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

Stem definition	Drug id	CAS RN
	1112	33419-42-0

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: etoposide etosid fytosid toposar zuyeyidal VP-16	A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle. Molecular weight: 588.56 Formula: C29H32O13 CLOGP: -0.11 LIPINSKI: 2 HAC: 13 HDO: 3 TPSA: 160.83 ALOGS: -2.78 ROTB: 5 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

etoposide
etosid
fytosid
toposar
zuyeyidal
VP-16

A semisynthetic derivative of PODOPHYLLOTOXIN that exhibits antitumor activity. Etoposide inhibits DNA synthesis by forming a complex with topoisomerase II and DNA. This complex induces breaks in double stranded DNA and prevents repair by topoisomerase II binding. Accumulated breaks in DNA prevent entry into the mitotic phase of cell division, and lead to cell death. Etoposide acts primarily in the G2 and S phases of the cell cycle.

Molecular weight: 588.56
Formula: C29H32O13
CLOGP: -0.11
LIPINSKI: 2
HAC: 13
HDO: 3
TPSA: 160.83
ALOGS: -2.78
ROTB: 5

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)	3	Benet LZ, Broccatelli F, Oprea TI
S (Water solubility)	0.22 mg/mL	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	38 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	6.30 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability)	52 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution)	0.18 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	0.50 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.12 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	5.70 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
Nov. 10, 1983	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	2993.99	67.56	707	5600	10175	2341603
Neutropenia	1506.25	67.56	478	5829	21070	2330708
Off label use	1083.74	67.56	527	5780	73071	2278707
Mucosal inflammation	1032.48	67.56	262	6045	4962	2346816
Pancytopenia	990.23	67.56	300	6007	11152	2340626
Thrombocytopenia	958.34	67.56	331	5976	18800	2332978
Bone marrow failure	957.11	67.56	251	6056	5435	2346343
Sepsis	810.87	67.56	290	6017	18198	2333580
Acute myeloid leukaemia	805.63	67.56	189	6118	2521	2349257
Product use in unapproved indication	727.18	67.56	236	6071	10964	2340814
Pyrexia	640.26	67.56	335	5972	53373	2298405
Ovarian failure	578.99	67.56	98	6209	170	2351608
Myelodysplastic syndrome	572.43	67.56	142	6165	2418	2349360
Anaemia	558.41	67.56	266	6041	34526	2317252
Haematotoxicity	495.63	67.56	109	6198	1058	2350720
Haemophagocytic lymphohistiocytosis	487.98	67.56	111	6196	1272	2350506
Disease progression	486.82	67.56	196	6111	16899	2334879
Malignant neoplasm progression	444.13	67.56	167	6140	11961	2339817
Posterior reversible encephalopathy syndrome	442.89	67.56	115	6192	2365	2349413
Vomiting	439.39	67.56	291	6016	71311	2280467
Multiple organ dysfunction syndrome	438.78	67.56	147	6160	7494	2344284
Pneumonia	422.49	67.56	248	6059	49048	2302730
Tumour lysis syndrome	415.66	67.56	93	6214	982	2350796
Septic shock	402.15	67.56	135	6172	6919	2344859
Leukopenia	389.94	67.56	145	6162	10051	2341727
Maternal exposure before pregnancy	363.26	67.56	80	6227	780	2350998
