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

Stem definition	Drug id	CAS RN
nucleosides antiviral or antineoplastic agents, cytarabine or azacitidine derivatives	770	147-94-4

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: cytarabine hydrochloride cytarabine arabinocytosine Arabinoside C aracytidine cyclocide cytarabin cytarabinoside cytosine beta-D-arabinofuranoside cytarabine liposome cytarabine HCl	A pyrimidine nucleoside analog that is used mainly in the treatment of leukemia, especially acute non-lymphoblastic leukemia. Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Its actions are specific for the S phase of the cell cycle. It also has antiviral and immunosuppressant properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p472) Molecular weight: 243.22 Formula: C9H13N3O5 CLOGP: -2.20 LIPINSKI: 0 HAC: 8 HDO: 4 TPSA: 128.61 ALOGS: -0.74 ROTB: 2 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

cytarabine hydrochloride
cytarabine
arabinocytosine
Arabinoside C
aracytidine
cyclocide
cytarabin
cytarabinoside
cytosine beta-D-arabinofuranoside
cytarabine liposome
cytarabine HCl

A pyrimidine nucleoside analog that is used mainly in the treatment of leukemia, especially acute non-lymphoblastic leukemia. Cytarabine is an antimetabolite antineoplastic agent that inhibits the synthesis of DNA. Its actions are specific for the S phase of the cell cycle. It also has antiviral and immunosuppressant properties. (From Martindale, The Extra Pharmacopoeia, 30th ed, p472)

Molecular weight: 243.22
Formula: C9H13N3O5
CLOGP: -2.20
LIPINSKI: 0
HAC: 8
HDO: 4
TPSA: 128.61
ALOGS: -0.74
ROTB: 2

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
EoM (Fraction excreted unchanged in urine)	11 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	11.10 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability)	20 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution)	0.67 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	41.67 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.87 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	0.17 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
June 17, 1969	FDA

