pemetrexed 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
antineoplastics; thymidylate synthetase inhibitors	2073	137281-23-3

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: LY231514 pemetrexed diacid monohydrate pemetrexed sodium pemetrexed sodium hydrate pemetrexed pemetrexed disodium alimta pemetrexed disodium heptahydrate	Pemetrexed is a folate analog metabolic inhibitor that disrupts folate-dependent metabolic processes essential for cell replication. In vitro studies show that pemetrexed inhibits thymidylate synthase (TS), dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase (GARFT), which are folate-dependent enzymes involved in the de novo biosynthesis of thymidine and purine nucleotides. Pemetrexed is taken into cells by membrane carriers such as the reduced folate carrier and membrane folate binding protein transport systems. Once in the cell, pemetrexed is converted to polyglutamate forms by the enzyme folylpolyglutamate synthetase. The polyglutamate forms are retained in cells and are inhibitors of TS and GARFT. Molecular weight: 427.42 Formula: C20H21N5O6 CLOGP: -0.12 LIPINSKI: 2 HAC: 11 HDO: 6 TPSA: 186.97 ALOGS: -3.97 ROTB: 9 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

LY231514
pemetrexed diacid monohydrate
pemetrexed sodium
pemetrexed sodium hydrate
pemetrexed
pemetrexed disodium
alimta
pemetrexed disodium heptahydrate

Pemetrexed is a folate analog metabolic inhibitor that disrupts folate-dependent metabolic processes essential for cell replication. In vitro studies show that pemetrexed inhibits thymidylate synthase (TS), dihydrofolate reductase, and glycinamide ribonucleotide formyltransferase (GARFT), which are folate-dependent enzymes involved in the de novo biosynthesis of thymidine and purine nucleotides. Pemetrexed is taken into cells by membrane carriers such as the reduced folate carrier and membrane folate binding protein transport systems. Once in the cell, pemetrexed is converted to polyglutamate forms by the enzyme folylpolyglutamate synthetase. The polyglutamate forms are retained in cells and are inhibitors of TS and GARFT.

Molecular weight: 427.42
Formula: C20H21N5O6
CLOGP: -0.12
LIPINSKI: 2
HAC: 11
HDO: 6
TPSA: 186.97
ALOGS: -3.97
ROTB: 9

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)	100 mg/mL	Bocci G, Oprea TI, Benet LZ
EoM (Fraction excreted unchanged in urine)	80 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	1.38 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
Vd (Volume of distribution)	0.15 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	1.30 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.19 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	1.85 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company
Sept. 20, 2004	EMA	ELI LILLY NEDERLAND B.V.
Feb. 4, 2004	FDA	LILLY
Jan. 4, 2007	PMDA	Eli Lilly Japan K.K.

