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 510.29 17.15 148 20230 3882 46661802
Graft versus host disease 450.53 17.15 151 20227 6437 46659247
Mucosal inflammation 440.23 17.15 250 20128 38726 46626958
Plasma cell myeloma 346.73 17.15 225 20153 44253 46621431
Myelodysplastic syndrome 345.10 17.15 158 20220 15553 46650131
Venoocclusive liver disease 341.20 17.15 110 20268 4141 46661543
Adenovirus infection 327.71 17.15 97 20281 2733 46662951
Febrile neutropenia 319.98 17.15 291 20087 94336 46571348
Thrombotic microangiopathy 300.40 17.15 119 20259 8187 46657497
Acute graft versus host disease in skin 284.30 17.15 88 20290 2894 46662790
Cytomegalovirus infection 270.47 17.15 140 20238 18004 46647680
Chronic graft versus host disease 241.28 17.15 76 20302 2649 46663035
Neutropenia 229.73 17.15 297 20081 142907 46522777
Acute graft versus host disease in intestine 191.45 17.15 57 20321 1638 46664046
Acute myeloid leukaemia 180.04 17.15 102 20276 15676 46650008
Thrombocytopenia 177.54 17.15 246 20132 126335 46539349
Pancytopenia 172.89 17.15 199 20179 84859 46580825
Osteonecrosis 168.64 17.15 117 20261 25627 46640057
Graft versus host disease in skin 164.71 17.15 55 20323 2312 46663372
Venoocclusive disease 162.60 17.15 52 20326 1904 46663780
Cytomegalovirus infection reactivation 151.16 17.15 46 20332 1426 46664258
BK virus infection 139.71 17.15 51 20327 2798 46662886
Graft versus host disease in gastrointestinal tract 137.62 17.15 49 20329 2501 46663183
Epstein-Barr virus infection 132.68 17.15 63 20315 6721 46658963
Sepsis 124.24 17.15 217 20161 135797 46529887
Stem cell transplant 122.74 17.15 41 20337 1725 46663959
Product use in unapproved indication 121.30 17.15 172 20206 90101 46575583
Viraemia 117.76 17.15 35 20343 999 46664685
Haemophagocytic lymphohistiocytosis 109.05 17.15 59 20319 8283 46657401
Cystitis haemorrhagic 104.86 17.15 44 20334 3503 46662181
Headache 103.40 17.15 40 20338 478312 46187372
Human herpesvirus 6 infection 102.54 17.15 39 20339 2400 46663284
Post transplant lymphoproliferative disorder 101.32 17.15 44 20334 3812 46661872
Cytomegalovirus viraemia 101.29 17.15 46 20332 4432 46661252
Malignant transformation 100.05 17.15 24 20354 291 46665393
Plasma cell myeloma recurrent 95.86 17.15 37 20341 2370 46663314
Mucosal disorder 93.05 17.15 34 20344 1870 46663814
Bone marrow failure 91.80 17.15 87 20291 29582 46636102
Retinal pigment epitheliopathy 91.32 17.15 21 20357 209 46665475
Posterior reversible encephalopathy syndrome 90.28 17.15 65 20313 15076 46650608
Drug hypersensitivity 86.39 17.15 5 20373 243820 46421864
Prothrombin level increased 84.90 17.15 20 20358 223 46665461
Pyrexia 83.86 17.15 337 20041 348465 46317219
Chronic graft versus host disease in skin 83.85 17.15 24 20354 598 46665086
Engraftment syndrome 81.73 17.15 20 20358 265 46665419
Epstein-Barr viraemia 79.83 17.15 24 20354 713 46664971
Second primary malignancy 78.97 17.15 44 20334 6540 46659144
Arthralgia 76.21 17.15 32 20346 364571 46301113
Varicella zoster virus infection 75.80 17.15 31 20347 2312 46663372
Vitreous haemorrhage 75.77 17.15 29 20349 1815 46663869
Osteonecrosis of jaw 72.33 17.15 82 20296 34320 46631364
Premature menopause 72.07 17.15 22 20356 689 46664995
Acute graft versus host disease in liver 70.01 17.15 21 20357 619 46665065
Acute myeloid leukaemia recurrent 68.48 17.15 25 20353 1371 46664313
Iris atrophy 67.51 17.15 13 20365 48 46665636
Engraft failure 67.01 17.15 18 20360 352 46665332
Stomatitis 66.22 17.15 112 20266 68185 46597499
