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

Stem definition	Drug id	CAS RN
serotonin and/or norepinephrine reuptake inhibitors, fluoxetine derivatives	972	116539-59-4

Description:

Molecule

Description

Molfile Inchi Smiles Synonyms: yentreve cymbalta duloxetine (S)-Duloxetine duloxetine hydrochloride duloxetine HCl

A thiophene derivative and selective NEUROTRANSMITTER UPTAKE INHIBITOR for SEROTONIN and NORADRENALINE (SNRI). It is an ANTIDEPRESSIVE AGENT and ANXIOLYTIC, and is also used for the treatment of pain in patients with DIABETES MELLITUS and FIBROMYALGIA. Molecular weight: 297.42 Formula: C18H19NOS CLOGP: 4.26 LIPINSKI: 0 HAC: 2 HDO: 1 TPSA: 21.26 ALOGS: -5 ROTB: 6 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Drug dosage:

Dose	Unit	Route
60	mg	O

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	1	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	0 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	2.88 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability)	50 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
CL (Clearance)	8.57 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.04 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	12 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
Aug. 3, 2004	FDA	LILLY

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
Drug withdrawal syndrome	3864.21	10.10	1993	189127	25391	46469551
Dysphoria	3521.47	10.10	1130	189990	3459	46491483
Affect lability	2862.11	10.10	1118	190002	6902	46488040
Irritability	2179.88	10.10	1400	189720	27546	46467396
Suicidal ideation	1753.05	10.10	1610	189510	54772	46440170
Agitation	1621.65	10.10	1530	189590	53885	46441057
Paraesthesia	1359.47	10.10	2015	189105	115422	46379520
Sensory disturbance	1288.82	10.10	735	190385	11532	46483410
Vertigo	1172.17	10.10	1247	189873	50801	46444141
Insomnia	1162.00	10.10	2268	188852	162656	46332286
Hyperhidrosis	1125.62	10.10	1596	189524	87712	46407230
Anxiety	1061.44	10.10	2315	188805	179642	46315300
Nightmare	760.38	10.10	593	190527	16005	46478937
Mood swings	702.25	10.10	561	190559	15691	46479251
Dizziness	675.23	10.10	2967	188153	337447	46157495
Tinnitus	594.39	10.10	647	190473	27026	46467916
Hypomania	559.99	10.10	299	190821	4089	46490853
Confusional state	543.91	10.10	1662	189458	158230	46336712
Lethargy	501.31	10.10	814	190306	50357	46444585
Tremor	460.34	10.10	1272	189848	114367	46380575
Serotonin syndrome	424.86	10.10	510	190610	23710	46471232
Depression	359.96	10.10	1514	189606	168590	46326352
Headache	293.65	10.10	3117	188003	475235	46019707
Withdrawal syndrome	284.42	10.10	361	190759	17773	46477169
Sleep disorder	257.82	10.10	583	190537	46212	46448730
Neutropenia	235.02	10.10	148	190972	143056	46351886
Anaemia	224.84	10.10	442	190678	255337	46239605
Suicide attempt	222.26	10.10	609	190511	54427	46440515
Febrile neutropenia	221.43	10.10	57	191063	94570	46400372
Nausea	202.01	10.10	3936	187184	683518	45811424
Pyrexia	193.62	10.10	754	190366	348048	46146894
Acute kidney injury	190.09	10.10	428	190692	235427	46259515
Crying	189.08	10.10	323	190797	20818	46474124
Disturbance in attention	187.13	10.10	405	190715	31155	46463787
Fibromyalgia	176.55	10.10	432	190688	36031	46458911
Pemphigus	170.06	10.10	3	191117	45271	46449671
Fatigue	164.77	10.10	3444	187676	605253	45889689
Thrombocytopenia	163.55	10.10	166	190954	126415	46368527
Pancytopenia	143.52	10.10	85	191035	84973	46409969
Feeling abnormal	140.58	10.10	935	190185	124125	46370817
Pneumonia	134.65	10.10	945	190175	375375	46119567
Maternal exposure during pregnancy	133.00	10.10	134	190986	102415	46392527
Stubbornness	121.72	10.10	43	191077	190	46494752
Mood altered	120.64	10.10	202	190918	12805	46482137
Dyspnoea	118.90	10.10	1446	189674	514102	45980840
Anger	115.21	10.10	188	190932	11664	46483278
Alopecia	114.89	10.10	315	190805	162099	46332843
Memory impairment	113.53	10.10	620	190500	76717	46418225
Platelet count decreased	112.06	10.10	147	190973	99877	46395065
Panic attack	107.90	10.10	249	190871	19993	46474949
Electric shock	107.90	10.10	59	191061	848	46494094
Disease progression	103.49	10.10	133	190987	91167	46403775
Malignant neoplasm progression	102.50	10.10	70	191050	64856	46430086
Thinking abnormal	98.57	10.10	158	190962	9656	46485286
Completed suicide	98.45	10.10	971	190149	144949	46349993
Migraine	97.85	10.10	554	190566	69472	46425470
Cardiac failure	97.47	10.10	110	191010	79838	46415104
Rash	95.48	10.10	966	190154	355546	46139396
Septic shock	94.66	10.10	60	191060	57833	46437109
Death	94.12	10.10	899	190221	334649	46160293
Sepsis	91.60	10.10	270	190850	135744	46359198
Contraindicated product administered	89.02	10.10	118	191002	79829	46415113
Erythema	85.37	10.10	299	190821	142521	46352421
Haemoglobin decreased	84.65	10.10	259	190861	128690	46366252
Depressed mood	84.30	10.10	314	190806	33005	46461937
Drug reaction with eosinophilia and systemic symptoms	83.62	10.10	11	191109	29537	46465405
Treatment failure	83.22	10.10	159	190961	92928	46402014
Gastrointestinal tube insertion	81.18	10.10	53	191067	1070	46493872
Somnolence	79.18	10.10	984	190136	155537	46339405
Gastric bypass	78.88	10.10	56	191064	1303	46493639
Glossodynia	78.20	10.10	42	191078	44331	46450611
Drug intolerance	76.85	10.10	325	190795	146724	46348218
Hand deformity	76.78	10.10	23	191097	34551	46460391
Pleural effusion	75.64	10.10	140	190980	82812	46412130
Blood creatinine increased	73.22	10.10	125	190995	76278	46418664
Renal impairment	72.82	10.10	120	191000	74252	46420690
Neutrophil count decreased	72.38	10.10	44	191076	43382	46451560
Intentional product misuse	71.97	10.10	382	190738	46746	46448196
Interstitial lung disease	70.48	10.10	70	191050	53879	46441063
Renal failure	70.46	10.10	234	190886	113360	46381582
Mucosal inflammation	70.00	10.10	36	191084	38940	46456002
Atrial fibrillation	68.74	10.10	207	190913	103383	46391559
Synovitis	68.13	10.10	90	191030	60985	46433957
Rheumatoid arthritis	67.08	10.10	644	190476	239571	46255371
Systemic lupus erythematosus	65.86	10.10	103	191017	65077	46429865
Restless legs syndrome	65.59	10.10	177	190943	15666	46479276
Ascites	65.39	10.10	34	191086	36550	46458392
Tardive dyskinesia	64.49	10.10	113	191007	7430	46487512
Prescribed overdose	64.11	10.10	136	190984	10313	46484629
Bone marrow failure	63.63	10.10	21	191099	29648	46465294
General physical health deterioration	63.52	10.10	251	190869	115518	46379424
Multiple organ dysfunction syndrome	63.18	10.10	71	191049	51639	46443303
Off label use	63.11	10.10	1135	189985	378706	46116236
Cardiac failure congestive	62.56	10.10	181	190939	91569	46403373
Leukopenia	61.72	10.10	116	191004	68227	46426715
Amnesia	60.55	10.10	333	190787	41298	46453644
White blood cell count decreased	59.27	10.10	247	190873	111984	46382958
Aggression	58.92	10.10	216	190904	22528	46472414
Abnormal dreams	57.61	10.10	129	190991	10150	46484792
Hyperkalaemia	57.31	10.10	74	191046	50635	46444307
Hypotension	56.58	10.10	644	190476	231945	46262997
Infusion related reaction	56.43	10.10	218	190902	100990	46393952
Post-traumatic stress disorder	56.33	10.10	76	191044	3972	46490970
Somatic symptom disorder	56.21	10.10	53	191067	1859	46493083
Premature delivery	56.20	10.10	11	191109	22058	46472884
Affective disorder	56.05	10.10	83	191037	4732	46490210
Weight increased	55.50	10.10	964	190156	163509	46331433
Gastrointestinal haemorrhage	55.45	10.10	149	190971	77224	46417718
Multiple sclerosis relapse	54.11	10.10	326	190794	41799	46453143
Mania	54.08	10.10	130	190990	10716	46484226
Coordination abnormal	53.27	10.10	130	190990	10819	46484123
Alanine aminotransferase increased	53.13	10.10	575	190545	87876	46407066