Neutropenic sepsis	357.60	67.56	87	6220	1355	2350423
Nausea	351.29	67.56	305	6002	111884	2239894
Second primary malignancy	323.99	67.56	75	6232	931	2350847
Venoocclusive liver disease	315.47	67.56	67	6240	541	2351237
Platelet count decreased	309.04	67.56	139	6168	15674	2336104
Acute kidney injury	278.96	67.56	156	6151	27966	2323812
Colitis	258.48	67.56	90	6217	5136	2346642
Hypokalaemia	258.01	67.56	109	6198	10545	2341233
Renal failure	257.06	67.56	126	6181	17223	2334555
Infection	252.46	67.56	126	6181	17903	2333875
Diarrhoea	250.12	67.56	222	6085	83342	2268436
Neutrophil count decreased	242.05	67.56	91	6216	6476	2345302
Drug ineffective	240.79	67.56	237	6070	101387	2250391
Drug resistance	239.65	67.56	72	6235	2552	2349226
White blood cell count decreased	239.54	67.56	122	6185	18086	2333692
Cytomegalovirus infection	237.29	67.56	72	6235	2641	2349137
Febrile bone marrow aplasia	234.49	67.56	56	6251	801	2350977
Bacteraemia	231.89	67.56	64	6243	1666	2350112
Disease recurrence	228.35	67.56	74	6233	3377	2348401
Encephalopathy	219.57	67.56	77	6230	4484	2347294
Pleural effusion	216.46	67.56	99	6208	11569	2340209
Respiratory failure	214.59	67.56	103	6204	13425	2338353
Neuropathy peripheral	212.08	67.56	97	6210	11335	2340443
Hypotension	207.80	67.56	136	6171	32300	2319478
Venoocclusive disease	206.38	67.56	41	6266	227	2351551
Ovarian germ cell teratoma	200.15	67.56	30	6277	8	2351770
Dehydration	194.87	67.56	114	6193	22181	2329597
Stomatitis	188.31	67.56	85	6222	9625	2342153
Aplasia	176.54	67.56	40	6267	447	2351331
Aspergillus infection	173.40	67.56	45	6262	918	2350860
Clostridium difficile colitis	168.25	67.56	52	6255	2027	2349751
Oesophagitis	165.84	67.56	51	6256	1955	2349823
Candida infection	159.57	67.56	54	6253	2819	2348959
Hepatosplenic T-cell lymphoma	150.40	67.56	25	6282	36	2351742
Toxicity to various agents	148.07	67.56	111	6196	32643	2319135
Teratoma	145.58	67.56	25	6282	49	2351729
Enterococcal infection	144.49	67.56	37	6270	714	2351064
Disseminated intravascular coagulation	143.91	67.56	52	6255	3298	2348480
Stem cell transplant	141.84	67.56	32	6275	350	2351428
Neoplasm progression	140.96	67.56	56	6251	4612	2347166
Bronchopulmonary aspergillosis	138.47	67.56	38	6269	966	2350812
Ascites	137.56	67.56	58	6249	5562	2346216
General physical health deterioration	135.94	67.56	77	6230	14062	2337716
Staphylococcal infection	133.81	67.56	56	6251	5270	2346508
Decreased appetite	132.96	67.56	99	6208	28792	2322986
Haemoglobin decreased	128.09	67.56	81	6226	18070	2333708
Hyponatraemia	126.56	67.56	72	6235	13253	2338525
Asthenia	124.71	67.56	117	6190	46809	2304969
Pericardial effusion	124.20	67.56	49	6258	3960	2347818
Fatigue	120.67	67.56	152	6155	84721	2267057
Fungal infection	118.12	67.56	50	6257	4839	2346939
Abdominal pain	115.69	67.56	98	6209	34276	2317502
Dyspnoea	115.07	67.56	143	6164	78590	2273188
Tachycardia	112.70	67.56	72	6235	16337	2335441
Acute respiratory distress syndrome	111.74	67.56	43	6264	3249	2348529
Pulmonary oedema	110.39	67.56	54	6253	7309	2344469
BK virus infection	110.18	67.56	25	6282	281	2351497
Renal impairment	108.00	67.56	59	6248	10033	2341745