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
Febrile neutropenia	3463.17	63.34	784	5105	10098	2342098
Neutropenia	1071.51	63.34	364	5525	21184	2331012
Febrile bone marrow aplasia	971.04	63.34	179	5710	678	2351518
Sepsis	960.36	63.34	323	5566	18165	2334031
Pyrexia	952.98	63.34	429	5460	53279	2298917
Thrombocytopenia	836.46	63.34	294	5595	18837	2333359
Septic shock	732.66	63.34	210	5679	6844	2345352
Pancytopenia	725.87	63.34	233	5656	11219	2340977
Bone marrow failure	679.67	63.34	189	5700	5497	2346699
Mucosal inflammation	644.31	63.34	178	5711	5046	2347150
Pneumonia	553.61	63.34	289	5600	49007	2303189
Acute myeloid leukaemia	514.13	63.34	130	5759	2580	2349616
Venoocclusive liver disease	493.29	63.34	96	5793	512	2351684
Multiple organ dysfunction syndrome	465.05	63.34	151	5738	7490	2344706
Haematotoxicity	464.02	63.34	102	5787	1065	2351131
Hypotension	441.60	63.34	217	5672	32219	2319977
Colitis	416.74	63.34	127	5762	5099	2347097
Posterior reversible encephalopathy syndrome	411.70	63.34	107	5782	2373	2349823
Respiratory failure	391.31	63.34	154	5735	13374	2338822
Product use in unapproved indication	364.69	63.34	139	5750	11061	2341135
Pleural effusion	344.95	63.34	135	5754	11533	2340663
Platelet count decreased	338.01	63.34	145	5744	15668	2336528
Blood culture positive	328.74	63.34	71	5818	676	2351520
Alanine aminotransferase increased	307.49	63.34	131	5758	13901	2338295
Neutropenic colitis	302.48	63.34	57	5832	247	2351949
Acute lymphocytic leukaemia recurrent	292.84	63.34	53	5836	174	2352022
Bronchopulmonary aspergillosis	281.33	63.34	66	5823	938	2351258
Acute kidney injury	280.73	63.34	153	5736	27969	2324227
Vomiting	280.59	63.34	216	5673	71386	2280810
Hypofibrinogenaemia	280.30	63.34	48	5841	102	2352094
Neurotoxicity	277.91	63.34	76	5813	2054	2350142
Myelodysplastic syndrome	277.55	63.34	79	5810	2481	2349715
Neoplasm recurrence	277.45	63.34	56	5833	369	2351827
Tumour lysis syndrome	271.66	63.34	65	5824	1010	2351186
Bacteraemia	269.45	63.34	71	5818	1659	2350537
Seizure	260.55	63.34	139	5750	24327	2327869
Acute myeloid leukaemia recurrent	251.64	63.34	46	5843	162	2352034
Diarrhoea	239.01	63.34	210	5679	83354	2268842
Nausea	238.66	63.34	239	5650	111950	2240246
Hypoxia	230.52	63.34	85	5804	6142	2346054
Tachycardia	229.14	63.34	112	5777	16297	2335899
Hypokalaemia	221.79	63.34	96	5793	10558	2341638
Blood bilirubin increased	220.34	63.34	79	5810	5266	2346930
Haemophagocytic lymphohistiocytosis	216.49	63.34	57	5832	1326	2350870
Neutrophil count decreased	215.25	63.34	82	5807	6485	2345711
Off label use	214.33	63.34	187	5702	73411	2278785
Neutropenic sepsis	209.38	63.34	56	5833	1386	2350810
Acute respiratory distress syndrome	207.82	63.34	67	5822	3225	2348971
Bacterial infection	202.81	63.34	60	5829	2161	2350035
Aplasia	201.40	63.34	44	5845	443	2351753
Disease progression	198.49	63.34	103	5786	16992	2335204
Abdominal pain	194.56	63.34	130	5759	34244	2317952
Hyperbilirubinaemia	191.50	63.34	53	5836	1496	2350700
Venoocclusive disease	190.99	63.34	38	5851	230	2351966
Clostridium difficile colitis	189.11	63.34	56	5833	2023	2350173
Infection	187.69	63.34	101	5788	17928	2334268
Enterococcal infection	187.59	63.34	45	5844	706	2351490
Cytomegalovirus infection	186.81	63.34	59	5830	2654	2349542
Hypoalbuminaemia	182.99	63.34	50	5839	1344	2350852
Encephalopathy	182.65	63.34	66	5823	4495	2347701
Respiratory distress	182.39	63.34	68	5821	5061	2347135
Pulmonary oedema	182.02	63.34	75	5814	7288	2344908
Aspartate aminotransferase increased	181.72	63.34	88	5801	12524	2339672
Fungaemia	180.22	63.34	36	5853	223	2351973
Second primary malignancy	179.41	63.34	46	5843	960	2351236
Anaemia	176.49	63.34	123	5766	34669	2317527
Leukaemia recurrent	175.18	63.34	35	5854	217	2351979
Ascites	172.78	63.34	67	5822	5553	2346643
Renal failure	171.69	63.34	94	5795	17255	2334941
Pulmonary haemorrhage	170.42	63.34	46	5843	1179	2351017
Leukopenia	167.85	63.34	78	5811	10118	2342078
Graft versus host disease	162.00	63.34	42	5847	917	2351279
Myelopathy	160.67	63.34	35	5854	347	2351849
Staphylococcal sepsis	157.63	63.34	42	5847	1023	2351173
Aspergillus infection	156.99	63.34	41	5848	922	2351274
Device related infection	156.54	63.34	54	5835	3205	2348991
Hepatocellular injury	148.68	63.34	55	5834	4000	2348196
White blood cell count decreased	148.65	63.34	87	5802	18121	2334075
Fungal infection	145.71	63.34	57	5832	4832	2347364
Enterococcal bacteraemia	141.40	63.34	27	5862	127	2352069
Cytopenia	140.87	63.34	38	5851	971	2351225
Leukoencephalopathy	139.49	63.34	36	5853	771	2351425
Haemoglobin decreased	133.24	63.34	81	5808	18070	2334126
Disseminated intravascular coagulation	132.30	63.34	48	5841	3302	2348894
Headache	131.06	63.34	149	5740	80030	2272166
Disease recurrence	130.91	63.34	48	5841	3403	2348793
Staphylococcal infection	130.72	63.34	54	5835	5272	2346924
Mucormycosis	130.62	63.34	30	5859	385	2351811
Ejection fraction decreased	129.06	63.34	45	5844	2756	2349440
Mental status changes	128.27	63.34	54	5835	5528	2346668
