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	3952.10	9.73	1999	203533	26023	53117511
Dysphoria	3414.48	9.73	1129	204403	4220	53139314
Affect lability	2820.54	9.73	1136	204396	8239	53135295
Irritability	2203.63	9.73	1413	204119	29540	53113994
Suicidal ideation	1850.48	9.73	1667	203865	58844	53084690
Agitation	1655.92	9.73	1545	203987	57081	53086453
Paraesthesia	1357.24	9.73	2037	203495	125478	53018056
Sensory disturbance	1302.00	9.73	737	204795	12149	53131385
Hyperhidrosis	1206.26	9.73	1667	203865	95126	53048408
Vertigo	1194.68	9.73	1268	204264	54813	53088721
Anxiety	1148.55	9.73	2415	203117	194289	52949245
Insomnia	1119.25	9.73	2320	203212	184752	52958782
Nightmare	793.95	9.73	610	204922	17141	53126393
Dizziness	720.43	9.73	3087	202445	369172	52774362
Mood swings	719.49	9.73	572	204960	16914	53126620
Tinnitus	607.28	9.73	666	204866	29853	53113681
Hypomania	544.31	9.73	298	205234	4584	53138950
Lethargy	516.38	9.73	820	204712	52940	53090594
Tremor	501.49	9.73	1332	204200	124404	53019130
Serotonin syndrome	488.86	9.73	555	204977	25851	53117683
Confusional state	475.65	9.73	1736	203796	192485	52951049
Depression	423.75	9.73	1607	203925	181445	52962089
Pemphigus	383.49	9.73	3	205529	104028	53039506
Headache	314.34	9.73	3301	202231	533520	52610014
Withdrawal syndrome	298.27	9.73	370	205162	18931	53124603
Suicide attempt	268.86	9.73	652	204880	57516	53086018
Glossodynia	247.07	9.73	44	205488	100247	53043287
Nausea	241.77	9.73	4167	201365	751924	52391610
Maternal exposure during pregnancy	235.40	9.73	155	205377	155484	52988050
Neutropenia	232.14	9.73	165	205367	159020	52984514
Hand deformity	227.86	9.73	29	205503	84820	53058714
Alopecia	223.44	9.73	349	205183	234234	52909300
Febrile neutropenia	218.93	9.73	66	205466	104870	53038664
Sleep disorder	214.77	9.73	604	204928	58266	53085268
Anaemia	212.84	9.73	469	205063	276249	52867285
Systemic lupus erythematosus	212.21	9.73	109	205423	125305	53018229
Pyrexia	210.15	9.73	821	204711	402372	52741162
Contraindicated product administered	205.18	9.73	135	205397	135494	53008040
Crying	203.28	9.73	332	205200	21930	53121604
Disturbance in attention	193.87	9.73	417	205115	33966	53109568
Fibromyalgia	177.51	9.73	469	205063	43606	53099928
Synovitis	170.61	9.73	102	205430	107791	53035743
Feeling abnormal	169.42	9.73	994	204538	134307	53009227
Thrombocytopenia	168.91	9.73	171	205361	138556	53004978
Completed suicide	168.36	9.73	1008	204524	137193	53006341
Stubbornness	165.29	9.73	56	205476	229	53143305
Pericarditis	161.36	9.73	27	205505	64379	53079155
Acute kidney injury	161.33	9.73	474	205058	253394	52890140
Rash	155.99	9.73	1043	204489	445148	52698386
Wound	148.38	9.73	84	205448	91473	53052061
Drug intolerance	147.65	9.73	361	205171	205132	52938402
Mood altered	144.47	9.73	220	205312	13681	53129853
Pancytopenia	142.29	9.73	87	205445	90841	53052693
Treatment failure	137.05	9.73	176	205356	128227	53015307
Abdominal discomfort	135.91	9.73	419	205113	220643	52922891
Memory impairment	133.37	9.73	663	204869	84094	53059440
Rheumatoid arthritis	133.30	9.73	691	204841	313840	52829694
Fatigue	132.54	9.73	3714	201818	726792	52416742
Infusion related reaction	131.92	9.73	250	205282	155707	52987827
Hypersensitivity	121.34	9.73	411	205121	210254	52933280
Electric shock	120.31	9.73	65	205467	972	53142562
Thinking abnormal	120.25	9.73	174	205358	10334	53133200
Dyspnoea	119.88	9.73	1567	203965	584665	52558869
Anger	118.87	9.73	189	205343	12201	53131333
Arthropathy	117.66	9.73	229	205303	141224	53002310
Duodenal ulcer perforation	117.50	9.73	4	205528	35179	53108355
Somnolence	117.25	9.73	1072	204460	166662	52976872
Panic attack	116.43	9.73	256	205276	21162	53122372
Joint swelling	114.31	9.73	490	205042	234148	52909386
Migraine	109.93	9.73	605	204927	79812	53063722
Discomfort	106.97	9.73	126	205406	95346	53048188
Malignant neoplasm progression	105.73	9.73	73	205459	71468	53072066
Pneumonia	105.66	9.73	1031	204501	406138	52737396
General physical health deterioration	103.25	9.73	261	205271	146681	52996853
Lower respiratory tract infection	103.09	9.73	119	205413	90862	53052672
Disease progression	101.38	9.73	147	205385	101773	53041761
