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

Stem definition	Drug id	CAS RN
	1678	148-82-3

Description:

Molecule

Description

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:

Property	Value	Reference
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 µM/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:

Date	Agency	Company	Orphan
Jan. 17, 1964	FDA	GLAXOSMITHKLINE

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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 term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients 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:

Source	Code	Description
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)

Disease	Relation	SNOMED_ID	DOID
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 level	Dissociation constant	Type (acidic/basic)
pKa1	2.27	acidic
pKa2	9.25	Basic
pKa3	4.94	Basic

Orange Book patent data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Patent number	Patent expiration date	Patent 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 strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
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:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
L-type amino acid transporter 1	Transporter		LAT1_RAT		Ki	4.26		CHEMBL

External reference:

ID	Source
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:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
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