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
Malignant neoplasm progression	1138.68	18.70	545	19839	81576	63387062
Disease progression	414.89	18.70	331	20053	122427	63346211
Pancytopenia	309.49	18.70	253	20131	96680	63371958
Anaemia	266.18	18.70	394	19990	293036	63175602
Drug resistance	217.02	18.70	118	20266	22815	63445823
Neutropenia	212.72	18.70	271	20113	174734	63293904
Thrombocytopenia	185.07	18.70	235	20149	150922	63317716
Tubulointerstitial nephritis	178.90	18.70	99	20285	19804	63448834
Neoplasm progression	173.71	18.70	121	20263	36307	63432331
Therapy partial responder	169.43	18.70	78	20306	10580	63458058
Pneumonitis	140.51	18.70	105	20279	35117	63433521
Acquired gene mutation	139.62	18.70	37	20347	946	63467692
Metastases to central nervous system	133.95	18.70	71	20313	13034	63455604
Non-small cell lung cancer	128.42	18.70	47	20337	3548	63465090
Febrile neutropenia	127.56	18.70	173	20211	118276	63350362
Bone marrow failure	125.11	18.70	91	20293	29199	63439439
Acute kidney injury	104.04	18.70	248	20136	263167	63205471
Myelosuppression	97.51	18.70	72	20312	23631	63445007
Renal tubular necrosis	90.35	18.70	53	20331	11825	63456813
Arthralgia	87.31	18.70	37	20347	569673	62898965
Haematotoxicity	82.48	18.70	46	20338	9330	63459308
Pulmonary embolism	82.28	18.70	140	20244	116544	63352094
Metastases to adrenals	81.67	18.70	23	20361	742	63467896
Mucosal inflammation	80.74	18.70	87	20297	46841	63421797
Nephropathy toxic	79.30	18.70	45	20339	9434	63459204
Joint swelling	76.82	18.70	8	20376	327658	63140980
EGFR gene mutation	76.43	18.70	18	20366	279	63468359
Pain	75.75	18.70	76	20308	740552	62728086
Death	75.07	18.70	277	20107	374104	63094534
Pleural effusion	74.01	18.70	118	20266	93092	63375546
Immune-mediated hepatitis	72.42	18.70	24	20360	1347	63467291
Blood creatinine increased	72.22	18.70	113	20271	87731	63380907
Myocarditis	70.55	18.70	43	20341	10282	63458356
Dehydration	65.94	18.70	161	20223	173193	63295445
Abdominal discomfort	65.43	18.70	12	20372	320873	63147765
Nephritis	65.08	18.70	26	20358	2490	63466148
Subacute cutaneous lupus erythematosus	63.84	18.70	26	20358	2617	63466021
Colitis	61.70	18.70	77	20307	48451	63420187
Haemoptysis	61.65	18.70	60	20324	28666	63439972
Metastases to meninges	60.82	18.70	25	20359	2577	63466061
Neutrophil count decreased	60.05	18.70	82	20302	56324	63412314
Interstitial lung disease	59.96	18.70	86	20298	61822	63406816
Posterior reversible encephalopathy syndrome	58.86	18.70	47	20337	17298	63451340
Hepatocellular injury	58.40	18.70	57	20327	27324	63441314
Maternal exposure during pregnancy	58.29	18.70	3	20381	220059	63248579
Immune-mediated lung disease	58.12	18.70	17	20367	629	63468009
Fall	57.62	18.70	27	20357	392307	63076331
Contraindicated product administered	57.54	18.70	3	20381	217645	63250993
Pericardial effusion	57.53	18.70	59	20325	29999	63438639
General physical health deterioration	56.37	18.70	167	20217	201235	63267403
Skin toxicity	55.23	18.70	28	20356	4686	63463952
Osteonecrosis of jaw	55.01	18.70	62	20322	35061	63433577
Sinusitis	54.49	18.70	5	20379	226648	63241990
Renal failure	54.34	18.70	118	20266	117534	63351104
Lung adenocarcinoma	52.97	18.70	27	20357	4570	63464068
Drug hypersensitivity	52.84	18.70	17	20367	310670	63157968
Immune-mediated hepatic disorder	52.79	18.70	15	20369	500	63468138
Hepatitis	51.97	18.70	64	20320	39724	63428914
Product dose omission issue	51.72	18.70	7	20377	234306	63234332
Leukopenia	48.31	18.70	88	20296	77202	63391436
Malignant pleural effusion	47.53	18.70	21	20363	2585	63466053
Renal tubular disorder	46.95	18.70	21	20363	2661	63465977
Nasopharyngitis	46.74	18.70	12	20372	254245	63214393
Hepatotoxicity	45.85	18.70	58	20326	36983	63431655
Peripheral ischaemia	45.84	18.70	25	20359	4853	63463785
Glossodynia	45.65	18.70	3	20381	178873	63289765
Hypothyroidism	45.41	18.70	62	20322	42570	63426068
Melanoderma	45.32	18.70	11	20373	195	63468443
Metastases to bone	45.28	18.70	44	20340	20975	63447663
Rheumatoid arthritis	44.75	18.70	13	20371	253806	63214832
Lymphangiosis carcinomatosa	44.69	18.70	17	20367	1428	63467210
Lung cancer metastatic	44.52	18.70	20	20364	2560	63466078
Hepatic function abnormal	44.15	18.70	57	20327	37085	63431553
Immune-mediated pancreatitis	44.03	18.70	10	20374	131	63468507
Radiation pneumonitis	43.19	18.70	17	20367	1566	63467072
Proteinuria	42.98	18.70	41	20343	19104	63449534
Nausea	42.40	18.70	439	19945	854032	62614606
Metastases to lung	42.09	18.70	34	20350	12716	63455922
Therapeutic product effect decreased	42.09	18.70	6	20378	193181	63275457
Malignant transformation	42.09	18.70	12	20372	405	63468233
Swelling	41.89	18.70	18	20366	275360	63193278
Immune-mediated enterocolitis	41.71	18.70	18	20366	2093	63466545
Gamma-glutamyltransferase increased	41.66	18.70	53	20331	33978	63434660
Platelet count decreased	41.12	18.70	105	20279	116017	63352621
Hyperamylasaemia	40.42	18.70	12	20372	468	63468170
Tumour associated fever	39.79	18.70	11	20373	331	63468307
Arthropathy	39.63	18.70	13	20371	234779	63233859
Peripheral swelling	39.47	18.70	18	20366	265924	63202714
Metastases to liver	39.20	18.70	43	20341	23596	63445042
White blood cell count decreased	38.55	18.70	115	20269	138989	63329649
Systemic lupus erythematosus	38.12	18.70	10	20374	208908	63259730
Vomiting	37.54	18.70	307	20077	559310	62909328
Jaw operation	37.47	18.70	13	20371	839	63467799
Oesophagitis	37.27	18.70	34	20350	14974	63453664
Non-small cell lung cancer metastatic	37.07	18.70	12	20372	625	63468013
Hypokalaemia	36.89	18.70	94	20290	103710	63364928
Rash maculo-papular	36.43	18.70	48	20336	31848	63436790
Metastasis	36.42	18.70	22	20362	5175	63463463
Immune-mediated dermatitis	36.10	18.70	9	20375	179	63468459
Nephrogenic diabetes insipidus	35.97	18.70	13	20371	946	63467692
Wound	35.72	18.70	5	20379	163258	63305380
Toxic skin eruption	35.59	18.70	31	20353	12854	63455784
Gene mutation	35.56	18.70	15	20369	1650	63466988
Weight increased	35.19	18.70	20	20364	260772	63207866
Hepatitis toxic	34.30	18.70	18	20366	3235	63465403
Performance status decreased	32.22	18.70	18	20366	3660	63464978
Immune-mediated myocarditis	31.93	18.70	9	20375	291	63468347
Secondary hypertension	31.73	18.70	8	20376	167	63468471
Insomnia	31.27	18.70	15	20369	215237	63253401
Sepsis	31.15	18.70	114	20270	153009	63315629
BRAF V600E mutation positive	30.89	18.70	6	20378	34	63468604
Anaphylactic shock	30.83	18.70	38	20346	23595	63445043
Asthma	30.15	18.70	3	20381	127558	63341080
Infusion related reaction	30.13	18.70	21	20363	245500	63223138
Paronychia	30.10	18.70	20	20364	5545	63463093
Decreased appetite	29.77	18.70	159	20225	250893	63217745
Tracheal fistula	29.56	18.70	6	20378	44	63468594
Hypertransaminasaemia	29.27	18.70	21	20363	6588	63462050
Exposure during pregnancy	29.23	18.70	7	20377	155540	63313098
Respiratory failure	28.96	18.70	85	20299	101773	63366865
Cardiotoxicity	28.91	18.70	23	20361	8415	63460223
Discomfort	28.71	18.70	9	20375	167365	63301273
Autoimmune dermatitis	28.64	18.70	7	20377	128	63468510
Blister	28.34	18.70	4	20380	129810	63338828
Mixed deafness	28.30	18.70	5	20379	15	63468623
Transaminases increased	28.07	18.70	42	20342	31325	63437313
Lung neoplasm malignant	27.95	18.70	33	20351	19600	63449038
Hypomagnesaemia	27.92	18.70	40	20344	28697	63439941
Immune-mediated nephritis	27.90	18.70	7	20377	143	63468495
Hypophysitis	27.78	18.70	13	20371	1828	63466810
Drug intolerance	27.77	18.70	35	20349	308626	63160012
Adenocarcinoma	27.39	18.70	15	20369	2935	63465703
Neonatal respiratory depression	27.30	18.70	6	20378	67	63468571
Asthenia	27.04	18.70	213	20171	383391	63085247
Renal arteriosclerosis	26.98	18.70	6	20378	71	63468567
Hypocalcaemia	26.32	18.70	41	20343	31672	63436966
Contusion	25.85	18.70	8	20376	150036	63318602
Sarcomatoid carcinoma	25.80	18.70	5	20379	28	63468610
Muscle spasms	25.72	18.70	9	20375	156141	63312497
Non-small cell lung cancer recurrent	25.66	18.70	6	20378	90	63468548
Autoimmune myocarditis	25.24	18.70	6	20378	97	63468541
Pain in extremity	24.56	18.70	43	20341	331443	63137195
Cholestasis	24.35	18.70	38	20346	29396	63439242
Multiple-drug resistance	24.22	18.70	17	20367	5153	63463485
Vascular purpura	24.05	18.70	11	20373	1467	63467171
Feeling abnormal	23.68	18.70	9	20375	148383	63320255
Non-small cell lung cancer stage IV	23.63	18.70	6	20378	129	63468509
Headache	23.56	18.70	114	20270	633127	62835511
Febrile infection	23.51	18.70	11	20373	1546	63467092
Renal impairment	23.48	18.70	72	20312	88283	63380355
Systemic infection	23.42	18.70	16	20368	4644	63463994
Thrombophlebitis migrans	23.33	18.70	6	20378	136	63468502
Febrile bone marrow aplasia	23.06	18.70	19	20365	7306	63461332
Migraine	22.99	18.70	3	20381	103343	63365295
Immune-mediated hypothyroidism	22.92	18.70	7	20377	301	63468337
Dizziness	22.73	18.70	67	20317	429858	63038780
Autoimmune colitis	22.70	18.70	8	20376	541	63468097
Depression	22.56	18.70	18	20366	196474	63272164
Dermatitis bullous	22.56	18.70	20	20364	8488	63460150
Drug ineffective	22.55	18.70	221	20163	1044544	62424094
Dose calculation error	22.40	18.70	6	20378	160	63468478
Carcinoembryonic antigen increased	22.19	18.70	11	20373	1754	63466884
Metastatic neoplasm	22.18	18.70	15	20369	4280	63464358
Hepatic cytolysis	22.10	18.70	26	20358	15381	63453257
Leukoencephalopathy	21.82	18.70	15	20369	4398	63464240
Unmasking of previously unidentified disease	21.53	18.70	9	20375	967	63467671
Toxic epidermal necrolysis	21.37	18.70	33	20351	25301	63443337
Bicytopenia	21.24	18.70	12	20372	2493	63466145
Focal segmental glomerulosclerosis	21.02	18.70	10	20374	1458	63467180
Cholangitis	20.88	18.70	16	20368	5545	63463093
Burkholderia pseudomallei infection	20.70	18.70	4	20380	22	63468616
Meningitis herpes	20.67	18.70	6	20378	216	63468422
Alopecia	20.56	18.70	49	20335	337487	63131151
Ischaemic stroke	20.46	18.70	27	20357	17930	63450708
Gastrointestinal toxicity	20.13	18.70	18	20366	7723	63460915
Epistaxis	20.01	18.70	60	20324	72665	63395973
Skin hyperpigmentation	19.99	18.70	16	20368	5905	63462733
Diverticular perforation	19.81	18.70	13	20371	3529	63465109
Embolism	19.80	18.70	18	20366	7888	63460750
Diarrhoea	19.53	18.70	330	20054	715036	62753602
Pericarditis	19.36	18.70	9	20375	131570	63337068
Bronchitis	19.24	18.70	8	20376	124927	63343711
Nephropathy	19.03	18.70	16	20368	6325	63462313
Immune-mediated cholangitis	18.78	18.70	4	20380	38	63468600

