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
Acute graft versus host disease 524.33 17.77 152 22132 4165 53322617
Mucosal inflammation 523.73 17.77 285 21999 42499 53284283
Graft versus host disease 445.46 17.77 151 22133 6971 53319811
Plasma cell myeloma 392.55 17.77 246 22038 47628 53279154
Myelodysplastic syndrome 390.48 17.77 173 22111 16487 53310295
Adenovirus infection 383.46 17.77 112 22172 3150 53323632
Venoocclusive liver disease 370.81 17.77 118 22166 4454 53322328
Febrile neutropenia 351.74 17.77 315 21969 104621 53222161
Thrombotic microangiopathy 337.15 17.77 132 22152 9205 53317577
Acute graft versus host disease in skin 292.22 17.77 91 22193 3195 53323587
Cytomegalovirus infection 280.79 17.77 145 22139 19394 53307388
Chronic graft versus host disease 272.88 17.77 86 22198 3142 53323640
Neutropenia 250.74 17.77 320 21964 158865 53167917
Cytomegalovirus infection reactivation 241.19 17.77 74 22210 2470 53324312
Thrombocytopenia 216.97 17.77 278 22006 138449 53188333
Acute graft versus host disease in intestine 200.67 17.77 59 22225 1697 53325085
Acute myeloid leukaemia 196.44 17.77 109 22175 16823 53309959
Venoocclusive disease 187.30 17.77 58 22226 1997 53324785
Pancytopenia 184.33 17.77 208 22076 90720 53236062
Osteonecrosis 172.27 17.77 118 22166 26457 53300325
Graft versus host disease in skin 168.78 17.77 57 22227 2596 53324186
Post transplant lymphoproliferative disorder 162.00 17.77 63 22221 4308 53322474
BK virus infection 159.52 17.77 57 22227 3075 53323707
Product use in unapproved indication 152.30 17.77 210 22074 112079 53214703
Cystitis haemorrhagic 150.27 17.77 58 22226 3886 53322896
Sepsis 141.81 17.77 234 22050 146195 53180587
Graft versus host disease in gastrointestinal tract 136.05 17.77 50 22234 2924 53323858
Epstein-Barr virus infection 132.97 17.77 64 22220 7354 53319428
Viraemia 124.56 17.77 37 22247 1103 53325679
Stem cell transplant 122.74 17.77 41 22243 1804 53324978
Bone marrow failure 115.93 17.77 98 22186 30017 53296765
Haemophagocytic lymphohistiocytosis 114.74 17.77 62 22222 9075 53317707
Headache 112.63 17.77 42 22242 536779 52790003
Cytomegalovirus viraemia 111.01 17.77 50 22234 4941 53321841
Posterior reversible encephalopathy syndrome 98.23 17.77 69 22215 16091 53310691
Malignant transformation 98.17 17.77 24 22260 332 53326450
Retinal pigment epitheliopathy 97.37 17.77 22 22262 211 53326571
Human herpesvirus 6 infection 95.65 17.77 37 22247 2493 53324289
Mucosal disorder 95.16 17.77 35 22249 2051 53324731
Arthralgia 92.85 17.77 34 22250 439749 52887033
Plasma cell myeloma recurrent 92.56 17.77 37 22247 2720 53324062
Engraftment syndrome 90.39 17.77 23 22261 378 53326404
Epstein-Barr viraemia 90.38 17.77 27 22257 821 53325961
Off label use 87.54 17.77 409 21875 471803 52854979
Engraft failure 86.10 17.77 22 22262 368 53326414
Prothrombin level increased 84.98 17.77 20 22264 233 53326549
Drug hypersensitivity 84.70 17.77 7 22277 265235 53061547
Pyrexia 82.73 17.77 360 21924 402833 52923949
Chronic graft versus host disease in skin 81.69 17.77 24 22260 688 53326094
Second primary malignancy 80.20 17.77 45 22239 7087 53319695
Vitreous haemorrhage 79.63 17.77 30 22254 1880 53324902
Pain 77.74 17.77 79 22205 588319 52738463
Joint swelling 75.44 17.77 6 22278 234632 53092150
Osteonecrosis of jaw 75.37 17.77 84 22200 36062 53290720
Premature menopause 74.45 17.77 23 22261 785 53325997
Malaise 71.54 17.77 30 22254 357587 52969195
Acute myeloid leukaemia recurrent 71.29 17.77 26 22258 1487 53325295
Chorioretinal atrophy 71.10 17.77 14 22270 63 53326719
Varicella zoster virus infection 71.08 17.77 30 22254 2533 53324249
Acute graft versus host disease in liver 69.60 17.77 21 22263 661 53326121
Encephalitis viral 68.76 17.77 26 22258 1646 53325136
Viral haemorrhagic cystitis 67.58 17.77 21 22263 731 53326051
Fatigue 67.53 17.77 127 22157 730379 52596403
Iris atrophy 67.26 17.77 13 22271 52 53326730