Malaise 66.16 17.15 31 20347 331201 46334483
Chorioretinal atrophy 65.54 17.15 13 20365 58 46665626
Encephalitis viral 64.71 17.15 25 20353 1605 46664079
Infection 63.14 17.15 163 20215 133429 46532255
Viral haemorrhagic cystitis 62.27 17.15 19 20359 594 46665090
Eye excision 62.17 17.15 12 20366 45 46665639
Pneumonia fungal 61.65 17.15 32 20346 4128 46661556
Off label use 61.54 17.15 327 20051 379514 46286170
Acute lymphocytic leukaemia 61.18 17.15 28 20350 2745 46662939
Cytomegalovirus test positive 60.73 17.15 28 20350 2792 46662892
Aplasia 60.26 17.15 30 20348 3546 46662138
Progressive multifocal leukoencephalopathy 59.30 17.15 45 20333 11301 46654383
Neuropathy peripheral 57.16 17.15 124 20254 90769 46574915
Fall 55.39 17.15 38 20340 329059 46336625
Fatigue 54.95 17.15 115 20263 608582 46057102
Multiple organ dysfunction syndrome 54.42 17.15 88 20290 51622 46614062
Joint swelling 54.23 17.15 5 20373 166068 46499616
Dizziness 53.80 17.15 42 20336 340372 46325312
Pain 53.05 17.15 79 20299 476869 46188815
Bone debridement 52.70 17.15 15 20363 366 46665318
Tooth extraction 52.33 17.15 40 20338 10153 46655531
Choroidal infarction 51.78 17.15 11 20367 73 46665611
Refractory cytopenia with multilineage dysplasia 51.26 17.15 12 20366 130 46665554
Chronic myelomonocytic leukaemia 50.48 17.15 14 20364 310 46665374
Cytomegalovirus chorioretinitis 48.96 17.15 20 20358 1487 46664197
Bronchopulmonary aspergillosis 48.89 17.15 34 20344 7462 46658222
Bacterial sepsis 48.77 17.15 26 20352 3541 46662143
Plasmacytoma 48.41 17.15 23 20355 2454 46663230
Eyelid rash 48.23 17.15 10 20368 58 46665626
Septic shock 47.17 17.15 88 20290 57805 46607879
Enterococcal infection 46.29 17.15 32 20346 6955 46658729
Hypogonadism female 45.81 17.15 8 20370 14 46665670
Hepatitis B reactivation 45.48 17.15 19 20359 1495 46664189
Nasal abscess 45.00 17.15 11 20367 145 46665539
Pain in extremity 44.67 17.15 29 20349 258651 46407033
Enterococcal sepsis 44.27 17.15 18 20360 1322 46664362
Gastrointestinal fungal infection 43.60 17.15 12 20366 258 46665426
Abdominal discomfort 43.36 17.15 7 20371 151158 46514526
Epstein-Barr virus associated lymphoproliferative disorder 42.56 17.15 18 20360 1461 46664223
Pericardial effusion 42.39 17.15 54 20324 25489 46640195
Nasopharyngitis 42.28 17.15 8 20370 153990 46511694
Renal failure 42.18 17.15 127 20251 113467 46552217
Extraocular muscle disorder 41.78 17.15 10 20368 120 46665564
Morganella infection 41.15 17.15 13 20365 457 46665227
JC virus infection 40.54 17.15 18 20360 1644 46664040
Feeling abnormal 40.20 17.15 4 20374 125056 46540628
Product dose omission issue 39.89 17.15 12 20366 168508 46497176
Febrile bone marrow aplasia 39.85 17.15 29 20349 6833 46658851
Idiopathic pneumonia syndrome 39.80 17.15 12 20366 360 46665324
Anxiety 39.52 17.15 15 20363 181942 46483742
Mucocutaneous ulceration 39.35 17.15 10 20368 156 46665528
Plasma cell leukaemia 39.33 17.15 16 20362 1177 46664507
Bone disorder 39.15 17.15 46 20332 19987 46645697
Cardiac failure 38.19 17.15 98 20280 79850 46585834
Dyspnoea 38.09 17.15 108 20270 515440 46150244
Chest pain 37.53 17.15 15 20363 176309 46489375
Sinus polyp 37.24 17.15 11 20367 307 46665377
Eyelid oedema 37.14 17.15 33 20345 10324 46655360
Respiratory syncytial virus infection 36.47 17.15 24 20354 4811 46660873
Peripheral swelling 36.09 17.15 12 20366 158059 46507625
Heterochromia iridis 34.54 17.15 6 20372 10 46665674
Endocarditis bacterial 34.26 17.15 12 20366 583 46665101
Tonsillar haemorrhage 32.77 17.15 9 20369 192 46665492