Alveolar soft part sarcoma	107.76	67.56	16	6291	3	2351775
Nephroblastoma	106.67	67.56	17	6290	15	2351763
Cytomegalovirus viraemia	104.28	67.56	26	6281	448	2351330
Hypoxia	103.43	67.56	49	6258	6178	2345600
Alanine aminotransferase increased	102.42	67.56	64	6243	13968	2337810
Thrombotic microangiopathy	101.87	67.56	32	6275	1315	2350463
Pneumothorax	99.70	67.56	36	6271	2276	2349502
Capillary leak syndrome	99.68	67.56	24	6283	355	2351423
Human herpesvirus 6 infection	99.62	67.56	24	6283	356	2351422
Herpes zoster	98.96	67.56	55	6252	9670	2342108
Death	98.78	67.56	135	6172	81333	2270445
Acute promyelocytic leukaemia	97.89	67.56	22	6285	236	2351542
Cystitis haemorrhagic	96.70	67.56	26	6281	610	2351168
Plasma cell myeloma	96.69	67.56	51	6256	8082	2343696
Herpes simplex	96.16	67.56	29	6278	1038	2350740
Varicella zoster virus infection	95.86	67.56	23	6284	335	2351443
Teratoma benign	95.36	67.56	15	6292	11	2351767
Neutropenic colitis	94.30	67.56	22	6285	282	2351496
Bacterial infection	93.59	67.56	34	6273	2187	2349591
Amenorrhoea	93.32	67.56	34	6273	2205	2349573
Pulmonary haemorrhage	92.21	67.56	29	6278	1196	2350582
Seizure	91.08	67.56	74	6233	24392	2327386
Osteosarcoma	90.48	67.56	16	6291	40	2351738
Retinoblastoma	89.67	67.56	15	6292	23	2351755
Nephropathy toxic	88.91	67.56	28	6279	1160	2350618
Therapy non-responder	88.42	67.56	48	6259	8056	2343722
Product use issue	87.52	67.56	55	6252	12114	2339664
Respiratory distress	87.14	67.56	41	6266	5088	2346690
Deafness	87.11	67.56	34	6273	2667	2349111
Leukoencephalopathy	86.12	67.56	25	6282	782	2350996
Enterobacter infection	85.89	67.56	20	6287	254	2351524
Enterococcal sepsis	85.62	67.56	18	6289	137	2351641
Unmasking of previously unidentified disease	84.78	67.56	16	6291	64	2351714
Deep vein thrombosis	84.45	67.56	55	6252	12877	2338901
Respiratory symptom	84.27	67.56	19	6288	207	2351571
Acute lymphocytic leukaemia	83.86	67.56	22	6285	468	2351310
Hypertension	83.86	67.56	74	6233	27287	2324491
Hypomagnesaemia	81.72	67.56	32	6275	2532	2349246
Klebsiella infection	81.41	67.56	24	6283	793	2350985
Large intestinal ulcer perforation	81.03	67.56	12	6295	2	2351776
Primary hypogonadism	80.67	67.56	14	6293	30	2351748
Malignant transformation	80.36	67.56	14	6293	31	2351747
Neurotoxicity	80.13	67.56	30	6277	2100	2349678
Enteritis	78.80	67.56	25	6282	1061	2350717
Graft versus host disease	77.62	67.56	24	6283	935	2350843
Human bocavirus infection	76.75	67.56	12	6295	8	2351770
Therapeutic product effect incomplete	76.73	67.56	48	6259	10483	2341295
Fungaemia	76.42	67.56	18	6289	241	2351537
Secondary immunodeficiency	76.26	67.56	15	6292	78	2351700
Ototoxicity	75.68	67.56	18	6289	252	2351526
Ewing's sarcoma	75.66	67.56	14	6293	49	2351729
Pulmonary mycosis	75.63	67.56	16	6291	126	2351652
Cough	75.48	67.56	76	6231	33041	2318737
Cardiac failure	75.47	67.56	50	6257	12044	2339734
Epstein-Barr virus infection	74.14	67.56	24	6283	1087	2350691
Syncope	73.46	67.56	56	6251	16819	2334959
Acute lymphocytic leukaemia recurrent	73.44	67.56	17	6290	210	2351568
Treatment failure	71.06	67.56	40	6267	7199	2344579
Blood creatinine increased	69.26	67.56	45	6262	10488	2341290