Neuropathy peripheral 65.90 17.77 138 22146 103049 53223733
Aplasia 65.67 17.77 33 22251 4159 53322623
Abdominal discomfort 64.93 17.77 8 22276 221054 53105728
Cytomegalovirus test positive 63.99 17.77 29 22255 2906 53323876
Multiple organ dysfunction syndrome 63.48 17.77 96 22188 55581 53271201
Progressive multifocal leukoencephalopathy 62.80 17.77 47 22237 12082 53314700
Epstein-Barr virus infection reactivation 62.76 17.77 18 22266 473 53326309
Eye excision 62.70 17.77 12 22272 45 53326737
Acute lymphocytic leukaemia 61.49 17.77 28 22256 2837 53323945
Fall 59.90 17.77 38 22246 358402 52968380
Pneumonia fungal 59.58 17.77 32 22252 4624 53322158
Septic shock 56.84 17.77 97 22187 62132 53264650
Refractory cytopenia with multilineage dysplasia 56.42 17.77 13 22271 137 53326645
Chronic myelomonocytic leukaemia 55.00 17.77 15 22269 326 53326456
Dizziness 54.97 17.77 45 22239 372214 52954568
Polyneuropathy 54.93 17.77 45 22239 13188 53313594
Hepatitis B reactivation 54.01 17.77 23 22261 1985 53324797
Nasopharyngitis 53.99 17.77 8 22276 192287 53134495
Stomatitis 53.28 17.77 123 22161 98035 53228747
Tooth extraction 52.56 17.77 40 22244 10542 53316240
Choroidal infarction 52.01 17.77 11 22273 75 53326707
Febrile bone marrow aplasia 51.54 17.77 34 22250 7155 53319627
Peripheral swelling 50.57 17.77 12 22272 206096 53120686
Bronchopulmonary aspergillosis 50.34 17.77 36 22248 8629 53318153
Renal failure 50.15 17.77 135 22149 118317 53208465
Disturbance in social behaviour 49.53 17.77 24 22260 2797 53323985
Pericardial effusion 49.47 17.77 59 22225 27219 53299563
Bone debridement 49.25 17.77 14 22270 356 53326426
Plasmacytoma 48.48 17.77 23 22261 2558 53324224
Cytomegalovirus chorioretinitis 48.07 17.77 20 22264 1629 53325153
Alopecia 47.96 17.77 19 22265 234564 53092218
Infection 47.50 17.77 169 22115 172036 53154746
Enterococcal infection 47.47 17.77 33 22251 7565 53319217
Bacterial sepsis 47.28 17.77 26 22258 3936 53322846
Hypogonadism female 46.16 17.77 8 22276 14 53326768
Eyelid rash 45.66 17.77 10 22274 82 53326700
Nasal abscess 45.48 17.77 11 22273 145 53326637
Enterococcal sepsis 44.35 17.77 18 22266 1376 53325406
Mucocutaneous ulceration 44.29 17.77 11 22273 163 53326619
Epstein-Barr virus associated lymphoproliferative disorder 44.28 17.77 19 22265 1671 53325111
Haematotoxicity 44.03 17.77 32 22252 7865 53318917
Cardiac failure 43.78 17.77 105 22179 85739 53241043
Gastrointestinal fungal infection 43.78 17.77 12 22272 266 53326516
Product dose omission issue 43.51 17.77 13 22271 191607 53135175
Transplant failure 42.82 17.77 18 22266 1504 53325278
Pruritus 42.75 17.77 36 22248 293796 53032986
Respiratory syncytial virus infection 42.63 17.77 27 22257 5301 53321481
Extraocular muscle disorder 42.29 17.77 10 22274 119 53326663
Feeling abnormal 41.99 17.77 4 22280 135297 53191485
Eyelid oedema 41.94 17.77 35 22249 10519 53316263
Arthropathy 41.80 17.77 5 22279 141448 53185334
Anxiety 41.76 17.77 15 22269 196689 53130093
Pain in extremity 41.37 17.77 35 22249 285015 53041767
Tonsillar haemorrhage 40.78 17.77 11 22273 229 53326553
Idiopathic pneumonia syndrome 40.32 17.77 12 22272 360 53326422
JC virus infection 39.57 17.77 18 22266 1819 53324963
Chest pain 39.53 17.77 15 22269 190170 53136612
Plasma cell leukaemia 39.50 17.77 16 22268 1217 53325565
Morganella infection 38.93 17.77 13 22271 571 53326211
Dyspnoea 38.92 17.77 121 22163 586111 52740671
Bone disorder 37.93 17.77 45 22239 20638 53306144
Cytopenia 37.67 17.77 31 22253 9139 53317643
Sinus polyp 37.45 17.77 11 22273 315 53326467
Cardiac failure acute 35.82 17.77 30 22254 9062 53317720
Disease progression 35.21 17.77 108 22176 101812 53224970
Heterochromia iridis 34.81 17.77 6 22278 10 53326772
Infusion related reaction 34.64 17.77 11 22273 155946 53170836
Condition aggravated 34.63 17.77 44 22240 297090 53029692
Cardiomyopathy 34.39 17.77 39 22245 17049 53309733