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
Malignant neoplasm progression	1002.57	16.70	744	30998	87302	34837887
Pancytopenia	508.11	16.70	523	31219	94634	34830555
Interstitial lung disease	307.41	16.70	336	31406	64946	34860243
Neutropenia	293.06	16.70	516	31226	156262	34768927
Anaemia	286.79	16.70	644	31098	232691	34692498
Thrombocytopenia	278.84	16.70	504	31238	155743	34769446
Disease progression	225.71	16.70	374	31368	107703	34817486
Myelosuppression	166.83	16.70	139	31603	19126	34906063
Pneumonitis	163.83	16.70	177	31565	33701	34891488
Bone marrow failure	161.40	16.70	164	31578	29089	34896100
Febrile neutropenia	153.47	16.70	365	31377	136484	34788705
General physical health deterioration	149.12	16.70	347	31395	127922	34797267
Febrile bone marrow aplasia	144.26	16.70	91	31651	8118	34917071
Mucosal inflammation	135.28	16.70	171	31571	38451	34886738
Immune-mediated hepatic disorder	126.71	16.70	44	31698	979	34924210
Neoplasm progression	121.95	16.70	127	31615	23173	34902016
Immune-mediated lung disease	118.14	16.70	47	31695	1544	34923645
Tubulointerstitial nephritis	100.11	16.70	109	31633	20915	34904274
Decreased appetite	98.29	16.70	353	31389	166039	34759150
Therapy partial responder	97.25	16.70	76	31666	9540	34915649
Pleural effusion	96.15	16.70	222	31520	81324	34843865
Leukopenia	93.46	16.70	188	31554	62668	34862521
Neutrophil count decreased	84.65	16.70	160	31582	50944	34874245
Haematotoxicity	81.22	16.70	64	31678	8130	34917059
Metastases to central nervous system	81.14	16.70	64	31678	8141	34917048
Immune-mediated enterocolitis	75.58	16.70	41	31701	2758	34922431
Colitis	75.06	16.70	128	31614	37622	34887567
Completed suicide	72.84	16.70	4	31738	98164	34827025
Product dose omission issue	72.65	16.70	11	31731	119700	34805489
Skin toxicity	71.69	16.70	48	31694	4736	34920453
Non-small cell lung cancer	70.02	16.70	44	31698	3896	34921293
Platelet count decreased	68.91	16.70	252	31490	119465	34805724
Enteritis	66.85	16.70	57	31685	8085	34917104
Neutropenic sepsis	66.62	16.70	72	31670	13695	34911494
Lichenoid keratosis	60.21	16.70	34	31708	2474	34922715
Aplasia	59.24	16.70	42	31700	4546	34920643
Drug interaction	59.11	16.70	71	31671	225875	34699314
EGFR gene mutation	57.78	16.70	16	31726	161	34925028
Fall	57.16	16.70	60	31682	202825	34722364
Pseudocellulitis	54.05	16.70	12	31730	42	34925147
Adrenocorticotropic hormone deficiency	53.46	16.70	23	31719	924	34924265
Immune-mediated adverse reaction	53.27	16.70	20	31722	560	34924629
Diarrhoea	52.42	16.70	562	31180	389350	34535839
Tumour pseudoprogression	52.41	16.70	19	31723	481	34924708
Hypopituitarism	52.26	16.70	30	31712	2252	34922937
Septic shock	51.67	16.70	163	31579	71671	34853518
Immune-mediated renal disorder	50.54	16.70	14	31728	141	34925048
Hepatic cytolysis	50.42	16.70	64	31678	14432	34910757
Headache	49.38	16.70	66	31676	200569	34724620
Pulmonary toxicity	48.37	16.70	42	31700	6105	34919084
Nephropathy toxic	47.67	16.70	58	31684	12530	34912659
Overdose	47.60	16.70	12	31730	91047	34834142
Vomiting	46.77	16.70	384	31358	247237	34677952
Dehydration	45.79	16.70	236	31506	129733	34795456
Extremity necrosis	45.36	16.70	26	31716	1946	34923243
Respiratory failure	45.32	16.70	207	31535	108365	34816824
Nausea	42.43	16.70	483	31259	339425	34585764
Pain in extremity	42.09	16.70	32	31710	126481	34798708
Bradycardia	41.27	16.70	9	31733	75409	34849780
Muscle spasms	40.94	16.70	9	31733	74992	34850197
White blood cell count decreased	40.59	16.70	183	31559	95262	34829927
Pulmonary embolism	40.38	16.70	175	31567	89571	34835618
Haemoptysis	39.77	16.70	94	31648	34912	34890277
Pneumothorax	39.61	16.70	66	31676	19026	34906163
Hiccups	39.06	16.70	47	31695	10035	34915154
Drug resistance	39.03	16.70	78	31664	25849	34899340
Lung adenocarcinoma	38.96	16.70	33	31709	4638	34920551
Large intestine perforation	38.58	16.70	43	31699	8460	34916729
Radiation pneumonitis	38.39	16.70	26	31716	2614	34922575
Superior vena cava syndrome	37.85	16.70	16	31726	615	34924574
Rash	37.59	16.70	337	31405	222415	34702774
Lung disorder	37.09	16.70	91	31651	34605	34890584
Acquired gene mutation	37.00	16.70	20	31722	1335	34923854
Blood pressure increased	36.73	16.70	17	31725	88085	34837104
Hypersensitivity pneumonitis	36.61	16.70	21	31721	1574	34923615
Tremor	35.91	16.70	15	31727	82572	34842617
Acute kidney injury	35.62	16.70	428	31314	304560	34620629
Hepatocellular injury	34.85	16.70	68	31674	22143	34903046
Drug ineffective	34.19	16.70	259	31483	456492	34468697
Erysipelas	33.84	16.70	31	31711	4832	34920357
Eastern Cooperative Oncology Group performance status worsened	33.59	16.70	17	31725	991	34924198
Nasopharyngitis	33.29	16.70	11	31731	69957	34855232
Pneumonia	33.27	16.70	487	31255	362140	34563049
Toxicity to various agents	31.64	16.70	86	31656	200276	34724913
Immune-mediated myocarditis	31.34	16.70	15	31727	774	34924415
Pyrexia	31.23	16.70	449	31293	332564	34592625
Small intestinal perforation	30.66	16.70	21	31721	2150	34923039
Nephritis	30.63	16.70	22	31720	2429	34922760
Peritonitis	30.56	16.70	54	31688	16311	34908878
Metastases to meninges	30.35	16.70	18	31724	1436	34923753
Secondary adrenocortical insufficiency	30.17	16.70	18	31724	1452	34923737
Paraneoplastic syndrome	29.80	16.70	13	31729	540	34924649
Immune-mediated hypothyroidism	29.64	16.70	11	31731	298	34924891
Flagellate dermatitis	29.30	16.70	8	31734	76	34925113
Hypothyroidism	29.23	16.70	61	31681	20841	34904348
Musculoskeletal stiffness	28.97	16.70	4	31738	46676	34878513
Metastases to bone	28.41	16.70	44	31698	11926	34913263
Feeling abnormal	28.28	16.70	11	31731	63224	34861965
Disseminated intravascular coagulation	27.44	16.70	61	31681	21755	34903434
Peripheral swelling	27.23	16.70	18	31724	76523	34848666
Rhabdomyolysis	27.12	16.70	14	31728	68149	34857040
Depression	26.98	16.70	29	31713	97069	34828120
Weight increased	26.73	16.70	27	31715	93006	34832183
Anxiety	26.20	16.70	31	31711	99397	34825792
Performance status decreased	26.15	16.70	25	31717	4112	34921077
Lung cancer metastatic	25.97	16.70	21	31721	2766	34922423
Prostate cancer	25.57	16.70	3	31739	39646	34885543
Cardiac failure congestive	25.28	16.70	23	31719	83247	34841942
Injection site pain	25.03	16.70	3	31739	39002	34886187
Epistaxis	24.97	16.70	112	31630	58139	34867050
Renal failure	24.85	16.70	203	31539	130354	34794835
Immune-mediated dermatitis	24.84	16.70	10	31732	339	34924850
Insomnia	24.70	16.70	35	31707	103872	34821317
Hallucination	24.66	16.70	8	31734	51490	34873699
Adrenal insufficiency	24.50	16.70	45	31697	14002	34911187
Hypercreatininaemia	24.50	16.70	11	31731	490	34924699
Malignant pleural effusion	24.44	16.70	16	31726	1520	34923669
Sepsis	24.08	16.70	244	31498	166317	34758872
Agitation	24.04	16.70	11	31731	57388	34867801
Cardiac disorder	23.89	16.70	5	31737	43121	34882068
Pancreatic toxicity	23.85	16.70	6	31736	40	34925149
Neutropenic colitis	23.77	16.70	21	31721	3123	34922066
Dacryostenosis acquired	23.64	16.70	9	31733	262	34924927
Pericardial effusion	23.56	16.70	62	31680	24600	34900589
Arthralgia	23.23	16.70	78	31664	169963	34755226
Pericarditis malignant	23.23	16.70	6	31736	45	34925144
Purpura	23.22	16.70	37	31705	10274	34914915
Metastases to liver	22.87	16.70	43	31699	13620	34911569
Epidermolysis	22.81	16.70	9	31733	289	34924900
Autoimmune haemolytic anaemia	22.60	16.70	24	31718	4472	34920717
Hyperthyroidism	22.55	16.70	37	31705	10529	34914660
Electrocardiogram QT prolonged	22.17	16.70	5	31737	40947	34884242
Haemophagocytic lymphohistiocytosis	21.93	16.70	41	31701	12932	34912257
Gastrointestinal perforation	21.91	16.70	22	31720	3841	34921348
Asthma	21.56	16.70	6	31736	42650	34882539
Abdominal discomfort	21.37	16.70	14	31728	59821	34865368
Myalgia	21.34	16.70	27	31715	84083	34841106
Oral papule	21.25	16.70	4	31738	4	34925185
Opsoclonus myoclonus	21.10	16.70	6	31736	67	34925122
Dizziness	20.81	16.70	115	31627	218406	34706783
Lymphangiosis carcinomatosa	20.67	16.70	12	31730	920	34924269
Acute generalised exanthematous pustulosis	20.59	16.70	28	31714	6748	34918441
Myocarditis	20.39	16.70	41	31701	13641	34911548
Memory impairment	20.27	16.70	7	31735	43311	34881878
Immune-mediated adrenal insuficiency	20.14	16.70	7	31735	156	34925033
Hyperpyrexia	19.84	16.70	18	31724	2770	34922419
Dyspnoea	19.75	16.70	464	31278	376318	34548871
Superior mesenteric artery syndrome	19.73	16.70	6	31736	86	34925103
Renal impairment	19.64	16.70	150	31592	94363	34830826
Toxic epidermal necrolysis	19.25	16.70	53	31689	21593	34903596
Hypoglycaemia	19.23	16.70	13	31729	54627	34870562
Occipital neuralgia	19.19	16.70	5	31737	39	34925150
Immune-mediated neuropathy	18.97	16.70	5	31737	41	34925148
Vision blurred	18.95	16.70	9	31733	45954	34879235
Non-small cell lung cancer metastatic	18.89	16.70	10	31732	640	34924549
Thrombophlebitis migrans	18.85	16.70	7	31735	190	34924999
Tracheo-oesophageal fistula	18.79	16.70	9	31733	465	34924724
Intentional product use issue	18.78	16.70	16	31726	59800	34865389
Hypertransaminasaemia	18.31	16.70	24	31718	5582	34919607
Wrong technique in product usage process	18.30	16.70	5	31737	35981	34889208
Bicytopenia	18.17	16.70	16	31726	2368	34922821
Rash maculo-papular	18.13	16.70	62	31680	28389	34896800
Immune thrombocytopenia	18.13	16.70	31	31711	9121	34916068
Hepatitis	17.86	16.70	55	31687	23849	34901340
Dysphagia	17.74	16.70	107	31635	62274	34862915
Mobility decreased	17.74	16.70	3	31739	30125	34895064
Laryngeal leukoplakia	17.65	16.70	5	31737	55	34925134
Hyperhidrosis	17.49	16.70	26	31716	75666	34849523
Immune-mediated pancreatitis	17.38	16.70	6	31736	131	34925058
Lymphangitis	17.30	16.70	9	31733	556	34924633
Somnolence	17.28	16.70	48	31694	111068	34814121
Aphthous ulcer	17.28	16.70	22	31720	4973	34920216
Coma	17.27	16.70	10	31732	45668	34879521
Immune-mediated hepatitis	17.15	16.70	15	31727	2200	34922989
Rheumatoid nodule	17.11	16.70	17	31725	2930	34922259
Tumour necrosis	17.11	16.70	12	31730	1276	34923913
Diaphragmatic rupture	17.04	16.70	4	31738	19	34925170
Vasculitis	17.01	16.70	34	31708	11262	34913927
Heart rate decreased	16.94	16.70	4	31738	31741	34893448
Granulocyte count increased	16.91	16.70	8	31734	402	34924787
Asthenia	16.71	16.70	314	31428	244937	34680252
Human chorionic gonadotropin increased	16.71	16.70	4	31738	21	34925168