Growth failure 32.67 17.15 10 20368 316 46665368
Enophthalmos 32.64 17.15 6 20372 16 46665668
Neuralgic amyotrophy 32.11 17.15 6 20372 18 46665666
Nausea 31.64 17.15 174 20204 687280 45978404
Follicular thyroid cancer 31.59 17.15 7 20371 58 46665626
Retinoblastoma 31.47 17.15 8 20370 125 46665559
Gastrointestinal mucosal disorder 31.44 17.15 12 20366 745 46664939
Alopecia 31.15 17.15 16 20362 162398 46503286
Pruritus 31.10 17.15 36 20342 242316 46423368
Depression 30.82 17.15 18 20360 170086 46495598
Sequestrectomy 30.80 17.15 13 20365 1050 46664634
Epstein-Barr virus infection reactivation 30.27 17.15 9 20369 257 46665427
Herpes zoster 30.16 17.15 81 20297 67791 46597893
Pulmonary haemorrhage 30.08 17.15 24 20354 6481 46659203
Blood pressure increased 30.00 17.15 9 20369 126657 46539027
Chronic graft versus host disease in intestine 29.97 17.15 7 20371 75 46665609
Condition aggravated 29.75 17.15 38 20340 245014 46420670
Cardiac failure acute 29.49 17.15 26 20352 8052 46657632
Escherichia bacteraemia 29.20 17.15 17 20361 2744 46662940
Eyelid ptosis 28.97 17.15 23 20355 6165 46659519
Haematotoxicity 28.74 17.15 24 20354 6909 46658775
Transplant failure 28.73 17.15 13 20365 1241 46664443
Overdose 28.62 17.15 5 20373 101974 46563710
Urticaria 28.61 17.15 8 20370 117884 46547800
Drug interaction 28.47 17.15 28 20350 203066 46462618
Bacteraemia 28.44 17.15 33 20345 14146 46651538
Cardiomyopathy 28.29 17.15 35 20343 16038 46649646
Plastic surgery 28.05 17.15 7 20371 101 46665583
Disease progression 27.45 17.15 95 20283 91205 46574479
Osteolysis 27.41 17.15 16 20362 2596 46663088
Mucosal erosion 27.38 17.15 13 20365 1385 46664299
Bronchospasm 27.32 17.15 34 20344 15673 46650011
Peritonitis viral 27.26 17.15 6 20372 48 46665636
Loss of consciousness 26.92 17.15 7 20371 108231 46557453
Asthma 26.78 17.15 4 20374 91538 46574146
Ovarian failure 26.78 17.15 12 20366 1120 46664564
Polyneuropathy 26.60 17.15 29 20349 11615 46654069
Myelosuppression 26.54 17.15 24 20354 7679 46658005
Cytopenia 26.37 17.15 24 20354 7744 46657940
Adenoviral haemorrhagic cystitis 26.20 17.15 7 20371 134 46665550
Pneumonia cytomegaloviral 25.99 17.15 14 20364 1946 46663738
Hyperhidrosis 25.91 17.15 4 20374 89304 46576380
Blood stem cell transplant failure 25.54 17.15 7 20371 148 46665536
Complications of bone marrow transplant 25.45 17.15 9 20369 450 46665234
Leukopenia 24.96 17.15 76 20302 68267 46597417
Encephalopathy 24.81 17.15 49 20329 33540 46632144
Hepatitis B 24.67 17.15 17 20361 3676 46662008
Disease recurrence 24.47 17.15 35 20343 18436 46647248
Gait disturbance 24.08 17.15 17 20361 145246 46520438
Actinomycosis 24.05 17.15 11 20367 1077 46664607
Jaw operation 23.96 17.15 10 20368 785 46664899
Infection reactivation 23.94 17.15 10 20368 787 46664897
Osteomyelitis 23.40 17.15 38 20340 22345 46643339
Iris neovascularisation 23.06 17.15 5 20373 37 46665647
Fungaemia 23.04 17.15 13 20365 1978 46663706
Myocardial infarction 22.96 17.15 7 20371 97521 46568163
Purulent discharge 22.72 17.15 18 20360 4812 46660872
Acute respiratory distress syndrome 22.63 17.15 37 20341 21885 46643799
Urethritis 22.58 17.15 7 20371 231 46665453
Acute promyelocytic leukaemia 22.54 17.15 10 20368 911 46664773
Bone sequestrum 22.33 17.15 12 20366 1661 46664023
Gastrointestinal toxicity 22.24 17.15 17 20361 4314 46661370
Chest discomfort 22.14 17.15 6 20372 90263 46575421
Arthropathy 21.99 17.15 5 20373 84695 46580989
Refractory cancer 21.90 17.15 5 20373 48 46665636
Lymphopenia 21.77 17.15 30 20348 15263 46650421
Graft versus host disease in liver 21.72 17.15 8 20370 450 46665234
