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

Stem definition	Drug id	CAS RN
aromatase inhibitors, imidazole-triazole derivatives	1556	112809-51-5

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: CGS-20267 CGS 20267 letrozole lerozole letrazole	Letrozole is a nonsteroidal competitive inhibitor of the aromatase enzyme system; it inhibits the conversion of androgens to estrogens. Used in treatment of hormonally responsive breast cancer (i.e., estrogen and/or progesterone receptor positive or receptor unknown) Molecular weight: 285.31 Formula: C17H11N5 CLOGP: 1.70 LIPINSKI: 0 HAC: 5 HDO: 0 TPSA: 78.29 ALOGS: -3.55 ROTB: 3 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

CGS-20267
CGS 20267
letrozole
lerozole
letrazole

Letrozole is a nonsteroidal competitive inhibitor of the aromatase enzyme system; it inhibits the conversion of androgens to estrogens. Used in treatment of hormonally responsive breast cancer (i.e., estrogen and/or progesterone receptor positive or receptor unknown)

Molecular weight: 285.31
Formula: C17H11N5
CLOGP: 1.70
LIPINSKI: 0
HAC: 5
HDO: 0
TPSA: 78.29
ALOGS: -3.55
ROTB: 3

Status: OFP

Legend:
OFP - off patent
OFM - off market
ONP - on patent

Drug dosage:

Dose	Unit	Route
2.50	mg	O

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	1	Benet LZ, Broccatelli F, Oprea TI
S (Water solubility)	0.04 mg/mL	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	3.90 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	0.15 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability)	99 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution)	1.90 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	0.57 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.41 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	45 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
July 25, 1997	FDA	NOVARTIS PHARMS