FDA Adverse Event Reporting System (Geriatric)

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
Malignant neoplasm progression	1803.73	15.54	1043	42251	134947	79566147
Pancytopenia	756.91	15.54	664	42630	165081	79536013
Disease progression	584.72	15.54	604	42690	183758	79517336
Anaemia	476.67	15.54	859	42435	444156	79256938
Neutropenia	441.59	15.54	654	42640	287056	79414038
Thrombocytopenia	427.33	15.54	617	42677	264642	79436452
Interstitial lung disease	340.47	15.54	360	42934	112240	79588854
Pneumonitis	277.41	15.54	244	43050	60616	79640478
Myelosuppression	269.26	15.54	202	43092	40094	79661000
Tubulointerstitial nephritis	267.42	15.54	197	43097	38038	79663056
Therapy partial responder	266.17	15.54	147	43147	17250	79683844
Bone marrow failure	265.77	15.54	221	43073	50886	79650208
Febrile neutropenia	246.45	15.54	446	42848	230553	79470541
Drug resistance	239.36	15.54	192	43102	42021	79659073
Neoplasm progression	227.13	15.54	203	43091	51479	79649615
Metastases to central nervous system	198.74	15.54	119	43175	16256	79684838
Immune-mediated hepatic disorder	191.01	15.54	59	43235	1535	79699559
Immune-mediated lung disease	181.67	15.54	62	43232	2228	79698866
Non-small cell lung cancer	181.26	15.54	82	43212	6278	79694816
Acquired gene mutation	159.89	15.54	56	43238	2177	79698917
Haematotoxicity	155.91	15.54	100	43194	15419	79685675
Febrile bone marrow aplasia	151.24	15.54	92	43202	12928	79688166
General physical health deterioration	151.01	15.54	407	42887	274831	79426263
Mucosal inflammation	148.68	15.54	194	43100	75386	79625708
Acute kidney injury	147.83	15.54	615	42679	518789	79182305
Skin toxicity	140.35	15.54	75	43219	8239	79692855
EGFR gene mutation	137.96	15.54	35	43259	429	79700665
Colitis	136.23	15.54	183	43111	73124	79627970
Leukopenia	127.90	15.54	228	43066	116285	79584809
Pleural effusion	127.03	15.54	258	43036	145004	79556090
Neutrophil count decreased	123.16	15.54	199	43095	93760	79607334
Completed suicide	119.24	15.54	3	43291	245764	79455330
Immune-mediated enterocolitis	115.04	15.54	55	43239	4775	79696319
Fall	114.68	15.54	61	43233	487568	79213526
Decreased appetite	111.33	15.54	423	42871	341995	79359099
Arthralgia	107.10	15.54	92	43202	571711	79129383
Pain	103.23	15.54	139	43155	703663	78997431
Nephropathy toxic	101.34	15.54	86	43208	20333	79680761
Platelet count decreased	94.00	15.54	275	43019	194389	79506705
Joint swelling	93.72	15.54	21	43273	288625	79412469
Product dose omission issue	93.57	15.54	12	43282	247525	79453569
Hepatocellular injury	90.22	15.54	120	43174	47473	79653621
Tumour pseudoprogression	89.31	15.54	27	43267	652	79700442
Lichenoid keratosis	84.04	15.54	42	43252	4015	79697079
Lung cancer metastatic	81.69	15.54	40	43254	3659	79697435
Headache	81.55	15.54	144	43150	653628	79047466
Lung adenocarcinoma	79.79	15.54	51	43243	7813	79693281
Metastases to meninges	79.70	15.54	39	43255	3562	79697532
Nasopharyngitis	79.39	15.54	20	43274	253861	79447233
Musculoskeletal stiffness	78.44	15.54	4	43290	175004	79526090
Abdominal discomfort	77.92	15.54	20	43274	250707	79450387
Myocarditis	77.41	15.54	76	43218	21657	79679437
Renal tubular necrosis	77.22	15.54	81	43213	24958	79676136
Pulmonary embolism	76.71	15.54	236	43058	171418	79529676
Radiation pneumonitis	76.45	15.54	39	43255	3894	79697200
Haemoptysis	75.25	15.54	120	43174	55879	79645215
Hypothyroidism	74.19	15.54	115	43179	52277	79648817
Hepatic cytolysis	73.51	15.54	82	43212	27069	79674025
Aplasia	72.68	15.54	48	43246	7772	79693322
Contraindicated product administered	72.56	15.54	3	43291	157535	79543559
Blood creatinine increased	70.98	15.54	215	43079	154842	79546252
Immune-mediated hepatitis	70.33	15.54	36	43258	3620	79697474
Pain in extremity	70.19	15.54	57	43237	364481	79336613
Hypopituitarism	69.85	15.54	35	43259	3364	79697730
Peripheral swelling	68.99	15.54	30	43264	269587	79431507
Subacute cutaneous lupus erythematosus	68.31	15.54	35	43259	3526	79697568
Osteonecrosis of jaw	67.04	15.54	99	43195	43127	79657967
Immune-mediated adverse reaction	66.23	15.54	23	43271	871	79700223
Pericardial effusion	66.18	15.54	102	43192	46135	79654959
Nephritis	65.51	15.54	36	43258	4178	79696916
Enteritis	65.45	15.54	58	43236	14525	79686569
Immune-mediated renal disorder	64.56	15.54	16	43278	177	79700917
Metastases to liver	64.10	15.54	78	43216	28236	79672858
Sinusitis	63.88	15.54	14	43280	195487	79505607
Septic shock	63.62	15.54	178	43116	122623	79578471
Diarrhoea	63.53	15.54	743	42551	879746	78821348
Adrenocorticotropic hormone deficiency	63.36	15.54	25	43269	1360	79699734
Pseudocellulitis	61.83	15.54	13	43281	63	79701031
Therapeutic product effect decreased	61.77	15.54	8	43286	163855	79537239
Maternal exposure during pregnancy	61.57	15.54	3	43291	136535	79564559
Pulmonary toxicity	61.24	15.54	53	43241	12861	79688233
Metastases to adrenals	60.82	15.54	24	43270	1306	79699788
Weight increased	60.42	15.54	38	43256	277348	79423746
Hepatic function abnormal	59.33	15.54	126	43168	72981	79628113
Respiratory failure	59.08	15.54	224	43070	180687	79520407
Hepatitis	58.48	15.54	107	43187	55620	79645474
Renal failure	57.71	15.54	239	43055	200729	79500365
Drug hypersensitivity	57.20	15.54	47	43247	298869	79402225
Immune-mediated myocarditis	56.94	15.54	22	43272	1131	79699963
Rash maculo-papular	55.50	15.54	105	43189	55973	79645121
Arthropathy	55.26	15.54	14	43280	177097	79523997
Injection site pain	55.07	15.54	4	43290	129834	79571260
Immune-mediated dermatitis	54.84	15.54	18	43276	572	79700522
White blood cell count decreased	54.12	15.54	224	43070	188064	79513030
Neutropenic sepsis	54.01	15.54	70	43224	26994	79674100
Immune-mediated pancreatitis	53.06	15.54	15	43279	284	79700810
Immune-mediated hypothyroidism	52.78	15.54	18	43276	645	79700449