Leukaemia 21.61 17.15 15 20363 3280 46662404
Acute kidney injury 21.46 17.15 176 20202 235679 46430005
Cerebral vasoconstriction 21.44 17.15 10 20368 1023 46664661
Acinetobacter infection 21.25 17.15 11 20367 1411 46664273
Contusion 21.11 17.15 6 20372 87481 46578203
Platelet count decreased 21.04 17.15 93 20285 99931 46565753
Infusion related reaction 20.89 17.15 9 20369 101199 46564485
Culture stool positive 20.63 17.15 7 20371 309 46665375
Oral disorder 20.57 17.15 21 20357 7801 46657883
Chronic myeloid leukaemia 20.51 17.15 13 20365 2445 46663239
Weight decreased 20.49 17.15 38 20340 210811 46454873
Pseudomonal sepsis 20.31 17.15 12 20366 1990 46663694
Graft versus host disease in lung 20.25 17.15 7 20371 327 46665357
Pityriasis 20.21 17.15 3 20375 0 46665684
Klebsiella bacteraemia 20.21 17.15 10 20368 1166 46664518
Oral fungal infection 20.14 17.15 13 20365 2521 46663163
Chronic graft versus host disease in liver 20.13 17.15 6 20372 173 46665511
Gastrooesophageal reflux disease 20.10 17.15 4 20374 74340 46591344
Hepatic vein occlusion 19.86 17.15 5 20373 75 46665609
Toxicity to various agents 19.79 17.15 159 20219 211607 46454077
Intraductal proliferative breast lesion 19.74 17.15 13 20365 2609 46663075
Osteitis 19.73 17.15 14 20364 3171 46662513
Myalgia 19.63 17.15 15 20363 123073 46542611
Encephalitis 19.59 17.15 20 20358 7428 46658256
Insomnia 19.56 17.15 26 20352 164898 46500786
Aspartate aminotransferase increased 19.55 17.15 77 20301 78623 46587061
Schistocytosis 19.32 17.15 4 20374 23 46665661
Memory impairment 19.23 17.15 5 20373 77332 46588352
Arthritis 19.22 17.15 5 20373 77311 46588373
Leukaemia recurrent 19.20 17.15 10 20368 1299 46664385
Bronchiolitis obliterans syndrome 19.11 17.15 5 20373 88 46665596
Respiratory failure 19.08 17.15 87 20291 94729 46570955
Aspergillus infection 19.04 17.15 19 20359 6871 46658813
JC virus CSF test positive 19.04 17.15 4 20374 25 46665659
Type III immune complex mediated reaction 18.88 17.15 6 20372 215 46665469
Hypogammaglobulinaemia 18.85 17.15 17 20361 5421 46660263
Palpitations 18.83 17.15 9 20369 95250 46570434
Hypersensitivity 18.55 17.15 23 20355 150298 46515386
Refractory anaemia with an excess of blasts 18.44 17.15 7 20371 428 46665256
Heart rate increased 18.28 17.15 5 20373 74786 46590898
Gastroenteritis rotavirus 18.23 17.15 5 20373 106 46665578
Abdominal pain upper 18.17 17.15 22 20356 145283 46520401
IIIrd nerve disorder 18.13 17.15 3 20375 3 46665681
Hospitalisation 18.02 17.15 3 20375 63382 46602302
Cerebrovascular accident 17.86 17.15 11 20367 101028 46564656
Endothelial dysfunction 17.68 17.15 5 20373 119 46665565
Choroidal dystrophy 17.67 17.15 3 20375 4 46665680
Uterine atrophy 17.56 17.15 4 20374 38 46665646
Retinal depigmentation 17.44 17.15 6 20372 276 46665408
Acetabulum fracture 17.30 17.15 6 20372 283 46665401

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
Acute graft versus host disease 585.58 16.35 211 25193 5653 29921421
Venoocclusive liver disease 564.49 16.35 212 25192 6401 29920673
Myelodysplastic syndrome 480.41 16.35 259 25145 18519 29908555
Mucosal inflammation 443.05 16.35 292 25112 30202 29896872
Plasma cell myeloma 390.03 16.35 339 25065 53123 29873951
Acute myeloid leukaemia 372.31 16.35 216 25188 17790 29909284
Graft versus host disease 331.37 16.35 165 25239 9985 29917089
Febrile neutropenia 328.24 16.35 427 24977 106266 29820808
Acute graft versus host disease in skin 287.14 16.35 117 25287 4399 29922675
Chronic graft versus host disease 242.47 16.35 101 25303 4018 29923056