Endocarditis bacterial 33.85 17.77 12 22272 632 53326150
Pneumonia cytomegaloviral 33.73 17.77 17 22267 2155 53324627
Urticaria 33.14 17.77 8 22276 135877 53190905
Growth failure 32.98 17.77 10 22274 320 53326462
Blood pressure increased 32.86 17.77 9 22275 140470 53186312
Leukaemia 32.73 17.77 20 22264 3686 53323096
Gastrointestinal mucosal disorder 31.86 17.77 12 22272 751 53326031
Asthma 31.83 17.77 4 22280 108968 53217814
Retinoblastoma 31.82 17.77 8 22276 125 53326657
Encephalopathy 31.80 17.77 56 22228 36752 53290030
Pulmonary haemorrhage 31.80 17.77 25 22259 6908 53319874
Follicular thyroid cancer 31.79 17.77 7 22277 59 53326723
Neuralgic amyotrophy 31.67 17.77 6 22278 21 53326761
Overdose 31.36 17.77 4 22280 107732 53219050
Sequestrectomy 31.36 17.77 13 22271 1049 53325733
Leukopenia 31.34 17.77 84 22200 73379 53253403
Depression 31.08 17.77 19 22265 183033 53143749
Herpes zoster 30.94 17.77 84 22200 73935 53252847
Bacteraemia 30.47 17.77 35 22249 15514 53311268
Ovarian failure 30.39 17.77 13 22271 1134 53325648
Oesophagitis 30.39 17.77 34 22250 14643 53312139
Chronic graft versus host disease in intestine 30.19 17.77 7 22277 76 53326706
Disease recurrence 29.57 17.77 40 22244 20906 53305876
Adenoviral haemorrhagic cystitis 29.46 17.77 8 22276 171 53326611
Eyelid ptosis 28.88 17.77 23 22261 6474 53320308
Bronchospasm 28.62 17.77 35 22249 16563 53310219
Infection reactivation 28.44 17.77 12 22272 1012 53325770
Drug interaction 28.21 17.77 30 22254 219299 53107483
Plastic surgery 28.11 17.77 7 22277 105 53326677
Contusion 28.04 17.77 6 22278 110726 53216056
Hypersensitivity 28.01 17.77 28 22256 210637 53116145
Wound 27.64 17.77 3 22281 91554 53235228
Mucosal erosion 27.57 17.77 13 22271 1426 53325356
Peritonitis viral 27.52 17.77 6 22278 48 53326734
Loss of consciousness 27.31 17.77 7 22277 114205 53212577
Osteolysis 27.11 17.77 16 22268 2769 53324013
Escherichia bacteraemia 27.06 17.77 17 22267 3291 53323491
Enophthalmos 26.90 17.77 6 22278 54 53326728
Lymphopenia 26.62 17.77 34 22250 16809 53309973
Endothelial dysfunction 26.56 17.77 7 22277 133 53326649
Paranoia 26.33 17.77 28 22256 11396 53315386
Acute respiratory distress syndrome 26.25 17.77 40 22244 23292 53303490
Hypogammaglobulinaemia 26.00 17.77 21 22263 6029 53320753
Acute promyelocytic leukaemia 25.98 17.77 11 22273 936 53325846
Gastrointestinal toxicity 25.87 17.77 19 22265 4743 53322039
Complications of bone marrow transplant 25.78 17.77 9 22275 453 53326329
Nausea 25.69 17.77 198 22086 755893 52570889
Blood stem cell transplant failure 25.54 17.77 7 22277 155 53326627
Retinal detachment 25.34 17.77 20 22264 5555 53321227
Weight increased 25.18 17.77 29 22255 204538 53122244
Gait disturbance 24.92 17.77 18 22266 158824 53167958
Acute kidney injury 24.70 17.77 186 22098 253682 53073100
Actinomycosis 24.65 17.77 11 22273 1063 53325719
Hepatitis B 24.54 17.77 17 22267 3875 53322907
Jaw operation 24.05 17.77 10 22274 813 53325969
Chest discomfort 24.05 17.77 6 22278 99689 53227093
Myocardial infarction 23.93 17.77 6 22278 99348 53227434
Toxicity to various agents 23.73 17.77 165 22119 219433 53107349
Myelosuppression 23.67 17.77 28 22256 12800 53313982
Weight decreased 23.23 17.77 39 22245 234909 53091873
Iris neovascularisation 23.16 17.77 5 22279 38 53326744
Transplantation complication 22.96 17.77 6 22278 110 53326672
Purulent discharge 22.83 17.77 18 22266 4992 53321790
Bone sequestrum 22.73 17.77 12 22272 1674 53325108
Insomnia 22.51 17.77 27 22257 187045 53139737
Fungaemia 22.49 17.77 13 22271 2164 53324618
Klebsiella bacteraemia 22.46 17.77 11 22273 1311 53325471
Osteomyelitis 22.41 17.77 38 22246 24197 53302585
Platelet count decreased 22.39 17.77 97 22187 108002 53218780
Aspergillus infection 22.10 17.77 21 22263 7475 53319307
Pulmonary veno-occlusive disease 21.91 17.77 10 22274 1018 53325764
Urethritis 21.69 17.77 7 22277 276 53326506
Retinal depigmentation 21.66 17.77 7 22277 277 53326505