Lymphangiosis carcinomatosa	52.74	15.54	25	43269	2129	79698965
Melanoderma	52.63	15.54	16	43278	394	79700700
Swelling	52.50	15.54	26	43268	216685	79484409
Muscle spasms	52.27	15.54	15	43279	174715	79526379
Extremity necrosis	51.90	15.54	28	43266	3133	79697961
Pyrexia	50.75	15.54	577	42717	678132	79022962
Rheumatoid arthritis	50.52	15.54	25	43269	208445	79492649
Drug intolerance	49.94	15.54	42	43252	264077	79437017
Depression	49.59	15.54	28	43266	216762	79484332
Overdose	49.53	15.54	19	43275	184187	79516907
Wound	48.08	15.54	4	43290	116175	79584919
Asthma	47.67	15.54	8	43286	135087	79566007
Gene mutation	47.51	15.54	25	43269	2661	79698433
Pneumothorax	47.02	15.54	67	43227	28256	79672838
Hypertransaminasaemia	46.81	15.54	44	43250	11880	79689214
Hepatotoxicity	45.77	15.54	92	43202	51260	79649834
Hyperthyroidism	45.19	15.54	58	43236	22151	79678943
Malignant pleural effusion	44.77	15.54	26	43268	3354	79697740
Dizziness	44.72	15.54	142	43152	526299	79174795
Hypophysitis	44.72	15.54	28	43266	4138	79696956
Blood pressure increased	44.59	15.54	30	43264	211330	79489764
Dehydration	44.51	15.54	258	43036	247929	79453165
Glossodynia	44.35	15.54	3	43291	103334	79597760
Contusion	44.08	15.54	13	43281	148763	79552331
Vomiting	43.59	15.54	552	42742	665276	79035818
Hiccups	43.24	15.54	39	43255	9992	79691102
Renal impairment	43.22	15.54	185	43109	157598	79543496
Thrombophlebitis migrans	43.02	15.54	14	43280	433	79700661
Toxic epidermal necrolysis	42.30	15.54	82	43212	44499	79656595
Sepsis	41.95	15.54	270	43024	269158	79431936
Toxic skin eruption	41.91	15.54	56	43238	22237	79678857
Feeling abnormal	41.84	15.54	17	43277	159182	79541912
Bicytopenia	41.80	15.54	28	43266	4642	79696452
Insomnia	41.61	15.54	43	43251	245127	79455967
Tracheal fistula	41.24	15.54	11	43283	166	79700928
Infusion related reaction	40.66	15.54	39	43255	230198	79470896
Peritonitis	40.32	15.54	62	43232	27974	79673120
Intentional product misuse	40.16	15.54	3	43291	95162	79605932
Bradycardia	39.88	15.54	12	43282	135545	79565549
Performance status decreased	39.38	15.54	30	43264	6083	79695011
Malignant transformation	38.86	15.54	17	43277	1201	79699893
Tremor	38.84	15.54	22	43272	170061	79531033
Skin hyperpigmentation	38.80	15.54	32	43262	7271	79693823
Proteinuria	38.74	15.54	66	43228	32436	79668658
Non-small cell lung cancer metastatic	37.99	15.54	16	43278	1030	79700064
Exposure during pregnancy	37.95	15.54	5	43289	101127	79599967
Nausea	37.93	15.54	729	42565	956467	78744627
Metastases to pleura	37.93	15.54	18	43276	1536	79699558
Tumour associated fever	36.90	15.54	15	43279	882	79700212
Secondary adrenocortical insufficiency	36.81	15.54	22	43272	2992	79698102
Transaminases increased	36.14	15.54	84	43210	51659	79649435
Pericarditis malignant	35.55	15.54	8	43286	56	79701038
Oesophagitis	35.33	15.54	54	43240	24235	79676859
Small intestinal perforation	34.99	15.54	22	43272	3275	79697819
Metastases to lung	34.72	15.54	46	43248	18117	79682977
Autoimmune colitis	34.20	15.54	17	43277	1606	79699488
Adrenal insufficiency	34.15	15.54	58	43236	28429	79672665
Suicide attempt	33.92	15.54	3	43291	82929	79618165
Mobility decreased	33.85	15.54	12	43282	122163	79578931
Osteoarthritis	33.53	15.54	4	43290	87305	79613789
Hypersensitivity	33.28	15.54	57	43237	262182	79438912
Gamma-glutamyltransferase increased	33.09	15.54	84	43210	54596	79646498
Large intestine perforation	32.76	15.54	40	43254	14527	79686567
Haemophagocytic lymphohistiocytosis	32.40	15.54	49	43245	21788	79679306
Metastases to bone	32.33	15.54	52	43242	24375	79676719
Erysipelas	31.50	15.54	34	43260	10816	79690278
Jaw operation	31.18	15.54	13	43281	816	79700278
Blister	31	15.54	13	43281	119463	79581631
Toxicity to various agents	30.88	15.54	121	43173	421419	79279675
Asthenia	30.82	15.54	418	42876	511271	79189823
Influenza	30.70	15.54	16	43278	129590	79571504
Anxiety	30.64	15.54	55	43239	248457	79452637
Suicidal ideation	30.59	15.54	3	43291	76337	79624757
Drug interaction	30.52	15.54	119	43175	415064	79286030
Systemic lupus erythematosus	30.14	15.54	14	43280	121135	79579959
Hypersensitivity pneumonitis	30.10	15.54	21	43273	3718	79697376
Pancreatic toxicity	29.96	15.54	7	43287	59	79701035
Epistaxis	29.94	15.54	130	43164	111385	79589709
Nephrogenic diabetes insipidus	29.82	15.54	17	43277	2117	79698977
Hypoaesthesia	29.81	15.54	32	43262	179320	79521774
Disseminated intravascular coagulation	29.33	15.54	62	43232	35780	79665314
Carcinoembryonic antigen increased	29.28	15.54	17	43277	2192	79698902
Memory impairment	29.24	15.54	12	43282	111722	79589372
Purpura	29.24	15.54	44	43250	19483	79681611
Discomfort	29.03	15.54	16	43278	125601	79575493
Cholangitis	28.60	15.54	35	43259	12741	79688353
Pneumonia	28.55	15.54	510	42784	659736	79041358
Paraneoplastic syndrome	28.22	15.54	13	43281	1037	79700057
Nasal congestion	28.21	15.54	4	43290	76548	79624546
Gastrointestinal toxicity	28.21	15.54	28	43266	8081	79693013
Metastasis	28.19	15.54	26	43268	6854	79694240
Peripheral ischaemia	28.10	15.54	30	43264	9427	79691667
Hepatic enzyme increased	27.75	15.54	35	43259	182575	79518519
Treatment failure	27.69	15.54	31	43263	170455	79530639
Somnolence	27.61	15.54	55	43239	238926	79462168
Renal tubular disorder	27.53	15.54	25	43269	6461	79694633
Cholestasis	27.42	15.54	76	43218	52033	79649061
Sarcomatoid carcinoma	26.79	15.54	6	43288	41	79701053
Gastrointestinal perforation	26.73	15.54	24	43270	6113	79694981
Hospitalisation	26.54	15.54	9	43285	94227	79606867
Multiple-drug resistance	26.27	15.54	28	43266	8780	79692314
Neutropenic colitis	26.21	15.54	23	43271	5684	79695410
Mixed deafness	26.20	15.54	5	43289	13	79701081
Immune-mediated cholangitis	26.08	15.54	8	43286	203	79700891
Superior vena cava syndrome	26.07	15.54	13	43281	1236	79699858