Hypersensitivity	52.34	10.10	380	190740	149941	46345001
Cough	51.98	10.10	648	190472	229601	46265341
Product substitution issue	51.62	10.10	157	190963	14874	46480068
Infection	50.82	10.10	329	190791	133263	46361679
Cytomegalovirus infection	50.76	10.10	7	191113	18137	46476805
White blood cell count abnormal	50.68	10.10	82	191038	5050	46489892
Hepatic enzyme increased	50.20	10.10	534	190586	81253	46413689
Pneumonia aspiration	50.19	10.10	259	190861	31346	46463596
Sopor	49.43	10.10	186	190934	19642	46475300
Abdominal discomfort	49.37	10.10	389	190731	150776	46344166
Dehydration	48.27	10.10	419	190701	159121	46335821
Therapy interrupted	48.17	10.10	124	190996	10667	46484275
Neck deformity	48.13	10.10	48	191072	1806	46493136
Respiratory failure	47.41	10.10	213	190907	94603	46400339
Inappropriate antidiuretic hormone secretion	47.21	10.10	146	190974	13956	46480986
Extremity contracture	47.03	10.10	39	191081	1150	46493792
Lactic acidosis	46.63	10.10	42	191078	33867	46461075
Joint swelling	46.41	10.10	445	190675	165628	46329314
Abnormal behaviour	46.39	10.10	190	190930	20868	46474074
Coma blister	46.22	10.10	19	191101	136	46494806
Pulmonary oedema	45.91	10.10	87	191033	51018	46443924
Device expulsion	45.77	10.10	28	191092	27514	46467428
Oedema peripheral	44.60	10.10	428	190692	159278	46335664
Bradycardia	44.31	10.10	132	190988	66166	46428776
Intentional self-injury	43.32	10.10	205	190915	23961	46470981
Loss of consciousness	43.05	10.10	652	190468	107586	46387356
Palmar-plantar erythrodysaesthesia syndrome	42.94	10.10	15	191105	20436	46474506
Hypocalcaemia	42.10	10.10	29	191091	26756	46468186
Fall	41.77	10.10	1695	189425	327402	46167540
Hallucination	41.57	10.10	348	190772	49603	46445339
Dry mouth	41.21	10.10	374	190746	54552	46440390
Coma	40.12	10.10	390	190730	57959	46436983
Drug ineffective	39.88	10.10	2321	188799	675517	45819425
Cognitive disorder	39.72	10.10	273	190847	36610	46458332
Wound	39.21	10.10	72	191048	42730	46452212
Lower respiratory tract infection	38.78	10.10	107	191013	54982	46439960
Epistaxis	38.14	10.10	135	190985	64170	46430772
Rapid eye movements sleep abnormal	37.91	10.10	15	191105	96	46494846
Deep vein thrombosis	37.64	10.10	183	190937	79590	46415352
Pericarditis	37.48	10.10	26	191094	23901	46471041
Neoplasm progression	36.75	10.10	33	191087	26650	46468292
Myocardial infarction	36.66	10.10	241	190879	97287	46397655
Balance disorder	36.25	10.10	414	190706	64107	46430835
Product use in unapproved indication	36.03	10.10	219	190901	90054	46404888
Intervertebral discitis	35.84	10.10	48	191072	2491	46492451
Urinary retention	35.60	10.10	205	190915	25856	46469086
Pulmonary fibrosis	35.42	10.10	19	191101	20073	46474869
Colitis microscopic	35.32	10.10	81	191039	6475	46488467
Aspartate aminotransferase increased	35.23	10.10	484	190636	78216	46416726
Muscle twitching	35.23	10.10	136	190984	14536	46480406
Metabolic surgery	34.64	10.10	30	191090	940	46494002
Tachyphrenia	34.51	10.10	34	191086	1260	46493682
Neck mass	34.42	10.10	54	191066	3239	46491703
Sacroiliitis	33.71	10.10	43	191077	2126	46492816
Coronary artery disease	33.46	10.10	54	191066	33698	46461244
Sleep apnoea syndrome	33.23	10.10	179	190941	22022	46472920
Restlessness	33.07	10.10	198	190922	25326	46469616
Peripheral swelling	33.01	10.10	452	190668	157619	46337323
Melaena	32.98	10.10	39	191081	27733	46467209
Psychotic disorder due to a general medical condition	32.31	10.10	16	191104	185	46494757
Rash maculo-papular	32.19	10.10	40	191080	27834	46467108
Akathisia	31.75	10.10	86	191034	7628	46487314
Dyskinesia	31.68	10.10	215	190905	28710	46466232
Abdominal pain	31.60	10.10	709	190411	229322	46265620
Hallucination, visual	31.59	10.10	151	190969	17722	46477220
Seizure	31.56	10.10	692	190428	122362	46372580
Eosinophilia	31.29	10.10	20	191100	19197	46475745
Paranoia	31.20	10.10	105	191015	10492	46484450
Anaphylactic reaction	31.16	10.10	112	191008	53000	46441942
Arthropathy	30.98	10.10	211	190909	84489	46410453
Stomatitis	30.89	10.10	159	190961	68138	46426804
Acute myeloid leukaemia	30.76	10.10	13	191107	15765	46479177
Impaired driving ability	30.71	10.10	59	191061	4165	46490777
Hypersomnia	30.67	10.10	135	190985	15304	46479638
Stiff person syndrome	30.55	10.10	15	191105	170	46494772
Bipolar disorder	30.53	10.10	81	191039	7096	46487846
Hypokalaemia	30.38	10.10	223	190897	87801	46407141
Surgery	30.36	10.10	212	190908	28573	46466369
Hypomagnesaemia	29.95	10.10	28	191092	22182	46472760
Libido decreased	29.03	10.10	44	191076	2561	46492381
Pulmonary eosinophilia	28.96	10.10	16	191104	235	46494707
Dissociation	28.84	10.10	37	191083	1840	46493102
Haemoptysis	28.79	10.10	39	191081	26150	46468792
Anorgasmia	28.76	10.10	22	191098	576	46494366
Proteinuria	28.68	10.10	16	191104	16537	46478405
Cerebral infarction	28.63	10.10	32	191088	23334	46471608
Nervousness	28.46	10.10	207	190913	28268	46466674
Hyperreflexia	28.40	10.10	65	191055	5189	46489753
Disseminated intravascular coagulation	28.02	10.10	22	191098	18983	46475959
Acute respiratory distress syndrome	27.99	10.10	29	191091	21893	46473049
Autonomic dysreflexia	27.96	10.10	15	191105	207	46494735
Drug interaction	27.81	10.10	1055	190065	202039	46292903
Agranulocytosis	27.60	10.10	30	191090	22155	46472787
Complex regional pain syndrome	27.56	10.10	38	191082	2028	46492914
Therapy cessation	27.43	10.10	195	190925	26434	46468508
Hypoxia	27.40	10.10	114	191006	51724	46443218
Hypoglycaemia	27.21	10.10	122	190998	54227	46440715
Rubber sensitivity	26.96	10.10	34	191086	1662	46493280
Dyspnoea exertional	26.95	10.10	110	191010	50179	46444763
Gastric banding	26.73	10.10	11	191109	79	46494863
Cholestasis	26.68	10.10	43	191077	26850	46468092
Temperature intolerance	26.63	10.10	80	191040	7527	46487415
Rheumatoid nodule	26.40	10.10	3	191117	9017	46485925
Hot flush	26.16	10.10	283	190837	43234	46451708
Pulmonary arterial hypertension	26.15	10.10	41	191079	25887	46469055
Bone density abnormal	26.10	10.10	46	191074	3038	46491904
Metastases to bone	26.06	10.10	20	191100	17456	46477486
Pruritus	25.34	10.10	777	190343	241575	46253367
Plasma cell myeloma	25.30	10.10	95	191025	44383	46450559
Gastrostomy	25.15	10.10	20	191100	555	46494387
Pulmonary malformation	25.10	10.10	11	191109	94	46494848
Hyperaesthesia	25.07	10.10	80	191040	7776	46487166
Vision blurred	25.01	10.10	462	190658	79246	46415696
Mental disorder	24.74	10.10	167	190953	22258	46472684
Myelodysplastic syndrome	24.70	10.10	17	191103	15694	46479248
Anovulatory cycle	24.67	10.10	12	191108	133	46494809
Pain	24.63	10.10	2269	188851	474679	46020263
Loss of libido	24.62	10.10	29	191091	1320	46493622
Disorientation	24.52	10.10	245	190875	36673	46458269
Drug resistance	24.50	10.10	21	191099	17347	46477595
Duodenal ulcer perforation	24.45	10.10	3	191117	8499	46486443
Bruxism	24.25	10.10	44	191076	2973	46491969
Product use issue	24.18	10.10	259	190861	94385	46400557
Pneumonitis	24.13	10.10	50	191070	28370	46466572
Multiple sclerosis	24.08	10.10	179	190941	24612	46470330
Oxygen saturation decreased	23.97	10.10	175	190945	68989	46425953
Pulmonary embolism	23.93	10.10	307	190813	108278	46386664
Concussion	23.90	10.10	73	191047	6930	46488012
Torsade de pointes	23.71	10.10	10	191110	12144	46482798
Formication	23.70	10.10	51	191069	3905	46491037
Sleep terror	23.56	10.10	22	191098	762	46494180
Nasal turbinate hypertrophy	23.35	10.10	17	191103	412	46494530
Tearfulness	23.29	10.10	52	191068	4083	46490859
Respiratory distress	23.21	10.10	61	191059	31855	46463087
Angioedema	23.05	10.10	83	191037	39259	46455683
Foetal death	23.03	10.10	4	191116	8739	46486203
Psychotic disorder	22.92	10.10	165	190955	22456	46472486