Platelet count decreased	99.78	9.73	164	205368	107935	53035599
Swelling	98.09	9.73	391	205141	190714	52952820
Depressed mood	96.65	9.73	338	205194	36626	53106908
Cardiac failure	93.30	9.73	116	205416	85728	53057806
Anti-cyclic citrullinated peptide antibody positive	93.26	9.73	52	205480	57120	53086414
Septic shock	92.62	9.73	63	205469	62166	53081368
Drug reaction with eosinophilia and systemic symptoms	88.54	9.73	11	205521	32789	53110745
Off label use	86.11	9.73	1291	204241	470921	52672613
Gastrointestinal tube insertion	84.74	9.73	54	205478	1113	53142421
Sepsis	83.36	9.73	287	205245	146142	52997392
Gastric bypass	83.16	9.73	59	205473	1461	53142073
Intentional product misuse	83.15	9.73	394	205138	48998	53094536
Folliculitis	82.35	9.73	12	205520	31697	53111837
C-reactive protein abnormal	79.73	9.73	5	205527	25865	53117669
Affective disorder	77.37	9.73	101	205431	5438	53138096
Sleep disorder due to general medical condition, insomnia type	77.21	9.73	4	205528	24345	53119189
Coordination abnormal	76.80	9.73	153	205379	11798	53131736
Restless legs syndrome	76.28	9.73	190	205342	17033	53126501
Infection	75.27	9.73	374	205158	171831	52971703
Erythema	75.04	9.73	330	205202	156639	52986895
Renal impairment	73.58	9.73	130	205402	83188	53060346
Neutrophil count decreased	72.68	9.73	50	205482	49048	53094486
Tardive dyskinesia	71.83	9.73	119	205413	7951	53135583
Inappropriate antidiuretic hormone secretion	71.62	9.73	170	205362	14781	53128753
Blood creatinine increased	71.18	9.73	131	205401	82531	53061003
Haemoglobin decreased	69.74	9.73	282	205250	137025	53006509
Mucosal inflammation	69.66	9.73	39	205493	42745	53100789
Interstitial lung disease	68.22	9.73	75	205457	58547	53084987
Aggression	67.34	9.73	221	205311	23182	53120352
Pleural effusion	67.23	9.73	151	205381	88428	53055106
Multiple sclerosis relapse	66.41	9.73	345	205187	44508	53099026
Abnormal behaviour	66.10	9.73	210	205322	21656	53121878
Post-traumatic stress disorder	65.28	9.73	86	205446	4672	53138862
Muscle injury	65.25	9.73	17	205515	29749	53113785
Premature delivery	65.25	9.73	11	205521	26093	53117441
Drug ineffective	65.23	9.73	2534	202998	814711	52328823
Fall	64.15	9.73	1821	203711	356619	52786915
Amnesia	64.07	9.73	344	205188	44944	53098590
Leukopenia	63.63	9.73	116	205416	73347	53070187
Ascites	63.57	9.73	37	205495	39698	53103836
Therapeutic product effect decreased	63.23	9.73	259	205273	125396	53018138
Stomatitis	63.16	9.73	182	205350	97976	53045558
Product substitution issue	63.01	9.73	168	205364	15698	53127836
Abnormal dreams	62.54	9.73	131	205401	10470	53133064
Death	62.51	9.73	984	204548	356248	52787286
Renal failure	60.95	9.73	242	205290	118210	53025324
Pneumonia aspiration	60.95	9.73	278	205254	34023	53109511
Blister	60.79	9.73	133	205399	78620	53064914
Therapy interrupted	59.98	9.73	188	205344	19248	53124286
Product use issue	59.36	9.73	306	205226	139278	53004256
Bone marrow failure	59.15	9.73	21	205511	30094	53113440
Atrial fibrillation	58.80	9.73	226	205306	111426	53032108
Somatic symptom disorder	58.56	9.73	55	205477	2043	53141491
Mania	58.29	9.73	136	205396	11693	53131841
Peripheral swelling	57.57	9.73	512	205020	205596	52937938
Prescribed overdose	57.33	9.73	149	205383	13710	53129824
Coma	57.19	9.73	421	205111	61362	53082172
Multiple organ dysfunction syndrome	56.64	9.73	79	205453	55598	53087936
Sopor	56.16	9.73	194	205338	20890	53122644
Loss of consciousness	56.15	9.73	680	204852	113532	53030002
Intentional self-injury	55.87	9.73	219	205313	25065	53118469
Alanine aminotransferase increased	55.25	9.73	585	204947	94510	53049024
Hallucination	53.38	9.73	373	205159	53465	53090069
Rheumatoid factor positive	53.34	9.73	48	205484	41150	53102384
Hyperkalaemia	53.20	9.73	79	205453	54177	53089357
White blood cell count abnormal	53.15	9.73	83	205449	5275	53138259
White blood cell count decreased	52.85	9.73	273	205259	124202	53019332
Impaired healing	52.43	9.73	105	205427	64100	53079434
Cytomegalovirus infection	51.66	9.73	7	205525	19532	53124002
Dry mouth	50.20	9.73	397	205135	59153	53084381
Lactic acidosis	49.94	9.73	42	205490	37211	53106323
Hypotension	49.90	9.73	684	204848	253392	52890142