Hypertriglyceridaemia	126.28	63.34	34	5855	862	2351334
Stomatitis	125.62	63.34	63	5826	9647	2342549
Hepatotoxicity	123.15	63.34	46	5843	3435	2348761
Neuropathy peripheral	118.71	63.34	64	5825	11368	2340828
Escherichia bacteraemia	113.61	63.34	26	5863	328	2351868
Neutropenic infection	112.19	63.34	23	5866	165	2352031
Decreased appetite	112.12	63.34	87	5802	28804	2323392
Clostridium test positive	111.81	63.34	25	5864	282	2351914
Rhinovirus infection	111.48	63.34	25	5864	286	2351910
Acute lymphocytic leukaemia	110.26	63.34	27	5862	463	2351733
Fluid overload	110.03	63.34	40	5849	2766	2349430
Cerebral haemorrhage	109.21	63.34	48	5841	5456	2346740
Left ventricular dysfunction	106.65	63.34	32	5857	1208	2350988
Cardiotoxicity	106.47	63.34	32	5857	1215	2350981
Hemiparesis	105.52	63.34	41	5848	3409	2348787
Cardiac failure	104.50	63.34	60	5829	12034	2340162
Malignant neoplasm progression	104.34	63.34	60	5829	12068	2340128
Candida infection	101.74	63.34	38	5851	2835	2349361
Unresponsive to stimuli	101.54	63.34	44	5845	4832	2347364
Palmar-plantar erythrodysaesthesia syndrome	101.06	63.34	42	5847	4159	2348037
Pseudomonas infection	99.89	63.34	30	5859	1136	2351060
Acute respiratory failure	99.68	63.34	38	5851	3000	2349196
Cystitis haemorrhagic	98.47	63.34	26	5863	610	2351586
Hyperglycaemia	98.20	63.34	43	5846	4842	2347354
Herpes simplex	98.13	63.34	29	5860	1038	2351158
Transaminases increased	97.50	63.34	42	5847	4545	2347651
Human herpesvirus 6 infection	96.07	63.34	23	5866	357	2351839
Cardiac arrest	95.30	63.34	61	5828	14869	2337327
Staphylococcal bacteraemia	94.79	63.34	25	5864	584	2351612
Neoplasm progression	93.54	63.34	41	5848	4627	2347569
Muscular weakness	92.95	63.34	60	5829	14837	2337359
Enterobacter infection	92.64	63.34	21	5868	253	2351943
Hypertension	92.47	63.34	76	5813	27285	2324911
Progressive multifocal leukoencephalopathy	92.22	63.34	33	5856	2179	2350017
Enterocolitis	91.31	63.34	26	5863	814	2351382
Hepatomegaly	90.83	63.34	31	5858	1778	2350418
Chills	90.59	63.34	60	5829	15492	2336704
Drug interaction	90.28	63.34	77	5812	29086	2323110
Hepatic failure	88.84	63.34	42	5847	5647	2346549
Diffuse large B-cell lymphoma recurrent	88.83	63.34	17	5872	81	2352115
Cellulitis	88.54	63.34	49	5840	9152	2343044
Atelectasis	88.32	63.34	31	5858	1934	2350262
Lung infiltration	87.73	63.34	32	5857	2232	2349964
Pneumonia fungal	85.38	63.34	21	5868	367	2351829
Pyomyositis	84.62	63.34	15	5874	42	2352154
Appendicitis	82.52	63.34	26	5863	1157	2351039
Aphasia	81.94	63.34	38	5851	4890	2347306
Dyspnoea	81.89	63.34	117	5772	78616	2273580
Sinusitis fungal	81.39	63.34	16	5873	90	2352106
Stem cell transplant	80.65	63.34	20	5869	362	2351834
Toxicity to various agents	80.63	63.34	76	5813	32678	2319518
Pseudomonas test positive	80.42	63.34	17	5872	144	2352052
Drug resistance	79.58	63.34	31	5858	2593	2349603
Hodgkin's disease refractory	78.84	63.34	12	5877	6	2352190
Ileus	77.89	63.34	29	5860	2143	2350053
Pancreatitis	77.66	63.34	43	5846	8036	2344160
Human bocavirus infection	77.58	63.34	12	5877	8	2352188
Escherichia sepsis	77.43	63.34	21	5868	547	2351649
Secondary immunodeficiency	77.29	63.34	15	5874	78	2352118
Tachypnoea	77.16	63.34	29	5860	2200	2349996
Systemic mycosis	76.61	63.34	16	5873	127	2352069
Hyponatraemia	76.60	63.34	51	5838	13274	2338922
Pericardial effusion	76.41	63.34	34	5855	3975	2348221
Gastrointestinal haemorrhage	74.89	63.34	49	5840	12386	2339810
Lung consolidation	74.15	63.34	20	5869	510	2351686
Systemic candida	73.04	63.34	18	5871	317	2351879
Pneumocystis jirovecii pneumonia	73.01	63.34	28	5861	2245	2349951
Haemorrhage intracranial	72.89	63.34	29	5860	2565	2349631
Haemodialysis	71.91	63.34	27	5862	2042	2350154
Death	71.71	63.34	112	5777	81356	2270840
Bacterial sepsis	71.03	63.34	19	5870	469	2351727
Toxic epidermal necrolysis	70.81	63.34	30	5859	3114	2349082
Streptococcal sepsis	69.31	63.34	16	5873	210	2351986
General physical health deterioration	69.18	63.34	49	5840	14090	2338106
Gamma-glutamyltransferase increased	68.70	63.34	35	5854	5527	2346669
Hypophosphataemia	68.38	63.34	22	5867	1048	2351148
Enteritis	68.06	63.34	22	5867	1064	2351132
Antithrombin III	67.93	63.34	10	5879	2	2352194
Malignant transformation	67.85	63.34	12	5877	33	2352163
Asthenia	67.72	63.34	82	5807	46844	2305352
C-reactive protein increased	67.64	63.34	36	5853	6219	2345977
Peripheral motor neuropathy	67.27	63.34	16	5873	241	2351955
Cough	66.90	63.34	69	5820	33048	2319148
Systemic inflammatory response syndrome	66.48	63.34	20	5869	761	2351435
Coagulopathy	66.32	63.34	28	5861	2881	2349315
Capillary leak syndrome	65.94	63.34	17	5872	362	2351834
Venous thrombosis	65.50	63.34	20	5869	801	2351395
Pseudomonal sepsis	65.29	63.34	16	5873	275	2351921
Perineal necrosis	65.05	63.34	10	5879	6	2352190
Fusarium infection	64.85	63.34	13	5876	82	2352114
Acute graft versus host disease in skin	64.74	63.34	17	5872	390	2351806
Enterococcus test positive	64.69	63.34	14	5875	134	2352062
Streptococcal bacteraemia	64.04	63.34	14	5875	141	2352055
Cardiomyopathy	63.93	63.34	27	5862	2780	2349416