Metastases to liver	22.73	10.10	28	191092	19557	46475385
Toxic epidermal necrolysis	22.69	10.10	35	191085	22243	46472699
Peritonitis	22.61	10.10	31	191089	20683	46474259
Metabolic acidosis	22.60	10.10	82	191038	38698	46456244
Ejection fraction decreased	22.60	10.10	24	191096	17913	46477029
Speech disorder	22.58	10.10	237	190883	35930	46459012
Shock	22.56	10.10	34	191086	21811	46473131
Decreased appetite	22.38	10.10	613	190507	193223	46301719
Drug hypersensitivity	22.14	10.10	1215	189905	242610	46252332
C-reactive protein increased	21.90	10.10	145	190975	58445	46436497
Delusion	21.60	10.10	97	191023	11091	46483851
Thrombotic microangiopathy	21.44	10.10	4	191116	8302	46486640
Haemorrhage	21.42	10.10	134	190986	54735	46440207
Fluid overload	21.29	10.10	50	191070	27135	46467807
Osteonecrosis of jaw	21.22	10.10	71	191049	34331	46460611
Hostility	21.17	10.10	27	191093	1335	46493607
Neuralgia	21.11	10.10	155	190965	21228	46473714
Depressive symptom	21.09	10.10	40	191080	2796	46492146
Circulatory collapse	21.05	10.10	35	191085	21589	46473353
Angina unstable	20.91	10.10	3	191117	7545	46487397
Right ventricular failure	20.88	10.10	21	191099	16072	46478870
Pneumocystis jirovecii pneumonia	20.83	10.10	19	191101	15229	46479713
Mydriasis	20.75	10.10	92	191028	10461	46484481
Haemodialysis	20.70	10.10	6	191114	9211	46485731
Influenza like illness	20.68	10.10	341	190779	57229	46437713
Peritonitis bacterial	20.64	10.10	5	191115	8648	46486294
Blood pressure increased	20.55	10.10	671	190449	125995	46368947
Cardiogenic shock	20.55	10.10	22	191098	16362	46478580
Pregnancy	20.40	10.10	51	191069	27086	46467856
Chronic obstructive pulmonary disease	20.37	10.10	145	190975	57488	46437454
Discomfort	20.34	10.10	110	191010	46560	46448382
Hypoalbuminaemia	20.30	10.10	8	191112	10119	46484823
Cardiac arrest	20.14	10.10	255	190865	90144	46404798
Toxic skin eruption	20.02	10.10	13	191107	12374	46482568
Morbid thoughts	19.84	10.10	17	191103	525	46494417
Psychomotor hyperactivity	19.82	10.10	85	191035	9528	46485414
Acute myocardial infarction	19.61	10.10	66	191054	31858	46463084
Emotional disorder	19.56	10.10	101	191019	12223	46482719
Infective pulmonary exacerbation of cystic fibrosis	19.37	10.10	10	191110	10797	46484145
Decreased interest	19.31	10.10	41	191079	3111	46491831
Hyperglycaemia	19.24	10.10	76	191044	34995	46459947
Tuberculosis	19.16	10.10	9	191111	10256	46484686
Antinuclear antibody negative	19.01	10.10	12	191108	228	46494714
Granulomatous liver disease	18.93	10.10	20	191100	806	46494136
Lung disorder	18.91	10.10	102	191018	43202	46451740
Accidental exposure to product	18.83	10.10	36	191084	21045	46473897
Swelling	18.75	10.10	378	190742	124133	46370809
Device related infection	18.74	10.10	36	191084	21005	46473937
Haematotoxicity	18.64	10.10	3	191117	6930	46488012
Aspergillus infection	18.49	10.10	3	191117	6887	46488055
Pulmonary congestion	18.42	10.10	20	191100	14779	46480163
Haemorrhage intracranial	18.42	10.10	15	191105	12709	46482233
Tubulointerstitial nephritis	18.39	10.10	20	191100	14768	46480174
Gastrooesophageal reflux disease	18.39	10.10	416	190704	73928	46421014
Hallucination, auditory	18.38	10.10	90	191030	10666	46484276
Ischaemic stroke	18.28	10.10	25	191095	16697	46478245
Libido increased	18.24	10.10	19	191101	753	46494189
Tension	18.16	10.10	38	191082	2854	46492088
Homicidal ideation	18.08	10.10	29	191091	1773	46493169
Premature labour	18.07	10.10	12	191108	11287	46483655
Sexual dysfunction	18.01	10.10	34	191086	2369	46492573
Coombs positive haemolytic anaemia	17.99	10.10	14	191106	376	46494566
Respiratory tract malformation	17.99	10.10	8	191112	71	46494871
Caesarean section	17.97	10.10	25	191095	16578	46478364
Conversion disorder	17.97	10.10	28	191092	1670	46493272
Pulmonary hypertension	17.89	10.10	81	191039	35912	46459030
Pustular psoriasis	17.77	10.10	46	191074	3971	46490971
Hepatitis C antibody positive	17.70	10.10	8	191112	74	46494868
Metastases to lung	17.59	10.10	11	191109	10685	46484257
Pseudomonas infection	17.54	10.10	9	191111	9749	46485193
Vomiting	17.53	10.10	2113	189007	450681	46044261
Flat affect	17.50	10.10	24	191096	1274	46493668
Oliguria	17.42	10.10	7	191113	8752	46486190
Graft versus host disease	17.38	10.10	3	191117	6585	46488357
Pulseless electrical activity	17.37	10.10	4	191116	7163	46487779
Second primary malignancy	17.37	10.10	3	191117	6581	46488361
Galactorrhoea	17.33	10.10	44	191076	3753	46491189
Aplastic anaemia	17.32	10.10	4	191116	7149	46487793
Disability	17.32	10.10	85	191035	10082	46484860
Gastric ulcer	17.29	10.10	40	191080	21823	46473119
Pre-existing condition improved	17.29	10.10	63	191057	6549	46488393
Heart rate decreased	17.24	10.10	69	191051	31654	46463288
CYP3A4 polymorphism	17.16	10.10	8	191112	80	46494862
Apathy	17.14	10.10	67	191053	7201	46487741
Acute hepatic failure	17.13	10.10	21	191099	14700	46480242
Liver function test increased	17.08	10.10	43	191077	22783	46472159
Lymphadenopathy	16.86	10.10	75	191045	33413	46461529
Haematuria	16.86	10.10	55	191065	26803	46468139
Chest discomfort	16.78	10.10	264	190856	90005	46404937
Bacteraemia	16.74	10.10	20	191100	14159	46480783
Hypnopompic hallucination	16.72	10.10	6	191114	28	46494914
Cerebrovascular accident	16.67	10.10	302	190818	100737	46394205
Inflammation	16.62	10.10	124	190996	48657	46446285
Live birth	16.48	10.10	11	191109	10319	46484623
Reversible cerebral vasoconstriction syndrome	16.37	10.10	27	191093	1690	46493252
Transfusion	16.34	10.10	18	191102	13213	46481729
Therapy non-responder	16.32	10.10	100	191020	41052	46453890
Clonus	16.30	10.10	45	191075	4035	46490907
Abdominal distension	16.30	10.10	207	190913	73144	46421798
Hepatic function abnormal	16.21	10.10	79	191041	34342	46460600
Bronchial neoplasm	16.19	10.10	11	191109	238	46494704
Product dose omission issue	16.12	10.10	844	190276	167676	46327266
Head injury	16.12	10.10	163	190957	24473	46470469
Major depression	16.05	10.10	62	191058	6628	46488314
Foetal exposure during pregnancy	16.01	10.10	68	191052	30679	46464263
Dysphemia	16.01	10.10	32	191088	2326	46492616
Asthma	15.94	10.10	271	190849	91271	46403671
Asphyxia	15.88	10.10	53	191067	5273	46489669
Cerebral haemorrhage	15.87	10.10	61	191059	28310	46466632
Red blood cell count decreased	15.87	10.10	74	191046	32549	46462393
Opsoclonus myoclonus	15.72	10.10	9	191111	142	46494800
Bipolar I disorder	15.67	10.10	25	191095	1521	46493421
Drug screen positive	15.63	10.10	43	191077	3848	46491094
Pathogen resistance	15.47	10.10	3	191117	6057	46488885
Hypercalcaemia	15.47	10.10	40	191080	21006	46473936
Breast cancer metastatic	15.41	10.10	20	191100	13658	46481284
Condition aggravated	15.40	10.10	833	190287	244219	46250723
Productive cough	15.40	10.10	133	190987	50582	46444360
Skin necrosis	15.37	10.10	8	191112	8596	46486346
Panic disorder	15.33	10.10	33	191087	2528	46492414
Anaphylactic shock	15.32	10.10	38	191082	20236	46474706
Metastases to central nervous system	15.30	10.10	14	191106	11207	46483735
Respiratory tract infection	15.17	10.10	67	191053	29905	46465037
Pulmonary haemorrhage	15.05	10.10	4	191116	6501	46488441
Diffuse large B-cell lymphoma	15.03	10.10	3	191117	5935	46489007
Haemolytic anaemia	15.01	10.10	11	191109	9831	46485111
Oedema	15.01	10.10	189	190931	66882	46428060
Lung cyst	15.00	10.10	8	191112	109	46494833
Stillbirth	15.00	10.10	4	191116	6487	46488455
Hypoaesthesia	14.96	10.10	612	190508	118257	46376685
Cataplexy	14.93	10.10	21	191099	1142	46493800
Abortion spontaneous	14.85	10.10	111	191009	43535	46451407
Chest pain	14.78	10.10	581	190539	175743	46319199
Bronchospasm	14.76	10.10	26	191094	15681	46479261
Sleep talking	14.76	10.10	19	191101	948	46493994