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	2462.50	11.51	1573	96816	66551	50440184
Neutropenia	2395.06	11.51	2108	96281	145857	50360878
Neoplasm progression	2041.57	11.51	1038	97351	28119	50478616
Metastases to bone	1957.87	11.51	868	97521	17127	50489608
Metastases to liver	1255.01	11.51	663	97726	19441	50487294
White blood cell count decreased	1031.94	11.51	1201	97188	115521	50391214
Disease progression	717.20	11.51	907	97482	94959	50411776
Drug ineffective	632.36	11.51	411	97978	818922	49687813
Hot flush	611.17	11.51	578	97811	43591	50463144
Leukopenia	577.82	11.51	684	97705	66844	50439891
Breast cancer metastatic	568.89	11.51	314	98075	10050	50496685
Osteonecrosis of jaw	565.16	11.51	484	97905	32042	50474693
Metastases to lung	532.15	11.51	307	98082	10713	50496022
Bone pain	488.38	11.51	528	97861	46701	50460034
Tumour marker increased	419.69	11.51	186	98203	3654	50503081
Metastases to lymph nodes	405.35	11.51	220	98169	6804	50499931
Fatigue	387.16	11.51	2519	95870	705082	49801653
Breast cancer	322.14	11.51	407	97982	42483	50464252
Carbohydrate antigen 15-3 increased	310.84	11.51	107	98282	1025	50505710
Breast cancer recurrent	296.82	11.51	146	98243	3662	50503073
Rheumatoid arthritis	258.43	11.51	42	98347	202508	50304227
Second primary malignancy	257.29	11.51	163	98226	6751	50499984
Neutrophil count decreased	249.35	11.51	373	98016	45653	50461082
Therapeutic product effect decreased	244.09	11.51	4	98385	136046	50370689
Alopecia	243.67	11.51	1032	97357	244015	50262720
Contraindicated product administered	239.80	11.51	12	98377	148946	50357789
Drug hypersensitivity	235.09	11.51	97	98292	250913	50255822
Systemic lupus erythematosus	227.41	11.51	11	98378	140611	50366124
Maternal exposure during pregnancy	223.07	11.51	25	98364	159753	50346982
Infusion related reaction	216.61	11.51	35	98354	169522	50337213
PIK3CA-activated mutation	212.50	11.51	74	98315	736	50505999
Completed suicide	211.09	11.51	11	98378	131878	50374857
Polyneuropathy	209.53	11.51	180	98209	11951	50494784
Thrombocytopenia	209.49	11.51	634	97755	127039	50379696
Bone lesion	207.79	11.51	128	98261	5042	50501693
Osteonecrosis	198.84	11.51	232	98157	22285	50484450
Metastases to spine	195.52	11.51	100	98289	2731	50504004
Metastasis	193.04	11.51	115	98274	4260	50502475
Pleural effusion	190.40	11.51	461	97928	80993	50425742
Metastases to pleura	184.88	11.51	76	98313	1230	50505505
Joint swelling	182.49	11.51	127	98262	245159	50261576
Skin hypopigmentation	178.54	11.51	61	98328	570	50506165
Metastases to skin	177.34	11.51	75	98314	1308	50505427
Hand deformity	171.68	11.51	5	98384	100194	50406541
Decreased appetite	171.49	11.51	809	97580	200114	50306621
Full blood count abnormal	170.89	11.51	219	98170	23169	50483566
Toxicity to various agents	170.37	11.51	101	98288	212398	50294337
Hypersensitivity	161.88	11.51	110	98279	215051	50291684
Synovitis	157.18	11.51	26	98363	123839	50382896
Arthropathy	156.04	11.51	56	98333	157850	50348885
Treatment failure	151.84	11.51	40	98349	137597	50369138
Off label use	149.84	11.51	451	97938	473975	50032760
Nausea	148.27	11.51	2051	96338	703347	49803388
Lymphoedema	144.77	11.51	129	98260	8993	50497742
Metastases to central nervous system	143.36	11.51	141	98248	11141	50495594
Neuropathy peripheral	142.51	11.51	463	97926	96294	50410441
Gamma-glutamyltransferase increased	127.24	11.51	216	98173	29407	50477328
Anaemia	122.44	11.51	875	97514	251581	50255154
Glossodynia	121.13	11.51	37	98352	115532	50391203
Injection site pain	115.54	11.51	36	98353	110988	50395747
Injection site erythema	114.57	11.51	8	98381	74928	50431807
Sinusitis	113.21	11.51	99	98290	170459	50336276
Pericarditis	113.14	11.51	11	98378	78678	50428057
Bone disorder	110.23	11.51	158	98231	18594	50488141
Wound	108.85	11.51	35	98354	105759	50400976
Haematotoxicity	108.46	11.51	103	98286	7792	50498943
Ascites	108.45	11.51	225	98164	35636	50471099
Swelling	108.27	11.51	139	98250	200733	50306002
Condition aggravated	106.60	11.51	265	98124	296793	50209942
Carcinoembryonic antigen increased	104.50	11.51	53	98336	1421	50505314
Dry skin	103.59	11.51	247	98142	42944	50463791
Hepatotoxicity	102.03	11.51	187	98202	27039	50479696
Hypotension	101.97	11.51	189	98200	235280	50271455
Palmar-plantar erythrodysaesthesia syndrome	101.89	11.51	158	98231	19940	50486795
Stomatitis	98.23	11.51	424	97965	100920	50405815
Ejection fraction decreased	94.45	11.51	146	98243	18374	50488361
Red blood cell count decreased	93.89	11.51	205	98184	33630	50473105
Aspartate aminotransferase increased	92.91	11.51	348	98041	77650	50429085
Mucosal dryness	92.47	11.51	58	98331	2359	50504376
Malignant pleural effusion	91.89	11.51	57	98332	2273	50504462
Intentional overdose	91.82	11.51	8	98381	62496	50444239
Overdose	90.88	11.51	40	98349	99687	50407048
Nail disorder	90.69	11.51	103	98286	9605	50497130
Intentional product use issue	85.47	11.51	22	98367	76896	50429839
Tooth extraction	84.29	11.51	96	98293	8979	50497756
Metastases to peritoneum	84.07	11.51	58	98331	2775	50503960
Ovarian hyperstimulation syndrome	83.74	11.51	61	98328	3183	50503552
Electrocardiogram QT prolonged	83.40	11.51	256	98133	51630	50455105
Helicobacter infection	83.26	11.51	3	98386	49699	50457036
Hepatic lesion	80.69	11.51	65	98324	3943	50502792
Taste disorder	80.63	11.51	90	98299	8234	50498501
Epistaxis	80.07	11.51	290	98099	63664	50443071
Exposure during pregnancy	79.36	11.51	71	98318	120944	50385791
Psoriatic arthropathy	78.23	11.51	3	98386	47029	50459706
Injection site reaction	77.48	11.51	5	98384	50027	50456708
Pseudocirrhosis	76.92	11.51	33	98356	597	50506138
Seizure	76.29	11.51	70	98319	117804	50388931
Diarrhoea	76.08	11.51	1583	96806	586893	49919842
Full blood count decreased	74.46	11.51	146	98243	22200	50484535
Constipation	74.46	11.51	616	97773	185092	50321643
Irritable bowel syndrome	71.85	11.51	8	98381	51433	50455302
Bone marrow failure	71.73	11.51	163	98226	27461	50479274
General physical health deterioration	71.43	11.51	498	97891	141936	50364799
Mucosal inflammation	71.10	11.51	205	98184	39937	50466798
Product use issue	71.04	11.51	113	98276	149362	50357373
Lymphangiosis carcinomatosa	70.49	11.51	38	98351	1158	50505577
Drug intolerance	69.85	11.51	207	98182	218897	50287838
Alanine aminotransferase increased	69.61	11.51	348	98041	88011	50418724
Neoplasm malignant	69.60	11.51	147	98242	23568	50483167
Spinal pain	69.40	11.51	95	98294	10708	50496027
Cardio-respiratory arrest	69.03	11.51	11	98378	53881	50452854
Drug abuse	68.66	11.51	16	98373	59830	50446905
Onychoclasis	67.99	11.51	66	98323	5130	50501605
Abdominal discomfort	67.42	11.51	228	98161	231413	50275322
Discomfort	67.05	11.51	67	98322	108313	50398422
Drug interaction	66.25	11.51	185	98204	199436	50307299
Progesterone increased	65.13	11.51	16	98373	36	50506699
Trigger finger	64.98	11.51	56	98333	3732	50503003
Metastases to chest wall	64.90	11.51	27	98362	451	50506284
Multiple sclerosis relapse	64.49	11.51	5	98384	42959	50463776
Arthralgia	64.26	11.51	1203	97186	437499	50069236
Duodenal ulcer perforation	63.94	11.51	7	98382	45604	50461131
Skin toxicity	63.41	11.51	56	98333	3857	50502878
Pleural neoplasm	63.15	11.51	22	98367	219	50506516
Psoriasis	62.34	11.51	28	98361	68972	50437763
Erysipelas	61.54	11.51	70	98319	6538	50500197
Suicide attempt	61.02	11.51	13	98376	51719	50455016
Pneumonitis	60.50	11.51	159	98230	29351	50477384
Pulmonary embolism	59.72	11.51	370	98019	101334	50405401
Metastases to pelvis	57.72	11.51	23	98366	342	50506393
Oxygen saturation decreased	56.96	11.51	36	98353	73212	50433523
Muscle injury	56.61	11.51	4	98385	37107	50469628
Blood alkaline phosphatase increased	56.47	11.51	181	98208	37345	50469390
Injection site bruising	55.98	11.51	4	98385	36764	50469971
Bone marrow infiltration	55.45	11.51	24	98365	444	50506291
Breast cancer female	54.48	11.51	67	98322	6795	50499940
Breast pain	54.08	11.51	70	98319	7474	50499261
Adverse event	53.70	11.51	10	98379	43753	50462982
Asthenia	53.44	11.51	894	97495	318148	50188587
Therapeutic product effect incomplete	52.78	11.51	60	98329	91455	50415280
Blister	52.61	11.51	53	98336	85365	50421370
Urticaria	52.54	11.51	108	98281	129453	50377282
Knee arthroplasty	51.54	11.51	5	98384	35841	50470894
Cardiac arrest	51.41	11.51	52	98337	83599	50423136
Loss of personal independence in daily activities	51.03	11.51	37	98352	70013	50436722
Lymphadenopathy	50.79	11.51	162	98227	33337	50473398
Anaphylactic reaction	50.32	11.51	21	98368	54034	50452701
Unevaluable event	49.61	11.51	14	98375	46052	50460683
Pyelitis	49.18	11.51	17	98372	165	50506570
Transaminases increased	49.17	11.51	142	98247	27682	50479053
Myalgia	49.04	11.51	411	97978	123908	50382827
Eastern Cooperative Oncology Group performance status worsened	48.35	11.51	24	98365	614	50506121
Peripheral swelling	48.22	11.51	221	98168	205715	50301020
Hormone receptor positive breast cancer	48.20	11.51	22	98367	464	50506271
Ill-defined disorder	48.10	11.51	23	98366	54631	50452104
Wrong technique in product usage process	47.88	11.51	24	98365	55486	50451249
Exposed bone in jaw	47.23	11.51	41	98348	2759	50503976
Lacrimation increased	47.18	11.51	103	98286	16889	50489846
Hepatorenal failure	46.63	11.51	23	98366	580	50506155
Device related thrombosis	46.60	11.51	30	98359	1277	50505458
Osteolysis	46.31	11.51	39	98350	2518	50504217
Hepatic enzyme increased	45.78	11.51	127	98262	137253	50369482
Metastases to the mediastinum	45.74	11.51	21	98368	449	50506286
Metastases to thorax	45.73	11.51	17	98372	207	50506528
Infection	45.16	11.51	178	98211	172776	50333959
Hydronephrosis	44.48	11.51	68	98321	8473	50498262
Madarosis	44.23	11.51	38	98351	2522	50504213
Coma	44.16	11.51	28	98361	56851	50449884
Neoplasm	44.06	11.51	56	98333	5872	50500863
Cancer pain	43.88	11.51	38	98351	2549	50504186
Metastases to adrenals	43.58	11.51	23	98366	671	50506064
Dysgeusia	43.33	11.51	170	98219	38746	50467989
Pregnancy	42.86	11.51	4	98385	29573	50477162
Sequestrectomy	42.79	11.51	24	98365	792	50505943
Bone sequestrum	42.76	11.51	29	98360	1349	50505386
Musculoskeletal stiffness	42.64	11.51	119	98270	128362	50378373
Gastrointestinal disorder	42.45	11.51	74	98315	94382	50412353
C-reactive protein abnormal	42.41	11.51	3	98386	27806	50478929
Folliculitis	42.09	11.51	12	98377	39213	50467522
Metastases to stomach	40.70	11.51	15	98374	178	50506557