Venoocclusive disease 199.19 16.35 77 25327 2513 29924561
Malignant transformation 171.40 16.35 50 25354 663 29926411
Cytomegalovirus infection 170.04 16.35 149 25255 23525 29903549
Adenovirus infection 168.29 16.35 79 25325 4189 29922885
Graft versus host disease in gastrointestinal tract 166.42 16.35 71 25333 2998 29924076
Acute graft versus host disease in intestine 165.59 16.35 66 25338 2339 29924735
Human herpesvirus 6 infection 160.55 16.35 61 25343 1897 29925177
Thrombotic microangiopathy 158.77 16.35 96 25308 8514 29918560
Second primary malignancy 133.24 16.35 77 25327 6279 29920795
Osteonecrosis 133.13 16.35 110 25294 16025 29911049
Chorioretinal atrophy 131.54 16.35 27 25377 63 29927011
Graft versus host disease in skin 129.72 16.35 61 25343 3246 29923828
Product use in unapproved indication 126.23 16.35 225 25179 73468 29853606
Off label use 123.11 16.35 476 24928 248814 29678260
Neutropenia 119.60 16.35 306 25098 128234 29798840
Multiple organ dysfunction syndrome 112.78 16.35 197 25207 63290 29863784
Epstein-Barr virus infection 108.98 16.35 69 25335 6637 29920437
Stem cell transplant 107.99 16.35 47 25357 2084 29924990
Mucosal disorder 104.40 16.35 42 25362 1525 29925549
Cytomegalovirus viraemia 103.35 16.35 63 25341 5666 29921408
Drug interaction 102.80 16.35 22 25382 199546 29727528
Plasma cell myeloma recurrent 101.12 16.35 52 25352 3362 29923712
Pancytopenia 96.77 16.35 219 25185 84833 29842241
Tooth extraction 92.19 16.35 55 25349 4756 29922318
Engraftment syndrome 90.75 16.35 32 25372 801 29926273
Bronchopulmonary aspergillosis 89.53 16.35 78 25326 12206 29914868
Sepsis 87.66 16.35 298 25106 146097 29780977
Retinal pigment epitheliopathy 86.33 16.35 23 25381 213 29926861
Bone disorder 82.15 16.35 58 25346 6683 29920391
Basal cell carcinoma 80.68 16.35 83 25321 15985 29911089
Choroidal dystrophy 78.05 16.35 16 25388 37 29927037
Haemophagocytic lymphohistiocytosis 77.11 16.35 65 25339 9726 29917348
Epstein-Barr viraemia 76.77 16.35 29 25375 887 29926187
Thrombocytopenia 75.97 16.35 272 25132 136772 29790302
Headache 75.74 16.35 30 25374 182276 29744798
Aspergillus infection 74.72 16.35 65 25339 10149 29916925
Acute graft versus host disease in liver 74.62 16.35 31 25373 1223 29925851
Refractory anaemia with an excess of blasts 74.56 16.35 23 25381 373 29926701
Pyrexia 72.81 16.35 462 24942 294027 29633047
Choroidal infarction 68.91 16.35 16 25388 78 29926996
Fatigue 68.56 16.35 104 25300 320569 29606505
Chronic graft versus host disease in skin 68.43 16.35 25 25379 695 29926379
Stomatitis 67.85 16.35 117 25287 37162 29889912
Dizziness 66.07 16.35 42 25362 194867 29732207
Cystitis haemorrhagic 64.94 16.35 44 25360 4743 29922331
Blood stem cell transplant failure 64.73 16.35 21 25383 404 29926670
Engraft failure 63.42 16.35 21 25383 432 29926642
Progressive multifocal leukoencephalopathy 63.21 16.35 56 25348 8957 29918117
Extraocular muscle disorder 61.84 16.35 17 25387 179 29926895
BK virus infection 61.33 16.35 41 25363 4323 29922751
Neuropathy peripheral 60.51 16.35 163 25241 70312 29856762
Parainfluenzae virus infection 60.23 16.35 31 25373 2007 29925067
Vitreous haemorrhage 59.22 16.35 31 25373 2079 29924995
Malaise 57.91 16.35 35 25369 166927 29760147
Aplasia 56.91 16.35 38 25366 3999 29923075
Bacterial sepsis 56.84 16.35 41 25363 4885 29922189
Product dose omission issue 56.45 16.35 6 25398 91625 29835449
Arthralgia 53.69 16.35 24 25380 135767 29791307
Diffuse large B-cell lymphoma 53.56 16.35 48 25356 7793 29919281