Arthritis 21.55 17.77 5 22279 87293 53239489
Respiratory failure 21.43 17.77 91 22193 100421 53226361
Hyperhidrosis 21.18 17.77 7 22277 96786 53229996
Acinetobacter infection 21.13 17.77 11 22273 1492 53325290
Myalgia 21.10 17.77 15 22269 133476 53193306
Encephalitis 21.07 17.77 21 22263 7923 53318859
Graft versus host disease in liver 21.07 17.77 8 22276 512 53326270
Cerebral vasoconstriction 21.07 17.77 10 22274 1113 53325669
Aspartate aminotransferase increased 21.05 17.77 80 22204 83949 53242833
Culture stool positive 20.91 17.77 7 22277 310 53326472
Oesophageal squamous cell carcinoma stage IV 20.90 17.77 4 22280 15 53326767
Memory impairment 20.64 17.77 5 22279 84752 53242030
Drug intolerance 20.41 17.77 34 22250 205459 53121323
Pityriasis 20.34 17.77 3 22281 0 53326782
Hepatic enzyme increased 20.19 17.77 14 22270 126181 53200601
Oral disorder 20.02 17.77 21 22263 8414 53318368
Abdominal pain upper 20.00 17.77 24 22260 166267 53160515
Osteitis 19.99 17.77 14 22270 3245 53323537
Hepatic vein occlusion 19.95 17.77 5 22279 77 53326705
Pseudomonal sepsis 19.86 17.77 12 22272 2167 53324615
Chronic myeloid leukaemia 19.85 17.77 13 22271 2701 53324081
Graft versus host disease in lung 19.77 17.77 7 22277 367 53326415
Palpitations 19.75 17.77 9 22275 102339 53224443
Oral fungal infection 19.72 17.77 13 22271 2731 53324051
Swelling 19.56 17.77 31 22253 191074 53135708
Acute lymphocytic leukaemia recurrent 19.52 17.77 12 22272 2236 53324546
Schistocytosis 19.50 17.77 4 22280 23 53326759
Refractory cancer 19.44 17.77 5 22279 86 53326696
Intraductal proliferative breast lesion 19.42 17.77 13 22271 2801 53323981
JC virus CSF test positive 19.21 17.77 4 22280 25 53326757
Diarrhoea 18.88 17.77 366 21918 625180 52701602
Leukaemia recurrent 18.80 17.77 10 22274 1417 53325365
Pneumonia respiratory syncytial viral 18.65 17.77 8 22276 703 53326079
Refractory anaemia with an excess of blasts 18.62 17.77 7 22277 436 53326346
Bronchiolitis obliterans syndrome 18.54 17.77 5 22279 104 53326678
Blister 18.49 17.77 5 22279 78748 53248034
Pneumococcal infection 18.39 17.77 7 22277 451 53326331
IIIrd nerve disorder 18.27 17.77 3 22281 3 53326779
Chronic graft versus host disease in liver 18.05 17.77 6 22278 260 53326522
Type III immune complex mediated reaction 18.05 17.77 6 22278 260 53326522
Heart rate increased 17.93 17.77 6 22278 82309 53244473
Choroidal dystrophy 17.80 17.77 3 22281 4 53326778

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
Venoocclusive liver disease 607.52 17.12 231 27670 7134 32478491
Acute graft versus host disease 599.20 17.12 220 27681 6150 32479475
Mucosal inflammation 516.19 17.12 334 27567 33100 32452525
Myelodysplastic syndrome 497.40 17.12 272 27629 19766 32465859
Plasma cell myeloma 426.00 17.12 370 27531 57244 32428381
Acute myeloid leukaemia 423.26 17.12 241 27660 18933 32466692
Febrile neutropenia 358.02 17.12 475 27426 119091 32366534
Graft versus host disease 334.21 17.12 170 27731 10636 32474989
Acute graft versus host disease in skin 285.26 17.12 120 27781 4837 32480788
Chronic graft versus host disease 240.59 17.12 103 27798 4337 32481288
Venoocclusive disease 215.09 17.12 83 27818 2663 32482962
Thrombotic microangiopathy 208.60 17.12 119 27782 9363 32476262
Adenovirus infection 206.08 17.12 94 27807 4610 32481015
Graft versus host disease in gastrointestinal tract 200.31 17.12 84 27817 3357 32482268
Malignant transformation 168.01 17.12 51 27850 772 32484853
Acute graft versus host disease in intestine 167.35 17.12 68 27833 2505 32483120
Cytomegalovirus infection 166.92 17.12 153 27748 25311 32460314
Second primary malignancy 163.19 17.12 91 27810 6850 32478775
Graft versus host disease in skin 160.96 17.12 73 27828 3531 32482094
Human herpesvirus 6 infection 154.16 17.12 60 27841 1970 32483655
Off label use 152.64 17.12 591 27310 305729 32179896
Osteonecrosis 133.24 17.12 112 27789 16510 32469115