Osteomyelitis	40.39	11.51	115	98274	22238	50484497
Musculoskeletal chest pain	40.36	11.51	102	98287	18384	50488351
Concomitant disease aggravated	40.16	11.51	63	98326	8028	50498707
Blood bilirubin increased	39.84	11.51	145	98244	31893	50474842
Generalised tonic-clonic seizure	39.66	11.51	3	98386	26307	50480428
Thoracic vertebral fracture	39.38	11.51	44	98345	4029	50502706
Metastases to meninges	39.31	11.51	32	98357	1970	50504765
Abortion spontaneous	39.25	11.51	16	98373	41756	50464979
Adverse drug reaction	39.15	11.51	30	98359	55192	50451543
Onychomadesis	39.09	11.51	41	98348	3495	50503240
Loss of consciousness	38.99	11.51	91	98298	104262	50402473
Platelet count decreased	38.13	11.51	330	98059	100396	50406339
Lower respiratory tract infection	38.04	11.51	80	98309	95121	50411614
Pneumonia	38.00	11.51	513	97876	377888	50128847
Fibromyalgia	37.97	11.51	20	98369	44958	50461777
Blood lactate dehydrogenase increased	37.67	11.51	103	98286	19459	50487276
Nail dystrophy	37.56	11.51	22	98367	789	50505946
Bone debridement	37.52	11.51	15	98374	225	50506510
Asthma	37.47	11.51	73	98316	89264	50417471
Mobility decreased	36.50	11.51	62	98327	79886	50426849
Blood creatinine increased	36.22	11.51	263	98126	75897	50430838
Drug reaction with eosinophilia and systemic symptoms	35.95	11.51	6	98383	28418	50478317
Somnolence	35.86	11.51	167	98222	154818	50351917
Hypermetabolism	35.76	11.51	13	98376	148	50506587
Respiratory failure	35.29	11.51	78	98311	91103	50415632
Skin weeping	35.27	11.51	17	98372	407	50506328
Gastrointestinal haemorrhage	35.21	11.51	55	98334	73266	50433469
Metastases to ovary	35.20	11.51	16	98373	334	50506401
Heart rate increased	35.18	11.51	60	98329	77190	50429545
Back pain	35.12	11.51	612	97777	219418	50287317
Interstitial lung disease	34.74	11.51	199	98190	52977	50453758
No adverse event	34.71	11.51	11	98378	33567	50473168
Metabolic acidosis	34.68	11.51	16	98373	38809	50467926
Electrocardiogram PR shortened	34.55	11.51	14	98375	218	50506517
Pain	34.49	11.51	860	97529	578043	49928692
Osteosclerosis	34.46	11.51	38	98351	3429	50503306
Respiratory arrest	34.46	11.51	8	98381	30001	50476734
Metastases to bladder	34.42	11.51	13	98376	166	50506569
Recall phenomenon	33.71	11.51	18	98371	538	50506197
Urinary tract inflammation	33.62	11.51	9	98380	32	50506703
Invasive ductal breast carcinoma	33.49	11.51	49	98340	5872	50500863
Septic shock	33.49	11.51	37	98352	57138	50449597
Flushing	33.41	11.51	49	98340	66966	50439769
Therapy non-responder	33.35	11.51	30	98359	50992	50455743
Encephalopathy	33.18	11.51	12	98377	33699	50473036
Invasive lobular breast carcinoma	33.09	11.51	19	98370	656	50506079
Isosthenuria	32.66	11.51	11	98378	98	50506637
Weight increased	32.63	11.51	244	98145	201647	50305088
Oral pain	32.58	11.51	115	98274	24918	50481817
Gingivitis	32.45	11.51	54	98335	7230	50499505
Drug withdrawal syndrome	32.39	11.51	5	98384	25076	50481659
Premature delivery	32.25	11.51	4	98385	23659	50483076
Bladder hypertrophy	31.87	11.51	13	98376	206	50506529
Orthostatic hypotension	31.67	11.51	9	98380	29472	50477263
Gastroenteritis radiation	31.65	11.51	16	98373	426	50506309
Tumour pain	31.46	11.51	23	98366	1207	50505528
Lymphadenopathy mediastinal	31.19	11.51	31	98358	2480	50504255
Intentional product misuse	31.12	11.51	27	98362	46707	50460028
Blood pressure increased	31.06	11.51	143	98246	132989	50373746
Jaw disorder	31.05	11.51	43	98346	4900	50501835
Purulent discharge	30.75	11.51	40	98349	4292	50502443
Superinfection	30.50	11.51	28	98361	2028	50504707
Cardiac failure congestive	30.39	11.51	75	98314	84307	50422428
Abdominal lymphadenopathy	30.30	11.51	18	98371	663	50506072
Debridement	30.05	11.51	22	98367	1157	50505578
Myelosuppression	29.94	11.51	75	98314	13442	50493293
Hallucination	29.82	11.51	28	98361	46629	50460106
Metastases to muscle	29.74	11.51	11	98378	132	50506603
Tumour marker decreased	29.66	11.51	9	98380	55	50506680
Dental fistula	29.48	11.51	17	98372	592	50506143
Bradycardia	29.37	11.51	50	98339	64376	50442359
Osteoma cutis	29.04	11.51	6	98383	3	50506732
Rash	29.04	11.51	639	97750	436832	50069903
Depressed level of consciousness	28.94	11.51	35	98354	51918	50454817
Blood pressure fluctuation	28.69	11.51	17	98372	35806	50470929
Gingival swelling	28.44	11.51	36	98353	3759	50502976
Wheezing	28.43	11.51	48	98341	61999	50444736
Glomerular filtration rate decreased	28.32	11.51	67	98322	11585	50495150
Heart rate decreased	28.28	11.51	18	98371	36479	50470256
Jaundice	28.25	11.51	114	98275	26315	50480420
Recurrent cancer	28.18	11.51	25	98364	1732	50505003
Injection site haemorrhage	28.15	11.51	4	98385	21342	50485393
Hypocalcaemia	28.13	11.51	115	98274	26701	50480034
Delirium	28.03	11.51	20	98369	38172	50468563
Hip arthroplasty	28.03	11.51	12	98377	30417	50476318
Hospitalisation	27.21	11.51	57	98332	67880	50438855
Product quality issue	27.13	11.51	13	98376	30845	50475890
Concomitant disease progression	26.80	11.51	26	98363	2019	50504716
Unresponsive to stimuli	26.75	11.51	13	98376	30596	50476139
Osteitis	26.54	11.51	31	98358	2979	50503756
Cytopenia	26.45	11.51	55	98334	8720	50498015
Medication error	26.38	11.51	19	98370	36085	50470650
Bone trimming	26.34	11.51	7	98382	24	50506711
Confusional state	26.24	11.51	233	98156	185695	50321040
Injury	26.16	11.51	34	98355	48891	50457844
Pleural disorder	25.74	11.51	15	98374	533	50506202
Drug dependence	25.37	11.51	4	98385	19755	50486980
Premature baby	25.23	11.51	3	98386	18334	50488401
Nephrosclerosis	25.21	11.51	18	98371	910	50505825
Hypoglycaemia	24.96	11.51	41	98348	53540	50453195
Plasma cell myeloma	24.89	11.51	15	98374	31307	50475428
Calcium deficiency	24.83	11.51	18	98371	932	50505803
Elliptocytosis	24.75	11.51	7	98382	32	50506703
Nasopharyngitis	24.57	11.51	248	98141	192679	50314056
Incorrect dose administered	24.52	11.51	35	98354	48379	50458356
Dysarthria	24.43	11.51	22	98367	37381	50469354
Staphylococcal infection	24.42	11.51	20	98369	35596	50471139
Ovarian rupture	24.41	11.51	7	98382	34	50506701
Therapy partial responder	24.34	11.51	45	98344	6546	50500189
Lymphopenia	24.09	11.51	76	98313	15545	50491190
Vitiligo	23.84	11.51	19	98370	1135	50505600
Agitation	23.81	11.51	42	98347	53342	50453393
Skin lesion	23.73	11.51	109	98280	26618	50480117
Fall	23.72	11.51	484	97905	334448	50172287
Neoplasm recurrence	23.61	11.51	26	98363	2343	50504392
Pulmonary mass	23.54	11.51	85	98304	18620	50488115
Metastases to eye	23.27	11.51	9	98380	123	50506612
Muscle spasticity	23.18	11.51	3	98386	17181	50489554
Blood pressure decreased	23.16	11.51	46	98343	55863	50450872
Malignant peritoneal neoplasm	23.14	11.51	15	98374	646	50506089
Pathological fracture	22.98	11.51	48	98341	7634	50499101
CYP3A4 polymorphism	22.93	11.51	8	98381	80	50506655
Mental status changes	22.91	11.51	22	98367	36250	50470485
Decreased immune responsiveness	22.85	11.51	33	98356	3908	50502827
Granulocyte count decreased	22.74	11.51	16	98373	790	50505945
Coronary artery disease	22.57	11.51	15	98374	29711	50477024
Carbohydrate antigen 27.29 increased	22.38	11.51	7	98382	48	50506687
Toothache	22.32	11.51	78	98311	16816	50489919
Cytomegalovirus infection	22.26	11.51	4	98385	17958	50488777
Metastases to abdominal wall	22.25	11.51	8	98381	88	50506647
Hypertensive crisis	22.15	11.51	66	98323	13088	50493647
Multiple pregnancy	22.01	11.51	7	98382	51	50506684
Tremor	21.99	11.51	132	98257	114771	50391964
Dyschezia	21.91	11.51	22	98367	1782	50504953
Superior vena cava syndrome	21.75	11.51	14	98375	596	50506139
Plastic surgery	21.66	11.51	7	98382	54	50506681
Tumour marker abnormal	21.56	11.51	10	98379	219	50506516
Type 2 diabetes mellitus	21.53	11.51	21	98368	34354	50472381
Skin exfoliation	21.44	11.51	125	98264	33487	50473248
Injection site rash	21.41	11.51	3	98386	16174	50490561
Antisynthetase syndrome	21.33	11.51	7	98382	57	50506678
Hepatic steatosis	21.32	11.51	99	98290	24285	50482450
Ear infection	21.26	11.51	12	98377	25958	50480777
Dyskinesia	21.23	11.51	14	98375	27847	50478888
Hepatic failure	21.21	11.51	121	98268	32162	50474573
Neutrophil count abnormal	21.14	11.51	25	98364	2434	50504301
Sleep apnoea syndrome	21.06	11.51	10	98379	23858	50482877
Keloid scar	20.92	11.51	9	98380	164	50506571
Suicidal ideation	20.92	11.51	48	98341	55337	50451398
Congestive cardiomyopathy	20.79	11.51	38	98351	5480	50501255
RET gene mutation	20.75	11.51	5	98384	10	50506725
Bile duct stenosis	20.71	11.51	17	98372	1059	50505676
Nail toxicity	20.59	11.51	11	98378	329	50506406
Intestinal metastasis	20.58	11.51	8	98381	111	50506624
BRCA1 gene mutation	20.43	11.51	5	98384	11	50506724
Foot deformity	20.38	11.51	6	98383	19204	50487531
Hypoxia	20.38	11.51	43	98346	51080	50455655
Contusion	20.37	11.51	131	98258	112052	50394683
Vitreous detachment	20.19	11.51	21	98368	1773	50504962
Metastases to neck	20.15	11.51	7	98382	69	50506666
Peri-implantitis	20.15	11.51	6	98383	34	50506701
Therapy cessation	20.15	11.51	102	98287	25909	50480826
Mouth swelling	20.14	11.51	31	98358	3885	50502850
Basophil count increased	20.03	11.51	15	98374	817	50505918
Sedation	20.00	11.51	18	98371	30592	50476143
Blood cholesterol increased	19.94	11.51	49	98340	55166	50451569
Radiation oesophagitis	19.93	11.51	10	98379	262	50506473
Myeloproliferative neoplasm	19.91	11.51	12	98377	454	50506281
Anisocytosis	19.89	11.51	13	98376	568	50506167
Dermatitis	19.88	11.51	67	98322	14184	50492551
Mastectomy	19.86	11.51	19	98370	1450	50505285
Periodontitis	19.73	11.51	27	98362	3042	50503693
Metastases to spinal cord	19.72	11.51	6	98383	37	50506698
Breast neoplasm	19.71	11.51	18	98371	1295	50505440
Adjusted calcium decreased	19.66	11.51	8	98381	126	50506609
Body surface area decreased	19.58	11.51	5	98384	14	50506721
Radiation skin injury	19.54	11.51	15	98374	848	50505887
Tongue discomfort	19.48	11.51	21	98368	1847	50504888
Vulvovaginal inflammation	19.47	11.51	13	98376	589	50506146
Hydrothorax	19.45	11.51	14	98375	717	50506018
Thirst	19.44	11.51	55	98334	10595	50496140
Myocardial infarction	19.37	11.51	98	98291	88929	50417806
Breast cancer stage IV	19.26	11.51	13	98376	600	50506135
Arthritis	19.13	11.51	95	98294	86626	50420109
Chronic cutaneous lupus erythematosus	19.10	11.51	8	98381	136	50506599
Clostridium difficile infection	19.10	11.51	13	98376	25426	50481309
Adjusted calcium increased	19.08	11.51	5	98384	16	50506719