Herpes zoster 51.91 16.35 92 25312 29851 29897223
Apoptosis 51.27 16.35 15 25389 201 29926873
Posterior reversible encephalopathy syndrome 51.15 16.35 49 25355 8658 29918416
Fall 50.44 16.35 48 25356 181824 29745250
Dyspnoea 49.85 16.35 133 25271 333162 29593912
Staphylococcal sepsis 49.40 16.35 50 25354 9441 29917633
Transplant failure 48.95 16.35 29 25375 2475 29924599
Haematotoxicity 48.66 16.35 41 25363 6129 29920945
Overdose 48.34 16.35 7 25397 84330 29842744
Post transplant lymphoproliferative disorder 47.59 16.35 38 25366 5268 29921806
Epstein-Barr virus associated lymphoproliferative disorder 47.39 16.35 25 25379 1703 29925371
Prothrombin level increased 47.02 16.35 13 25391 140 29926934
Septic shock 46.65 16.35 139 25265 63468 29863606
Weight decreased 46.50 16.35 36 25368 150885 29776189
Chest pain 46.16 16.35 21 25383 117606 29809468
Bone debridement 45.28 16.35 15 25389 309 29926765
Eyelid oedema 44.97 16.35 36 25368 5009 29922065
Debridement 43.97 16.35 20 25384 985 29926089
Cytopenia 43.90 16.35 44 25360 8212 29918862
Sequestrectomy 43.69 16.35 15 25389 346 29926728
Cytomegalovirus test positive 43.57 16.35 31 25373 3614 29923460
Pneumonia cytomegaloviral 43.51 16.35 28 25376 2768 29924306
Bone sequestrum 43.21 16.35 18 25386 715 29926359
Gastrointestinal mucosal disorder 43.13 16.35 15 25389 360 29926714
Transformation to acute myeloid leukaemia 41.95 16.35 17 25387 629 29926445
Acute lymphocytic leukaemia 41.11 16.35 28 25376 3044 29924030
Bacterial infection 40.97 16.35 52 25352 12558 29914516
Juvenile melanoma benign 40.64 16.35 10 25394 65 29927009
Death 40.61 16.35 161 25243 357122 29569952
Neutropenic sepsis 40.19 16.35 49 25355 11360 29915714
Cerebral toxoplasmosis 39.53 16.35 21 25383 1451 29925623
Depression 38.97 16.35 14 25390 90423 29836651
Systemic candida 38.91 16.35 26 25378 2738 29924336
Myocardial infarction 38.64 16.35 30 25374 125595 29801479
Ameloblastoma 38.40 16.35 10 25394 84 29926990
Cerebrovascular accident 37.57 16.35 12 25392 83465 29843609
Bone marrow failure 37.54 16.35 80 25324 29705 29897369
Hepatitis B 37.24 16.35 35 25369 6037 29921037
Hepatic infection fungal 37.15 16.35 11 25393 154 29926920
Rhabdomyolysis 37.08 16.35 5 25399 63575 29863499
Eyelid rash 37.03 16.35 8 25396 26 29927048
Squamous cell carcinoma of skin 36.91 16.35 42 25362 9053 29918021
Blood pressure increased 36.81 16.35 8 25396 71920 29855154
Meningomyelitis herpes 36.15 16.35 8 25396 30 29927044
Acute respiratory distress syndrome 35.49 16.35 68 25336 23404 29903670
Peripheral swelling 35.15 16.35 5 25399 61069 29866005
Iris atrophy 34.73 16.35 9 25395 74 29927000
Metastases to retroperitoneum 34.13 16.35 11 25393 207 29926867
Anxiety 33.79 16.35 17 25387 89854 29837220
Chorioretinal disorder 33.35 16.35 7 25397 19 29927055
Refractory cytopenia with multilineage dysplasia 33.26 16.35 10 25394 148 29926926
Bone sarcoma 33.16 16.35 9 25395 90 29926984
JC virus infection 33.09 16.35 20 25384 1770 29925304
Myalgia 32.80 16.35 12 25392 76655 29850419
Asthenia 32.47 16.35 89 25315 221201 29705873
Drug hypersensitivity 32.38 16.35 9 25395 68510 29858564
Osteomyelitis 31.99 16.35 50 25354 14631 29912443
Hyperhidrosis 31.35 16.35 9 25395 67081 29859993
Somnolence 31.18 16.35 22 25382 96741 29830333
Osteosarcoma 31.14 16.35 10 25394 186 29926888
Ureaplasma infection 31.09 16.35 10 25394 187 29926887
Human herpesvirus 8 infection 31.06 16.35 14 25390 675 29926399
Hepatic vein occlusion 30.40 16.35 9 25395 126 29926948
Metastases to muscle 30.32 16.35 10 25394 203 29926871