Drug interaction	48.41	9.73	1146	204386	218183	52925351
Hallucination, visual	48.18	9.73	171	205361	18661	53124873
Gastrointestinal haemorrhage	47.36	9.73	155	205377	80175	53063359
Coma blister	47.34	9.73	19	205513	136	53143398
Cardiac failure congestive	46.77	9.73	191	205341	92566	53050968
Neck deformity	46.74	9.73	48	205484	1991	53141543
Hypocalcaemia	45.97	9.73	28	205504	29309	53114225
Extremity contracture	45.72	9.73	39	205493	1274	53142260
Nasal turbinate hypertrophy	45.45	9.73	30	205502	658	53142876
Intervertebral discitis	45.12	9.73	55	205477	2762	53140772
Respiratory failure	44.05	9.73	218	205314	100294	53043240
Device expulsion	43.27	9.73	31	205501	29782	53113752
Pulmonary oedema	42.90	9.73	89	205443	53634	53089900
Helicobacter infection	42.22	9.73	53	205479	39016	53104518
Muscle twitching	41.90	9.73	149	205383	16277	53127257
Weight increased	41.87	9.73	1058	204474	203509	52940025
Seizure	40.23	9.73	712	204820	128797	53014737
Neck mass	40.16	9.73	58	205474	3438	53140096
Sleep apnoea syndrome	39.87	9.73	202	205330	25800	53117734
Aspartate aminotransferase increased	39.86	9.73	497	205035	83532	53060002
Gastrointestinal disorder	39.56	9.73	195	205337	89809	53053725
Pulmonary fibrosis	39.28	9.73	22	205510	24113	53119421
Oedema peripheral	39.05	9.73	445	205087	170342	52973192
Cough	38.92	9.73	726	204806	256167	52887367
Rapid eye movements sleep abnormal	38.03	9.73	15	205517	102	53143432
Palmar-plantar erythrodysaesthesia syndrome	37.69	9.73	18	205514	21588	53121946
Colitis microscopic	37.66	9.73	84	205448	7010	53136524
Restlessness	37.48	9.73	210	205322	27877	53115657
Balance disorder	37.34	9.73	439	205093	72768	53070766
Vision blurred	37.10	9.73	498	205034	85106	53058428
Influenza like illness	37.04	9.73	378	205154	60481	53083053
Ill-defined disorder	36.93	9.73	85	205447	49359	53094175
Dehydration	36.88	9.73	443	205089	167967	52975567
Surgery	36.86	9.73	230	205302	31734	53111800
Dyskinesia	36.67	9.73	229	205303	31604	53111930
Hyperaesthesia	36.54	9.73	94	205438	8595	53134939
Neoplasm progression	36.24	9.73	37	205495	29882	53113652
Multiple sclerosis	36.22	9.73	203	205329	26950	53116584
Urinary retention	36.12	9.73	210	205322	28256	53115278
Nervousness	35.96	9.73	219	205313	29959	53113575
Product use in unapproved indication	35.86	9.73	269	205263	112020	53031514
Metabolic surgery	35.57	9.73	31	205501	1043	53142491
Concussion	35.51	9.73	87	205445	7717	53135817
Pruritus	35.30	9.73	862	204670	292970	52850564
Hyperreflexia	35.02	9.73	70	205462	5410	53138124
Hypomagnesaemia	34.47	9.73	27	205505	24784	53118750
Temperature intolerance	34.08	9.73	88	205444	8065	53135469
Tachyphrenia	33.97	9.73	34	205498	1367	53142167
Bradycardia	33.55	9.73	150	205382	70906	53072628
Pulmonary malformation	33.32	9.73	15	205517	147	53143387
Opsoclonus myoclonus	33.23	9.73	15	205517	148	53143386
Hypersomnia	33.21	9.73	138	205394	16217	53127317
Hot flush	33.18	9.73	302	205230	46858	53096676
Cognitive disorder	33.18	9.73	290	205242	44488	53099046
Epistaxis	33.08	9.73	144	205388	68566	53074968
Paranoia	32.97	9.73	108	205424	11316	53132218
Impaired driving ability	32.44	9.73	59	205473	4248	53139286
Akathisia	32.27	9.73	89	205443	8482	53135052
Rheumatoid nodule	31.97	9.73	4	205528	11860	53131674
Deep vein thrombosis	31.81	9.73	188	205344	82725	53060809
Bronchial neoplasm	31.73	9.73	20	205512	404	53143130
Morbid thoughts	31.68	9.73	23	205509	591	53142943
Rubber sensitivity	31.51	9.73	38	205494	1887	53141647
Rash maculo-papular	31.48	9.73	41	205491	29708	53113826
Hypokalaemia	31.40	9.73	230	205302	96287	53047247
Psychotic disorder due to a general medical condition	31.38	9.73	16	205516	211	53143323
Sacroiliitis	30.97	9.73	43	205489	2457	53141077
Disorientation	30.26	9.73	257	205275	39102	53104432
Bipolar disorder	30.13	9.73	81	205451	7605	53135929
Therapy cessation	30.06	9.73	198	205334	27827	53115707
Melaena	29.95	9.73	41	205491	29088	53114446
Libido decreased	29.75	9.73	44	205488	2665	53140869
Acute myeloid leukaemia	29.69	9.73	14	205518	16918	53126616
Hostility	29.59	9.73	34	205498	1603	53141931
Anorgasmia	29.59	9.73	22	205510	587	53142947