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
Febrile neutropenia	4782.91	51.34	1194	6911	9906	1728770
Neutropenia	1549.18	51.34	566	7539	17694	1720982
Pyrexia	1228.63	51.34	631	7474	45769	1692907
Sepsis	1166.59	51.34	469	7636	18969	1719707
Pancytopenia	921.76	51.34	342	7763	11015	1727661
Thrombocytopenia	913.67	51.34	405	7700	20844	1717832
Septic shock	856.49	51.34	297	7808	7812	1730864
Mucosal inflammation	824.04	51.34	246	7859	3923	1734753
Bone marrow failure	820.33	51.34	258	7847	4942	1733734
Venoocclusive liver disease	780.78	51.34	174	7931	759	1737917
Febrile bone marrow aplasia	780.21	51.34	172	7933	706	1737970
Haematotoxicity	748.93	51.34	169	7936	789	1737887
Acute myeloid leukaemia	704.20	51.34	203	7902	2838	1735838
Product use in unapproved indication	680.95	51.34	261	7844	9161	1729515
Multiple organ dysfunction syndrome	614.34	51.34	241	7864	9001	1729675
Pneumonia	603.17	51.34	399	7706	45783	1692893
Respiratory failure	572.21	51.34	261	7844	14244	1724432
Myelodysplastic syndrome	563.35	51.34	174	7931	3115	1735561
Off label use	499.58	51.34	332	7773	38239	1700437
Acute kidney injury	474.66	51.34	310	7795	34634	1704042
Hypotension	467.14	51.34	289	7816	29365	1709311
Colitis	447.54	51.34	155	7950	4025	1734651
Bronchopulmonary aspergillosis	445.87	51.34	123	7982	1443	1737233
Hyperbilirubinaemia	399.85	51.34	123	7982	2164	1736512
Fungal infection	375.80	51.34	117	7988	2145	1736531
Aspergillus infection	364.00	51.34	102	8003	1271	1737405
Platelet count decreased	346.14	51.34	194	7911	16329	1722347
Tumour lysis syndrome	343.81	51.34	103	8002	1648	1737028
Bacteraemia	336.59	51.34	103	8002	1777	1736899
Leukoencephalopathy	328.48	51.34	84	8021	716	1737960
Anaemia	324.53	51.34	230	7875	29227	1709449
Neutropenic sepsis	306.94	51.34	91	8014	1401	1737275
Stomatitis	299.88	51.34	124	7981	5280	1733396
Blood bilirubin increased	299.62	51.34	129	7976	6081	1732595
Aplasia	299.48	51.34	70	8035	390	1738286
Hypoxia	298.02	51.34	127	7978	5836	1732840
Alanine aminotransferase increased	295.18	51.34	158	7947	12120	1726556
Infection	294.19	51.34	158	7947	12202	1726474
Neutropenic colitis	293.15	51.34	63	8042	221	1738455
Blood culture positive	291.42	51.34	76	8029	705	1737971
Hypertriglyceridaemia	280.68	51.34	81	8024	1128	1737548
Myelopathy	280.40	51.34	63	8042	285	1738391
Acute lymphocytic leukaemia recurrent	278.14	51.34	61	8044	241	1738435
Pleural effusion	275.54	51.34	146	7959	10964	1727712
Neoplasm progression	269.67	51.34	100	8005	3167	1735509
Acute myeloid leukaemia recurrent	268.01	51.34	58	8047	212	1738464
Abdominal pain	262.57	51.34	179	7926	21311	1717365
Second primary malignancy	259.47	51.34	74	8031	985	1737691
Hypofibrinogenaemia	257.18	51.34	54	8051	164	1738512
Cytomegalovirus infection	250.45	51.34	95	8010	3206	1735470
Vomiting	248.43	51.34	219	7886	38096	1700580
Staphylococcal infection	237.58	51.34	101	8004	4606	1734070
Renal failure	233.27	51.34	162	7943	19855	1718821
Diarrhoea	228.92	51.34	244	7861	53608	1685068
Neutrophil count decreased	228.23	51.34	106	7999	5975	1732701
White blood cell count decreased	223.60	51.34	135	7970	13014	1725662
Device related infection	222.30	51.34	79	8026	2207	1736469
Posterior reversible encephalopathy syndrome	218.71	51.34	70	8035	1405	1737271
Tachycardia	210.44	51.34	128	7977	12500	1726176
Nausea	206.97	51.34	226	7879	50970	1687706
Venoocclusive disease	203.87	51.34	49	8056	313	1738363
Disease progression	201.70	51.34	140	7965	17123	1721553
Hepatotoxicity	199.26	51.34	79	8026	3005	1735671
Malignant neoplasm progression	196.98	51.34	128	7977	14030	1724646
Cytopenia	192.05	51.34	57	8048	879	1737797
Mucormycosis	191.09	51.34	54	8051	693	1737983
Aspartate aminotransferase increased	189.43	51.34	113	7992	10643	1728033
Leukopenia	189.29	51.34	104	8001	8376	1730300
Acute respiratory distress syndrome	185.14	51.34	78	8027	3473	1735203
Cytomegalovirus chorioretinitis	184.73	51.34	46	8059	347	1738329
Candida infection	180.30	51.34	65	8040	1893	1736783
Drug ineffective	171.50	51.34	229	7876	63572	1675104
Escherichia sepsis	166.38	51.34	47	8058	602	1738074
Respiratory distress	166.24	51.34	81	8024	5076	1733600
Leukaemia recurrent	165.94	51.34	40	8065	259	1738417
Pulmonary oedema	158.69	51.34	85	8020	6501	1732175
Clostridium difficile colitis	158.06	51.34	56	8049	1548	1737128
Neurotoxicity	152.54	51.34	58	8047	1966	1736710
Nervous system disorder	152.02	51.34	61	8044	2393	1736283
Haemophagocytic lymphohistiocytosis	151.60	51.34	53	8052	1407	1737269
Seizure	146.52	51.34	124	7981	20317	1718359
Neuropathy peripheral	144.36	51.34	90	8015	9163	1729513
Osteonecrosis	142.17	51.34	67	8038	3895	1734781
Acute lymphocytic leukaemia	141.04	51.34	40	8065	520	1738156
Enterococcal infection	138.64	51.34	44	8061	857	1737819
Bacterial infection	137.93	51.34	53	8052	1849	1736827
Staphylococcal bacteraemia	135.85	51.34	42	8063	748	1737928
Malignant transformation	133.92	51.34	26	8079	45	1738631
Graft versus host disease	133.44	51.34	49	8056	1504	1737172
Pulmonary haemorrhage	132.77	51.34	50	8055	1649	1737027
Encephalopathy	131.78	51.34	66	8039	4386	1734290
Bacterial sepsis	130.32	51.34	39	8066	619	1738057
Gamma-glutamyltransferase increased	129.00	51.34	68	8037	5030	1733646
Hypokalaemia	128.08	51.34	73	8032	6301	1732375
Pneumonia fungal	127.86	51.34	36	8069	455	1738221
Escherichia infection	126.40	51.34	42	8063	951	1737725
Diffuse large B-cell lymphoma	125.00	51.34	43	8062	1086	1737590
Chills	122.94	51.34	89	8016	11598	1727078
Disseminated intravascular coagulation	120.15	51.34	58	8047	3556	1735120
Transaminases increased	118.67	51.34	59	8046	3858	1734818
Chloroma	118.51	51.34	25	8080	78	1738598
Disease recurrence	115.76	51.34	51	8054	2531	1736145
Systemic candida	114.27	51.34	31	8074	338	1738338
Diffuse large B-cell lymphoma recurrent	112.33	51.34	25	8080	107	1738569
Toxicity to various agents	109.28	51.34	124	7981	29017	1709659
Ascites	106.93	51.34	62	8043	5524	1733152
Atrial fibrillation	106.81	51.34	91	8014	15020	1723656