Immunisation reaction	14.75	10.10	5	191115	19	46494923
Cataract	14.74	10.10	117	191003	45298	46449644
Herpes simplex reactivation	14.64	10.10	12	191108	348	46494594
Eyelid myoclonus	14.47	10.10	6	191114	44	46494898
Congenital tricuspid valve atresia	14.47	10.10	6	191114	44	46494898
Hypophosphataemia	14.47	10.10	6	191114	7361	46487581
Feelings of worthlessness	14.35	10.10	11	191109	289	46494653
Impulse-control disorder	14.31	10.10	16	191104	688	46494254
Blood lactate dehydrogenase increased	14.29	10.10	40	191080	20460	46474482
Basal cell carcinoma	14.26	10.10	40	191080	20447	46474495
Feeling of despair	14.10	10.10	26	191094	1779	46493163
Gait disturbance	13.99	10.10	728	190392	144535	46350407
Tic	13.95	10.10	21	191099	1215	46493727
Drug eruption	13.86	10.10	43	191077	21286	46473656
Clostridium difficile colitis	13.84	10.10	35	191085	18518	46476424
Abortion induced	13.76	10.10	13	191107	10247	46484695
Metastases to lymph nodes	13.69	10.10	5	191115	6626	46488316
Rectal haemorrhage	13.63	10.10	96	191024	38159	46456783
Femur fracture	13.60	10.10	92	191028	36905	46458037
Phobia of driving	13.51	10.10	3	191117	0	46494942
Hyperacusis	13.51	10.10	26	191094	1838	46493104
Ophthalmic vein thrombosis	13.51	10.10	8	191112	135	46494807
Hyponatraemic encephalopathy	13.50	10.10	10	191110	249	46494693
Phagophobia	13.50	10.10	5	191115	26	46494916
Chronic kidney disease	13.40	10.10	105	191015	40766	46454176
Ankle fracture	13.40	10.10	109	191011	15402	46479540
Polyarthritis	13.39	10.10	5	191115	6537	46488405
Pain in jaw	13.33	10.10	97	191023	38275	46456667
Road traffic accident	13.29	10.10	152	190968	23539	46471403
Depression suicidal	13.18	10.10	23	191097	1507	46493435
Food craving	13.16	10.10	20	191100	1167	46493775
Demyelination	13.11	10.10	52	191068	5628	46489314
Impatience	13.10	10.10	11	191109	330	46494612
Autonomic nervous system imbalance	13.10	10.10	30	191090	2396	46492546
Escherichia infection	13.05	10.10	15	191105	10802	46484140
Self-injurious ideation	13.04	10.10	29	191091	2271	46492671
Uraemic encephalopathy	13.03	10.10	9	191111	200	46494742
Spinal operation	13.01	10.10	51	191069	5489	46489453
Myocardial ischaemia	13.01	10.10	20	191100	12729	46482213
Bronchial haemorrhage	12.99	10.10	11	191109	334	46494608
Diplopia	12.99	10.10	129	190991	19276	46475666
Therapeutic product effect decreased	12.97	10.10	249	190871	82352	46412590
Blood calcium decreased	12.95	10.10	28	191092	15645	46479297
Holmes-Adie pupil	12.91	10.10	5	191115	30	46494912
Renal injury	12.90	10.10	12	191108	9529	46485413
Herpes zoster	12.78	10.10	198	190922	67674	46427268
Renal disorder	12.71	10.10	61	191059	26625	46468317
Blood pressure diastolic abnormal	12.57	10.10	5	191115	6289	46488653
Gun shot wound	12.54	10.10	7	191113	105	46494837
Tumour lysis syndrome	12.53	10.10	7	191113	7229	46487713
Rapid eye movement sleep behaviour disorder	12.45	10.10	8	191112	157	46494785
Pericardial effusion	12.39	10.10	58	191062	25485	46469457
Leukopenia neonatal	12.38	10.10	5	191115	34	46494908
Status epilepticus	12.37	10.10	24	191096	13955	46480987
Mean cell haemoglobin concentration increased	12.26	10.10	12	191108	441	46494501
Hepatobiliary scan abnormal	12.22	10.10	6	191114	68	46494874
Panic reaction	12.17	10.10	38	191082	3651	46491291
Unintended pregnancy	12.15	10.10	4	191116	5656	46489286
Nasal congestion	12.15	10.10	132	190988	47981	46446961
Hepatic steatosis	12.06	10.10	151	190969	23891	46471051
Rales	12.01	10.10	13	191107	9618	46485324
Therapeutic response changed	11.99	10.10	15	191105	727	46494215
Tenosynovitis	11.99	10.10	8	191112	7507	46487435
Myoclonus	11.94	10.10	100	191020	14252	46480690
Suspected product quality issue	11.86	10.10	8	191112	171	46494771
Neuropsychiatric symptoms	11.81	10.10	12	191108	462	46494480
Acute pulmonary oedema	11.80	10.10	9	191111	7882	46487060
Haemolysis	11.80	10.10	5	191115	6054	46488888
Enterococcal infection	11.75	10.10	7	191113	6980	46487962
Vasculitis	11.74	10.10	24	191096	13687	46481255
Radiation fibrosis	11.69	10.10	5	191115	40	46494902
Staphylococcal infection	11.68	10.10	92	191028	35679	46459263
Lung infiltration	11.67	10.10	25	191095	14018	46480924
Rebound nasal congestion	11.64	10.10	4	191116	16	46494926
Anuria	11.60	10.10	18	191102	11413	46483529
Osteonecrosis	11.60	10.10	60	191060	25684	46469258
Alcoholism	11.51	10.10	27	191093	2191	46492751
Bone erosion	11.49	10.10	13	191107	9430	46485512
Disease recurrence	11.47	10.10	38	191082	18433	46476509
Hypoaesthesia teeth	11.44	10.10	3	191117	3	46494939
Atelectasis	11.44	10.10	39	191081	18751	46476191
Phonophobia	11.40	10.10	10	191110	319	46494623
Dry skin	11.39	10.10	110	191010	40906	46454036
Low birth weight baby	11.38	10.10	4	191116	5430	46489512
Pneumothorax	11.38	10.10	27	191093	14602	46480340
Eczema	11.32	10.10	44	191076	20356	46474586
Swelling face	11.32	10.10	151	190969	52908	46442034
Bradyphrenia	11.27	10.10	53	191067	6177	46488765
Scar	11.23	10.10	86	191034	11933	46483009
Polyneuropathy	11.19	10.10	19	191101	11625	46483317
Middle insomnia	11.19	10.10	72	191048	9443	46485499
Urinary hesitation	11.19	10.10	24	191096	1834	46493108
Polyglandular autoimmune syndrome type II	11.18	10.10	5	191115	45	46494897
Skin discolouration	11.17	10.10	83	191037	32597	46462345
Osteopenia	11.16	10.10	34	191086	16927	46478015
Duodenal ulcer	11.10	10.10	8	191112	7210	46487732
Poor quality sleep	11.00	10.10	103	191017	15150	46479792
Feeling drunk	10.99	10.10	38	191082	3849	46491093
Feeling jittery	10.98	10.10	80	191040	10928	46484014
Posterior reversible encephalopathy syndrome	10.96	10.10	29	191091	15112	46479830
Tricuspid valve incompetence	10.93	10.10	25	191095	13692	46481250
Blood urea increased	10.91	10.10	60	191060	25292	46469650
Sluggishness	10.87	10.10	43	191077	4648	46490294
Spasmodic dysphonia	10.87	10.10	6	191114	88	46494854
Embolism	10.86	10.10	8	191112	7130	46487812
Coagulopathy	10.85	10.10	39	191081	18460	46476482
Osteoporosis	10.82	10.10	110	191010	40498	46454444
Impulsive behaviour	10.82	10.10	21	191099	1494	46493448
Purple glove syndrome	10.81	10.10	8	191112	199	46494743
Sleep disorder due to general medical condition, insomnia type	10.76	10.10	4	191116	5245	46489697
Lung neoplasm	10.76	10.10	5	191115	5735	46489207
Daydreaming	10.74	10.10	10	191110	345	46494597
Accommodation disorder	10.74	10.10	10	191110	345	46494597
Alveolar bone resorption	10.73	10.10	5	191115	50	46494892
Blood pressure decreased	10.68	10.10	167	190953	56992	46437950
Injection site haemorrhage	10.66	10.10	46	191074	20663	46474279
Blister	10.65	10.10	124	190996	44507	46450435
Angina pectoris	10.65	10.10	65	191055	26710	46468232
Haematocrit decreased	10.61	10.10	92	191028	34965	46459977
Skin lesion	10.55	10.10	65	191055	26648	46468294
Gambling disorder	10.54	10.10	19	191101	1277	46493665
International normalised ratio increased	10.53	10.10	132	190988	46751	46448191
Nasopharyngitis	10.52	10.10	519	190601	153479	46341463
Clostridium difficile infection	10.48	10.10	60	191060	25043	46469899
Rash erythematous	10.46	10.10	90	191030	34260	46460682
Acute respiratory failure	10.44	10.10	73	191047	29065	46465877
Maternal exposure during breast feeding	10.40	10.10	30	191090	2759	46492183
Ventricular hypoplasia	10.40	10.10	7	191113	149	46494793
Drug-induced liver injury	10.40	10.10	61	191059	25307	46469635
Flushing	10.38	10.10	194	190926	64420	46430522
Skin ulcer	10.36	10.10	84	191036	32374	46462568
Shock haemorrhagic	10.36	10.10	12	191108	8612	46486330
Dialysis	10.20	10.10	16	191104	10100	46484842
Intestinal cyst	10.19	10.10	6	191114	100	46494842
Intervertebral disc protrusion	10.17	10.10	128	190992	20277	46474665
Hepatitis A antibody positive	10.16	10.10	5	191115	57	46494885