Pulmonary eosinophilia	29.51	9.73	16	205516	241	53143293
Haemoptysis	29.30	9.73	39	205493	28000	53115534
Loss of libido	29.30	9.73	31	205501	1332	53142202
Stiff person syndrome	29.28	9.73	16	205516	245	53143289
Product dose omission issue	29.21	9.73	955	204577	190665	52952869
Personality disorder	29.12	9.73	55	205477	4076	53139458
Proteinuria	28.65	9.73	17	205515	18051	53125483
Bruxism	28.58	9.73	48	205484	3243	53140291
Mental disorder	28.48	9.73	176	205356	24200	53119334
Gastric banding	28.37	9.73	11	205521	71	53143463
C-reactive protein increased	28.18	9.73	150	205382	67736	53075798
Bronchial haemorrhage	28.02	9.73	20	205512	500	53143034
Blood pressure increased	27.97	9.73	724	204808	139755	53003779
Formication	27.69	9.73	53	205479	3968	53139566
Pre-existing condition improved	27.54	9.73	81	205451	8008	53135526
Condition aggravated	27.44	9.73	904	204628	296230	52847304
Drug resistance	27.38	9.73	22	205510	19940	53123594
Bone density abnormal	27.30	9.73	46	205486	3116	53140418
Complex regional pain syndrome	27.19	9.73	38	205494	2185	53141349
Dissociation	27.04	9.73	38	205494	2196	53141338
Anaphylactic reaction	27.01	9.73	124	205408	58202	53085332
Agranulocytosis	26.95	9.73	31	205501	23718	53119816
Reversible cerebral vasoconstriction syndrome	26.90	9.73	38	205494	2207	53141327
Metastases to bone	26.89	9.73	21	205511	19307	53124227
Tearfulness	26.30	9.73	53	205479	4121	53139413
Gastrooesophageal reflux disease	26.21	9.73	456	205076	82207	53061327
Coronary artery disease	26.18	9.73	56	205476	33381	53110153
Autonomic dysreflexia	26.02	9.73	16	205516	309	53143225
Hip arthroplasty	25.94	9.73	42	205490	27820	53115714
Acute respiratory distress syndrome	25.90	9.73	31	205501	23301	53120233
Speech disorder	25.61	9.73	247	205285	38934	53104600
Live birth	25.58	9.73	13	205519	15046	53128488
Cerebral infarction	25.54	9.73	34	205498	24410	53119124
Gastrostomy	25.53	9.73	20	205512	578	53142956
Disseminated intravascular coagulation	25.50	9.73	23	205509	19696	53123838
Anovulatory cycle	25.37	9.73	12	205520	133	53143401
Pregnancy	25.17	9.73	52	205480	31389	53112145
Pulmonary arterial hypertension	25.14	9.73	41	205491	27081	53116453
Vomiting	25.10	9.73	2232	203300	494907	52648627
Libido increased	24.99	9.73	26	205506	1095	53142439
Delusion	24.91	9.73	102	205430	11907	53131627
Hypoglycaemia	24.71	9.73	130	205402	58883	53084651
Ejection fraction decreased	24.66	9.73	24	205508	19824	53123710
Metastases to liver	24.46	9.73	28	205504	21468	53122066
Oesophageal spasm	24.39	9.73	39	205493	2529	53141005
Major depression	24.00	9.73	74	205458	7508	53136026
Torsade de pointes	23.99	9.73	10	205522	12995	53130539
Pneumonitis	23.96	9.73	52	205480	30836	53112698
Neuralgia	23.92	9.73	164	205368	23357	53120177
Head injury	23.87	9.73	176	205356	25657	53117877
Plasma cell myeloma	23.86	9.73	99	205433	47775	53095759
Rebound nasal congestion	23.75	9.73	8	205524	32	53143502
Psychotic disorder	23.61	9.73	168	205364	24217	53119317
Psychomotor hyperactivity	23.57	9.73	89	205443	10007	53133527
Sleep terror	23.40	9.73	22	205510	818	53142716
Cholestasis	23.36	9.73	47	205485	28648	53114886
Foetal death	23.22	9.73	4	205528	9343	53134191
Thrombotic microangiopathy	23.19	9.73	4	205528	9333	53134201
Hypoxia	23.12	9.73	123	205409	55557	53087977
Emotional disorder	22.69	9.73	105	205427	12925	53130609
Drug hypersensitivity	22.68	9.73	1244	204288	263998	52879536
Nasopharyngitis	22.28	9.73	567	204965	191728	52951806
Respiratory distress	22.28	9.73	62	205470	33765	53109769
Endometrial ablation	22.18	9.73	22	205510	875	53142659
Thunderclap headache	22.12	9.73	12	205520	181	53143353
Myelodysplastic syndrome	22.06	9.73	19	205513	16641	53126893
Dyspnoea exertional	22.01	9.73	123	205409	54877	53088657
Eosinophilia	21.97	9.73	30	205502	21305	53122229
Hyperglycaemia	21.83	9.73	80	205452	40004	53103530
Peritonitis bacterial	21.67	9.73	5	205527	9500	53134034
Angioedema	21.60	9.73	86	205446	41990	53101544
Toxic epidermal necrolysis	21.46	9.73	36	205496	23514	53120020
Shock	21.43	9.73	35	205497	23104	53120430
Hallucination, auditory	21.34	9.73	96	205436	11677	53131857
Hypoaesthesia	21.34	9.73	667	204865	132328	53011206