Tachyarrhythmia	19.05	11.51	31	98358	4074	50502661
SAPHO syndrome	19.00	11.51	7	98382	83	50506652
Malaise	18.95	11.51	502	97887	335030	50171705
Dilatation ventricular	18.94	11.51	23	98366	2302	50504433
Transaminases	18.85	11.51	7	98382	85	50506650
Cardiotoxicity	18.83	11.51	42	98347	6985	50499750
Ovarian fibrosis	18.75	11.51	4	98385	3	50506732
Drug level increased	18.73	11.51	7	98382	19261	50487474
Visual impairment	18.64	11.51	209	98180	68066	50438669
Pain in jaw	18.43	11.51	133	98256	38295	50468440
Paraneoplastic syndrome	18.43	11.51	12	98377	521	50506214
Aggression	18.40	11.51	9	98380	21107	50485628
Carcinoid tumour pulmonary	18.35	11.51	11	98378	412	50506323
Headache	18.30	11.51	802	97587	505733	50001002
Oral discomfort	18.30	11.51	45	98344	7972	50498763
Gene mutation	18.26	11.51	17	98372	1254	50505481
Left ventricular dilatation	18.23	11.51	11	98378	417	50506318
Pericardial effusion	18.20	11.51	98	98291	25491	50481244
Cutaneous lupus erythematosus	18.12	11.51	23	98366	2408	50504327
Sopor	18.05	11.51	8	98381	19871	50486864
Inappropriate schedule of product administration	18.05	11.51	75	98314	71756	50434979
Carbohydrate antigen 125 increased	17.85	11.51	23	98366	2444	50504291
Hepatic calcification	17.84	11.51	5	98384	22	50506713
Meningeal disorder	17.82	11.51	9	98380	239	50506496
Withdrawal syndrome	17.76	11.51	6	98383	17584	50489151
Congestive hepatopathy	17.66	11.51	23	98366	2471	50504264
Triple negative breast cancer	17.63	11.51	7	98382	103	50506632
Onycholysis	17.62	11.51	17	98372	1311	50505424
Radiation pneumonitis	17.55	11.51	17	98372	1318	50505417
Pancreatic neoplasm	17.53	11.51	13	98376	697	50506038
Malignant ascites	17.52	11.51	14	98375	839	50505896
Migraine	17.46	11.51	81	98308	75199	50431536
Multiple sclerosis	17.46	11.51	9	98380	20484	50486251
Abscess jaw	17.30	11.51	17	98372	1341	50505394
Nasal congestion	17.21	11.51	47	98342	51073	50455662
Dysaesthesia	17.05	11.51	28	98361	3707	50503028
Nail growth abnormal	17.05	11.51	11	98378	470	50506265
Bursitis	17.04	11.51	11	98378	22124	50484611
Macular hole	17.01	11.51	13	98376	730	50506005
Mucosal hypertrophy	17.00	11.51	5	98384	27	50506708
Metastatic neoplasm	16.95	11.51	28	98361	3726	50503009
Gait deviation	16.94	11.51	6	98383	63	50506672
Hypersensitivity vasculitis	16.87	11.51	29	98360	3986	50502749
Tachycardia	16.86	11.51	119	98270	99644	50407091
Dental discomfort	16.82	11.51	10	98379	369	50506366
Metastases to kidney	16.81	11.51	8	98381	186	50506549
Biopsy bone abnormal	16.70	11.51	5	98384	29	50506706
Gingival erythema	16.70	11.51	12	98377	613	50506122
Bone fistula	16.69	11.51	6	98383	66	50506669
Body surface area increased	16.60	11.51	4	98385	8	50506727
Status epilepticus	16.58	11.51	3	98386	13403	50493332
Vulvovaginal dryness	16.57	11.51	21	98368	2196	50504539
Prescribed overdose	16.55	11.51	4	98385	14596	50492139
Respiratory distress	16.49	11.51	21	98368	30468	50476267
Jaw operation	16.45	11.51	13	98376	767	50505968
Dental care	16.44	11.51	14	98375	918	50505817
Pelvic fluid collection	16.40	11.51	13	98376	770	50505965
Adenocarcinoma	16.21	11.51	22	98367	2459	50504276
Red blood cell sedimentation rate increased	16.19	11.51	20	98369	29396	50477339
Liver function test increased	16.18	11.51	95	98294	25511	50481224
Peripheral sensory neuropathy	16.12	11.51	38	98351	6553	50500182
Soft tissue infection	16.12	11.51	19	98370	1843	50504892
Pneumonia aspiration	16.11	11.51	22	98367	30982	50475753
Metastases to uterus	16.00	11.51	6	98383	75	50506660
Bone marrow oedema syndrome	15.99	11.51	4	98385	10	50506725
Bronchitis	15.82	11.51	128	98261	104031	50402704
Nail avulsion	15.81	11.51	7	98382	137	50506598
Hormone receptor positive HER2 negative breast cancer	15.74	11.51	3	98386	0	50506735
Hydroxyproline increased	15.74	11.51	3	98386	0	50506735
Aortic thrombosis	15.72	11.51	14	98375	975	50505760
Ostectomy	15.71	11.51	4	98385	11	50506724
Multiple organ dysfunction syndrome	15.68	11.51	48	98341	50289	50456446
Breast mass	15.58	11.51	37	98352	6412	50500323
Tooth loss	15.56	11.51	36	98353	6134	50500601
Hormone refractory breast cancer	15.46	11.51	4	98385	12	50506723
Androgenetic alopecia	15.45	11.51	7	98382	145	50506590
Pneumonia herpes viral	15.43	11.51	5	98384	39	50506696
Cor pulmonale acute	15.41	11.51	9	98380	321	50506414
Oestradiol increased	15.38	11.51	6	98383	84	50506651
Oestrogen receptor assay positive	15.38	11.51	10	98379	433	50506302
Peritoneal disorder	15.28	11.51	10	98379	438	50506297
Neutrophil Pelger-Huet anomaly present	15.26	11.51	6	98383	86	50506649
Orthopnoea	15.24	11.51	34	98355	5655	50501080
Blood calcium increased	15.22	11.51	41	98348	7678	50499057
Ocular vasculitis	15.21	11.51	5	98384	41	50506694
Kidney fibrosis	15.08	11.51	17	98372	1572	50505163
Acute promyelocytic leukaemia	15.02	11.51	13	98376	871	50505864
Dyspnoea exertional	14.98	11.51	159	98230	51074	50455661
Radiculopathy	14.93	11.51	31	98358	4910	50501825
Cytogenetic analysis abnormal	14.81	11.51	12	98377	734	50506001
Jugular vein thrombosis	14.80	11.51	22	98367	2674	50504061
Polyglandular autoimmune syndrome type II	14.80	11.51	5	98384	45	50506690
Infusion site pain	14.77	11.51	3	98386	12343	50494392
Toxic nodular goitre	14.57	11.51	4	98385	16	50506719
Humerus fracture	14.55	11.51	40	98349	7578	50499157
Mean cell volume increased	14.55	11.51	23	98366	2949	50503786
Drug ineffective for unapproved indication	14.53	11.51	12	98377	21269	50485466
Malignant neoplasm of pleura	14.51	11.51	5	98384	48	50506687
Pulmonary arterial hypertension	14.45	11.51	11	98378	20308	50486427
Hypervolaemia	14.39	11.51	17	98372	25482	50481253
Aortic arteriosclerosis	14.24	11.51	32	98357	5350	50501385
Swollen tongue	14.20	11.51	21	98368	28609	50478126
Psychomotor disadaptation syndrome	14.20	11.51	4	98385	18	50506717
Soft tissue inflammation	14.15	11.51	8	98381	268	50506467
B-cell lymphoma stage III	14.02	11.51	4	98385	19	50506716
Actinomycosis	14.00	11.51	13	98376	956	50505779
Paralysis recurrent laryngeal nerve	13.99	11.51	5	98384	54	50506681
Paraesthesia	13.97	11.51	319	98070	119924	50386811
Cyanosis	13.96	11.51	6	98383	15178	50491557
Angioedema	13.95	11.51	33	98356	37643	50469092
Libido decreased	13.93	11.51	20	98369	2356	50504379
Uterine mass	13.86	11.51	8	98381	279	50506456
Lymphatic obstruction	13.85	11.51	4	98385	20	50506715
Corneal infection	13.83	11.51	5	98384	56	50506679
Chronic kidney disease	13.81	11.51	36	98353	39735	50467000
Lung opacity	13.66	11.51	18	98371	1955	50504780
Primary pulmonary melanoma	13.66	11.51	3	98386	3	50506732
Bone erosion	13.65	11.51	3	98386	11684	50495051
Ovarian disorder	13.60	11.51	11	98378	671	50506064
Prescribed underdose	13.59	11.51	7	98382	15942	50490793
Superior vena cava occlusion	13.59	11.51	5	98384	59	50506676
Right ventricular failure	13.51	11.51	7	98382	15886	50490849
Groin pain	13.48	11.51	43	98346	8848	50497887
Chest wall mass	13.37	11.51	5	98384	62	50506673
Papillary thyroid cancer	13.37	11.51	18	98371	1997	50504738
Premature labour	13.30	11.51	3	98386	11473	50495262
Cardiac valve sclerosis	13.24	11.51	4	98385	24	50506711
Aphthous ulcer	13.20	11.51	48	98341	10549	50496186
Peritoneal lesion	13.20	11.51	3	98386	4	50506731
Joint range of motion decreased	13.19	11.51	10	98379	18502	50488233
Cachexia	13.18	11.51	28	98361	4505	50502230
Denture wearer	13.18	11.51	7	98382	207	50506528
Hilar lymphadenopathy	13.14	11.51	13	98376	1034	50505701
Ovarian cancer recurrent	13.06	11.51	12	98377	870	50505865
Eating disorder	13.06	11.51	62	98327	15347	50491388
Creatinine renal clearance increased	12.98	11.51	10	98379	568	50506167
Poisoning	12.97	11.51	4	98385	12425	50494310
Spondylitic myelopathy	12.97	11.51	4	98385	26	50506709
Blood phosphorus decreased	12.92	11.51	25	98364	3764	50502971
Bone cancer metastatic	12.83	11.51	6	98383	134	50506601
Fibrous histiocytoma	12.69	11.51	9	98380	450	50506285
Chronic obstructive pulmonary disease	12.69	11.51	57	98332	53378	50453357
Dyspepsia	12.48	11.51	208	98181	73889	50432846
Grip strength decreased	12.47	11.51	4	98385	12117	50494618
Progesterone abnormal	12.45	11.51	3	98386	6	50506729
Nitrituria	12.45	11.51	3	98386	6	50506729
Rectosigmoid cancer recurrent	12.45	11.51	3	98386	6	50506729
Coagulopathy	12.40	11.51	10	98379	17934	50488801
Cellulitis	12.39	11.51	200	98189	70598	50436137
Emotional distress	12.38	11.51	23	98366	28640	50478095
Device malfunction	12.36	11.51	7	98382	15114	50491621
Post procedural complication	12.33	11.51	7	98382	15097	50491638
Gastroenteritis viral	12.33	11.51	11	98378	18775	50487960
Malignant neoplasm of choroid	12.14	11.51	3	98386	7	50506728
Mediastinal disorder	12.13	11.51	8	98381	355	50506380
Posterior reversible encephalopathy syndrome	12.07	11.51	7	98382	14921	50491814
Metastases to soft tissue	12.07	11.51	6	98383	154	50506581
Limb injury	11.97	11.51	13	98376	20237	50486498
Altered state of consciousness	11.95	11.51	15	98374	21895	50484840
Supraventricular tachyarrhythmia	11.94	11.51	5	98384	85	50506650
Tooth development disorder	11.94	11.51	4	98385	35	50506700
Congenital haematological disorder	11.94	11.51	4	98385	35	50506700
Change of bowel habit	11.93	11.51	16	98373	1768	50504967
Pustule	11.86	11.51	13	98376	1165	50505570
White blood cell count abnormal	11.86	11.51	30	98359	5410	50501325
Anaphylactic shock	11.85	11.51	13	98376	20142	50486593
Lymphangitis	11.84	11.51	11	98378	809	50505926
KL-6 increased	11.84	11.51	4	98385	36	50506699
Subclavian vein thrombosis	11.83	11.51	16	98373	1783	50504952
Disability	11.83	11.51	5	98384	12770	50493965
Psychotic disorder	11.82	11.51	15	98374	21797	50484938
Bone cancer	11.78	11.51	13	98376	1174	50505561
Blood oestrogen increased	11.78	11.51	5	98384	88	50506647
Obstructive airways disorder	11.75	11.51	8	98381	15644	50491091
Pneumocystis jirovecii pneumonia	11.68	11.51	7	98382	14656	50492079
Vertigo	11.67	11.51	153	98236	51679	50455056
Acute cutaneous lupus erythematosus	11.66	11.51	7	98382	263	50506472
Hyponatraemia	11.64	11.51	125	98264	96014	50410721
Red blood cell poikilocytes present	11.59	11.51	3	98386	9	50506726
Inferior vena caval occlusion	11.59	11.51	3	98386	9	50506726
Polychromic red blood cells present	11.59	11.51	3	98386	9	50506726
Actinic elastosis	11.59	11.51	3	98386	9	50506726
Monoplegia	11.56	11.51	20	98369	2763	50503972
Fear	11.51	11.51	7	98382	14542	50492193