Hepatotoxicity	69.06	67.56	31	6276	3450	2348328
Fungal oesophagitis	68.39	67.56	14	6293	92	2351686
Gastrointestinal fungal infection	67.92	67.56	13	6294	57	2351721
Blood bilirubin increased	67.74	67.56	35	6272	5310	2346468
Left ventricular dysfunction	67.61	67.56	23	6284	1217	2350561
Neoplasm recurrence	67.57	67.56	18	6289	407	2351371

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	3851.64	55.66	1035	8147	10065	1727534
Neutropenia	1974.37	55.66	699	8483	17561	1720038
Off label use	1465.28	55.66	698	8484	37873	1699726
Thrombocytopenia	1432.93	55.66	577	8605	20672	1716927
Pancytopenia	1249.44	55.66	442	8740	10915	1726684
Bone marrow failure	1042.24	55.66	319	8863	4881	1732718
Mucosal inflammation	1040.40	55.66	303	8879	3866	1733733
Sepsis	908.27	55.66	408	8774	19030	1718569
Acute myeloid leukaemia	860.90	55.66	244	8938	2797	1734802
Pyrexia	860.27	55.66	523	8659	45877	1691722
Product use in unapproved indication	845.23	55.66	316	8866	9106	1728493
Myelodysplastic syndrome	788.87	55.66	232	8950	3057	1734542
Anaemia	724.95	55.66	400	8782	29057	1708542
Pneumonia	693.08	55.66	456	8726	45726	1691873
Septic shock	665.26	55.66	255	8927	7854	1729745
Malignant neoplasm progression	596.14	55.66	277	8905	13881	1723718
Leukopenia	584.01	55.66	235	8947	8245	1729354
Venoocclusive liver disease	549.36	55.66	134	9048	799	1736800
Second primary malignancy	483.15	55.66	124	9058	935	1736664
Acute kidney injury	427.30	55.66	305	8877	34639	1702960
Respiratory failure	411.09	55.66	217	8965	14288	1723311
Vomiting	402.11	55.66	305	8877	38010	1699589
Disease progression	397.24	55.66	225	8957	17038	1720561
Stomatitis	396.72	55.66	157	9025	5247	1732352
Multiple organ dysfunction syndrome	391.95	55.66	182	9000	9060	1728539
Tumour lysis syndrome	377.89	55.66	114	9068	1637	1735962
Drug ineffective	369.42	55.66	361	8821	63440	1674159
Colitis	369.35	55.66	139	9043	4041	1733558
Neutrophil count decreased	341.92	55.66	146	9036	5935	1731664
Diarrhoea	328.76	55.66	314	8868	53538	1684061
Neutropenic sepsis	325.62	55.66	98	9084	1394	1736205
Renal failure	323.45	55.66	208	8974	19809	1717790
Nausea	305.66	55.66	295	8887	50901	1686698
White blood cell count decreased	303.81	55.66	172	9010	12977	1724622
Haemophagocytic lymphohistiocytosis	293.37	55.66	90	9092	1370	1736229
Haematotoxicity	280.17	55.66	79	9103	879	1736720
Posterior reversible encephalopathy syndrome	275.59	55.66	86	9096	1389	1736210
Hypotension	271.20	55.66	218	8964	29436	1708163
Neuropathy peripheral	263.33	55.66	139	9043	9114	1728485
Platelet count decreased	257.60	55.66	168	9014	16355	1721244
Aspergillus infection	252.10	55.66	79	9103	1294	1736305
Dyspnoea	252.00	55.66	268	8914	51791	1685808
Bronchopulmonary aspergillosis	241.88	55.66	79	9103	1487	1736112
Encephalopathy	221.09	55.66	98	9084	4354	1733245
Febrile bone marrow aplasia	219.12	55.66	64	9118	814	1736785
Pulmonary embolism	216.28	55.66	138	9044	12921	1724678
Bacteraemia	200.98	55.66	72	9110	1808	1735791
Aplasia	195.75	55.66	51	9131	409	1737190
Pleural effusion	192.89	55.66	121	9061	10989	1726610
Neurotoxicity	188.43	55.66	70	9112	1954	1735645