Hepatic failure	106.36	51.34	63	8042	5840	1732836
Atelectasis	105.84	51.34	44	8061	1890	1736786
Parainfluenzae virus infection	105.23	51.34	26	8079	189	1738487
Lung infiltration	104.45	51.34	45	8060	2114	1736562
Agranulocytosis	102.84	51.34	52	8053	3524	1735152
Staphylococcal sepsis	102.77	51.34	38	8067	1189	1737487
Clostridium difficile infection	102.48	51.34	42	8063	1739	1736937
Pancreatitis	102.30	51.34	66	8039	7121	1731555
Mental status changes	102.11	51.34	62	8043	6013	1732663
Oedema	101.85	51.34	65	8040	6883	1731793
Headache	100.64	51.34	129	7976	34247	1704429
Coagulopathy	99.65	51.34	47	8058	2734	1735942
Escherichia bacteraemia	99.47	51.34	27	8078	295	1738381
Viral haemorrhagic cystitis	98.95	51.34	21	8084	68	1738608
Epstein-Barr virus infection	98.50	51.34	36	8069	1089	1737587
Neoplasm recurrence	97.00	51.34	28	8077	389	1738287
Muscular weakness	96.42	51.34	73	8032	10176	1728500
Hypertension	96.33	51.34	96	8009	19352	1719324
Cystitis haemorrhagic	96.19	51.34	31	8074	635	1738041
Klebsiella infection	93.95	51.34	32	8073	783	1737893
Cerebral haemorrhage	92.69	51.34	59	8046	6218	1732458
Acute promyelocytic leukaemia	91.03	51.34	22	8083	144	1738532
Systemic mycosis	89.88	51.34	22	8083	153	1738523
Pneumonia cytomegaloviral	89.81	51.34	26	8079	365	1738311
Cardiac failure	89.24	51.34	76	8029	12526	1726150
Cytogenetic abnormality	88.44	51.34	23	8082	210	1738466
Condition aggravated	87.84	51.34	95	8010	21055	1717621
Sinusitis	86.98	51.34	53	8052	5170	1733506
Dyspnoea	86.86	51.34	150	7955	51909	1686767
Cardiotoxicity	85.72	51.34	30	8075	798	1737878
Stem cell transplant	85.26	51.34	26	8079	441	1738235
Cholestasis	84.58	51.34	46	8059	3619	1735057
Fluid overload	83.82	51.34	38	8067	2017	1736659
Cellulitis	81.36	51.34	55	8050	6413	1732263
Therapy non-responder	80.54	51.34	54	8051	6212	1732464
Cytokine release syndrome	80.51	51.34	26	8079	536	1738140
Pericardial effusion	79.48	51.34	43	8062	3347	1735329
Hypoalbuminaemia	79.15	51.34	33	8072	1427	1737249
Tachypnoea	78.83	51.34	38	8067	2320	1736356
Blood creatinine increased	78.72	51.34	74	8031	13872	1724804
Retinal haemorrhage	78.13	51.34	31	8074	1178	1737498
Lymphopenia	77.91	51.34	36	8069	1997	1736679
Hepatomegaly	77.83	51.34	34	8071	1651	1737025
Ejection fraction decreased	77.54	51.34	37	8068	2208	1736468
Decreased appetite	76.82	51.34	94	8011	23777	1714899
Stenotrophomonas infection	76.67	51.34	20	8085	185	1738491
Sinus tachycardia	76.26	51.34	38	8067	2494	1736182
Cough	75.81	51.34	84	8021	19113	1719563
Drug resistance	75.81	51.34	41	8064	3189	1735487
Blindness	75.57	51.34	39	8066	2757	1735919
Dysphagia	75.42	51.34	63	8042	10105	1728571
Fusarium infection	74.85	51.34	18	8087	115	1738561
Epistaxis	73.35	51.34	57	8048	8249	1730427
Haemoglobin decreased	73.00	51.34	78	8027	17036	1721640
Palmar-plantar erythrodysaesthesia syndrome	72.65	51.34	41	8064	3466	1735210
Progressive multifocal leukoencephalopathy	72.24	51.34	32	8073	1607	1737069
Pneumocystis jirovecii pneumonia	71.44	51.34	36	8069	2420	1736256
Glioma	70.88	51.34	16	8089	74	1738602
Metabolic acidosis	70.49	51.34	47	8058	5355	1733321
Cardio-respiratory arrest	69.79	51.34	58	8047	9235	1729441
Encephalitis	69.45	51.34	28	8077	1110	1737566
Pseudomonas test positive	69.35	51.34	17	8088	119	1738557
General physical health deterioration	69.08	51.34	67	8038	13051	1725625
Autoimmune lymphoproliferative syndrome	68.98	51.34	12	8093	6	1738670
Shock	68.70	51.34	42	8063	4119	1734557
Capillary leak syndrome	68.61	51.34	20	8085	288	1738388
Burkitt's lymphoma	67.70	51.34	17	8088	133	1738543
Hyperglycaemia	67.54	51.34	45	8060	5120	1733556
Facial paralysis	67.46	51.34	32	8073	1884	1736792
Confusional state	67.16	51.34	83	8022	21195	1717481
Blood HIV RNULL increased	66.44	51.34	18	8087	195	1738481
Post transplant lymphoproliferative disorder	65.65	51.34	24	8081	726	1737950
Treatment failure	64.04	51.34	41	8064	4360	1734316
Gastrointestinal wall thickening	62.86	51.34	16	8089	133	1738543
Systemic inflammatory response syndrome	62.84	51.34	24	8081	822	1737854
Enterobacter infection	62.08	51.34	18	8087	254	1738422
Haemodynamic instability	61.82	51.34	27	8078	1310	1737366
Asthenia	61.80	51.34	103	8002	34567	1704109
Cardiac arrest	61.66	51.34	69	8036	15861	1722815
Enterocolitis	61.37	51.34	24	8081	877	1737799
Hepatosplenic candidiasis	61.36	51.34	12	8093	22	1738654
Paraplegia	61.33	51.34	21	8084	522	1738154
Hyponatraemia	61.08	51.34	53	8052	8947	1729729
Left ventricular dysfunction	61.06	51.34	26	8079	1185	1737491
Dialysis	60.58	51.34	32	8073	2372	1736304
Hepatitis B	60.57	51.34	27	8078	1376	1737300
Skin toxicity	59.31	51.34	21	8084	578	1738098
Lung consolidation	58.94	51.34	21	8084	589	1738087
Intracranial pressure increased	58.23	51.34	22	8083	731	1737945
Paraesthesia	58.07	51.34	55	8050	10396	1728280
Hypogammaglobulinaemia	57.99	51.34	21	8084	618	1738058
Respiratory tract infection fungal	57.24	51.34	14	8091	97	1738579
Pneumonia klebsiella	57.01	51.34	18	8087	344	1738332
Oxygen saturation decreased	56.84	51.34	42	8063	5633	1733043
Adenovirus infection	56.67	51.34	19	8086	442	1738234
Dehydration	55.89	51.34	69	8036	17589	1721087
Acute graft versus host disease	55.71	51.34	22	8083	825	1737851
Klebsiella sepsis	55.70	51.34	16	8089	218	1738458
Dysarthria	55.11	51.34	40	8065	5219	1733457
Ileus	54.48	51.34	30	8075	2416	1736260
Intussusception	54.41	51.34	14	8091	122	1738554
Geotrichum infection	54.36	51.34	11	8094	26	1738650
Guillain-Barre syndrome	54.11	51.34	22	8083	891	1737785
Basal cell carcinoma	54.06	51.34	30	8075	2453	1736223
Therapeutic product effect incomplete	53.85	51.34	40	8065	5408	1733268
Haemorrhage intracranial	53.58	51.34	33	8072	3277	1735399
Appendicitis	52.48	51.34	23	8082	1125	1737551
Trichosporon infection	51.96	51.34	13	8092	100	1738576
Brain oedema	51.87	51.34	28	8077	2168	1736508
Pseudomonal sepsis	51.86	51.34	17	8088	368	1738308
Hepatocellular injury	51.76	51.34	32	8073	3199	1735477
Skin lesion	51.63	51.34	31	8074	2941	1735735
Hemiparesis	51.37	51.34	30	8075	2704	1735972