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
Product use issue	115.33	29.02	48	926	51396	29522157
Metastases to lung	63.08	29.02	19	955	7836	29565717
Epiphysiolysis	46.32	29.02	7	967	98	29573455
Hyporesponsive to stimuli	42.02	29.02	9	965	942	29572611
Hot flush	36.93	29.02	15	959	14855	29558698
Drug exposure before pregnancy	35.05	29.02	4	970	3	29573550
Wrong patient received product	34.19	29.02	9	965	2273	29571280
Neoplasm progression	33.68	29.02	15	959	18597	29554956
PIK3CA-activated mutation	31.64	29.02	5	969	95	29573458
Breast cancer recurrent	30.13	29.02	4	970	20	29573533
Pathological fracture	29.52	29.02	9	965	3846	29569707
Multiple congenital abnormalities	29.14	29.02	6	968	518	29573035

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
Neoplasm progression	1726.68	12.02	873	73368	40091	64384400
Metastases to bone	1418.06	12.02	615	73626	19820	64404671
Neutropenia	1362.29	12.02	1521	72720	238103	64186388
White blood cell count decreased	1028.64	12.02	1078	73163	156759	64267732
Malignant neoplasm progression	968.09	12.02	896	73345	111975	64312516
Metastases to liver	804.96	12.02	439	73802	23502	64400989
Fatigue	576.87	12.02	2026	72215	746704	63677787
Hot flush	562.82	12.02	449	73792	45786	64378705
Breast cancer metastatic	517.44	12.02	222	74019	6947	64417544
Alopecia	513.12	12.02	781	73460	164909	64259582
Osteonecrosis of jaw	403.87	12.02	348	73893	39477	64385014
Tumour marker increased	398.85	12.02	150	74091	3300	64421191
Metastases to lung	394.94	12.02	236	74005	15028	64409463
Disease progression	367.14	12.02	616	73625	141064	64283427
Drug ineffective	342.05	12.02	281	73960	839966	63584525
Bone pain	341.66	12.02	343	73898	47229	64377262
Metastases to lymph nodes	338.38	12.02	176	74065	8541	64415950
Carbohydrate antigen 15-3 increased	300.32	12.02	89	74152	898	64423593
Breast cancer recurrent	283.04	12.02	108	74133	2475	64422016
Completed suicide	219.52	12.02	9	74232	224405	64200086
Nausea	218.68	12.02	1597	72644	784203	63640288
Breast cancer	208.91	12.02	210	74031	28938	64395553
Toxicity to various agents	197.10	12.02	86	74155	363427	64061064
Full blood count abnormal	194.46	12.02	204	74037	29553	64394938
Bone lesion	194.45	12.02	102	74139	5035	64419456
Skin hypopigmentation	190.63	12.02	61	74180	810	64423681
Neutrophil count decreased	176.67	12.02	318	73923	76878	64347613
Second primary malignancy	172.15	12.02	130	74111	12207	64412284
Osteonecrosis	148.93	12.02	173	74068	28056	64396435
Neuropathy peripheral	138.95	12.02	371	73870	117154	64307337
Stomatitis	138.78	12.02	355	73886	109250	64315241
PIK3CA-activated mutation	132.52	12.02	41	74200	484	64424007
Metastases to skin	131.89	12.02	53	74188	1399	64423092
Leukopenia	130.34	12.02	330	73911	100912	64323579
Arthralgia	121.22	12.02	897	73344	441363	63983128
Therapeutic product effect decreased	118.52	12.02	3	74238	115348	64309143
Decreased appetite	117.83	12.02	636	73605	280653	64143838
Hypotension	116.72	12.02	161	74080	380813	64043678
Metastases to spine	114.64	12.02	64	74177	3579	64420912
Metastases to pleura	110.90	12.02	45	74196	1219	64423272
Full blood count decreased	110.20	12.02	133	74108	22449	64402042
Lymphoedema	109.46	12.02	91	74150	9814	64414677
Infusion related reaction	107.97	12.02	28	74213	164439	64260052
Drug interaction	106.95	12.02	157	74084	361926	64062565
Carcinoembryonic antigen increased	106.23	12.02	49	74192	1824	64422667
Drug hypersensitivity	104.52	12.02	73	74168	237742	64186749
Off label use	102.62	12.02	379	73862	632427	63792064
Rheumatoid arthritis	102.22	12.02	31	74210	164263	64260228
Metastases to central nervous system	101.07	12.02	101	74140	13811	64410680
Drug abuse	98.21	12.02	17	74224	132357	64292134
Red blood cell count decreased	97.75	12.02	189	74052	48197	64376294
Diarrhoea	97.53	12.02	1263	72978	721441	63703050
Dry skin	95.11	12.02	193	74048	50968	64373523
Pseudocirrhosis	92.96	12.02	33	74208	612	64423879
Nail disorder	92.75	12.02	78	74163	8546	64415945
Metastasis	90.70	12.02	65	74176	5630	64418861
Tooth extraction	87.47	12.02	79	74162	9522	64414969
Contraindicated product administered	86.55	12.02	11	74230	107818	64316673
Overdose	82.84	12.02	40	74201	159526	64264965
Ejection fraction decreased	82.55	12.02	131	74110	28576	64395915
Constipation	81.18	12.02	496	73745	228841	64195650
Cardiac arrest	77.90	12.02	40	74201	154024	64270467
Bone disorder	75.79	12.02	95	74146	16664	64407827
Joint swelling	75.38	12.02	82	74159	215300	64209191
Intentional overdose	75.11	12.02	8	74233	89936	64334555
Maternal exposure during pregnancy	74.07	12.02	11	74230	95873	64328618
Progesterone increased	73.79	12.02	16	74225	35	64424456
Ovarian hyperstimulation syndrome	73.60	12.02	44	74197	2801	64421690
Pleural effusion	73.02	12.02	314	73927	126245	64298246
Malignant pleural effusion	71.89	12.02	44	74197	2923	64421568
Haematotoxicity	69.63	12.02	80	74161	12816	64411675
Mucosal dryness	68.89	12.02	43	74198	2958	64421533
Oral pain	65.08	12.02	115	74126	27378	64397113
Thrombocytopenia	64.59	12.02	460	73781	223341	64201150
Metastases to the mediastinum	64.57	12.02	24	74217	510	64423981
Systemic lupus erythematosus	64.56	12.02	7	74234	77605	64346886
Hepatic lesion	63.30	12.02	53	74188	5771	64418720
Lymphangiosis carcinomatosa	62.84	12.02	34	74207	1787	64422704
Gastrointestinal haemorrhage	61.63	12.02	38	74203	132274	64292217
Hypersensitivity	61.09	12.02	82	74159	196370	64228121
Taste disorder	60.41	12.02	64	74177	9369	64415122
Cardio-respiratory arrest	60.40	12.02	19	74222	98374	64326117
Trigger finger	60.01	12.02	42	74199	3503	64420988
Spinal pain	59.40	12.02	73	74168	12548	64411943
Dysgeusia	59.09	12.02	152	74089	46895	64377596
Seizure	58.98	12.02	63	74178	166829	64257662
Treatment failure	58.05	12.02	31	74210	116785	64307706
Madarosis	57.60	12.02	35	74206	2295	64422196
Pleural neoplasm	57.54	12.02	18	74223	221	64424270
Intentional product use issue	57.50	12.02	19	74222	95345	64329146
Invasive ductal breast carcinoma	57.12	12.02	47	74194	4995	64419496
Arthropathy	55.98	12.02	35	74206	120932	64303559
Synovitis	55.91	12.02	22	74219	99068	64325423
Pneumonia	55.89	12.02	396	73845	559180	63865311
Injection site erythema	54.96	12.02	8	74233	70792	64353699
Epistaxis	54.70	12.02	241	74000	97890	64326601
Pulmonary embolism	53.93	12.02	320	73921	146036	64278455
Palmar-plantar erythrodysaesthesia syndrome	52.70	12.02	108	74133	28711	64395780
Breast pain	52.65	12.02	52	74189	7009	64417482
Respiratory failure	52.45	12.02	65	74176	161118	64263373
Bone marrow failure	52.25	12.02	147	74094	47805	64376686
Injection site pain	51.88	12.02	32	74209	111376	64313115
Asthenia	51.68	12.02	734	73507	427310	63997181
Condition aggravated	50.88	12.02	238	74003	372188	64052303
Suicide attempt	50.76	12.02	10	74231	70997	64353494
Multiple organ dysfunction syndrome	50.26	12.02	27	74214	101386	64323105
Coronary artery disease	46.51	12.02	7	74234	60426	64364065
Back pain	46.01	12.02	465	73776	249706	64174785
Coma	45.39	12.02	22	74219	87593	64336898
Breast mass	45.07	12.02	42	74199	5268	64419223
Anaemia	44.34	12.02	646	73595	378034	64046457
Septic shock	44.15	12.02	34	74207	105403	64319088
Metastases to ovary	43.91	12.02	15	74226	247	64424244
Hepatorenal failure	43.58	12.02	23	74218	1149	64423342
Device related thrombosis	43.19	12.02	28	74213	2057	64422434
Myocardial infarction	43.15	12.02	78	74163	165743	64258748
Oxygen saturation decreased	43.08	12.02	36	74205	107140	64317351
Metabolic acidosis	43.02	12.02	14	74227	70944	64353547
Drug reaction with eosinophilia and systemic symptoms	42.38	12.02	6	74235	54211	64370280
Metastases to chest wall	41.59	12.02	16	74225	375	64424116
BRCA1 gene mutation	41.41	12.02	9	74232	20	64424471
Lymphadenopathy	41.31	12.02	133	74108	46553	64377938
Pneumonia aspiration	41.02	12.02	9	74232	59262	64365229
Pericarditis	40.32	12.02	11	74230	62505	64361986
Osteolysis	40.13	12.02	30	74211	2773	64421718
Metastases to peritoneum	40.05	12.02	33	74208	3514	64420977
Metastases to meninges	40.01	12.02	30	74211	2785	64421706
Ascites	39.79	12.02	159	74082	61842	64362649
Electrocardiogram PR shortened	39.52	12.02	14	74227	258	64424233
Orthostatic hypotension	39.42	12.02	4	74237	46734	64377757
Nail dystrophy	39.14	12.02	19	74222	794	64423697
Respiratory arrest	38.85	12.02	7	74234	52978	64371513
Gingivitis	38.82	12.02	46	74195	7613	64416878
Exposed bone in jaw	38.45	12.02	32	74209	3455	64421036
Onychoclasis	38.36	12.02	36	74205	4556	64419935
Hepatotoxicity	38.26	12.02	117	74124	39845	64384646