Cytomegalovirus infection	184.50	55.66	79	9103	3222	1734377
Lymphopenia	184.47	55.66	69	9113	1964	1735635
Stem cell transplant	175.88	55.66	47	9135	420	1737179
Hypokalaemia	173.43	55.66	93	9089	6281	1731318
Cytopenia	168.22	55.66	53	9129	883	1736716
Disease recurrence	165.05	55.66	68	9114	2514	1735085
Acute lymphocytic leukaemia	162.88	55.66	46	9136	514	1737085
Pneumonitis	162.23	55.66	76	9106	3839	1733760
Hyponatraemia	158.63	55.66	99	9083	8901	1728698
Neutropenic colitis	157.95	55.66	39	9143	245	1737354
Neoplasm progression	156.01	55.66	70	9112	3197	1734402
Staphylococcal infection	154.76	55.66	78	9104	4629	1732970
Infection	152.76	55.66	109	9073	12251	1725348
Pneumocystis jirovecii pneumonia	151.30	55.66	63	9119	2393	1735206
Hypoxia	148.32	55.66	82	9100	5881	1731718
Diffuse large B-cell lymphoma	146.62	55.66	50	9132	1079	1736520
Asthenia	145.53	55.66	166	9016	34504	1703095
Abdominal pain	143.11	55.66	132	9050	21358	1716241
Drug resistance	140.94	55.66	65	9117	3165	1734434
Cytomegalovirus chorioretinitis	140.67	55.66	38	9144	355	1737244
Candida infection	140.36	55.66	56	9126	1902	1735697
Bone marrow toxicity	139.41	55.66	37	9145	321	1737278
Haemoglobin decreased	137.60	55.66	117	9065	16997	1720602
Toxicity to various agents	136.83	55.66	148	9034	28993	1708606
Malignant transformation	136.72	55.66	27	9155	44	1737555
Hepatitis B	136.00	55.66	50	9132	1353	1736246
Enterococcal infection	133.23	55.66	44	9138	857	1736742
Venoocclusive disease	129.56	55.66	35	9147	327	1737272
Clostridium difficile colitis	129.48	55.66	50	9132	1554	1736045
Acute respiratory distress syndrome	129.03	55.66	63	9119	3488	1734111
Respiratory distress	128.46	55.66	71	9111	5086	1732513
Fungal infection	125.92	55.66	54	9128	2208	1735391
Nephropathy toxic	125.76	55.66	50	9132	1682	1735917
Cough	122.14	55.66	115	9067	19082	1718517
Device related infection	122.09	55.66	53	9129	2233	1735366
Hepatotoxicity	122.00	55.66	58	9124	3026	1734573
Cystitis haemorrhagic	120.87	55.66	38	9144	628	1736971
Neoplasm recurrence	120.12	55.66	34	9148	383	1737216
Agranulocytosis	119.70	55.66	60	9122	3516	1734083
Deep vein thrombosis	119.12	55.66	86	9096	9834	1727765
Alanine aminotransferase increased	115.50	55.66	92	9090	12186	1725413
Staphylococcal bacteraemia	110.51	55.66	37	9145	753	1736846
Renal impairment	108.90	55.66	89	9093	12225	1725374
Epstein-Barr virus infection	108.69	55.66	40	9142	1085	1736514
Decreased appetite	108.06	55.66	119	9063	23752	1713847
Disseminated intravascular coagulation	107.50	55.66	56	9126	3558	1734041
Product use issue	104.47	55.66	75	9107	8496	1729103
Chills	104.46	55.66	85	9097	11602	1725997
Chloroma	104.26	55.66	23	9159	80	1737519
Pulmonary haemorrhage	102.66	55.66	43	9139	1656	1735943
Thrombotic microangiopathy	99.67	55.66	39	9143	1256	1736343
Hypertension	98.64	55.66	103	9079	19345	1718254
Systemic candida	96.92	55.66	28	9154	341	1737258
Bacterial sepsis	96.75	55.66	32	9150	626	1736973
Retinal haemorrhage	95.13	55.66	37	9145	1172	1736427
Hodgkin's disease	95.06	55.66	33	9149	752	1736847
Treatment failure	94.50	55.66	55	9127	4346	1733253
Klebsiella infection	93.85	55.66	33	9149	782	1736817