Feeling abnormal 29.68 16.35 6 25398 56750 29870324
Meningoencephalitis herpetic 29.43 16.35 14 25390 764 29926310
Idiopathic pneumonia syndrome 29.23 16.35 10 25394 228 29926846
Lymphopenia 28.92 16.35 45 25359 13118 29913956
Human herpesvirus 6 encephalitis 28.89 16.35 9 25395 151 29926923
Coronary artery disease 28.77 16.35 4 25400 49708 29877366
Short stature 28.52 16.35 7 25397 45 29927029
Polyneuropathy 28.21 16.35 42 25362 11781 29915293
Carbamoyl phosphate synthetase deficiency 28.14 16.35 6 25398 18 29927056
Urticaria 28.08 16.35 6 25398 54600 29872474
Viral haemorrhagic cystitis 28.08 16.35 14 25390 847 29926227
Acute lymphocytic leukaemia recurrent 28.06 16.35 21 25383 2646 29924428
Plasmacytoma 27.91 16.35 23 25381 3333 29923741
Neoplasm recurrence 27.34 16.35 18 25386 1849 29925225
Autoimmune neutropenia 27.27 16.35 10 25394 281 29926793
Expanded disability status scale score increased 26.91 16.35 9 25395 191 29926883
Bradycardia 26.80 16.35 11 25393 65515 29861559
Pruritus 26.45 16.35 37 25367 118167 29808907
Obliterative bronchiolitis 26.40 16.35 15 25389 1183 29925891
Pain 26.39 16.35 68 25336 172573 29754501
Adenocarcinoma of colon 26.21 16.35 22 25382 3270 29923804
Eye excision 26.06 16.35 6 25398 28 29927046
Autoimmune haemolytic anaemia 26.06 16.35 24 25380 4035 29923039
Respiratory syncytial virus infection 25.78 16.35 22 25382 3346 29923728
Inflammatory myofibroblastic tumour 25.69 16.35 8 25396 134 29926940
Metastases to spleen 25.67 16.35 10 25394 333 29926741
Nasopharyngitis 25.53 16.35 9 25395 58840 29868234
Staphylococcal bacteraemia 25.36 16.35 30 25374 6738 29920336
Chronic graft versus host disease in intestine 25.31 16.35 9 25395 231 29926843
Myelitis 25.00 16.35 12 25392 668 29926406
Bacteraemia 24.66 16.35 46 25358 15514 29911560
Premature ageing 24.63 16.35 7 25397 84 29926990
Purulent discharge 24.51 16.35 20 25384 2859 29924215
Klebsiella sepsis 23.81 16.35 16 25388 1701 29925373
Hypoglycaemia 23.52 16.35 7 25397 50974 29876100
Chest discomfort 23.38 16.35 5 25399 45475 29881599
Graft versus host disease in liver 23.31 16.35 13 25391 989 29926085
Cytogenetic abnormality 23.24 16.35 12 25392 782 29926292
Iris neovascularisation 23.21 16.35 5 25399 16 29927058
Gait disturbance 22.79 16.35 18 25386 74759 29852315
Blood glucose increased 22.58 16.35 12 25392 61518 29865556
Hospitalisation 22.52 16.35 5 25399 44314 29882760
Neurotoxicity 22.19 16.35 40 25364 13142 29913932
Blood creatine phosphokinase increased 22.18 16.35 5 25399 43843 29883231
Myositis 22.13 16.35 35 25369 10342 29916732
Papilloma 22.11 16.35 7 25397 124 29926950
Complications of bone marrow transplant 22.11 16.35 8 25396 216 29926858
Tooth impacted 22.10 16.35 6 25398 60 29927014
Metastases to bone marrow 21.86 16.35 10 25394 499 29926575
Pneumonia 21.81 16.35 401 25003 333905 29593169
Capillary leak syndrome 21.80 16.35 15 25389 1657 29925417
Mycobacterium kansasii infection 21.77 16.35 8 25396 226 29926848
Exophthalmos 21.67 16.35 10 25394 509 29926565
Heterochromia iridis 21.52 16.35 4 25400 4 29927070
Plasma cell leukaemia 21.52 16.35 12 25392 913 29926161
Cytomegalovirus infection reactivation 21.46 16.35 15 25389 1700 29925374
Pain in extremity 21.34 16.35 38 25366 110183 29816891
Gingival erythema 21.28 16.35 7 25397 141 29926933
Pulmonary alveolar haemorrhage 21.15 16.35 27 25377 6554 29920520
Balance disorder 20.97 16.35 3 25401 36490 29890584
Inflammatory pseudotumour 20.96 16.35 5 25399 28 29927046
Laryngeal cancer metastatic 20.74 16.35 6 25398 77 29926997