Isosthenuria	38.04	12.02	11	74230	101	64424390
Exposure during pregnancy	38.02	12.02	21	74220	77654	64346837
Delirium	37.99	12.02	16	74225	69178	64355313
Metastases to bladder	37.83	12.02	13	74228	218	64424273
Skin weeping	37.51	12.02	17	74224	607	64423884
Pathological fracture	37.49	12.02	49	74192	8956	64415535
Breast cancer female	36.98	12.02	37	74204	5066	64419425
Polyneuropathy	36.90	12.02	75	74166	19819	64404672
Injection site reaction	36.86	12.02	5	74236	46659	64377832
Encephalopathy	36.74	12.02	11	74230	58808	64365683
Thoracic vertebral fracture	36.71	12.02	35	74206	4518	64419973
Metastases to stomach	36.43	12.02	13	74228	245	64424246
Musculoskeletal chest pain	36.36	12.02	78	74163	21401	64403090
Unevaluable event	36.32	12.02	7	74234	50482	64374009
Loss of consciousness	35.80	12.02	73	74168	148292	64276199
Wrong technique in product usage process	35.71	12.02	15	74226	64959	64359532
Wound	35.55	12.02	22	74219	76455	64348036
Bradycardia	35.07	12.02	51	74190	118168	64306323
Generalised tonic-clonic seizure	34.71	12.02	3	74238	39854	64384637
Osteoma cutis	34.61	12.02	6	74235	0	64424491
Metastases to eye	34.24	12.02	12	74229	214	64424277
Psoriasis	34.21	12.02	20	74221	71683	64352808
Multiple sclerosis relapse	33.48	12.02	4	74237	41131	64383360
Metastases to pelvis	33.43	12.02	15	74226	523	64423968
Gastroenteritis radiation	33.38	12.02	16	74225	650	64423841
Carbohydrate antigen 125 increased	33.00	12.02	23	74218	1905	64422586
Bone sequestrum	32.61	12.02	19	74222	1153	64423338
Cardiac failure congestive	32.58	12.02	63	74178	130517	64293974
Sinusitis	32.56	12.02	75	74166	145853	64278638
Sequestrectomy	32.54	12.02	17	74224	832	64423659
Urinary tract inflammation	32.33	12.02	9	74232	71	64424420
Aggression	32.03	12.02	7	74234	46225	64378266
Cytomegalovirus infection	31.85	12.02	3	74238	37196	64387295
Mucosal inflammation	31.37	12.02	149	74092	62435	64362056
Pyelitis	31.36	12.02	12	74229	277	64424214
Neoplasm malignant	31.24	12.02	80	74161	24608	64399883
Tumour marker decreased	31.22	12.02	8	74233	44	64424447
Hallucination	31.07	12.02	23	74218	72765	64351726
Injection site bruising	30.97	12.02	3	74238	36370	64388121
Unresponsive to stimuli	30.44	12.02	10	74231	50383	64374108
Hypermetabolism	30.43	12.02	12	74229	301	64424190
Bone trimming	30.22	12.02	7	74234	23	64424468
Invasive lobular breast carcinoma	30.10	12.02	14	74227	531	64423960
Electrocardiogram QT prolonged	30.07	12.02	175	74066	79273	64345218
Gamma-glutamyltransferase increased	30.01	12.02	123	74118	48387	64376104
Decreased immune responsiveness	29.95	12.02	31	74210	4417	64420074
Plasma cell myeloma	29.92	12.02	8	74233	46067	64378424
Hyperkalaemia	29.63	12.02	44	74197	101085	64323406
Agitation	29.41	12.02	35	74206	88332	64336159
Tachycardia	29.40	12.02	82	74159	149497	64274994
Ovarian rupture	29.35	12.02	7	74234	27	64424464
Cancer pain	29.26	12.02	30	74211	4227	64420264
Lacrimation increased	29.21	12.02	65	74176	18281	64406210
Skin toxicity	29.17	12.02	37	74204	6565	64417926
Pneumonitis	29.05	12.02	125	74116	50240	64374251
Anaphylactic reaction	28.92	12.02	22	74219	68642	64355849
Keloid scar	28.66	12.02	9	74232	112	64424379
Blood pressure fluctuation	28.47	12.02	12	74229	51859	64372632
Elliptocytosis	28.39	12.02	7	74234	32	64424459
Myalgia	28.25	12.02	293	73948	158324	64266167
Dental fistula	27.96	12.02	13	74228	493	64423998
Therapy non-responder	27.90	12.02	21	74220	65878	64358613
Mental status changes	27.87	12.02	18	74223	61144	64363347
Drug dependence	27.71	12.02	3	74238	33309	64391182
Depressed level of consciousness	27.37	12.02	32	74209	81404	64343087
Adverse event	27.32	12.02	6	74235	39483	64385008
Irritable bowel syndrome	27.26	12.02	5	74236	37364	64387127
Recall phenomenon	27.17	12.02	16	74225	990	64423501
Therapeutic product effect incomplete	26.62	12.02	49	74192	103433	64321058
Urticaria	26.61	12.02	84	74157	147233	64277258
Bladder hypertrophy	26.61	12.02	13	74228	551	64423940
Acute kidney injury	26.54	12.02	361	73880	448879	63975612
Mouth swelling	26.43	12.02	31	74210	5076	64419415
Bone debridement	26.36	12.02	12	74229	433	64424058
Cutaneous lupus erythematosus	26.28	12.02	23	74218	2659	64421832
Pleural disorder	26.19	12.02	14	74227	718	64423773
Injury	26.17	12.02	16	74225	55976	64368515
Superinfection	26.02	12.02	27	74214	3859	64420632
Osteitis	25.76	12.02	26	74215	3596	64420895
Osteomyelitis	25.69	12.02	80	74161	27507	64396984
Hypoglycaemia	25.48	12.02	40	74201	89852	64334639
Heart rate decreased	25.37	12.02	16	74225	55051	64369440
Hypoxia	25.20	12.02	39	74202	88110	64336381
Nephrosclerosis	25.17	12.02	18	74223	1553	64422938
Acute myocardial infarction	24.97	12.02	26	74215	69692	64354799
Osteosclerosis	24.75	12.02	25	74216	3461	64421030
Intentional product misuse	24.74	12.02	28	74213	72267	64352224
Blood calcium increased	24.58	12.02	39	74202	8503	64415988
Cough	24.54	12.02	486	73755	301662	64122829
Duodenal ulcer perforation	24.48	12.02	5	74236	34620	64389871
Postmenopausal haemorrhage	24.29	12.02	17	74224	1418	64423073
Rhabdomyolysis	23.98	12.02	43	74198	91683	64332808
Breast cancer stage IV	23.84	12.02	12	74229	543	64423948
Paraesthesia	23.72	12.02	248	73993	134274	64290217
CYP3A4 polymorphism	23.67	12.02	7	74234	70	64424421
Hormone receptor positive breast cancer	23.44	12.02	10	74231	308	64424183
Peri-implantitis	23.42	12.02	6	74235	33	64424458
Macular hole	23.38	12.02	13	74228	721	64423770
Vitiligo	23.27	12.02	18	74223	1750	64422741
Dental care	23.27	12.02	13	74228	728	64423763
Drug withdrawal syndrome	23.23	12.02	4	74237	31287	64393204
C-reactive protein abnormal	23.21	12.02	3	74238	29044	64395447
Nail growth abnormal	23.09	12.02	11	74230	441	64424050
Ovarian fibrosis	23.07	12.02	4	74237	0	64424491
Multiple pregnancy	22.84	12.02	6	74235	37	64424454
Ovarian disorder	22.79	12.02	11	74230	454	64424037
White blood cell count abnormal	22.72	12.02	28	74213	4826	64419665
Dysarthria	22.60	12.02	21	74220	59385	64365106
Tongue discomfort	22.60	12.02	19	74222	2080	64422411
Skin exfoliation	22.59	12.02	107	74134	44778	64379713
Renal failure	22.53	12.02	120	74121	181568	64242923
Insomnia	22.50	12.02	336	73905	197500	64226991
Malignant peritoneal neoplasm	22.24	12.02	12	74229	627	64423864
Hair texture abnormal	22.17	12.02	22	74219	2982	64421509
Adjusted calcium decreased	22.16	12.02	8	74233	156	64424335
Aspartate aminotransferase increased	22.14	12.02	223	74018	119565	64304926
Blood pressure decreased	22.01	12.02	41	74200	86158	64338333
Metastases to spinal cord	21.94	12.02	6	74235	44	64424447
Syncope	21.91	12.02	100	74141	157535	64266956
Vitreous detachment	21.77	12.02	18	74223	1926	64422565
Wheezing	21.77	12.02	37	74204	80542	64343949
Respiratory distress	21.74	12.02	17	74224	52314	64372177
Nail avulsion	21.47	12.02	7	74234	99	64424392
Biopsy bone abnormal	21.45	12.02	5	74236	17	64424474
Dyspepsia	21.36	12.02	162	74079	80150	64344341
Blood alkaline phosphatase increased	21.32	12.02	124	74117	56155	64368336
Knee arthroplasty	21.07	12.02	3	74238	26996	64397495
Medication error	21.05	12.02	16	74225	49950	64374541
Body surface area decreased	21.02	12.02	5	74236	19	64424472
Pulmonary mass	20.86	12.02	68	74173	23948	64400543
Lymphadenopathy mediastinal	20.85	12.02	24	74217	3852	64420639
Fall	20.80	12.02	346	73895	416480	64008011
Loss of personal independence in daily activities	20.76	12.02	32	74209	72422	64352069
Skin lesion	20.62	12.02	90	74151	36392	64388099
Jaw disorder	20.60	12.02	26	74215	4591	64419900
Therapy cessation	20.58	12.02	83	74158	32406	64392085
Tumour marker abnormal	20.50	12.02	8	74233	195	64424296
Cardiogenic shock	20.36	12.02	6	74235	32421	64392070
Swelling	20.32	12.02	105	74136	160113	64264378
Drug level increased	20.28	12.02	7	74234	34189	64390302
Blood pressure increased	20.28	12.02	116	74125	172436	64252055
Gait deviation	20.12	12.02	6	74235	62	64424429
Neoplasm	20.09	12.02	32	74209	6999	64417492
Haematuria	20.06	12.02	24	74217	60447	64364044
Hepatic enzyme increased	19.54	12.02	80	74161	129863	64294628
Chronic cutaneous lupus erythematosus	19.53	12.02	8	74233	222	64424269
Vulvovaginal inflammation	19.51	12.02	10	74231	470	64424021
Mastectomy	19.46	12.02	13	74228	1005	64423486
Therapy partial responder	19.44	12.02	39	74202	10209	64414282
Myelosuppression	19.39	12.02	66	74175	23764	64400727
Antisynthetase syndrome	19.23	12.02	7	74234	140	64424351
Nail toxicity	19.22	12.02	9	74232	347	64424144
Bone marrow infiltration	19.09	12.02	10	74231	492	64423999