Product use in unapproved indication 133.05 17.12 255 27646 86949 32398676
Neutropenia 131.32 17.12 340 27561 141835 32343790
Chorioretinal atrophy 130.93 17.12 27 27874 64 32485561
Multiple organ dysfunction syndrome 114.89 17.12 211 27690 69643 32415982
Drug interaction 110.37 17.12 26 27875 218159 32267466
Stem cell transplant 108.68 17.12 48 27853 2179 32483446
Cytomegalovirus viraemia 108.03 17.12 69 27832 6658 32478967
Epstein-Barr virus infection 107.15 17.12 70 27831 7020 32478605
Plasma cell myeloma recurrent 105.48 17.12 56 27845 3821 32481804
Pancytopenia 103.14 17.12 236 27665 90999 32394626
Engraftment syndrome 101.65 17.12 36 27865 902 32484723
Mucosal disorder 99.92 17.12 42 27859 1687 32483938
Retinal pigment epitheliopathy 93.79 17.12 25 27876 229 32485396
Sepsis 92.61 17.12 323 27578 158511 32327114
Tooth extraction 88.08 17.12 54 27847 4848 32480777
Epstein-Barr viraemia 87.11 17.12 33 27868 1005 32484620
Aspergillus infection 86.64 17.12 75 27826 11499 32474126
Thrombocytopenia 85.93 17.12 301 27600 147998 32337627
Bronchopulmonary aspergillosis 85.32 17.12 80 27821 13607 32472018
Pyrexia 83.89 17.12 514 27387 319454 32166171
Haemophagocytic lymphohistiocytosis 81.92 17.12 72 27829 11263 32474362
Headache 81.92 17.12 33 27868 196164 32289461
Bone disorder 80.47 17.12 58 27843 6822 32478803
Post transplant lymphoproliferative disorder 79.48 17.12 54 27847 5780 32479845
Choroidal infarction 79.24 17.12 18 27883 77 32485548
Acute graft versus host disease in liver 78.19 17.12 33 27868 1339 32484286
Choroidal dystrophy 77.86 17.12 16 27885 37 32485588
Basal cell carcinoma 77.18 17.12 85 27816 17483 32468142
Dizziness 75.68 17.12 43 27858 209575 32276050
Haematotoxicity 74.44 17.12 55 27846 6721 32478904
Stomatitis 74.42 17.12 128 27773 40101 32445524
Neuropathy peripheral 73.90 17.12 187 27714 76795 32408830
Refractory anaemia with an excess of blasts 72.58 17.12 23 27878 404 32485221
Chronic graft versus host disease in skin 71.75 17.12 27 27874 807 32484818
Fatigue 71.21 17.12 120 27781 350581 32135044
BK virus infection 70.86 17.12 47 27854 4834 32480791
Progressive multifocal leukoencephalopathy 69.80 17.12 61 27840 9470 32476155
Cystitis haemorrhagic 66.50 17.12 46 27855 5068 32480557
Product dose omission issue 66.03 17.12 6 27895 102569 32383056
Malaise 65.85 17.12 35 27866 177103 32308522
Bacterial sepsis 64.96 17.12 46 27855 5262 32480363
Blood stem cell transplant failure 64.54 17.12 21 27880 403 32485222
Polyneuropathy 63.41 17.12 67 27834 13148 32472477
Engraft failure 62.46 17.12 21 27880 448 32485177
Arthralgia 61.87 17.12 25 27876 148423 32337202
Dyspnoea 60.42 17.12 139 27762 361906 32123719
Extraocular muscle disorder 60.24 17.12 17 27884 196 32485429
Cytopenia 59.24 17.12 57 27844 10007 32475618
Fall 59.14 17.12 49 27852 196152 32289473
Aplasia 57.87 17.12 40 27861 4402 32481223
Vitreous haemorrhage 57.43 17.12 31 27870 2186 32483439
Parainfluenzae virus infection 55.90 17.12 31 27870 2306 32483319
Diffuse large B-cell lymphoma 53.77 17.12 50 27851 8412 32477213
Transplant failure 53.61 17.12 32 27869 2736 32482889
Weight decreased 52.38 17.12 39 27862 164779 32320846
Chest pain 51.56 17.12 21 27880 124116 32361509
Acute lymphocytic leukaemia 51.37 17.12 34 27867 3484 32482141
Overdose 51.23 17.12 7 27894 87070 32398555
Apoptosis 49.84 17.12 15 27886 220 32485405
Death 49.55 17.12 166 27735 382351 32103274
Epstein-Barr virus associated lymphoproliferative disorder 47.90 17.12 26 27875 1854 32483771
Septic shock 47.87 17.12 149 27752 68840 32416785
Staphylococcal sepsis 47.10 17.12 50 27851 9863 32475762
Prothrombin level increased 46.87 17.12 13 27888 140 32485485
Posterior reversible encephalopathy syndrome 46.74 17.12 49 27852 9527 32476098
Herpes zoster 46.08 17.12 92 27809 32249 32453376
Bone debridement 45.61 17.12 15 27886 298 32485327
Cytomegalovirus infection reactivation 45.37 17.12 31 27870 3348 32482277