Pharmacologic Action:

Source	Code	Description
ATC	L01BC01	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS ANTIMETABOLITES Pyrimidine analogues
ATC	L01XY01	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS OTHER ANTINEOPLASTIC AGENTS Combinations of antineoplastic agents
FDA MoA	N0000000233	Nucleic Acid Synthesis Inhibitors
FDA EPC	N0000175595	Nucleoside Metabolic Inhibitor
CHEBI has role	CHEBI:35610	antineoplastic agent
CHEBI has role	CHEBI:35705	immunosuppressive agent
MeSH PA	D000890	Anti-Infective Agents
MeSH PA	D000963	Antimetabolites
MeSH PA	D000964	Antimetabolites, Antineoplastic
MeSH PA	D000970	Antineoplastic Agents
MeSH PA	D000998	Antiviral Agents
MeSH PA	D007155	Immunologic Factors
MeSH PA	D007166	Immunosuppressive Agents
MeSH PA	D009676	Noxae

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Acute lymphoid leukemia	indication	91857003	DOID:9952
Acute myeloid leukemia, disease	indication	91861009
Acute promyelocytic leukemia, FAB M3	indication	110004001
Lymphomatous meningitis	indication	426128009
Meningeal Leukemia	indication
Allogeneic bone marrow transplantation	off-label use	58390007
Chronic myeloid leukemia	off-label use	92818009	DOID:8552
Diffuse non-Hodgkin's lymphoma, large cell	off-label use	109969005
Myelodysplastic syndrome	off-label use	109995007
Burkitt's lymphoma	off-label use	118617000
Progressive Diffuse Large B-Cell Lymphoma	off-label use
Adjunct for CNS Disease Prevention in Non-Hodgkin's Lymphoma	off-label use
Necrotizing enterocolitis in fetus OR newborn	contraindication	2707005
Mycosis	contraindication	3218000	DOID:1564
Pulmonary edema	contraindication	19242006	DOID:11396
Viral disease	contraindication	34014006	DOID:934
Hyperuricemia	contraindication	35885006	DOID:1920
Gastrointestinal ulcer	contraindication	40845000
Stomatitis	contraindication	61170000	DOID:9637
Diarrhea	contraindication	62315008
Adult respiratory distress syndrome	contraindication	67782005	DOID:11394
Leukopenia	contraindication	84828003	DOID:615
Cardiomyopathy	contraindication	85898001	DOID:0050700
Bacterial infectious disease	contraindication	87628006
Kidney disease	contraindication	90708001	DOID:557
Infectious disease of central nervous system	contraindication	128117002
Acute pancreatitis	contraindication	197456007	DOID:2913
Disease of liver	contraindication	235856003	DOID:409
Anemia	contraindication	271737000	DOID:2355
Pregnancy, function	contraindication	289908002
Thrombocytopenic disorder	contraindication	302215000	DOID:1588
Peripheral nerve disease	contraindication	302226006
Bone marrow depression	contraindication	307762000
Coma	contraindication	371632003
Breastfeeding (mother)	contraindication	413712001
Acute cerebellar syndrome	contraindication	417017003
Granulocytopenic disorder	contraindication	417672002
Vomiting	contraindication	422400008
Protozoal Infection	contraindication
Intestinal Ischemic Necrosis	contraindication