Child-Pugh-Turcotte score abnormal	19.04	12.02	4	74237	7	64424484
Aortic thrombosis	19.03	12.02	15	74226	1499	64422992
Transaminases	18.94	12.02	6	74235	77	64424414
SAPHO syndrome	18.91	12.02	7	74234	147	64424344
Anisocytosis	18.89	12.02	12	74229	851	64423640
Emotional distress	18.74	12.02	9	74232	36029	64388462
Heart rate increased	18.72	12.02	55	74186	98620	64325871
RET gene mutation	18.69	12.02	4	74237	8	64424483
Gingival erythema	18.61	12.02	10	74231	518	64423973
Myeloproliferative neoplasm	18.57	12.02	12	74229	877	64423614
Cytopenia	18.41	12.02	49	74192	15422	64409069
Muscle injury	18.32	12.02	4	74237	26433	64398058
Trichorrhexis	18.27	12.02	11	74230	709	64423782
Abdominal lymphadenopathy	18.27	12.02	13	74228	1113	64423378
Triple negative breast cancer	18.20	12.02	6	74235	88	64424403
Hydronephrosis	18.11	12.02	46	74195	14079	64410412
Staphylococcal infection	18.03	12.02	19	74222	50659	64373832
Meningeal disorder	17.94	12.02	9	74232	404	64424087
Metastases to thorax	17.81	12.02	7	74234	174	64424317
Epiphysiolysis	17.78	12.02	6	74235	95	64424396
Blister	17.74	12.02	42	74199	80925	64343566
B-cell lymphoma stage III	17.54	12.02	4	74237	12	64424479
Somnolence	17.49	12.02	150	74091	203495	64220996
Drug ineffective for unapproved indication	17.41	12.02	7	74234	31126	64393365
Hydroxyproline increased	17.31	12.02	3	74238	0	64424491
Purulent discharge	17.20	12.02	26	74215	5435	64419056
Confusional state	17.19	12.02	205	74036	260939	64163552
Cellulitis	17.14	12.02	174	74067	93483	64331008
Flushing	17.07	12.02	41	74200	78607	64345884
Angioedema	17.06	12.02	28	74213	61793	64362698
Mucosal hypertrophy	17	12.02	5	74236	49	64424442
Hypersensitivity vasculitis	16.93	12.02	29	74212	6732	64417759
Invasive breast carcinoma	16.77	12.02	9	74232	465	64424026
Adjusted calcium increased	16.73	12.02	5	74236	52	64424439
No adverse event	16.67	12.02	6	74235	28555	64395936
Dental discomfort	16.67	12.02	8	74233	326	64424165
Bone marrow oedema syndrome	16.65	12.02	4	74237	16	64424475
Coagulopathy	16.55	12.02	8	74233	31912	64392579
Pancreatitis acute	16.48	12.02	15	74226	42840	64381651
Metastases to uterus	16.32	12.02	5	74236	57	64424434
Gastrointestinal toxicity	16.29	12.02	25	74216	5297	64419194
Visual impairment	16.23	12.02	143	74098	73934	64350557
Hyponatraemia	16.23	12.02	102	74139	148237	64276254
Chronic kidney disease	16.20	12.02	26	74215	57893	64366598
Injection site haemorrhage	16.17	12.02	4	74237	24274	64400217
Dyskinesia	16.11	12.02	13	74228	39375	64385116
Dysaesthesia	16.05	12.02	24	74217	4971	64419520
Thirst	16.05	12.02	44	74197	14093	64410398
Debridement	16.04	12.02	14	74227	1612	64422879
Pustule	16.04	12.02	13	74228	1352	64423139
Dilatation ventricular	16.02	12.02	21	74220	3849	64420642
Blood pressure systolic increased	16.01	12.02	20	74221	49433	64375058
Vomiting	15.92	12.02	781	73460	550336	63874155
Paraneoplastic syndrome	15.88	12.02	11	74230	902	64423589
Acute promyelocytic leukaemia	15.85	12.02	13	74228	1375	64423116
Pneumocystis jirovecii pneumonia	15.81	12.02	6	74235	27628	64396863
Pancreatic neoplasm	15.80	12.02	13	74228	1382	64423109
Plastic surgery	15.79	12.02	5	74236	64	64424427
Fibrous histiocytoma	15.69	12.02	9	74232	530	64423961
Congestive hepatopathy	15.59	12.02	21	74220	3952	64420539
Glossodynia	15.45	12.02	32	74209	64664	64359827
Right ventricular failure	15.39	12.02	3	74238	21468	64403023
Sedation	15.37	12.02	15	74226	41447	64383044
Asthma	15.36	12.02	57	74184	95168	64329323
Subclavian vein thrombosis	15.35	12.02	16	74225	2298	64422193
Acute respiratory failure	15.34	12.02	21	74220	49913	64374578
Jaw operation	15.25	12.02	10	74231	749	64423742
Primary pulmonary melanoma	15.23	12.02	3	74238	3	64424488
Upper gastrointestinal haemorrhage	15.20	12.02	11	74230	35209	64389282
Fractured sacrum	15.16	12.02	13	74228	1462	64423029
Adenocarcinoma	15.15	12.02	19	74222	3332	64421159
Breast discharge	15.12	12.02	9	74232	568	64423923
Vertigo	15.11	12.02	118	74123	58893	64365598
Neoplasm recurrence	15.03	12.02	20	74221	3719	64420772
Pain in jaw	14.92	12.02	89	74152	40666	64383825
Haematochezia	14.88	12.02	34	74207	66339	64358152
Angina pectoris	14.84	12.02	18	74223	45063	64379428
Hydrothorax	14.83	12.02	12	74229	1245	64423246
Androgenetic alopecia	14.80	12.02	6	74235	162	64424329
Tooth resorption	14.79	12.02	4	74237	28	64424463
Toothache	14.78	12.02	49	74192	17410	64407081
Discomfort	14.68	12.02	46	74195	80832	64343659
Granulocyte count decreased	14.68	12.02	12	74229	1264	64423227
Psychomotor disadaptation syndrome	14.67	12.02	4	74237	29	64424462
Change of bowel habit	14.66	12.02	16	74225	2422	64422069
Depressed mood	14.65	12.02	89	74152	40923	64383568
Jugular vein thrombosis	14.65	12.02	20	74221	3811	64420680
Infection	14.64	12.02	139	74102	184741	64239750
Sopor	14.54	12.02	8	74233	29653	64394838
Cor pulmonale acute	14.50	12.02	9	74232	613	64423878
Ventricular tachycardia	14.40	12.02	11	74230	34254	64390237
Gastrointestinal disorder	14.27	12.02	54	74187	89655	64334836
Prescribed overdose	14.24	12.02	3	74238	20328	64404163
Bone cancer metastatic	14.21	12.02	6	74235	180	64424311
Hospitalisation	14.20	12.02	42	74199	75165	64349326
Creatinine renal clearance increased	14.16	12.02	10	74231	846	64423645
Mobility decreased	14.09	12.02	51	74190	85789	64338702
Ill-defined disorder	14.07	12.02	18	74223	44034	64380457
Neutrophil count abnormal	14.03	12.02	17	74224	2879	64421612
Product dose omission in error	14.02	12.02	16	74225	2543	64421948
Progesterone abnormal	14.02	12.02	3	74238	6	64424485
Congenital haematological disorder	14.00	12.02	4	74237	35	64424456
Shock	13.99	12.02	14	74227	38226	64386265
Ventricular fibrillation	13.95	12.02	5	74236	23855	64400636
Disorientation	13.86	12.02	27	74214	55801	64368690
Poisoning	13.83	12.02	4	74237	21875	64402616
Incorrect dose administered	13.73	12.02	31	74210	60734	64363757
Altered state of consciousness	13.72	12.02	14	74227	37888	64386603
Carcinoid tumour pulmonary	13.72	12.02	7	74234	326	64424165
Anaphylactic shock	13.71	12.02	9	74232	30319	64394172
Toxic nodular goitre	13.71	12.02	4	74237	38	64424453
Blood phosphorus decreased	13.67	12.02	24	74217	5681	64418810
Transaminases increased	13.61	12.02	93	74148	44501	64379990
Withdrawal syndrome	13.60	12.02	5	74236	23487	64401004
Joint stiffness	13.53	12.02	70	74171	30334	64394157
Aphthous ulcer	13.50	12.02	39	74202	12867	64411624
Clostridium difficile infection	13.50	12.02	13	74228	36150	64388341
Urinary tract infection	13.32	12.02	355	73886	231241	64193250
Actinomycosis	13.30	12.02	10	74231	932	64423559
Recurrent cancer	13.28	12.02	15	74226	2358	64422133
Tremor	13.26	12.02	108	74133	148122	64276369
Acute cutaneous lupus erythematosus	13.17	12.02	7	74234	355	64424136
Interstitial lung disease	13.13	12.02	171	74070	97561	64326930
Kidney fibrosis	13.11	12.02	17	74224	3084	64421407
Adverse drug reaction	13.10	12.02	20	74221	45444	64379047
Carbohydrate antigen 27.29 increased	13.02	12.02	4	74237	46	64424445
Bronchopulmonary aspergillosis	13.00	12.02	3	74238	19082	64405409
Superior vena cava occlusion	12.92	12.02	5	74236	119	64424372
Anuria	12.88	12.02	3	74238	18961	64405530
Pregnancy	12.85	12.02	4	74237	20861	64403630
Gingival swelling	12.83	12.02	19	74222	3901	64420590
Tooth development disorder	12.79	12.02	4	74237	49	64424442
Lymphopenia	12.79	12.02	61	74180	25596	64398895
Paralysis recurrent laryngeal nerve	12.77	12.02	5	74236	123	64424368
Alanine aminotransferase increased	12.77	12.02	228	74013	138803	64285688
Lung opacity	12.69	12.02	17	74224	3182	64421309
Platelet count decreased	12.68	12.02	267	73974	167444	64257047
Pericardial effusion	12.67	12.02	83	74158	39171	64385320
Metastases to breast	12.63	12.02	6	74235	239	64424252
Red blood cell poikilocytes present	12.49	12.02	3	74238	12	64424479
Polychromic red blood cells present	12.49	12.02	3	74238	12	64424479
Clostridium difficile colitis	12.42	12.02	8	74233	27215	64397276
Pulmonary hypertension	12.41	12.02	19	74222	43120	64381371
Blood creatine phosphokinase increased	12.33	12.02	31	74210	58527	64365964
KL-6 increased	12.31	12.02	4	74237	56	64424435
Mucosal pain	12.30	12.02	3	74238	13	64424478
Psychotic disorder	12.26	12.02	13	74228	34565	64389926
Cholangitis sclerosing	12.25	12.02	13	74228	1906	64422585
Folliculitis	12.21	12.02	10	74231	30067	64394424
HER2 positive breast cancer	12.14	12.02	6	74235	261	64424230
Toxic epidermal necrolysis	12.07	12.02	15	74226	37151	64387340
Lymphangioleiomyomatosis	12.04	12.02	5	74236	144	64424347