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
Drug withdrawal syndrome	1283.72	10.91	684	61471	19125	29871198
Dysphoria	1257.28	10.91	367	61788	1781	29888542
Affect lability	1165.00	10.91	386	61769	3032	29887291
Suicidal ideation	748.38	10.91	611	61544	35503	29854820
Irritability	673.96	10.91	479	61676	22571	29867752
Sensory disturbance	575.71	10.91	268	61887	5543	29884780
Paraesthesia	516.11	10.91	599	61556	53728	29836595
Vertigo	515.52	10.91	405	61750	22230	29868093
Agitation	476.86	10.91	574	61581	53499	29836824
Anxiety	456.45	10.91	731	61424	89140	29801183
Insomnia	446.67	10.91	739	61416	92597	29797726
Hyperhidrosis	365.71	10.91	564	61591	66526	29823797
Nightmare	292.03	10.91	224	61931	11852	29878471
Dizziness	268.95	10.91	951	61204	193958	29696365
Tinnitus	243.74	10.91	228	61927	15860	29874463
Confusional state	224.99	10.91	702	61453	134132	29756191
Lethargy	224.65	10.91	339	61816	39180	29851143
Tremor	224.61	10.91	488	61667	74875	29815448
Hypomania	217.06	10.91	102	62053	2154	29888169
Mood swings	216.95	10.91	156	61999	7470	29882853
Serotonin syndrome	191.25	10.91	210	61945	17681	29872642
Completed suicide	174.14	10.91	527	61628	98965	29791358
Headache	164.75	10.91	781	61374	181525	29708798
Depression	161.97	10.91	483	61672	89954	29800369
Nausea	141.14	10.91	1075	61080	295882	29594441
Sleep disorder	129.21	10.91	203	61952	24276	29866047
Pyrexia	125.66	10.91	265	61890	294224	29596099
Suicide attempt	122.39	10.91	249	61906	36448	29853875
Febrile neutropenia	108.19	10.91	43	62112	106650	29783673
Fatigue	101.64	10.91	1063	61092	319610	29570713
Thrombocytopenia	99.50	10.91	83	62072	136961	29753362
Anger	97.71	10.91	118	62037	11002	29879321
Acute kidney injury	95.09	10.91	274	61881	273568	29616755
Gastrointestinal tube insertion	87.82	10.91	46	62109	1235	29889088
Anaemia	82.13	10.91	195	61960	207797	29682526
Withdrawal syndrome	80.83	10.91	108	62047	11142	29879181
Intentional self-injury	72.47	10.91	113	62042	13419	29876904
Somnolence	72.00	10.91	393	61762	96370	29793953
Pancytopenia	70.14	10.91	45	62110	85007	29805316
Feeling abnormal	68.67	10.91	266	61889	56490	29833833
Neutropenia	65.95	10.91	103	62052	128437	29761886
Dyspnoea	65.28	10.91	415	61740	332880	29557443
Disturbance in attention	62.05	10.91	140	62015	21989	29868334
Memory impairment	57.61	10.91	189	61966	36985	29853338
Fall	57.38	10.91	603	61552	181269	29709054
Sepsis	54.77	10.91	141	62014	146254	29744069
Hepatic enzyme increased	52.54	10.91	171	61984	33323	29857000
Sexual dysfunction	49.99	10.91	62	62093	5939	29884384
Platelet count decreased	49.83	10.91	90	62065	106039	29784284
Disease progression	48.00	10.91	57	62098	79817	29810506
Blood creatinine increased	47.04	10.91	73	62082	91302	29799021
Renal failure	46.12	10.91	127	62028	128839	29761484
Leukopenia	45.89	10.91	30	62125	56129	29834194
Multiple organ dysfunction syndrome	45.34	10.91	39	62116	63448	29826875
Haemoglobin decreased	44.92	10.91	107	62048	113991	29776332
Pleural effusion	44.35	10.91	53	62102	74013	29816310
Loss of consciousness	42.94	10.91	297	61858	79078	29811245
Respiratory failure	42.36	10.91	91	62064	100551	29789772
Cardiac failure	41.65	10.91	68	62087	83350	29806973
Mucosal inflammation	40.89	10.91	7	62148	30487	29859836
Malignant neoplasm progression	37.92	10.91	57	62098	72230	29818093
Gastric bypass	37.63	10.91	16	62139	264	29890059
Urinary retention	37.15	10.91	151	62004	32766	29857557
Migraine	36.70	10.91	82	62073	12792	29877531
Urinary hesitation	35.78	10.91	33	62122	2251	29888072
Intentional overdose	35.31	10.91	175	61980	41306	29849017
Cytomegalovirus infection	35.11	10.91	4	62151	23670	29866653
Antidepressant drug level above therapeutic	34.55	10.91	13	62142	153	29890170
Septic shock	34.49	10.91	49	62106	63558	29826765
Cough	34.41	10.91	139	62016	125503	29764820
Pneumonia	34.06	10.91	489	61666	333817	29556506
Balance disorder	33.98	10.91	158	61997	36335	29853988
Respiratory disorder neonatal	33.09	10.91	24	62131	1164	29889159
Metabolic acidosis	32.00	10.91	19	62136	37442	29852881
Therapy interrupted	31.80	10.91	43	62112	4486	29885837
Myoclonus	31.66	10.91	79	62076	13233	29877090
Mania	31.54	10.91	63	62092	9091	29881232
Toxicity to various agents	31.33	10.91	529	61626	176654	29713669
Road traffic accident	31.25	10.91	92	62063	16979	29873344
Major depression	31.04	10.91	40	62115	3982	29886341
General physical health deterioration	31.01	10.91	105	62050	99839	29790484
Aggression	30.91	10.91	155	62000	36752	29853571
Haemorrhage	30.88	10.91	30	62125	46049	29844274
Atrial fibrillation	29.99	10.91	119	62036	108005	29782318
Dehydration	29.99	10.91	143	62012	123396	29766927
Analgesic drug level above therapeutic	29.65	10.91	13	62142	232	29890091
Ascites	29.59	10.91	19	62136	35902	29854421
Pain	29.27	10.91	512	61643	172129	29718194
Disorientation	29.23	10.91	136	62019	31282	29859041
Drug hypersensitivity	28.96	10.91	242	61913	68277	29822046
Amnesia	28.58	10.91	113	62042	24208	29866115
Drug resistance	28.41	10.91	4	62151	20129	29870194
Renal impairment	27.81	10.91	86	62069	84098	29806225
Self esteem decreased	27.50	10.91	16	62139	530	29889793
C-reactive protein increased	27.21	10.91	30	62125	43443	29846880
Yawning	27.20	10.91	16	62139	541	29889782
Abnormal dreams	26.95	10.91	55	62100	8060	29882263
Myocardial infarction	26.79	10.91	152	62003	125473	29764850
Interstitial lung disease	26.52	10.91	53	62102	60144	29830179
Product use in unapproved indication	25.99	10.91	73	62082	73620	29816703
Disseminated intravascular coagulation	25.84	10.91	7	62148	22164	29868159
Initial insomnia	25.27	10.91	29	62126	2560	29887763
Sedation	25.13	10.91	83	62072	16290	29874033
Homicidal ideation	24.74	10.91	28	62127	2435	29887888
Bone marrow failure	24.20	10.91	16	62139	29769	29860554
Erectile dysfunction	23.65	10.91	87	62068	18015	29872308
Agranulocytosis	23.63	10.91	8	62147	21934	29868389
Fibromyalgia	23.35	10.91	28	62127	2590	29887733
Feeling jittery	23.25	10.91	34	62121	3814	29886509
Acute respiratory distress syndrome	22.89	10.91	10	62145	23462	29866861
Surgery	22.84	10.91	64	62091	11487	29878836
Convulsive threshold lowered	22.74	10.91	14	62141	515	29889808
Rash	22.65	10.91	272	61883	191617	29698706
Multiple sclerosis relapse	22.28	10.91	61	62094	10801	29879522
Hypokalaemia	22.27	10.91	44	62111	50148	29840175
Overdose	22.15	10.91	270	61885	84067	29806256
Hallucination, auditory	22.14	10.91	57	62098	9732	29880591
Cardiac failure congestive	22.09	10.91	95	62060	84312	29806011
White blood cell count decreased	21.65	10.91	95	62060	83852	29806471
Hallucination	21.11	10.91	174	61981	48885	29841438
International normalised ratio increased	21.05	10.91	42	62113	47697	29842626
Somnambulism	20.30	10.91	29	62126	3185	29887138
Toxic epidermal necrolysis	20.28	10.91	6	62149	17934	29872389
Wrong drug	19.98	10.91	7	62148	66	29890257
Erythema	19.76	10.91	88	62067	77363	29812960
Bradyphrenia	19.74	10.91	32	62123	3925	29886398
Neonatal tachypnoea	19.69	10.91	8	62147	117	29890206
Abnormal behaviour	19.64	10.91	105	62050	25518	29864805