Bacterial infection 45.35 17.12 58 27843 13948 32471677
Juvenile melanoma benign 44.64 17.12 11 27890 71 32485554
Retinopathy proliferative 44.00 17.12 11 27890 76 32485549
Cytomegalovirus test positive 43.89 17.12 32 27869 3830 32481795
Transformation to acute myeloid leukaemia 43.66 17.12 18 27883 688 32484937
Sequestrectomy 43.59 17.12 15 27886 344 32485281
Neutropenic sepsis 43.36 17.12 54 27847 12645 32472980
Bone sequestrum 43.15 17.12 18 27883 709 32484916
Eyelid oedema 43.11 17.12 36 27865 5253 32480372
Gastrointestinal mucosal disorder 43.07 17.12 15 27886 357 32485268
Depression 42.66 17.12 15 27886 97045 32388580
Bacteraemia 42.03 17.12 63 27838 17570 32468055
Pneumonia cytomegaloviral 41.65 17.12 28 27873 2944 32482681
Peripheral swelling 41.39 17.12 5 27896 68340 32417285
Cerebral toxoplasmosis 40.77 17.12 22 27879 1550 32484075
Rhabdomyolysis 40.54 17.12 5 27896 67260 32418365
Debridement 40.41 17.12 19 27882 998 32484627
Acute respiratory distress syndrome 39.84 17.12 75 27826 25178 32460447
Blood pressure increased 38.97 17.12 10 27891 79344 32406281
Squamous cell carcinoma of skin 38.81 17.12 45 27856 9781 32475844
JC virus infection 38.75 17.12 23 27878 1946 32483679
Anxiety 38.63 17.12 17 27884 95988 32389637
Cerebrovascular accident 38.52 17.12 13 27888 86307 32399318
Myocardial infarction 38.31 17.12 31 27870 125645 32359980
Ameloblastoma 38.28 17.12 10 27891 84 32485541
Asthenia 38.12 17.12 92 27809 235852 32249773
Bone marrow failure 38.05 17.12 82 27819 30322 32455303
Myalgia 36.65 17.12 12 27889 81218 32404407
Systemic candida 36.55 17.12 26 27875 2995 32482630
Drug hypersensitivity 36.53 17.12 9 27892 73391 32412234
Idiopathic pneumonia syndrome 36.41 17.12 12 27889 240 32485385
Somnolence 36.39 17.12 22 27879 103775 32381850
Eyelid rash 36.27 17.12 8 27893 29 32485596
Meningomyelitis herpes 36.06 17.12 8 27893 30 32485595
Viral haemorrhagic cystitis 35.72 17.12 17 27884 918 32484707
Chorioretinal disorder 35.65 17.12 8 27893 32 32485593
Hepatitis B 35.60 17.12 35 27866 6306 32479319
Hepatic infection fungal 35.27 17.12 11 27890 183 32485442
Hyperhidrosis 34.89 17.12 9 27892 71159 32414466
Iris atrophy 34.63 17.12 9 27892 74 32485551
Autoimmune haemolytic anaemia 34.06 17.12 29 27872 4345 32481280
Lymphopenia 33.53 17.12 51 27850 14405 32471220
Metastases to retroperitoneum 33.24 17.12 11 27890 223 32485402
Refractory cytopenia with multilineage dysplasia 33.08 17.12 10 27891 149 32485476
Bone sarcoma 32.96 17.12 9 27892 91 32485534
Feeling abnormal 32.95 17.12 6 27895 60417 32425208
Epstein-Barr virus infection reactivation 31.73 17.12 13 27888 489 32485136
Ureaplasma infection 30.97 17.12 10 27891 187 32485438
Meningoencephalitis herpetic 30.97 17.12 15 27886 842 32484783
Neutropenic colitis 30.70 17.12 22 27879 2563 32483062
Eye excision 30.26 17.12 7 27894 33 32485592
Pruritus 29.91 17.12 40 27861 128662 32356963
Bradycardia 29.86 17.12 12 27889 71550 32414075
Metastases to muscle 29.84 17.12 10 27891 211 32485414
Autoimmune neutropenia 29.80 17.12 11 27890 311 32485314
Pain 29.59 17.12 74 27827 187482 32298143
Human herpesvirus 6 encephalitis 29.58 17.12 10 27891 217 32485408
Hepatic vein occlusion 29.48 17.12 9 27892 139 32485486
Acute lymphocytic leukaemia recurrent 29.47 17.12 23 27878 3049 32482576
Osteomyelitis 29.22 17.12 50 27851 15583 32470042
Coronary artery disease 29.21 17.12 4 27897 49702 32435923
B precursor type acute leukaemia 28.95 17.12 9 27892 148 32485477
Plasmacytoma 28.93 17.12 24 27877 3469 32482156
Chronic graft versus host disease in intestine 28.75 17.12 10 27891 237 32485388
Osteosarcoma 28.67 17.12 10 27891 239 32485386
Candida sepsis 28.45 17.12 16 27885 1223 32484402
Urticaria 28.35 17.12 8 27893 59606 32426019
Metapneumovirus infection 28.30 17.12 13 27888 647 32484978
Human herpesvirus 8 infection 28.21 17.12 14 27887 829 32484796
Carbamoyl phosphate synthetase deficiency 28.07 17.12 6 27895 18 32485607