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	11.91	acidic
pKa2	12.58	acidic
pKa3	12.97	acidic
pKa4	4.04	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
100MG	VYXEOS	CELATOR PHARMS	N209401	Aug. 3, 2017	RX	POWDER	INTRAVENOUS	8431806	April 22, 2025	FOR THE TREATMENT OF ADULTS WITH NEWLY-DIAGNOSED THERAPY-RELATED ACUTE MYELOID LEUKEMIA (T-AML) OR AML WITH MYELODYSPLASIA-RELATED CHANGES (AML-MRC)
100MG	VYXEOS	CELATOR PHARMS	N209401	Aug. 3, 2017	RX	POWDER	INTRAVENOUS	7850990	Jan. 23, 2027	FOR THE TREATMENT OF ADULTS WITH NEWLY-DIAGNOSED THERAPY-RELATED ACUTE MYELOID LEUKEMIA (T-AML) OR AML WITH MYELODYSPLASIA-RELATED CHANGES (AML-MRC)
100MG	VYXEOS	CELATOR PHARMS	N209401	Aug. 3, 2017	RX	POWDER	INTRAVENOUS	8022279	Sept. 14, 2027	FOR THE TREATMENT OF ADULTS WITH NEWLY-DIAGNOSED THERAPY-RELATED ACUTE MYELOID LEUKEMIA (T-AML) OR AML WITH MYELODYSPLASIA-RELATED CHANGES (AML-MRC)
100MG	VYXEOS	CELATOR PHARMS	N209401	Aug. 3, 2017	RX	POWDER	INTRAVENOUS	8092828	April 1, 2029	FOR THE TREATMENT OF ADULTS WITH NEWLY-DIAGNOSED THERAPY-RELATED ACUTE MYELOID LEUKEMIA (T-AML) OR AML WITH MYELODYSPLASIA-RELATED CHANGES (AML-MRC)
100MG	VYXEOS	CELATOR PHARMS	N209401	Aug. 3, 2017	RX	POWDER	INTRAVENOUS	10166184	Oct. 15, 2032	METHOD OF RECONSTITUTING A LYOPHILIZED LIPOSOMAL COMPOSITION FOR ADMINISTERING CYTARABINE AND DAUNORUBICIN TO TREAT ADULTS WITH NEWLY-DIAGNOSED THERAPY-RELATED ACUTE MYELOID LEUKEMIA (T-AML) OR AML WITH MYELODYSPLASIA-RELATED CHANGES (AML-MRC)
100MG	VYXEOS	CELATOR PHARMS	N209401	Aug. 3, 2017	RX	POWDER	INTRAVENOUS	10028912	Sept. 29, 2034	METHOD OF ADMINISTERING A RECONSTITUTED LIPOSOMAL COMPOSITION CONTAINING CYTARABINE AND DAUNORUBICIN TO TREAT ADULTS WITH NEWLY-DIAGNOSED THERAPY-RELATED ACUTE MYELOID LEUKEMIA (T-AML) OR AML WITH MYELODYSPLASIA-RELATED CHANGES (AML-MRC)
100MG	VYXEOS	CELATOR PHARMS	N209401	Aug. 3, 2017	RX	POWDER	INTRAVENOUS	10028912	Sept. 29, 2034	METHOD OF RECONSTITUTING A LYOPHILIZED LIPOSOMAL COMPOSITION FOR ADMINISTERING CYTARABINE AND DAUNORUBICIN TO TREAT ADULTS WITH NEWLY-DIAGNOSED THERAPY-RELATED ACUTE MYELOID LEUKEMIA (T-AML) OR AML WITH MYELODYSPLASIA-RELATED CHANGES (AML-MRC)