Delirium	19.62	10.91	148	62007	40483	29849840
Prescribed overdose	19.51	10.91	50	62105	8511	29881812
Peritonitis	19.47	10.91	10	62145	21365	29868958
Depression suicidal	19.15	10.91	18	62137	1258	29889065
Hypotension	19.10	10.91	297	61858	200268	29690055
Growth hormone deficiency	19.02	10.91	9	62146	193	29890130
Gastrointestinal haemorrhage	18.85	10.91	99	62056	83347	29806976
Neuralgia	18.77	10.91	56	62099	10410	29879913
Acute myeloid leukaemia	18.65	10.91	7	62148	17999	29872324
Dysmetropsia	18.49	10.91	4	62151	3	29890320
Psychotic disorder	18.46	10.91	91	62064	21424	29868899
Dystonia	18.36	10.91	53	62102	9674	29880649
Intentional product misuse	18.30	10.91	129	62026	34538	29855785
Feeling guilty	18.26	10.91	10	62145	294	29890029
Acute myocardial infarction	18.25	10.91	53	62102	52886	29837437
Blood lactate dehydrogenase increased	18.23	10.91	10	62145	20591	29869732
Muscle spasticity	18.23	10.91	36	62119	5152	29885171
Affective disorder	18.11	10.91	27	62128	3081	29887242
Acute stress disorder	17.98	10.91	8	62147	148	29890175
Haemoptysis	17.79	10.91	23	62132	31055	29859268
Death	17.76	10.91	586	61569	356697	29533626
Coronary artery disease	17.70	10.91	49	62106	49663	29840660
Infusion related reaction	17.62	10.91	36	62119	40528	29849795
Treatment failure	17.55	10.91	28	62127	34651	29855672
Therapy cessation	17.52	10.91	70	62085	15067	29875256
Respiratory distress	17.28	10.91	26	62129	32946	29857377
Angioedema	17.18	10.91	28	62127	34356	29855967
Pneumocystis jirovecii pneumonia	17.16	10.91	7	62148	17113	29873210
Steatohepatitis	17.08	10.91	10	62145	335	29889988
Speech sound disorder	17.00	10.91	6	62149	58	29890265
Haematuria	16.87	10.91	43	62112	44791	29845532
Hypocalcaemia	16.68	10.91	12	62143	21364	29868959
Ventricular hypoplasia	16.56	10.91	6	62149	63	29890260
Thinking abnormal	16.47	10.91	35	62120	5276	29885047
Tardive dyskinesia	16.47	10.91	34	62121	5023	29885300
Chills	16.24	10.91	86	62069	72252	29818071
Oedema peripheral	16.19	10.91	141	62014	105691	29784632
Orgasm abnormal	16.17	10.91	7	62148	121	29890202
Drug tolerance	15.90	10.91	21	62134	2141	29888182
Hyperlipasaemia	15.87	10.91	11	62144	496	29889827
Dry mouth	15.75	10.91	91	62064	22759	29867564
Sleep-related eating disorder	15.66	10.91	9	62146	291	29890032
Melaena	15.66	10.91	27	62128	32410	29857913
Restless legs syndrome	15.52	10.91	40	62115	6832	29883491
Delirium tremens	15.45	10.91	11	62144	518	29889805
Mental disorder	15.41	10.91	62	62093	13387	29876936
Rash maculo-papular	15.40	10.91	18	62137	25400	29864923
Depressed mood	15.31	10.91	73	62082	16956	29873367
Hypersomnia	15.30	10.91	55	62100	11261	29879062
Retrograde ejaculation	15.15	10.91	9	62146	310	29890013
Liver function test abnormal	15.09	10.91	113	62042	30837	29859486
Pericardial effusion	15.07	10.91	13	62142	21131	29869192
Muscle twitching	14.97	10.91	44	62111	8111	29882212
Urethral discharge	14.96	10.91	4	62151	13	29890310
Gait disturbance	14.95	10.91	228	61927	74549	29815774
Neonatal hyponatraemia	14.69	10.91	6	62149	89	29890234
Compulsive shopping	14.69	10.91	10	62145	438	29889885
Blood urea increased	14.36	10.91	27	62128	31354	29858969
Epistaxis	14.24	10.91	59	62096	52922	29837401
Neoplasm progression	14.22	10.91	10	62145	18013	29872310
Seizure	14.21	10.91	285	61870	98190	29792133
Eosinophilia	14.19	10.91	15	62140	22145	29868178
Paranoia	14.19	10.91	50	62105	10138	29880185
Lower respiratory tract infection	14.06	10.91	21	62134	26693	29863630
Libido decreased	14.06	10.91	30	62125	4536	29885787
Pneumonitis	14.05	10.91	22	62133	27432	29862891
Gastric ulcer	13.88	10.91	7	62148	15114	29875209
Stomatitis	13.84	10.91	36	62119	37243	29853080
Lymphopenia	13.83	10.91	5	62150	13158	29877165
Dyskinesia	13.80	10.91	85	62070	21749	29868574
Apathy	13.79	10.91	36	62119	6196	29884127
Complex regional pain syndrome	13.79	10.91	10	62145	485	29889838
Cholestasis	13.74	10.91	19	62136	24931	29865392
Concussion	13.66	10.91	19	62136	2035	29888288
Limb reduction defect	13.64	10.91	7	62148	180	29890143
Cerebral infarction	13.62	10.91	21	62134	26352	29863971
Drug screen positive	13.62	10.91	29	62126	4378	29885945
Drug reaction with eosinophilia and systemic symptoms	13.49	10.91	24	62131	28464	29861859
Sleep sex	13.47	10.91	3	62152	3	29890320
Helplessness	13.35	10.91	5	62150	58	29890265
Nephropathy toxic	13.09	10.91	3	62152	10636	29879687
Bipolar disorder	13.02	10.91	26	62129	3750	29886573
Angina pectoris	12.98	10.91	26	62129	29492	29860831
Akathisia	12.96	10.91	34	62121	5870	29884453
Facial spasm	12.90	10.91	7	62148	202	29890121
Psychomotor hyperactivity	12.90	10.91	42	62113	8182	29882141
Neutrophil count decreased	12.88	10.91	45	62110	42409	29847914
Suicidal behaviour	12.86	10.91	15	62140	1347	29888976
Myelodysplastic syndrome	12.84	10.91	12	62143	18766	29871557
Colitis ulcerative	12.78	10.91	7	62148	14427	29875896
Lung disorder	12.77	10.91	29	62126	31440	29858883
Productive cough	12.65	10.91	27	62128	29926	29860397
Reflexes abnormal	12.58	10.91	8	62147	312	29890011
Deep vein thrombosis	12.45	10.91	74	62081	60427	29829896
Rhabdomyolysis	12.44	10.91	79	62076	63501	29826822
Homicide	12.44	10.91	13	62142	1033	29889290
Autonomic dysreflexia	12.44	10.91	5	62150	71	29890252
Pulmonary embolism	12.43	10.91	103	62052	78032	29812291
Stiff person syndrome	12.30	10.91	6	62149	138	29890185
Pulmonary fibrosis	12.29	10.91	9	62146	15881	29874442
Clonus	12.29	10.91	20	62135	2461	29887862
Paedophilia	12.26	10.91	3	62152	6	29890317
Graft versus host disease	12.22	10.91	3	62152	10147	29880176
Drug screen false positive	12.21	10.91	11	62144	728	29889595
Lymphoma	12.17	10.91	3	62152	10118	29880205
Fluid overload	12.14	10.91	13	62142	19079	29871244
Palmar-plantar erythrodysaesthesia syndrome	12.06	10.91	8	62147	14862	29875461
Lymphadenopathy	12.03	10.91	20	62135	24356	29865967
Hypoalbuminaemia	12.02	10.91	4	62151	11088	29879235
Anaphylactic reaction	12.01	10.91	25	62130	27957	29862366
Central nervous system stimulation	11.94	10.91	3	62152	7	29890316
Fine motor delay	11.88	10.91	6	62149	149	29890174
Ileus	11.79	10.91	9	62146	15546	29874777
Tumour lysis syndrome	11.78	10.91	6	62149	12879	29877444
Cyanosis	11.77	10.91	5	62150	11930	29878393
Anti-neutrophil cytoplasmic antibody positive vasculitis	11.75	10.91	10	62145	613	29889710
Divorced	11.66	10.91	3	62152	8	29890315
Pulmonary valve disease	11.62	10.91	5	62150	85	29890238
Tubulointerstitial nephritis	11.58	10.91	12	62143	17879	29872444
Neuropathy peripheral	11.55	10.91	208	61947	70267	29820056
Device related infection	11.49	10.91	11	62144	17004	29873319
Social avoidant behaviour	11.46	10.91	21	62134	2842	29887481
Hyperkalaemia	11.44	10.91	85	62070	65925	29824398
Product monitoring error	11.42	10.91	16	62139	1725	29888598
Acute coronary syndrome	11.42	10.91	7	62148	13566	29876757
Loss of employment	11.37	10.91	9	62146	498	29889825
Loss of proprioception	11.36	10.91	7	62148	258	29890065
Blue toe syndrome	11.36	10.91	6	62149	164	29890159
Product prescribing error	11.12	10.91	66	62089	16667	29873656
Malnutrition	10.97	10.91	5	62150	11444	29878879