Pneumonia respiratory syncytial viral 27.91 17.12 14 27887 848 32484777
Febrile bone marrow aplasia 27.48 17.12 35 27866 8380 32477245
Neoplasm skin 27.01 17.12 12 27889 552 32485073
Short stature 26.67 17.12 7 27894 60 32485565
Pneumonia 26.64 17.12 440 27461 354812 32130813
Infection 26.53 17.12 143 27758 84572 32401053
Leukaemia 26.19 17.12 24 27877 3962 32481663
Obliterative bronchiolitis 25.95 17.12 15 27886 1208 32484417
Neoplasm recurrence 25.65 17.12 18 27883 2029 32483596
Inflammatory myofibroblastic tumour 25.60 17.12 8 27893 134 32485491
Blood glucose increased 25.54 17.12 12 27889 65229 32420396
Confusional state 25.36 17.12 53 27848 143062 32342563
Klebsiella sepsis 25.19 17.12 17 27884 1799 32483826
Stenotrophomonas infection 25.15 17.12 17 27884 1803 32483822
Hepatitis B reactivation 25.10 17.12 22 27879 3427 32482198
Atrophy of globe 25.02 17.12 6 27895 34 32485591
Enteritis 24.98 17.12 31 27870 7230 32478395
Expanded disability status scale score increased 24.88 17.12 9 27892 240 32485385
Adenocarcinoma of colon 24.88 17.12 22 27879 3467 32482158
Asthma 24.85 17.12 4 27897 44061 32441564
Metastases to spleen 24.77 17.12 10 27891 362 32485263
Pain in extremity 24.65 17.12 40 27861 118861 32366764
Hypoglycaemia 24.59 17.12 8 27893 54374 32431251
Nasopharyngitis 24.56 17.12 12 27889 63775 32421850
Product use issue 24.55 17.12 100 27801 52677 32432948
Premature ageing 24.55 17.12 7 27894 84 32485541
Joint swelling 24.49 17.12 7 27894 51728 32433897
Graft versus host disease in liver 24.46 17.12 14 27887 1107 32484518
Capillary leak syndrome 24.30 17.12 17 27884 1906 32483719
Gait disturbance 24.28 17.12 20 27881 80388 32405237
Staphylococcal bacteraemia 24.26 17.12 31 27870 7445 32478180
Purulent discharge 23.72 17.12 20 27881 2956 32482669
Myelitis 23.63 17.12 12 27889 746 32484879
Balance disorder 23.61 17.12 3 27898 39456 32446169
Hyperbilirubinaemia 23.54 17.12 49 27852 17681 32467944
Insomnia 23.50 17.12 31 27870 100317 32385308
Chest discomfort 23.40 17.12 7 27894 50223 32435402
Respiratory syncytial virus infection 23.18 17.12 22 27879 3796 32481829
Iris neovascularisation 22.92 17.12 5 27896 17 32485608
Bone marrow transplant rejection 22.60 17.12 8 27893 200 32485425
Hospitalisation 22.50 17.12 7 27894 48964 32436661
Myositis 22.42 17.12 37 27864 11198 32474427
Delayed engraftment 22.41 17.12 7 27894 117 32485508
Chronic obstructive pulmonary disease 22.34 17.12 7 27894 48746 32436879
Pulmonary alveolar haemorrhage 22.25 17.12 29 27872 7100 32478525
Cytogenetic abnormality 22.05 17.12 12 27889 860 32484765
B-cell lymphoma recurrent 22.04 17.12 11 27890 659 32484966
Tooth impacted 21.95 17.12 6 27895 61 32485564
Papilloma 21.93 17.12 7 27894 126 32485499
Complications of bone marrow transplant 21.92 17.12 8 27893 219 32485406
Therapy partial responder 21.90 17.12 24 27877 4906 32480719
Blood creatine phosphokinase increased 21.81 17.12 6 27895 45470 32440155
Pulmonary haemorrhage 21.77 17.12 34 27867 9823 32475802
Metastases to bone marrow 21.53 17.12 10 27891 511 32485114
Heterochromia iridis 21.48 17.12 4 27897 4 32485621
Tremor 21.27 17.12 23 27878 81254 32404371
Musculoskeletal stiffness 21.19 17.12 4 27897 39260 32446365
Gingival erythema 21.15 17.12 7 27894 142 32485483
Condition aggravated 21.13 17.12 66 27835 155595 32330030
Mycobacterium kansasii infection 20.89 17.12 8 27893 251 32485374
Vision blurred 20.87 17.12 6 27895 44180 32441445
Laryngeal cancer metastatic 20.67 17.12 6 27895 77 32485548
Adenocarcinoma gastric 20.62 17.12 13 27888 1225 32484400
Pneumonia mycoplasmal 20.50 17.12 10 27891 570 32485055
Neurotoxicity 20.42 17.12 42 27859 15028 32470597
Viraemia 20.38 17.12 13 27888 1250 32484375
Jaw operation 20.37 17.12 8 27893 269 32485356
Hyperkalaemia 20.26 17.12 18 27883 69732 32415893
Myelosuppression 20.08 17.12 36 27865 11640 32473985
Herpes zoster meningoencephalitis 20.07 17.12 8 27893 280 32485345