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	L02BG04	ANTINEOPLASTIC AND IMMUNOMODULATING AGENTS ENDOCRINE THERAPY HORMONE ANTAGONISTS AND RELATED AGENTS Aromatase inhibitors
FDA MoA	N0000175080	Aromatase Inhibitors
FDA EPC	N0000175563	Aromatase Inhibitor
MeSH PA	D000970	Antineoplastic Agents
MeSH PA	D047072	Aromatase Inhibitors
MeSH PA	D004791	Enzyme Inhibitors
MeSH PA	D004965	Estrogen Antagonists
MeSH PA	D006727	Hormone Antagonists
MeSH PA	D065088	Steroid Synthesis Inhibitors
CHEBI has role	CHEBI:35610	antineoplastic agents
CHEBI has role	CHEBI:50790	aromatase inhibitors

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

Disease	Relation	SNOMED_ID	DOID
Hormone receptor positive malignant neoplasm of breast	indication	417181009
Early Breast Cancer Hormone Receptor Positive and Postmenopausal	indication
Malignant tumor of ovary	off-label use	363443007	DOID:2394
Hypercholesterolemia	contraindication	13644009
Hyperbilirubinemia	contraindication	14783006	DOID:2741
Cirrhosis of liver	contraindication	19943007	DOID:5082
Hepatic failure	contraindication	59927004
Cerebrovascular disease	contraindication	62914000	DOID:6713
Osteoporosis	contraindication	64859006	DOID:11476
Liver function tests abnormal	contraindication	166603001
Pregnancy, function	contraindication	289908002
Osteopenia	contraindication	312894000
Thromboembolic disorder	contraindication	371039008
Cardiovascular event risk	contraindication	395112001
Dizziness	contraindication	404640003
Breastfeeding (mother)	contraindication	413712001

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	3.04	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
2.5MG;EQ 200MG BASE	KISQALI FEMARA CO-PACK (COPACKAGED)	NOVARTIS	N209935	May 4, 2017	RX	TABLET	ORAL	9416136	Aug. 20, 2029	AS INITIAL ENDOCRINE-BASED THERAPY FOR THE TREATMENT OF ADULT PATIENTS WITH HORMONE RECEPTOR (HR)-POSITIVE, HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 (HER2)-NEGATIVE ADVANCED OR METASTATIC BREAST CANCER
2.5MG;EQ 200MG BASE	KISQALI FEMARA CO-PACK (COPACKAGED)	NOVARTIS	N209935	May 4, 2017	RX	TABLET	ORAL	9416136	Aug. 20, 2029	TREATMENT OF PRE/PERIMENOPAUSAL WOMEN WITH HORMONE RECEPTOR (HR)-POSITIVE, HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 (HER2)-NEGATIVE ADVANCED OR METASTATIC BREAST CANCER
2.5MG;EQ 200MG BASE	KISQALI FEMARA CO-PACK (COPACKAGED)	NOVARTIS	N209935	May 4, 2017	RX	TABLET	ORAL	8962630	Dec. 9, 2029	AS INITIAL ENDOCRINE-BASED THERAPY FOR THE TREATMENT OF ADULT PATIENTS WITH HORMONE RECEPTOR (HR)-POSITIVE, HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 (HER2)-NEGATIVE ADVANCED OR METASTATIC BREAST CANCER
2.5MG;EQ 200MG BASE	KISQALI FEMARA CO-PACK (COPACKAGED)	NOVARTIS	N209935	May 4, 2017	RX	TABLET	ORAL	8962630	Dec. 9, 2029	TREATMENT OF PRE/PERIMENOPAUSAL WOMEN WITH HORMONE RECEPTOR (HR)-POSITIVE, HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 (HER2)-NEGATIVE ADVANCED OR METASTATIC BREAST CANCER
2.5MG;EQ 200MG BASE	KISQALI FEMARA CO-PACK (COPACKAGED)	NOVARTIS	N209935	May 4, 2017	RX	TABLET	ORAL	9868739	Nov. 9, 2031	AS INITIAL ENDOCRINE-BASED THERAPY FOR THE TREATMENT OF ADULT PATIENTS WITH HORMONE RECEPTOR (HR)-POSITIVE, HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 (HER2)-NEGATIVE ADVANCED OR METASTATIC BREAST CANCER
2.5MG;EQ 200MG BASE	KISQALI FEMARA CO-PACK (COPACKAGED)	NOVARTIS	N209935	May 4, 2017	RX	TABLET	ORAL	9868739	Nov. 9, 2031	TREATMENT OF PRE/PERIMENOPAUSAL WOMEN WITH HORMONE RECEPTOR (HR)-POSITIVE, HUMAN EPIDERMAL GROWTH FACTOR RECEPTOR 2 (HER2)-NEGATIVE ADVANCED OR METASTATIC BREAST CANCER

Orange Book exclusivity data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
2.5MG;EQ 200MG BASE	KISQALI FEMARA CO-PACK (COPACKAGED)	NOVARTIS	N209935	May 4, 2017	RX	TABLET	ORAL	March 13, 2022	NEW CHEMICAL ENTITY
2.5MG;EQ 200MG BASE	KISQALI FEMARA CO-PACK (COPACKAGED)	NOVARTIS	N209935	May 4, 2017	RX	TABLET	ORAL	Dec. 10, 2024	NEW PATIENT POPULATION

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Aromatase	Enzyme	P11511	CP19A_HUMAN	INHIBITOR	IC50	8.22	WOMBAT-PK	CHEMBL
Cytochrome P450 11B1, mitochondrial	Enzyme	P15538	C11B1_HUMAN		IC50	5.58	CHEMBL
Cytochrome P450 11B2, mitochondrial	Enzyme	P19099	C11B2_HUMAN		IC50	5.85	CHEMBL

External reference:

ID	Source
4021049	VUID
N0000148513	NUI
D00964	KEGG_DRUG
4021049	VANDF
C0246421	UMLSCUI
CHEBI:6413	CHEBI
CHEMBL1444	ChEMBL_ID
DB01006	DRUGBANK_ID
D000077289	MESH_DESCRIPTOR_UI
3902	PUBCHEM_CID
5209	IUPHAR_LIGAND_ID
7118	INN_ID
7LKK855W8I	UNII
72965	RXNORM
173561	MMSL
4963	MMSL
d04156	MMSL
006298	NDDF
108777007	SNOMEDCT_US
386911004	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Femara	HUMAN PRESCRIPTION DRUG LABEL	1	0078-0249	TABLET, FILM COATED	2.50 mg	ORAL	NDA	27 sections
Femara	HUMAN PRESCRIPTION DRUG LABEL	1	0078-0249	TABLET, FILM COATED	2.50 mg	ORAL	NDA	27 sections
Letrozole	HUMAN PRESCRIPTION DRUG LABEL	1	0093-7620	TABLET, FILM COATED	2.50 mg	ORAL	ANDA	26 sections
Letrozole	HUMAN PRESCRIPTION DRUG LABEL	1	0093-7620	TABLET, FILM COATED	2.50 mg	ORAL	ANDA	26 sections
Letrozole	HUMAN PRESCRIPTION DRUG LABEL	1	16729-034	TABLET, FILM COATED	2.50 mg	ORAL	ANDA	25 sections
Letrozole	HUMAN PRESCRIPTION DRUG LABEL	1	17856-0032	TABLET, FILM COATED	2.50 mg	ORAL	ANDA	25 sections
LETROZOLE	HUMAN PRESCRIPTION DRUG LABEL	1	24535-0801	TABLET, FILM COATED	2.50 mg	ORAL	ANDA	26 sections
LETROZOLE	Human Prescription Drug Label	1	24724-030	TABLET	2.50 mg	ORAL	ANDA	26 sections
Letrozole	HUMAN PRESCRIPTION DRUG LABEL	1	42254-243	TABLET, FILM COATED	2.50 mg	ORAL	ANDA	27 sections
Letrozole	HUMAN PRESCRIPTION DRUG LABEL	1	42291-374	TABLET, FILM COATED	2.50 mg	ORAL	ANDA	27 sections
Letrozole	HUMAN PRESCRIPTION DRUG LABEL	1	50090-3474	TABLET, FILM COATED	2.50 mg	ORAL	ANDA	25 sections
LETROZOLE	HUMAN PRESCRIPTION DRUG LABEL	1	50268-476	TABLET	2.50 mg	ORAL	ANDA	28 sections
LETROZOLE	HUMAN PRESCRIPTION DRUG LABEL	1	51991-759	TABLET	2.50 mg	ORAL	ANDA	28 sections
Femara	HUMAN PRESCRIPTION DRUG LABEL	1	54868-4151	TABLET, FILM COATED	2.50 mg	ORAL	NDA	26 sections
LETROZOLE	HUMAN PRESCRIPTION DRUG LABEL	1	54868-6252	TABLET, FILM COATED	2.50 mg	ORAL	ANDA	27 sections
Letrozole	HUMAN PRESCRIPTION DRUG LABEL	1	55111-646	TABLET, FILM COATED	2.50 mg	ORAL	ANDA	27 sections
LETROZOLE	HUMAN PRESCRIPTION DRUG LABEL	1	57884-2021	TABLET	2.50 mg	ORAL	ANDA	26 sections
Letrozole	Human Prescription Drug Label	1	59651-180	TABLET, FILM COATED	2.50 mg	ORAL	ANDA	27 sections
LETROZOLE	HUMAN PRESCRIPTION DRUG LABEL	1	62135-491	TABLET, FILM COATED	2.50 mg	ORAL	ANDA	24 sections
Letrozole	HUMAN PRESCRIPTION DRUG LABEL	1	63629-7819	TABLET, FILM COATED	2.50 mg	ORAL	ANDA	25 sections
Letrozole	Human Prescription Drug Label	1	63850-0025	TABLET	2.50 mg	ORAL	ANDA	27 sections
Letrozole	HUMAN PRESCRIPTION DRUG LABEL	1	68071-5264	TABLET, FILM COATED	2.50 mg	ORAL	ANDA	24 sections
Letrozole	HUMAN PRESCRIPTION DRUG LABEL	1	69117-0004	TABLET, FILM COATED	2.50 mg	ORAL	ANDA	27 sections
Letrozole	HUMAN PRESCRIPTION DRUG LABEL	1	71205-587	TABLET, FILM COATED	2.50 mg	ORAL	ANDA	27 sections
LETROZOLE	HUMAN PRESCRIPTION DRUG LABEL	1	71335-1526	TABLET	2.50 mg	ORAL	ANDA	27 sections