Irritable bowel syndrome	21.27	9.73	91	205441	43541	53099993
Depressive symptom	21.23	9.73	42	205490	3222	53140312
Decreased interest	21.15	9.73	42	205490	3231	53140303
Myocardial infarction	21.11	9.73	263	205269	99091	53044443
Mydriasis	21.02	9.73	93	205439	11233	53132301
Peritonitis	20.85	9.73	32	205500	21655	53121879
Hypoalbuminaemia	20.84	9.73	8	205524	10928	53132606
Circulatory collapse	20.44	9.73	35	205497	22679	53120855
Blood calcium decreased	20.21	9.73	28	205504	19766	53123768
Right ventricular failure	20.20	9.73	21	205511	16822	53126712
Pneumocystis jirovecii pneumonia	20.12	9.73	20	205512	16358	53127176
Metabolic acidosis	20.04	9.73	89	205443	42153	53101381
Toxic skin eruption	19.95	9.73	13	205519	13126	53130408
Accidental exposure to product	19.94	9.73	38	205494	23636	53119898
Granulomatous liver disease	19.87	9.73	20	205512	810	53142724
Galactorrhoea	19.76	9.73	46	205486	3949	53139585
Aplastic anaemia	19.73	9.73	4	205528	8317	53135217
Skin necrosis	19.71	9.73	8	205524	10564	53132970
Clonus	19.70	9.73	48	205484	4243	53139291
Antinuclear antibody negative	19.68	9.73	12	205520	228	53143306
Abdominal pain	19.68	9.73	796	204736	255107	52888427
Tuberculosis	19.65	9.73	9	205523	11062	53132472
Cardiogenic shock	19.64	9.73	23	205509	17459	53126075
Pulmonary congestion	19.54	9.73	20	205512	16136	53127398
Haemodialysis	19.44	9.73	6	205526	9398	53134136
Phagophobia	19.37	9.73	7	205525	36	53143498
Tubulointerstitial nephritis	19.32	9.73	21	205511	16483	53127051
Homicidal ideation	19.26	9.73	29	205503	1785	53141749
Aspergillus infection	19.09	9.73	3	205529	7493	53136041
Macular degeneration	19.08	9.73	12	205520	12349	53131185
Angina unstable	18.99	9.73	3	205529	7465	53136069
Liver function test increased	18.91	9.73	47	205485	26581	53116953
Hypercalcaemia	18.88	9.73	41	205491	24307	53119227
Coombs positive haemolytic anaemia	18.75	9.73	14	205518	376	53143158
Flat affect	18.67	9.73	25	205507	1380	53142154
Metastases to lung	18.58	9.73	11	205521	11693	53131841
Ankle fracture	18.52	9.73	118	205414	16397	53127137
Conversion disorder	18.50	9.73	28	205504	1731	53141803
Osteonecrosis of jaw	18.48	9.73	74	205458	36072	53107462
Infective pulmonary exacerbation of cystic fibrosis	18.40	9.73	10	205522	11146	53132388
Fluid overload	18.33	9.73	51	205481	27780	53115754
Haematotoxicity	18.31	9.73	4	205528	7893	53135641
Asphyxia	18.13	9.73	57	205475	5844	53137690
Demyelination	18.09	9.73	59	205473	6168	53137366
Bacteraemia	17.97	9.73	20	205512	15529	53128005
Hypnopompic hallucination	17.95	9.73	7	205525	46	53143488
Pustular psoriasis	17.93	9.73	46	205486	4198	53139336
Ischaemic stroke	17.83	9.73	26	205506	17967	53125567
Gait disturbance	17.77	9.73	765	204767	158077	52985457
Tenosynovitis	17.77	9.73	8	205524	9931	53133603
Premature labour	17.75	9.73	13	205519	12349	53131185
Respiratory tract malformation	17.72	9.73	8	205524	79	53143455
Acute myocardial infarction	17.66	9.73	67	205465	33168	53110366
CYP3A4 polymorphism	17.63	9.73	8	205524	80	53143454
Decreased appetite	17.54	9.73	664	204868	214310	52929224
Road traffic accident	17.45	9.73	163	205369	25468	53118066
Drug screen positive	17.44	9.73	43	205489	3829	53139705
Tension	17.38	9.73	39	205493	3267	53140267
Hyperacusis	17.38	9.73	29	205503	1949	53141585
Inflammation	17.24	9.73	139	205393	56997	53086537
Oliguria	17.21	9.73	7	205525	9231	53134303
Device related infection	17.15	9.73	39	205493	22747	53120787
Lung cyst	17.05	9.73	9	205523	128	53143406
Dysphemia	17.05	9.73	33	205499	2491	53141043
Middle insomnia	16.99	9.73	84	205448	10624	53132910
Spinal operation	16.87	9.73	59	205473	6392	53137142
Pulseless electrical activity	16.83	9.73	4	205528	7450	53136084
Pulmonary embolism	16.81	9.73	325	205207	114117	53029417
Panic disorder	16.78	9.73	34	205498	2654	53140880
Haemorrhage	16.62	9.73	143	205389	57844	53085690
Drug eruption	16.52	9.73	46	205486	25048	53118486
Impulse-control disorder	16.39	9.73	18	205514	807	53142727
Breast cancer metastatic	16.34	9.73	21	205511	15307	53128227
Caesarean section	16.23	9.73	26	205506	17294	53126240
Sleep talking	16.22	9.73	20	205512	1016	53142518
Basal cell carcinoma	16.22	9.73	42	205490	23427	53120107