Exophthalmos 20.04 17.12 10 27891 599 32485026
Retinoblastoma 19.94 17.12 5 27896 35 32485590
Retinal toxicity 19.90 17.12 9 27892 432 32485193
Bone lesion 19.88 17.12 18 27883 2925 32482700
Genotoxicity 19.82 17.12 5 27896 36 32485589
Acute myeloid leukaemia recurrent 19.71 17.12 15 27886 1915 32483710
Inflammatory pseudotumour 19.70 17.12 5 27896 37 32485588
Amyloidosis 19.67 17.12 16 27885 2250 32483375
Colitis 19.65 17.12 69 27832 33882 32451743
Electrocardiogram QT prolonged 19.45 17.12 5 27896 39636 32445989
VIth nerve paresis 19.36 17.12 5 27896 40 32485585
Transplantation associated food allergy 19.25 17.12 5 27896 41 32485584
Autoimmune pancytopenia 19.01 17.12 6 27895 104 32485521
Agitation 18.86 17.12 13 27888 57223 32428402
Activated partial thromboplastin time shortened 18.74 17.12 9 27892 496 32485129
Device related infection 18.69 17.12 45 27856 17888 32467737
Injection site pain 18.64 17.12 3 27898 33055 32452570
Disease recurrence 18.59 17.12 42 27859 16022 32469603
Plasma cell leukaemia 18.54 17.12 11 27890 930 32484695
Osteolysis 18.48 17.12 14 27887 1775 32483850
Cytomegalovirus gastroenteritis 18.48 17.12 7 27894 213 32485412
Cystitis viral 18.45 17.12 9 27892 513 32485112
Streptococcal bacteraemia 18.41 17.12 14 27887 1786 32483839
Muscle spasms 18.34 17.12 20 27881 70398 32415227
Retinal artery stenosis 18.19 17.12 3 27898 0 32485625
Gastrointestinal toxicity 18.17 17.12 15 27886 2154 32483471
Cardiac failure congestive 18.09 17.12 28 27873 84824 32400801
American trypanosomiasis 18.00 17.12 7 27894 229 32485396
International normalised ratio increased 17.73 17.12 10 27891 49025 32436600
Loss of therapeutic response 17.59 17.12 7 27894 244 32485381
Adenoviral hepatitis 17.53 17.12 7 27894 246 32485379
Gastrointestinal injury 17.46 17.12 8 27893 396 32485229
Disseminated varicella zoster virus infection 17.46 17.12 11 27890 1036 32484589
Adenosquamous cell lung cancer 17.44 17.12 4 27897 18 32485607
Back pain 17.34 17.12 44 27857 111009 32374616
Blast crisis in myelogenous leukaemia 17.32 17.12 9 27892 587 32485038
Pneumonia fungal 17.24 17.12 24 27877 6256 32479369
Flushing 17.16 17.12 3 27898 31124 32454501

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
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
CHEBI has role CHEBI:35610 cytostatic
CHEBI has role CHEBI:35705 immunosuppressant
CHEBI has role CHEBI:50903 cancerogene
CHEBI has role CHEBI:88188 allergenic drug

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)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 50MG BASE/VIAL EVOMELA ACROTECH N207155 March 10, 2016 RX POWDER INTRAVENOUS 10940128 June 14, 2030 FOR HIGH-DOSE CONDITIONING TREATMENT PRIOR TO HEMATOPOIETIC PROGENITOR (STEM) CELL TRANSPLANTATION IN PATIENTS WITH MULTIPLE MYELOMA

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
L-type amino acid transporter 1 Transporter Ki 4.26 CHEMBL

External reference:

IDSource
4020558 VUID
N0000022818 NUI
D00369 KEGG_DRUG
3223-07-2 SECONDARY_CAS_RN
4018763 VANDF
4020558 VANDF
C0025241 UMLSCUI
CHEBI:28876 CHEBI
CHEMBL852 ChEMBL_ID
CHEMBL250892 ChEMBL_ID
CHEMBL1200863 ChEMBL_ID
DB01042 DRUGBANK_ID
D008558 MESH_DESCRIPTOR_UI
460612 PUBCHEM_CID
7620 IUPHAR_LIGAND_ID
745 INN_ID
Q41OR9510P UNII
151325 RXNORM
167596 MMSL
1789 MMSL
31570 MMSL
5038 MMSL
d00287 MMSL
002633 NDDF
004144 NDDF
387297002 SNOMEDCT_US
426388000 SNOMEDCT_US
544002 SNOMEDCT_US

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Melphalan HUMAN PRESCRIPTION DRUG LABEL 1 47781-200 TABLET 2 mg ORAL ANDA 22 sections
ALKERAN HUMAN PRESCRIPTION DRUG LABEL 1 52609-0001 TABLET, FILM COATED 2 mg ORAL NDA 24 sections
EVOMELA Human Prescription Drug Label 1 68152-109 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 mg INTRAVENOUS NDA 26 sections
EVOMELA Human Prescription Drug Label 1 72893-001 INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION 50 mg INTRAVENOUS NDA 26 sections