Acute promyelocytic leukaemia	93.33	55.66	23	9159	143	1737456
Diffuse large B-cell lymphoma recurrent	93.32	55.66	22	9160	110	1737489
Lymphadenopathy	92.56	55.66	53	9129	4061	1733538
Hyperbilirubinaemia	90.40	55.66	43	9139	2244	1735355
Pulmonary fibrosis	89.68	55.66	44	9138	2460	1735139
Tachycardia	88.69	55.66	80	9102	12548	1725051
General physical health deterioration	88.01	55.66	81	9101	13037	1724562
Embolism	87.24	55.66	34	9148	1083	1736516
Systemic mycosis	87.15	55.66	22	9160	153	1737446
Osteonecrosis	86.35	55.66	50	9132	3912	1733687
Osteosarcoma	86.01	55.66	18	9164	45	1737554
Condition aggravated	84.72	55.66	99	9083	21051	1716548
Nervous system disorder	84.55	55.66	42	9140	2412	1735187
Escherichia infection	83.87	55.66	32	9150	961	1736638
Lung infiltration	83.53	55.66	40	9142	2119	1735480
Confusional state	82.58	55.66	98	9084	21180	1716419
Cardiotoxicity	82.05	55.66	30	9152	798	1736801
Progressive multifocal leukoencephalopathy	81.03	55.66	36	9146	1603	1735996
Renal tubular disorder	80.44	55.66	30	9152	845	1736754
Cardiomyopathy	80.00	55.66	42	9140	2710	1734889
C-reactive protein increased	79.83	55.66	55	9127	5830	1731769
Plasma cell myeloma	79.44	55.66	68	9114	9946	1727653
Bacterial infection	78.98	55.66	37	9145	1865	1735734
Pulmonary toxicity	77.99	55.66	29	9153	810	1736789
Pneumothorax	77.72	55.66	41	9141	2671	1734928
Seizure	77.43	55.66	93	9089	20348	1717251
Interstitial lung disease	77.23	55.66	66	9116	9630	1727969
Transaminases increased	76.37	55.66	46	9136	3871	1733728
Dehydration	76.34	55.66	86	9096	17572	1720027
Cytogenetic abnormality	76.26	55.66	21	9161	212	1737387
Ameloblastoma	75.67	55.66	13	9169	3	1737596
Pneumonia klebsiella	75.58	55.66	23	9159	339	1737260
Intestinal perforation	75.06	55.66	34	9148	1585	1736014
Bicytopenia	74.88	55.66	21	9161	228	1737371
Electrolyte imbalance	74.73	55.66	33	9149	1448	1736151
Acute graft versus host disease	74.08	55.66	28	9154	819	1736780
Human herpesvirus 6 infection	74.06	55.66	23	9159	364	1737235
Escherichia bacteraemia	73.87	55.66	22	9160	300	1737299
Cerebral infarction	73.77	55.66	50	9132	5159	1732440
Graft versus host disease	73.22	55.66	33	9149	1520	1736079
Atelectasis	72.30	55.66	35	9147	1899	1735700
Herpes zoster	72.27	55.66	47	9135	4526	1733073
Enterococcal bacteraemia	71.76	55.66	19	9163	163	1737436
Gastrointestinal haemorrhage	69.50	55.66	74	9108	14193	1723406
Hodgkin's disease refractory	68.89	55.66	12	9170	4	1737595
Hypoalbuminaemia	68.76	55.66	31	9151	1429	1736170
Dysphagia	68.59	55.66	63	9119	10105	1727494
Streptococcal infection	68.51	55.66	25	9157	661	1736938
Blood creatinine increased	67.34	55.66	72	9110	13874	1723725
Papillary thyroid cancer	65.88	55.66	18	9164	176	1737423
Therapy partial responder	65.76	55.66	20	9162	294	1737305
Cerebral haemorrhage	65.39	55.66	50	9132	6227	1731372
Fanconi syndrome	64.14	55.66	20	9162	321	1737278
Shock	63.88	55.66	42	9140	4119	1733480
Metastasis	63.64	55.66	25	9157	813	1736786
Therapy non-responder	63.28	55.66	49	9133	6217	1731382
Deafness	62.88	55.66	32	9150	1934	1735665
Therapeutic product effect incomplete	62.54	55.66	46	9136	5402	1732197