Therapeutic response changed	16.20	9.73	19	205513	916	53142618
Diplopia	16.17	9.73	136	205396	20629	53122905
Muscle spasms	16.17	9.73	654	204878	134141	53009393
Diffuse large B-cell lymphoma	16.10	9.73	3	205529	6622	53136912
Myoclonus	16.08	9.73	110	205422	15654	53127880
Polyarthritis	16.05	9.73	5	205527	7784	53135750
Mean cell haemoglobin concentration increased	16.04	9.73	14	205518	472	53143062
Gastric ulcer	16.01	9.73	42	205490	23327	53120207
Apathy	16.00	9.73	69	205463	8243	53135291
Bipolar I disorder	15.98	9.73	26	205506	1711	53141823
Tic	15.98	9.73	23	205509	1359	53142175
Pathogen resistance	15.88	9.73	3	205529	6557	53136977
Self-injurious ideation	15.79	9.73	31	205501	2365	53141169
Second primary malignancy	15.77	9.73	4	205528	7128	53136406
Heart rate decreased	15.69	9.73	81	205451	36866	53106668
Metastases to central nervous system	15.66	9.73	14	205518	12043	53131491
Chronic obstructive pulmonary disease	15.61	9.73	155	205377	60918	53082616
Hyponatraemic encephalopathy	15.55	9.73	11	205521	271	53143263
Mobility decreased	15.42	9.73	204	205328	76067	53067467
Feeling of despair	15.39	9.73	28	205504	2017	53141517
Feelings of worthlessness	15.37	9.73	12	205520	345	53143189
Hepatitis C antibody positive	15.33	9.73	8	205524	111	53143423
Respiratory tract infection	15.16	9.73	71	205461	33153	53110381
Intervertebral disc protrusion	15.16	9.73	140	205392	21805	53121729
Pulmonary haemorrhage	15.12	9.73	4	205528	6929	53136605
Pulmonary hypertension	15.10	9.73	83	205449	37187	53106347
Therapy non-responder	15.05	9.73	119	205413	49001	53094533
Intentional overdose	15.05	9.73	352	205180	66853	53076681
Haemolytic anaemia	14.96	9.73	11	205521	10428	53133106
Metastases to lymph nodes	14.93	9.73	5	205527	7435	53136099
Pseudomonas infection	14.93	9.73	11	205521	10417	53133117
Poor quality sleep	14.87	9.73	116	205416	17207	53126327
Intentional dose omission	14.83	9.73	48	205484	4997	53138537
Congenital tricuspid valve atresia	14.83	9.73	6	205526	44	53143490
Stillbirth	14.67	9.73	4	205528	6793	53136741
Lung disorder	14.67	9.73	116	205416	47763	53095771
Herpes simplex reactivation	14.65	9.73	12	205520	370	53143164
Panic reaction	14.64	9.73	41	205491	3942	53139592
Haematuria	14.59	9.73	58	205474	28331	53115203
Ophthalmic vein thrombosis	14.55	9.73	8	205524	124	53143410
Red blood cell count decreased	14.53	9.73	80	205452	35823	53107711
Impatience	14.52	9.73	12	205520	375	53143159
Anaphylactic shock	14.51	9.73	40	205492	21853	53121681
Immunisation reaction	14.47	9.73	5	205527	22	53143512
Oesophageal food impaction	14.45	9.73	9	205523	178	53143356
Transfusion	14.34	9.73	19	205513	13668	53129866
Oxygen saturation decreased	14.16	9.73	209	205323	76516	53067018
Cataplexy	14.10	9.73	21	205511	1280	53142254
Chest discomfort	14.07	9.73	285	205247	99410	53044124
Arteriosclerosis coronary artery	13.90	9.73	67	205465	8387	53135147
Spondyloarthropathy	13.90	9.73	16	205516	756	53142778
Scar	13.81	9.73	90	205442	12603	53130931
Cerebral haemorrhage	13.75	9.73	64	205468	29932	53113602
Bradyphrenia	13.74	9.73	57	205475	6693	53136841
Phobia of driving	13.69	9.73	3	205529	0	53143534
Overdose	13.69	9.73	526	205006	107210	53036324
Productive cough	13.67	9.73	146	205386	56583	53086951
Alcoholism	13.66	9.73	28	205504	2203	53141331
Tachyphylaxis	13.57	9.73	10	205522	263	53143271
Rales	13.57	9.73	13	205519	10819	53132715
Abortion induced	13.56	9.73	13	205519	10813	53132721
Blood lactate dehydrogenase increased	13.55	9.73	41	205491	21740	53121794
Uraemic encephalopathy	13.49	9.73	9	205523	201	53143333
Bronchial disorder	13.46	9.73	20	205512	1216	53142318
Trigeminal neuralgia	13.42	9.73	35	205497	3226	53140308
Red blood cell sedimentation rate increased	13.38	9.73	59	205473	27998	53115536
Bone erosion	13.27	9.73	14	205518	11138	53132396
Feeling drunk	13.27	9.73	40	205492	4009	53139525
Depression suicidal	13.25	9.73	23	205509	1596	53141938
Oedema	13.21	9.73	204	205328	74142	53069392
Lung diffusion test decreased	13.18	9.73	15	205517	700	53142834
Poisoning	13.16	9.73	95	205437	13755	53129779
Drug abuse	13.11	9.73	338	205194	65188	53078346
Tumour lysis syndrome	13.07	9.73	7	205525	7867	53135667