BRAF V600E mutation positive	25.96	15.54	6	43288	48	79701046
Rash	25.79	15.54	449	42845	577909	79123185
Non-small cell lung cancer recurrent	25.36	15.54	7	43287	121	79700973
Loss of personal independence in daily activities	25.30	15.54	12	43282	102568	79598526
Immune-mediated nephritis	25.03	15.54	10	43284	562	79700532
Eastern Cooperative Oncology Group performance status worsened	25.03	15.54	15	43279	2050	79699044
Lung neoplasm malignant	25.01	15.54	50	43244	27742	79673352
Cardiotoxicity	24.95	15.54	32	43262	12207	79688887
Oesophagobronchial fistula	24.56	15.54	8	43286	248	79700846
Metastatic neoplasm	24.53	15.54	21	43273	5021	79696073
Posterior reversible encephalopathy syndrome	24.51	15.54	48	43246	26233	79674861
Autoimmune myocarditis	24.33	15.54	9	43285	410	79700684
Hepatitis toxic	24.15	15.54	21	43273	5126	79695968
Hyperamylasaemia	24.13	15.54	12	43282	1135	79699959
Hyperhidrosis	24.11	15.54	28	43266	151464	79549630
Flagellate dermatitis	24.06	15.54	8	43286	265	79700829
Lung adenocarcinoma recurrent	23.82	15.54	5	43289	24	79701070
Autoimmune dermatitis	23.60	15.54	7	43287	158	79700936
Oral papule	23.31	15.54	4	43290	4	79701090
Malaise	23.28	15.54	163	43131	489706	79211388
Intentional product use issue	23.27	15.54	29	43265	152083	79549011
Lung disorder	23.24	15.54	96	43198	80461	79620633
Heart rate decreased	23.02	15.54	5	43289	70311	79630783
Cardiac failure congestive	23.01	15.54	26	43268	142376	79558718
Sleep disorder	22.75	15.54	9	43285	85668	79615426
Adenocarcinoma	22.70	15.54	18	43276	3868	79697226
Acute coronary syndrome	22.70	15.54	41	43253	21092	79680002
Urinary tract infection	22.60	15.54	75	43219	274437	79426657
Enterocolitis	22.15	15.54	33	43261	14479	79686615
Autoimmune haemolytic anaemia	22.15	15.54	25	43269	8355	79692739
Bronchitis	22.05	15.54	23	43271	130621	79570473
Hypoglycaemia	21.98	15.54	14	43280	101580	79599514
Dacryostenosis acquired	21.92	15.54	9	43285	543	79700551
Immune-mediated adrenal insuficiency	21.71	15.54	7	43287	210	79700884
Gastrooesophageal reflux disease	21.70	15.54	15	43279	104231	79596863
Secondary hypertension	21.43	15.54	8	43286	374	79700720
Alopecia	21.33	15.54	60	43234	231295	79469799
Myasthenic syndrome	21.31	15.54	10	43284	832	79700262
Fulminant type 1 diabetes mellitus	21.23	15.54	12	43282	1471	79699623
Hyperpyrexia	21.13	15.54	21	43273	6071	79695023
Tracheo-oesophageal fistula	21.11	15.54	9	43285	597	79700497
Radiation neuropathy	21.07	15.54	4	43290	10	79701084
Cardiac disorder	20.88	15.54	5	43289	65752	79635342
Cerebral infarction	20.55	15.54	63	43231	45613	79655481
Death	20.50	15.54	426	42868	566088	79135006
Coma	20.27	15.54	15	43279	100634	79600460
Laryngeal leukoplakia	20.12	15.54	5	43289	56	79701038
Oropharyngeal pain	19.91	15.54	18	43276	109335	79591759
Constipation	19.87	15.54	238	43056	282812	79418282
Diverticular perforation	19.86	15.54	20	43274	5873	79695221
Immune thrombocytopenia	19.71	15.54	35	43259	17770	79683324
Adrenal disorder	19.50	15.54	13	43281	2138	79698956
Back pain	19.38	15.54	92	43202	304088	79397006
Immune-mediated hyperthyroidism	19.25	15.54	6	43288	161	79700933
Pulmonary artery thrombosis	19.22	15.54	11	43283	1381	79699713
Hypercreatininaemia	19.19	15.54	10	43284	1043	79700051
Lymphangitis	19.10	15.54	11	43283	1397	79699697
Impaired healing	19.07	15.54	12	43282	87643	79613451
Drug ineffective	18.95	15.54	445	42849	1080468	78620626
Incorrect dose administered	18.84	15.54	9	43285	76621	79624473
Renal arteriosclerosis	18.80	15.54	7	43287	325	79700769
Ureteric dilatation	18.77	15.54	6	43288	175	79700919
Pericardial effusion malignant	18.67	15.54	6	43288	178	79700916
Agitation	18.65	15.54	16	43278	99699	79601395
Hypokalaemia	18.62	15.54	138	43156	143902	79557192
Vision blurred	18.61	15.54	18	43276	105880	79595214
Abdominal pain upper	18.52	15.54	61	43233	223758	79477336
Superior mesenteric artery syndrome	18.42	15.54	6	43288	186	79700908
Capillary leak syndrome	18.39	15.54	16	43278	3909	79697185
Hallucination	18.30	15.54	12	43282	85733	79615361
Small cell lung cancer	18.25	15.54	14	43280	2866	79698228
Urticaria	17.84	15.54	47	43247	185154	79515940
Intestinal perforation	17.70	15.54	33	43261	17393	79683701
Product use issue	17.49	15.54	57	43237	209765	79491329
Embolism	17.47	15.54	29	43265	13953	79687141
Arthritis	17.46	15.54	22	43272	114858	79586236
Dyspepsia	17.39	15.54	20	43274	108667	79592427
Opsoclonus myoclonus	17.31	15.54	6	43288	226	79700868
Meningitis herpes	17.28	15.54	6	43288	227	79700867
Psoriasis	17.22	15.54	14	43280	89573	79611521
Myalgia	17.21	15.54	48	43246	185593	79515501
Dose calculation error	17.13	15.54	6	43288	233	79700861
Oral fungal infection	17.02	15.54	15	43279	3728	79697366
Lip oedema	16.96	15.54	19	43275	6297	79694797
Muscle injury	16.85	15.54	3	43291	48558	79652536
Acute generalised exanthematous pustulosis	16.69	15.54	32	43262	17222	79683872
Leukoencephalopathy	16.59	15.54	21	43273	7908	79693186
Heart rate increased	16.47	15.54	25	43269	120699	79580395
Hypocalcaemia	16.42	15.54	62	43232	49862	79651232
Allergic colitis	16.42	15.54	4	43290	41	79701053
Autoimmune nephritis	16.34	15.54	8	43286	731	79700363
Wrong technique in product usage process	16.23	15.54	10	43284	73865	79627229
Liver disorder	16.17	15.54	80	43214	72337	79628757
Amnesia	16.13	15.54	7	43287	63050	79638044
Scleroderma-like reaction	15.97	15.54	5	43289	136	79700958
Fluid retention	15.97	15.54	9	43285	69800	79631294
Tumour necrosis	15.95	15.54	11	43283	1911	79699183
Injection site reaction	15.84	15.54	5	43289	54780	79646314
Burning sensation	15.83	15.54	6	43288	58626	79642468
Kidney fibrosis	15.74	15.54	14	43280	3521	79697573
Cataract	15.73	15.54	7	43287	62113	79638981
Hypotension	15.70	15.54	158	43136	440159	79260935
Palpitations	15.61	15.54	28	43266	126582	79574512