Pharmacologic Action:

Source	Code	Description
ATC	N06AX21	NERVOUS SYSTEM PSYCHOANALEPTICS ANTIDEPRESSANTS Other antidepressants
FDA MoA	N0000000102	Norepinephrine Uptake Inhibitors
FDA MoA	N0000000109	Serotonin Uptake Inhibitors
FDA EPC	N0000175749	Serotonin and Norepinephrine Reuptake Inhibitor
MeSH PA	D000700	Analgesics
MeSH PA	D000928	Antidepressive Agents
MeSH PA	D002491	Central Nervous System Agents
MeSH PA	D015259	Dopamine Agents
MeSH PA	D049990	Membrane Transport Modulators
MeSH PA	D018377	Neurotransmitter Agents
MeSH PA	D014179	Neurotransmitter Uptake Inhibitors
MeSH PA	D018373	Peripheral Nervous System Agents
MeSH PA	D011619	Psychotropic Drugs
MeSH PA	D018689	Sensory System Agents
MeSH PA	D000068760	Serotonin and Noradrenaline Reuptake Inhibitors
CHEBI has role	CHEBI:35469	thymoanaleptics

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Generalized anxiety disorder	indication	21897009	DOID:14320
Female stress incontinence	indication	60241006	DOID:724
Fibromyalgia	indication	203082005	DOID:631
Major depressive disorder	indication	370143000
Diabetic peripheral neuropathy	indication	424736006
Chronic Musculoskeletal Pain	indication
Osteoarthritis	off-label use	396275006
Suicidal thoughts	contraindication	6471006
Alcoholism	contraindication	7200002
Bipolar disorder	contraindication	13746004	DOID:3312
Neuroleptic malignant syndrome	contraindication	15244003	DOID:14464
Jaundice	contraindication	18165001
Cirrhosis of liver	contraindication	19943007	DOID:5082
Orthostatic hypotension	contraindication	28651003
Hypertensive disorder	contraindication	38341003	DOID:10763
Alcoholic liver damage	contraindication	41309000
Syndrome of inappropriate vasopressin secretion	contraindication	55004003	DOID:3401
Acute nephropathy	contraindication	58574008
Blood coagulation disorder	contraindication	64779008	DOID:1247
Chronic hepatitis	contraindication	76783007	DOID:2237
Hyperglycemia	contraindication	80394007	DOID:4195
Epilepsy	contraindication	84757009	DOID:1826
Hyponatremia	contraindication	89627008
Inflammatory disease of liver	contraindication	128241005
Liver function tests abnormal	contraindication	166603001
Mania	contraindication	231494001
Hypomania	contraindication	231496004
Disease of liver	contraindication	235856003	DOID:409
Retention of urine	contraindication	267064002
Serotonin syndrome	contraindication	371089000
Angle-closure glaucoma	contraindication	392291006	DOID:13550
Gastrointestinal hypomotility	contraindication	421807004