Klebsiella sepsis	62.54	55.66	18	9164	216	1737383
Haemoptysis	62.45	55.66	44	9138	4832	1732767
Pleuritic pain	62.45	55.66	21	9161	433	1737166
Hypophosphataemia	62.32	55.66	28	9154	1280	1736319
Acute lymphocytic leukaemia recurrent	62.24	55.66	19	9163	283	1737316
Adenovirus infection	62.13	55.66	21	9161	440	1737159
Pneumonia cytomegaloviral	61.45	55.66	20	9162	371	1737228
Epistaxis	61.01	55.66	54	9128	8252	1729347
Burkitt's lymphoma	60.77	55.66	16	9166	134	1737465
Non-Hodgkin's lymphoma	60.73	55.66	25	9157	920	1736679
Clostridium difficile infection	59.92	55.66	30	9152	1751	1735848
Kaposi's sarcoma	59.36	55.66	24	9158	843	1736756
Ependymoma	59.18	55.66	12	9170	24	1737575
Hypogammaglobulinaemia	59.07	55.66	22	9160	617	1736982
Respiratory disorder	58.86	55.66	36	9146	3113	1734486
Basal cell carcinoma	58.56	55.66	33	9149	2450	1735149
Staphylococcal sepsis	57.61	55.66	26	9156	1201	1736398
Ascites	57.10	55.66	44	9138	5542	1732057
Muscular weakness	56.82	55.66	57	9125	10192	1727407
Myelitis transverse	56.37	55.66	16	9166	182	1737417
Small intestinal obstruction	56.29	55.66	29	9153	1798	1735801
Metabolic acidosis	56.20	55.66	43	9139	5359	1732240
Metastases to liver	55.83	55.66	31	9151	2236	1735363
Intentional product use issue	55.77	55.66	33	9149	2686	1734913
Recurrent cancer	55.77	55.66	17	9165	252	1737347
Pulmonary alveolar haemorrhage	55.70	55.66	25	9157	1140	1736459

Pharmacologic Action:

Source	Code	Description
ATC	L01CB01	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS PLANT ALKALOIDS AND OTHER NATURAL PRODUCTS Podophyllotoxin derivatives
FDA EPC	N0000175609	Topoisomerase Inhibitor
FDA MoA	N0000000176	Topoisomerase Inhibitors
MeSH PA	D000970	Antineoplastic Agents
MeSH PA	D000972	Antineoplastic Agents, Phytogenic
MeSH PA	D004791	Enzyme Inhibitors
CHEBI has role	CHEBI:35610	antineoplastic agent
MeSH PA	D059005	Topoisomerase II Inhibitors

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Small cell carcinoma of lung	indication	254632001	DOID:5409
Malignant tumor of testis	indication	363449006	DOID:2998
Allogeneic bone marrow transplantation	off-label use	58390007
Ewing's sarcoma	off-label use	76909002	DOID:3369
Acute myeloid leukemia, disease	off-label use	91861009
Kaposi's sarcoma	off-label use	109385007
Diffuse non-Hodgkin's lymphoma, large cell	off-label use	109969005
Multiple myeloma	off-label use	109989006	DOID:9538
Hodgkin's disease	off-label use	118599009
Burkitt's lymphoma	off-label use	118617000
Non-small cell lung cancer	off-label use	254637007	DOID:3908
Osteosarcoma of bone	off-label use	307576001	DOID:3376
Malignant tumor of ovary	off-label use	363443007	DOID:2394
Neuroblastoma	off-label use	432328008	DOID:769
Neuroendocrine Prostate Carcinoma	off-label use
Progressive Diffuse Large B-Cell Lymphoma	off-label use
Testicular Germ Cell Tumor	off-label use
Ovarian Germ Cell Tumor Carcinoma	off-label use
Acute hemorrhage	contraindication	8573003
Fibrosis of lung	contraindication	51615001	DOID:3770
Metabolic acidosis	contraindication	59455009
Acute infectious disease	contraindication	63171007
Interstitial pneumonia	contraindication	64667001
Leukopenia	contraindication	84828003	DOID:615