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	L01BA04	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ANTINEOPLASTIC AGENTS ANTIMETABOLITES Folic acid analogues
FDA MoA	N0000000111	Folic Acid Metabolism Inhibitors
FDA EPC	N0000175584	Folate Analog Metabolic Inhibitor
MeSH PA	D000970	Antineoplastic Agents
MeSH PA	D004791	Enzyme Inhibitors
MeSH PA	D005493	Folic Acid Antagonists
MeSH PA	D019384	Nucleic Acid Synthesis Inhibitors
CHEBI has role	CHEBI:35221	antimetabolite
CHEBI has role	CHEBI:35610	antineoplastic agents
CHEBI has role	CHEBI:50683	dihydrofolic acid reductase inhibitors
CHEBI has role	CHEBI:63720	dTMP synthase inhibitors
CHEBI has role	CHEBI:63721	glycinamide ribonucleotide formyltransferase inhibitors

Drug Use | Suggest Off label Use Form| |View source of the data|

Disease	Relation	SNOMED_ID	DOID
Non-small cell lung cancer	indication	254637007	DOID:3908
Malignant mesothelioma of pleura	indication	254645002	DOID:7474
Kidney disease	contraindication	90708001	DOID:557
Impaired renal function disorder	contraindication	197663003
Anemia	contraindication	271737000	DOID:2355
Pregnancy, function	contraindication	289908002
Thrombocytopenic disorder	contraindication	302215000	DOID:1588
Neutropenic disorder	contraindication	303011007	DOID:1227
Breastfeeding (mother)	contraindication	413712001
Concomitant yellow fever vaccine	contraindication	871717007

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	3.34	acidic
pKa2	5.15	acidic
pKa3	9.45	acidic
pKa4	13.09	acidic
pKa5	3.95	Basic