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	8.7	Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
EQ 20MG BASE	CYMBALTA	LILLY	N021427	Aug. 3, 2004	RX	CAPSULE, DELAYED REL PELLETS	ORAL	April 20, 2023	NEW PATIENT POPULATION
EQ 30MG BASE	CYMBALTA	LILLY	N021427	Aug. 3, 2004	RX	CAPSULE, DELAYED REL PELLETS	ORAL	April 20, 2023	NEW PATIENT POPULATION
EQ 60MG BASE	CYMBALTA	LILLY	N021427	Aug. 3, 2004	RX	CAPSULE, DELAYED REL PELLETS	ORAL	April 20, 2023	NEW PATIENT POPULATION

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Sodium-dependent noradrenaline transporter	Transporter	P23975	SC6A2_HUMAN	INHIBITOR	Ki	8.22		CHEMBL	CHEMBL
Sodium-dependent serotonin transporter	Transporter	P31645	SC6A4_HUMAN	INHIBITOR	Ki	9.62		CHEMBL	CHEMBL
5-hydroxytryptamine receptor 2C	GPCR	P28335	5HT2C_HUMAN	ANTAGONIST	Ki	6		IUPHAR
Sodium-dependent dopamine transporter	Transporter	Q01959	SC6A3_HUMAN		Ki	6.62		CHEMBL
5-hydroxytryptamine receptor 2B	GPCR	P41595	5HT2B_HUMAN		Ki	5.68		PDSP
5-hydroxytryptamine receptor 7	GPCR	P34969	5HT7R_HUMAN		Ki	5.65		PDSP
Histamine H1 receptor	GPCR	P35367	HRH1_HUMAN		Ki	5.64		PDSP
5-hydroxytryptamine receptor 1D	GPCR	P28221	5HT1D_HUMAN		Ki	5.52		PDSP
5-hydroxytryptamine receptor 1E	GPCR	P28566	5HT1E_HUMAN		Ki	5.43		PDSP
5-hydroxytryptamine receptor 1B	GPCR	P28222	5HT1B_HUMAN		Ki	5.40		PDSP
5-hydroxytryptamine receptor 1F	GPCR	P30939	5HT1F_HUMAN		Ki	5.35		PDSP
5-hydroxytryptamine receptor 6	GPCR	P50406	5HT6R_HUMAN	ANTAGONIST	Ki	6.40		IUPHAR
5-hydroxytryptamine receptor 1A	GPCR	P08908	5HT1A_HUMAN		Ki	5.30		PDSP
5-hydroxytryptamine receptor 2A	GPCR	P28223	5HT2A_HUMAN	ANTAGONIST	Ki	6.30		IUPHAR
Sodium-dependent dopamine transporter	Transporter		SC6A3_RAT		IC50	6.43		CHEMBL
Sodium-dependent serotonin transporter	Transporter		SC6A4_RAT		Ki	10.09		CHEMBL
Transporter	Transporter		Q63380_RAT		Ki	8.52		CHEMBL

External reference:

ID	Source
D01179	KEGG_DRUG
136434-34-9	SECONDARY_CAS_RN
4021477	VANDF
C4256038	UMLSCUI
CHEBI:36795	CHEBI
29E	PDB_CHEM_ID
60835	PUBCHEM_CID
CHEMBL1175	ChEMBL_ID
CHEMBL1200328	ChEMBL_ID
DB00476	DRUGBANK_ID
D000068736	MESH_DESCRIPTOR_UI
202	IUPHAR_LIGAND_ID
7012	INN_ID
O5TNM5N07U	UNII
476250	RXNORM
18760	MMSL
208014	MMSL
33554	MMSL
59319	MMSL
d05355	MMSL
008705	NDDF
008707	NDDF
407032004	SNOMEDCT_US
407033009	SNOMEDCT_US
426892003	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Cymbalta	HUMAN PRESCRIPTION DRUG LABEL	1	0002-3235	CAPSULE, DELAYED RELEASE	20 mg	ORAL	NDA	36 sections
Cymbalta	HUMAN PRESCRIPTION DRUG LABEL	1	0002-3240	CAPSULE, DELAYED RELEASE	30 mg	ORAL	NDA	36 sections
Cymbalta	HUMAN PRESCRIPTION DRUG LABEL	1	0002-3270	CAPSULE, DELAYED RELEASE	60 mg	ORAL	NDA	36 sections
Duloxetine	HUMAN PRESCRIPTION DRUG LABEL	1	0228-2890	CAPSULE, DELAYED RELEASE PELLETS	20 mg	ORAL	ANDA	29 sections
Duloxetine	HUMAN PRESCRIPTION DRUG LABEL	1	0228-2891	CAPSULE, DELAYED RELEASE PELLETS	30 mg	ORAL	ANDA	29 sections
Duloxetine	HUMAN PRESCRIPTION DRUG LABEL	1	0228-2892	CAPSULE, DELAYED RELEASE PELLETS	60 mg	ORAL	ANDA	29 sections
Duloxetine hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	0615-8203	CAPSULE, DELAYED RELEASE	30 mg	ORAL	ANDA	31 sections
Duloxetine hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	0615-8204	CAPSULE, DELAYED RELEASE	60 mg	ORAL	ANDA	31 sections
Duloxetine hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	0615-8290	CAPSULE, DELAYED RELEASE	20 mg	ORAL	ANDA	30 sections
Duloxetine Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	0904-6452	CAPSULE, DELAYED RELEASE	20 mg	ORAL	ANDA	30 sections
Duloxetine Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	0904-6453	CAPSULE, DELAYED RELEASE	30 mg	ORAL	ANDA	30 sections
Duloxetine Hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	0904-6454	CAPSULE, DELAYED RELEASE	60 mg	ORAL	ANDA	30 sections
Duloxetine	HUMAN PRESCRIPTION DRUG LABEL	1	0904-7043	CAPSULE, DELAYED RELEASE	20 mg	ORAL	ANDA	31 sections
Duloxetine	HUMAN PRESCRIPTION DRUG LABEL	1	0904-7044	CAPSULE, DELAYED RELEASE	30 mg	ORAL	ANDA	31 sections
Duloxetine	HUMAN PRESCRIPTION DRUG LABEL	1	0904-7045	CAPSULE, DELAYED RELEASE	60 mg	ORAL	ANDA	31 sections
Duloxetine hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	13668-109	CAPSULE, DELAYED RELEASE	20 mg	ORAL	ANDA	30 sections
Duloxetine hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	13668-110	CAPSULE, DELAYED RELEASE	30 mg	ORAL	ANDA	30 sections
Duloxetine hydrochloride	HUMAN PRESCRIPTION DRUG LABEL	1	13668-111	CAPSULE, DELAYED RELEASE	60 mg	ORAL	ANDA	30 sections
Cymbalta	HUMAN PRESCRIPTION DRUG LABEL	1	21695-145	CAPSULE, DELAYED RELEASE	30 mg	ORAL	NDA	34 sections
Cymbalta	HUMAN PRESCRIPTION DRUG LABEL	1	21695-146	CAPSULE, DELAYED RELEASE	60 mg	ORAL	NDA	34 sections
Cymbalta	HUMAN PRESCRIPTION DRUG LABEL	1	21695-657	CAPSULE, DELAYED RELEASE	20 mg	ORAL	NDA	34 sections
Duloxetine	Human Prescription Drug Label	1	27241-097	CAPSULE, DELAYED RELEASE	20 mg	ORAL	ANDA	31 sections
Duloxetine	Human Prescription Drug Label	1	27241-098	CAPSULE, DELAYED RELEASE	30 mg	ORAL	ANDA	31 sections
Duloxetine	Human Prescription Drug Label	1	27241-099	CAPSULE, DELAYED RELEASE	60 mg	ORAL	ANDA	31 sections
Duloxetine	Human Prescription Drug Label	1	27241-164	CAPSULE, DELAYED RELEASE	40 mg	ORAL	ANDA	31 sections
Irenka	HUMAN PRESCRIPTION DRUG LABEL	1	27437-298	CAPSULE, DELAYED RELEASE	40 mg	ORAL	ANDA	26 sections
Duloxetine	Human Prescription Drug Label	1	31722-581	CAPSULE, DELAYED RELEASE	20 mg	ORAL	ANDA	30 sections
Duloxetine	Human Prescription Drug Label	1	31722-582	CAPSULE, DELAYED RELEASE	30 mg	ORAL	ANDA	30 sections
Duloxetine	Human Prescription Drug Label	1	31722-583	CAPSULE, DELAYED RELEASE	60 mg	ORAL	ANDA	30 sections
Duloxetine Hydrochloride	Human Prescription Drug Label	1	33342-160	CAPSULE, DELAYED RELEASE	20 mg	ORAL	ANDA	31 sections