Hypoalbuminemia	contraindication	119247004
Impaired renal function disorder	contraindication	197663003
Drug-induced hepatitis	contraindication	235876009
Anemia	contraindication	271737000	DOID:2355
Pregnancy, function	contraindication	289908002
Thrombocytopenic disorder	contraindication	302215000	DOID:1588
Neutropenic disorder	contraindication	303011007	DOID:1227
Bone marrow depression	contraindication	307762000
Breastfeeding (mother)	contraindication	413712001

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	11.96	acidic
pKa2	13.08	acidic
pKa3	13.86	acidic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
DNA topoisomerase 2-alpha	Enzyme	P11388	TOP2A_HUMAN	INHIBITOR	IC50	7.30	IUPHAR	CHEMBL
Nuclear receptor subfamily 1 group I member 2	Nuclear hormone receptor	O75469	NR1I2_HUMAN				WOMBAT-PK
Canalicular multispecific organic anion transporter 2	Transporter	O15438	MRP3_HUMAN				WOMBAT-PK
Multidrug resistance-associated protein 6	Transporter	O95255	MRP6_HUMAN				WOMBAT-PK
ATP-binding cassette sub-family G member 2	Transporter	Q9UNQ0	ABCG2_HUMAN				WOMBAT-PK
Multidrug resistance-associated protein 1	Transporter	P33527	MRP1_HUMAN				WOMBAT-PK
Canalicular multispecific organic anion transporter 1	Transporter	Q92887	MRP2_HUMAN		Km	3.21	WOMBAT-PK
Multidrug resistance protein 1	Transporter	P08183	MDR1_HUMAN		Ki	3.28	WOMBAT-PK
Arachidonate 15-lipoxygenase	Enzyme		LOX15_RABIT		IC50	5.50	DRUG MATRIX

External reference:

ID	Source
D005047	MESH_DESCRIPTOR_UI
4018141	VUID
N0000146478	NUI
C0015133	UMLSCUI
D00125	KEGG_DRUG
6PLQ3CP4P3	UNII
3835	INN_ID
56928005	SNOMEDCT_US
4209	MMSL
4179	RXNORM
387316009	SNOMEDCT_US
4709	MMSL
d00230	MMSL
4018141	VANDF
002674	NDDF
CHEMBL44657	ChEMBL_ID
DB00773	DRUGBANK_ID
CHEMBL1200645	ChEMBL_ID
EVP	PDB_CHEM_ID
CHEBI:4911	CHEBI
36462	PUBCHEM_CID
6815	IUPHAR_LIGAND_ID

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Etoposide	HUMAN PRESCRIPTION DRUG LABEL	1	0143-9376	INJECTION	20 mg	INTRAVENOUS	ANDA	13 sections
Etoposide	HUMAN PRESCRIPTION DRUG LABEL	1	0143-9510	INJECTION	20 mg	INTRAVENOUS	ANDA	13 sections
Etoposide	HUMAN PRESCRIPTION DRUG LABEL	1	0143-9511	INJECTION	20 mg	INTRAVENOUS	ANDA	13 sections
Etoposide	HUMAN PRESCRIPTION DRUG LABEL	1	0143-9512	INJECTION	20 mg	INTRAVENOUS	ANDA	13 sections
Etoposide	HUMAN PRESCRIPTION DRUG LABEL	1	0378-3266	CAPSULE	50 mg	ORAL	ANDA	13 sections
Toposar	HUMAN PRESCRIPTION DRUG LABEL	1	0703-5653	INJECTION, SOLUTION, CONCENTRATE	20 mg	INTRAVENOUS	ANDA	14 sections
Toposar	HUMAN PRESCRIPTION DRUG LABEL	1	0703-5656	INJECTION, SOLUTION, CONCENTRATE	20 mg	INTRAVENOUS	ANDA	14 sections
Toposar	HUMAN PRESCRIPTION DRUG LABEL	1	0703-5657	INJECTION, SOLUTION, CONCENTRATE	20 mg	INTRAVENOUS	ANDA	14 sections
Etoposide	HUMAN PRESCRIPTION DRUG LABEL	1	16729-114	INJECTION	20 mg	INTRAVENOUS	ANDA	13 sections
Etoposide	HUMAN PRESCRIPTION DRUG LABEL	1	16729-262	INJECTION	20 mg	INTRAVENOUS	ANDA	12 sections
Etoposide	HUMAN PRESCRIPTION DRUG LABEL	1	63323-104	INJECTION, SOLUTION	20 mg	INTRAVENOUS	ANDA	14 sections
Etoposide	HUMAN PRESCRIPTION DRUG LABEL	1	68001-265	INJECTION	20 mg	INTRAVENOUS	ANDA	13 sections