Orange Book exclusivity data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
100MG	VYXEOS	CELATOR PHARMS	N209401	Aug. 3, 2017	RX	POWDER	INTRAVENOUS	Aug. 3, 2020	NEW PRODUCT

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
DNA polymerase (alpha/delta/epsilon)	Enzyme	P09884 P28340 Q07864	DPOD1_HUMAN DPOE1_HUMAN DPOLA_HUMAN	INHIBITOR			CHEMBL	CHEMBL
Prostatic acid phosphatase	Enzyme	P15309	PPAP_HUMAN		GI50	7	WOMBAT-PK
DNA polymerase beta	Enzyme	P06746	DPOLB_HUMAN				WOMBAT-PK
Enoyl-[acyl-carrier-protein] reductase [NADH]	Enzyme		Q5NGQ3_FRATT		IC50	4.23	CHEMBL

External reference:

ID	Source
D003561	MESH_DESCRIPTOR_UI
4018080	VUID
N0000146419	NUI
C0010711	UMLSCUI
D00168	KEGG_DRUG
04079A1RDZ	UNII
1709	INN_ID
69-74-9	SECONDARY_CAS_RN
89265009	SNOMEDCT_US
4018080	VANDF
002649	NDDF
372	MMSL
3041	RXNORM
387511003	SNOMEDCT_US
4526	MMSL
d00201	MMSL
6253	PUBCHEM_CID
CHEBI:28680	CHEBI
CHEMBL803	ChEMBL_ID
DB00987	DRUGBANK_ID
CHEMBL596186	ChEMBL_ID
AR3	PDB_CHEM_ID
4827	IUPHAR_LIGAND_ID
CHEMBL1256472	ChEMBL_ID
CHEMBL2092816	ChEMBL_ID

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
CYTARABINE	HUMAN PRESCRIPTION DRUG LABEL	1	61703-303	INJECTION, SOLUTION	20 mg	INTRAVENOUS	ANDA	14 sections
Cytarabine	HUMAN PRESCRIPTION DRUG LABEL	1	61703-304	INJECTION, SOLUTION	20 mg	INTRAVENOUS	ANDA	14 sections
Cytarabine	HUMAN PRESCRIPTION DRUG LABEL	1	61703-305	INJECTION, SOLUTION	20 mg	INTRAVENOUS	ANDA	14 sections
Cytarabine	HUMAN PRESCRIPTION DRUG LABEL	1	61703-319	INJECTION, SOLUTION	100 mg	INTRAVENOUS	ANDA	16 sections
Cytarabine	HUMAN PRESCRIPTION DRUG LABEL	1	63323-120	INJECTION, SOLUTION	100 mg	INTRAVENOUS	ANDA	14 sections
Cytarabine	HUMAN PRESCRIPTION DRUG LABEL	1	67457-452	INJECTION	2 g	INTRATHECAL	ANDA	14 sections
Cytarabine	HUMAN PRESCRIPTION DRUG LABEL	1	67457-454	INJECTION	20 mg	INTRAVENOUS	ANDA	14 sections
cytarabine	HUMAN PRESCRIPTION DRUG LABEL	1	67457-455	INJECTION	100 mg	INTRAVENOUS	ANDA	14 sections
Cytarabine	HUMAN PRESCRIPTION DRUG LABEL	1	68083-337	INJECTION, SOLUTION	100 mg	INTRAVENOUS	ANDA	13 sections
Cytarabine	HUMAN PRESCRIPTION DRUG LABEL	1	68083-343	INJECTION, SOLUTION	20 mg	INTRAVENOUS	ANDA	12 sections
VYXEOS	HUMAN PRESCRIPTION DRUG LABEL	2	68727-745	INJECTION, POWDER, LYOPHILIZED, FOR SUSPENSION	100 mg	INTRAVENOUS	NDA	17 sections
Cytarabine	HUMAN PRESCRIPTION DRUG LABEL	1	71288-109	INJECTION, SOLUTION	2 g	INTRAVENOUS	ANDA	14 sections