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
Thymidylate synthase	Enzyme	P04818	TYSY_HUMAN	INHIBITOR	IC50	6.47	WOMBAT-PK	CHEMBL
Dihydrofolate reductase	Enzyme	P00374	DYR_HUMAN	INHIBITOR	IC50	5.18	WOMBAT-PK	CHEMBL
Trifunctional purine biosynthetic protein adenosine-3	Enzyme	P22102	PUR2_HUMAN	INHIBITOR	Ki	6.42	CHEMBL	DRUG LABEL
Serine hydroxymethyltransferase, cytosolic	Enzyme	P34896	GLYC_HUMAN		Kd	4.77	CHEMBL
Folate receptor beta	Membrane receptor	P14207	FOLR2_HUMAN		IC50	7.22	CHEMBL
Proton-coupled folate transporter	Transporter	Q96NT5	PCFT_HUMAN		Ki	7.03	CHEMBL
Folate transporter 1	Transporter	P41440	S19A1_HUMAN		IC50	6.86	CHEMBL
Folate receptor alpha	Membrane receptor	P15328	FOLR1_HUMAN		IC50	7.38	CHEMBL
Folylpolyglutamate synthase, mitochondrial	Enzyme	Q05932	FOLC_HUMAN				WOMBAT-PK
Bifunctional dihydrofolate reductase-thymidylate synthase	Enzyme		DRTS_TOXGO		IC50	6.37	CHEMBL
Dihydrofolate reductase	Enzyme		DYR_MOUSE		Ki	6.25	CHEMBL
Dihydrofolate reductase	Enzyme		DYR_ECOLI		IC50	5.64	CHEMBL
Thymidylate synthase	Enzyme		TYSY_ECOLI		IC50	4.82	CHEMBL
Dihydrofolate reductase	Enzyme		DYR_LACCA		IC50	5.64	CHEMBL
Thymidylate synthase	Enzyme		TYSY_MOUSE		Ki	6.47	CHEMBL
Thymidylate synthase	Enzyme		TYSY_RAT		IC50	4.70	CHEMBL
Thymidylate synthase	Enzyme		TYSY_LACCA		Ki	6.26	CHEMBL
Dihydrofolate reductase	Enzyme		B0BL08_ECOLX		IC50	5.64	CHEMBL
Thymidylate synthase	Enzyme		C3SWJ7_ECOLX		IC50	5.96	CHEMBL
Thymidylate synthase (EC 2.1.1.45) (TS) (TSase)	Enzyme		E2QDN0_ECOLX		IC50	4.12	CHEMBL
Trifunctional purine biosynthetic protein adenosine-3	Enzyme		PUR2_MOUSE	INHIBITOR	Ki	5.03	IUPHAR

External reference:

ID	Source
4021417	VUID
N0000148831	NUI
D03828	KEGG_DRUG
150399-23-8	SECONDARY_CAS_RN
4021417	VANDF
C0210657	UMLSCUI
CHEBI:63724	CHEBI
4DW	PDB_CHEM_ID
CHEMBL225072	ChEMBL_ID
CHEMBL2360464	ChEMBL_ID
D000068437	MESH_DESCRIPTOR_UI
DB00642	DRUGBANK_ID
135410875	PUBCHEM_CID
6837	IUPHAR_LIGAND_ID
7675	INN_ID
357166-29-1	SECONDARY_CAS_RN
04Q9AIZ7NO	UNII
1666923	RXNORM
17856	MMSL
238966	MMSL
32871	MMSL
48646	MMSL
d05047	MMSL
008494	NDDF
008495	NDDF
409159000	SNOMEDCT_US
411089001	SNOMEDCT_US
735172002	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Alimta	HUMAN PRESCRIPTION DRUG LABEL	1	0002-7623	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	500 mg	INTRAVENOUS	NDA	33 sections
Alimta	HUMAN PRESCRIPTION DRUG LABEL	1	0002-7623	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	500 mg	INTRAVENOUS	NDA	33 sections
Alimta	HUMAN PRESCRIPTION DRUG LABEL	1	0002-7623	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	500 mg	INTRAVENOUS	NDA	33 sections
Alimta	HUMAN PRESCRIPTION DRUG LABEL	1	0002-7640	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	100 mg	INTRAVENOUS	NDA	33 sections
Alimta	HUMAN PRESCRIPTION DRUG LABEL	1	0002-7640	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	100 mg	INTRAVENOUS	NDA	33 sections
Alimta	HUMAN PRESCRIPTION DRUG LABEL	1	0002-7640	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	100 mg	INTRAVENOUS	NDA	33 sections
PEMETREXED	HUMAN PRESCRIPTION DRUG LABEL	1	0338-0720	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	100 mg	INTRAVENOUS	ANDA	27 sections
PEMETREXED	HUMAN PRESCRIPTION DRUG LABEL	1	0338-0720	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	100 mg	INTRAVENOUS	ANDA	27 sections
PEMETREXED	HUMAN PRESCRIPTION DRUG LABEL	1	0338-0722	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	500 mg	INTRAVENTRICULAR	ANDA	27 sections
PEMETREXED	HUMAN PRESCRIPTION DRUG LABEL	1	0338-0722	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	500 mg	INTRAVENTRICULAR	ANDA	27 sections
PEMETREXED	HUMAN PRESCRIPTION DRUG LABEL	1	0409-0004	INJECTION, SOLUTION, CONCENTRATE	1 g	INTRAVENOUS	NDA	30 sections
PEMETREXED	HUMAN PRESCRIPTION DRUG LABEL	1	0409-0020	INJECTION, SOLUTION, CONCENTRATE	100 mg	INTRAVENOUS	NDA	30 sections
PEMETREXED	HUMAN PRESCRIPTION DRUG LABEL	1	0409-0021	INJECTION, SOLUTION, CONCENTRATE	500 mg	INTRAVENOUS	NDA	30 sections
PEMETREXED	HUMAN PRESCRIPTION DRUG LABEL	1	0409-1045	INJECTION, SOLUTION, CONCENTRATE	100 mg	INTRAVENOUS	NDA	32 sections
PEMETREXED	HUMAN PRESCRIPTION DRUG LABEL	1	0409-2188	INJECTION, SOLUTION, CONCENTRATE	500 mg	INTRAVENOUS	NDA	32 sections
PEMETREXED	HUMAN PRESCRIPTION DRUG LABEL	1	0409-3532	INJECTION, SOLUTION, CONCENTRATE	1 g	INTRAVENOUS	NDA	32 sections
Pemetrexed	HUMAN PRESCRIPTION DRUG LABEL	1	0781-3518	INJECTION, SOLUTION	100 mg	INTRAVENOUS	NDA	27 sections
Pemetrexed	HUMAN PRESCRIPTION DRUG LABEL	1	0781-3518	INJECTION, SOLUTION	100 mg	INTRAVENOUS	NDA	27 sections
Pemetrexed	HUMAN PRESCRIPTION DRUG LABEL	1	0781-3519	INJECTION, SOLUTION	500 mg	INTRAVENOUS	NDA	27 sections
Pemetrexed	HUMAN PRESCRIPTION DRUG LABEL	1	0781-3519	INJECTION, SOLUTION	500 mg	INTRAVENOUS	NDA	27 sections
Pemetrexed	HUMAN PRESCRIPTION DRUG LABEL	1	0781-3520	INJECTION, SOLUTION	1000 mg	INTRAVENOUS	NDA	27 sections
Pemetrexed	HUMAN PRESCRIPTION DRUG LABEL	1	0781-3520	INJECTION, SOLUTION	1000 mg	INTRAVENOUS	NDA	27 sections
Pemetrexed disodium	HUMAN PRESCRIPTION DRUG LABEL	1	43598-370	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	1 g	INTRAVENOUS	ANDA	28 sections
Pemetrexed disodium	HUMAN PRESCRIPTION DRUG LABEL	1	43598-370	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	1 g	INTRAVENOUS	ANDA	28 sections
Pemetrexed disodium	HUMAN PRESCRIPTION DRUG LABEL	1	43598-386	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	100 mg	INTRAVENOUS	ANDA	28 sections
Pemetrexed disodium	HUMAN PRESCRIPTION DRUG LABEL	1	43598-386	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	100 mg	INTRAVENOUS	ANDA	28 sections
Pemetrexed disodium	HUMAN PRESCRIPTION DRUG LABEL	1	43598-387	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	500 mg	INTRAVENOUS	ANDA	28 sections
Pemetrexed disodium	HUMAN PRESCRIPTION DRUG LABEL	1	43598-387	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	500 mg	INTRAVENOUS	ANDA	28 sections
Pemetrexed	HUMAN PRESCRIPTION DRUG LABEL	1	60505-6065	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	100 mg	INTRAVENOUS	ANDA	27 sections
Pemetrexed	HUMAN PRESCRIPTION DRUG LABEL	1	60505-6065	INJECTION, POWDER, LYOPHILIZED, FOR SOLUTION	100 mg	INTRAVENOUS	ANDA	27 sections