSH PA D018906 Antineoplastic Agents, Alkylating
MeSH PA D007155 Immunologic Factors
MeSH PA D007166 Immunosuppressive Agents
MeSH PA D019653 Myeloablative Agonists
MeSH PA D009676 Noxae

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Multiple myeloma indication 109989006 DOID:9538
Malignant tumor of ovary indication 363443007 DOID:2394
Allogeneic bone marrow transplantation off-label use 58390007
Diffuse non-Hodgkin's lymphoma, large cell off-label use 109969005
Acute hemorrhage contraindication 8573003
Vasculitis contraindication 31996006 DOID:865
Fibrosis of lung contraindication 51615001 DOID:3770
Portal vein obstruction contraindication 57348003
Hemolytic anemia contraindication 61261009 DOID:583
Acute infectious disease contraindication 63171007
Interstitial pneumonia contraindication 64667001
Leukopenia contraindication 84828003 DOID:615
Kidney disease contraindication 90708001 DOID:557
Radiation oncology AND/OR radiotherapy contraindication 108290001
Liver function tests abnormal contraindication 166603001
Drug-induced hepatitis contraindication 235876009
Anemia contraindication 271737000 DOID:2355
Pregnancy, function contraindication 289908002
Thrombocytopenic disorder contraindication 302215000 DOID:1588
Bone marrow depression contraindication 307762000
Breastfeeding (mother) contraindication 413712001
Granulocytopenic disorder contraindication 417672002

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 2.27 acidic
pKa2 9.25 Basic
pKa3 4.94 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
EQ 50MG BASE/VIAL EVOMELA ACROTECH N207155 March 10, 2016 RX POWDER INTRAVENOUS March 10, 2023 FOR HIGH-DOSE CONDITIONING TREATMENT PRIOR TO HEMATOPOIETIC PROGENITOR (STEM) CELL TRANSPLANTATION IN PATIENTS WITH MULTIPLE MYELOMA

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
DNA DNA CROSS-LINKING AGENT DRUG LABEL DRUG LABEL
L-type amino acid transporter 1 Unclassified Ki 4.26 CHEMBL

External reference:

IDSource
4020558 VUID
N0000022818 NUI
C0771055 UMLSCUI
D00369 KEGG_DRUG
1VXP4V453T UNII
3223-07-2 SECONDARY_CAS_RN
544002 SNOMEDCT_US
4018763 VANDF
6718 RXNORM
387297002 SNOMEDCT_US
5038 MMSL
d00287 MMSL
167596 MMSL
002633 NDDF
CHEBI:28876 CHEBI
CHEMBL852 ChEMBL_ID
CHEMBL250892 ChEMBL_ID
DB01042 DRUGBANK_ID
CHEMBL1200863 ChEMBL_ID
745 INN_ID
460612 PUBCHEM_CID
D008558 MESH_DESCRIPTOR_UI
7620 IUPHAR_LIGAND_ID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Melphalan Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 10139-321 KIT 50 mg None ANDA 13 sections
Melphalan Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 43598-392 KIT 50 mg INTRAVENOUS ANDA 14 sections
Melphalan Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 45963-686 KIT 50 mg INTRAVENOUS ANDA 15 sections
Melphalan HUMAN PRESCRIPTION DRUG LABEL 1 47781-200 TABLET 2 mg ORAL ANDA 13 sections
MELPHALAN HYDROCHLORIDE HUMAN PRESCRIPTION DRUG LABEL 1 50742-477 KIT 50 mg None ANDA 13 sections
ALKERAN HUMAN PRESCRIPTION DRUG LABEL 1 52609-0001 TABLET, FILM COATED 2 mg ORAL NDA 14 sections
ALKERAN HUMAN PRESCRIPTION DRUG LABEL 1 52609-3001 KIT 50 mg None NDA 14 sections
Melphalan HUMAN PRESCRIPTION DRUG LABEL 1 63323-760 KIT 50 mg None ANDA 13 sections
Melphalan Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 67457-195 KIT 50 mg None ANDA 14 sections
Melphalan Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 67457-215 KIT 50 mg None ANDA 14 sections
Melphalan Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 67457-579 KIT 50 mg None ANDA 14 sections
Melphalan hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 68083-259 KIT 50 mg None ANDA 13 sections
EVOMELA HUMAN PRESCRIPTION DRUG LABEL 1 68152-109 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 mg INTRAVENOUS NDA 20 sections
Melphalan Hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 70860-214 KIT 50 mg INTRAVENOUS ANDA 14 sections
Melphalan hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 71288-112 KIT 50 mg INTRAVENOUS ANDA 14 sections
Melphalan hydrochloride HUMAN PRESCRIPTION DRUG LABEL 1 72266-128 KIT 50 mg None ANDA 13 sections
EVOMELA HUMAN PRESCRIPTION DRUG LABEL 1 72893-001 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 mg INTRAVENOUS NDA 20 sections