Gun shot wound	13.00	9.73	7	205525	104	53143430
Gambling disorder	12.94	9.73	21	205511	1379	53142155
Blood pressure diastolic abnormal	12.81	9.73	9	205523	8736	53134798
Urinary incontinence	12.81	9.73	178	205354	30643	53112891
Holmes-Adie pupil	12.80	9.73	5	205527	33	53143501
Sensitivity to weather change	12.70	9.73	52	205480	6070	53137464
Autonomic nervous system imbalance	12.67	9.73	30	205502	2604	53140930
Fear of injection	12.62	9.73	3	205529	5586	53137948
Cardiac arrest	12.56	9.73	270	205262	93397	53050137
Haemorrhage intracranial	12.55	9.73	20	205512	13332	53130202
Blood cholesterol increased	12.51	9.73	137	205395	52852	53090682
Clostridium difficile colitis	12.45	9.73	37	205495	19728	53123806
Hepatic function abnormal	12.45	9.73	87	205445	36812	53106722
Escherichia infection	12.35	9.73	17	205515	12033	53131501
Hepatobiliary scan abnormal	12.34	9.73	6	205526	71	53143463
Leukopenia neonatal	12.32	9.73	5	205527	37	53143497
Unintended pregnancy	12.27	9.73	4	205528	6049	53137485
Polyneuropathy	12.27	9.73	20	205512	13213	53130321
Enterococcal infection	12.26	9.73	7	205525	7591	53135943
Status epilepticus	12.25	9.73	25	205507	15159	53128375
Dysphagia	12.17	9.73	418	205114	83979	53059555
Intrusive thoughts	12.14	9.73	8	205524	175	53143359
Urinary hesitation	12.10	9.73	26	205506	2115	53141419
Femur fracture	12.08	9.73	96	205436	39489	53104045
Bronchospasm	12.02	9.73	29	205503	16569	53126965
Sexual dysfunction	11.99	9.73	34	205498	3292	53140242
Radiation fibrosis	11.98	9.73	5	205527	40	53143494
Haemolysis	11.98	9.73	5	205527	6491	53137043
Oesophageal pain	11.97	9.73	32	205500	2994	53140540
Eyelid myoclonus	11.88	9.73	5	205527	41	53143493
Cataract	11.83	9.73	128	205404	49492	53094042
Nephrotic syndrome	11.81	9.73	3	205529	5342	53138192
Suspected product quality issue	11.79	9.73	8	205524	184	53143350
Rapid eye movement sleep behaviour disorder	11.79	9.73	8	205524	184	53143350
Vasculitis	11.71	9.73	25	205507	14915	53128619
Hypophosphataemia	11.71	9.73	10	205522	8795	53134739
Scoliosis	11.65	9.73	55	205477	6827	53136707
Impulsive behaviour	11.64	9.73	21	205511	1503	53142031
Sciatic nerve injury	11.59	9.73	11	205521	414	53143120
Drug tolerance decreased	11.56	9.73	7	205525	7351	53136183
Lymphadenopathy	11.50	9.73	87	205445	36168	53107366
Polyglandular autoimmune syndrome type II	11.48	9.73	5	205527	45	53143489
Acute pulmonary oedema	11.44	9.73	9	205523	8246	53135288
Maternal exposure during breast feeding	11.43	9.73	34	205498	3383	53140151
Progressive multifocal leukoencephalopathy	11.41	9.73	83	205449	12046	53131488
Anuria	11.35	9.73	19	205513	12421	53131113
Daydreaming	11.31	9.73	10	205522	343	53143191
Supraventricular tachyarrhythmia	11.27	9.73	6	205526	87	53143447
Micturition urgency	11.26	9.73	64	205468	8538	53134996
Device difficult to use	11.25	9.73	14	205518	10345	53133189
Neuropsychiatric symptoms	11.23	9.73	13	205519	618	53142916
Lung infiltration	11.21	9.73	25	205507	14682	53128852
Renal injury	11.16	9.73	13	205519	9891	53133643
Food craving	11.15	9.73	21	205511	1553	53141981
Disturbance in sexual arousal	11.15	9.73	6	205526	89	53143445
Asthma	11.14	9.73	327	205205	108645	53034889
Posterior reversible encephalopathy syndrome	11.11	9.73	29	205503	16131	53127403
Phonophobia	11.09	9.73	10	205522	352	53143182
Hepatic steatosis	11.06	9.73	152	205380	26107	53117427
Cushingoid	11.05	9.73	7	205525	7175	53136359
Purple glove syndrome	11.04	9.73	8	205524	205	53143329
Alveolar bone resorption	11.02	9.73	5	205527	50	53143484
Duodenal ulcer	11.00	9.73	8	205524	7628	53135906
Visual impairment	10.99	9.73	363	205169	72549	53070985
Sluggishness	10.99	9.73	42	205490	4750	53138784
Feeling jittery	10.98	9.73	82	205450	12001	53131533
Spasmodic dysphonia	10.92	9.73	6	205526	93	53143441
Blood pressure diastolic decreased	10.91	9.73	31	205501	16772	53126762
Disability	10.90	9.73	84	205448	12414	53131120
Parosmia	10.86	9.73	41	205491	4609	53138925
Ventricular hypoplasia	10.75	9.73	7	205525	150	53143384
Electrolyte imbalance	10.74	9.73	37	205495	18847	53124687
Rectal haemorrhage	10.71	9.73	105	205427	41376	53102158