Vision blurred 20.69 16.35 5 25399 41811 29885263
Confusional state 20.67 16.35 53 25351 134781 29792293
Joint swelling 20.67 16.35 7 25397 46939 29880135
Retinoblastoma 20.66 16.35 5 25399 30 29927044
Activated partial thromboplastin time shortened 20.63 16.35 9 25395 401 29926673
Jaw operation 20.38 16.35 8 25396 272 29926802
Osteolysis 20.35 16.35 14 25390 1546 29925528
Therapy partial responder 20.23 16.35 20 25384 3671 29923403
Insomnia 20.10 16.35 30 25374 93306 29833768
Chronic obstructive pulmonary disease 20.10 16.35 7 25397 46119 29880955
Infection 20.07 16.35 124 25280 77950 29849124
B precursor type acute leukaemia 20.07 16.35 6 25398 87 29926987
Hyperkalaemia 19.98 16.35 16 25388 65994 29861080
Genotoxicity 19.88 16.35 5 25399 36 29927038
Autoimmune pancytopenia 19.82 16.35 6 25398 91 29926983
B-cell lymphoma recurrent 19.64 16.35 10 25394 633 29926441
Hyperbilirubinaemia 19.63 16.35 44 25360 16898 29910176
Agitation 19.18 16.35 11 25393 54062 29873012
Pulmonary haemorrhage 19.10 16.35 31 25373 9361 29917713
Adenocarcinoma gastric 19.09 16.35 12 25392 1139 29925935
Toxic erythema of chemotherapy 18.99 16.35 5 25399 44 29927030
American trypanosomiasis 18.85 16.35 7 25397 204 29926870
Cytomegalovirus gastroenteritis 18.75 16.35 7 25397 207 29926867
Asthma 18.55 16.35 4 25400 36170 29890904
Amyloidosis 18.50 16.35 15 25389 2124 29924950
Musculoskeletal stiffness 18.33 16.35 4 25400 35877 29891197
Gastrointestinal injury 18.31 16.35 8 25396 358 29926716
Cardiac failure congestive 18.30 16.35 27 25377 84380 29842694
Febrile bone marrow aplasia 18.23 16.35 28 25376 8069 29919005
Retinal artery stenosis 18.22 16.35 3 25401 0 29927074
Disseminated varicella zoster virus infection 18.20 16.35 11 25393 973 29926101
Varicella zoster virus infection 18.02 16.35 12 25392 1256 29925818
International normalised ratio increased 17.98 16.35 9 25395 47730 29879344
Neutropenic colitis 17.96 16.35 15 25389 2215 29924859
Disseminated cryptococcosis 17.95 16.35 11 25393 998 29926076
Dental care 17.83 16.35 7 25397 238 29926836
Bone lesion 17.62 16.35 16 25388 2641 29924433
Adenosquamous cell lung cancer 17.49 16.35 4 25400 18 29927056
Tremor 17.44 16.35 23 25381 75340 29851734
Mantle cell lymphoma stage IV 17.44 16.35 5 25399 62 29927012
Herpes zoster meningoencephalitis 17.27 16.35 7 25397 259 29926815
Gastrointestinal toxicity 17.20 16.35 14 25390 1994 29925080
Candida sepsis 17.08 16.35 11 25393 1088 29925986
Condition aggravated 16.96 16.35 60 25344 137806 29789268
Bronchospasm 16.93 16.35 31 25373 10307 29916767
Spirochaetal infection 16.83 16.35 4 25400 22 29927052
Medulloblastoma recurrent 16.76 16.35 5 25399 72 29927002
Pneumonia fungal 16.69 16.35 22 25382 5511 29921563
Disease recurrence 16.65 16.35 37 25367 14124 29912950
Retinal detachment 16.64 16.35 21 25383 5039 29922035
Atrophy of globe 16.53 16.35 4 25400 24 29927050
Leukaemia 16.48 16.35 17 25387 3280 29923794
Enteritis 16.42 16.35 24 25380 6621 29920453
Dysarthria 16.41 16.35 3 25401 30487 29896587
Electrocardiogram QT prolonged 16.38 16.35 5 25399 35830 29891244

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)

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
D00369 KEGG_DRUG
3223-07-2 SECONDARY_CAS_RN
4018763 VANDF
4020558 VANDF
C0025241 UMLSCUI
CHEBI:28876 CHEBI
CHEMBL852 ChEMBL_ID
CHEMBL1200863 ChEMBL_ID
CHEMBL250892 ChEMBL_ID
D008558 MESH_DESCRIPTOR_UI
460612 PUBCHEM_CID
DB01042 DRUGBANK_ID
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 21 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