Dissociative disorder	10.71	9.73	8	205524	215	53143319
Chronic kidney disease	10.70	9.73	111	205421	43259	53100275
Atelectasis	10.69	9.73	40	205492	19886	53123648
Skin haemorrhage	10.68	9.73	53	205479	6714	53136820
Arthralgia	10.61	9.73	1509	204023	438274	52705260
Tricuspid valve incompetence	10.54	9.73	25	205507	14371	53129163
Klebsiella infection	10.54	9.73	9	205523	7917	53135617
Muscular weakness	10.54	9.73	483	205049	100509	53043025
Intestinal cyst	10.53	9.73	6	205526	100	53143434
Alcohol use	10.51	9.73	24	205508	2034	53141500
Trigger finger	10.49	9.73	36	205496	3863	53139671
Myocardial ischaemia	10.49	9.73	21	205511	12823	53130711
Pain in jaw	10.48	9.73	103	205429	40566	53102968
Alcohol abuse	10.46	9.73	24	205508	2040	53141494
Abortion spontaneous	10.45	9.73	122	205410	46513	53097021
Hepatitis A antibody positive	10.45	9.73	5	205527	57	53143477
Knee arthroplasty	10.43	9.73	81	205451	33488	53110046
Osteopenia	10.41	9.73	36	205496	18319	53125215
Shock haemorrhagic	10.41	9.73	12	205520	9171	53134363
Epstein-Barr virus infection	10.39	9.73	8	205524	7410	53136124
Ligament injury	10.39	9.73	17	205515	1124	53142410
Electric shock sensation	10.39	9.73	7	205525	159	53143375
Skin ulcer	10.38	9.73	89	205443	36030	53107504
Pericardial effusion	10.38	9.73	62	205470	27216	53116318
Prescribed underdose	10.35	9.73	99	205433	15568	53127966
Accommodation disorder	10.33	9.73	10	205522	386	53143148
Blood alkaline phosphatase increased	10.31	9.73	220	205312	41142	53102392
Escherichia urinary tract infection	10.25	9.73	17	205515	11156	53132378
Chest pain	10.04	9.73	615	204917	189570	52953964
Suspected suicide attempt	10.03	9.73	6	205526	110	53143424
Acute hepatic failure	10.03	9.73	32	205500	16688	53126846
Colitis	9.98	9.73	107	205425	41445	53102089
Exposure via breast milk	9.97	9.73	20	205512	1550	53141984
Pyometra	9.94	9.73	6	205526	112	53143422
Acute respiratory failure	9.91	9.73	75	205457	31183	53112351
Foot amputation	9.91	9.73	9	205523	320	53143214
Exposure during pregnancy	9.88	9.73	387	205145	124473	53019061
Lung neoplasm	9.85	9.73	5	205527	5791	53137743
Central nervous system lesion	9.83	9.73	70	205462	10092	53133442
Post-traumatic neck syndrome	9.82	9.73	21	205511	1702	53141832
Osteonecrosis	9.80	9.73	61	205471	26514	53117020
Lactation disorder	9.79	9.73	9	205523	325	53143209
Clostridium difficile infection	9.79	9.73	65	205467	27828	53115706
Pneumothorax	9.79	9.73	29	205503	15478	53128056
Blood urea increased	9.78	9.73	60	205472	26171	53117363
Foetal exposure during pregnancy	9.77	9.73	86	205446	34629	53108905
Hepatotoxicity	9.77	9.73	65	205467	27815	53115719
Hyperuricaemia	9.76	9.73	4	205528	5252	53138282
Somnambulism	9.76	9.73	44	205488	5358	53138176
Tachypnoea	9.75	9.73	30	205502	15824	53127710

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	1283.76	11.33	685	65641	19546	32427654
Dysphoria	1236.90	11.33	367	65959	1944	32445256
Affect lability	1162.17	11.33	392	65934	3336	32443864
Suicidal ideation	768.60	11.33	630	65696	37453	32409747
Irritability	672.70	11.33	488	65838	24166	32423034
Sensory disturbance	568.56	11.33	268	66058	5810	32441390
Vertigo	500.69	11.33	407	65919	23876	32423324
Paraesthesia	499.41	11.33	608	65718	58336	32388864
Agitation	472.91	11.33	583	65743	56653	32390547
Anxiety	466.09	11.33	758	65568	95247	32351953
Insomnia	447.94	11.33	763	65563	99585	32347615
Hyperhidrosis	389.60	11.33	594	65732	70574	32376626
Nightmare	330.50	11.33	248	66078	12918	32434282
Dizziness	264.36	11.33	982	65344	208636	32238564
Tinnitus	258.22	11.33	241	66085	17008	32430192
Hypomania	233.81	11.33	109	66217	2300	32444900
Tremor	226.37	11.33	507	65819	80770	32366430
Confusional state	225.09	11.33	722	65604	142393	32304807
Lethargy	223.76	11.33	343	65983	40885	32406315
Completed suicide	219.46	11.33	542	65784	91975	32355225
Mood swings	214.28	11.33	158	66168	8007	32439193
Serotonin syndrome	192.98	11.33	216	66110	18901	32428299
Headache	166.84	11.33	816	65510	195381	32251819
Depression	163.73	11.33	502	65824	96558	32350642
Nausea	143.31	11.33	1130	65196	319719	32127481
Sleep disorder	134.55	11.33	215	66111	26537	32420663
Suicide attempt	132.46	11.33	261	66065	37983	32409217
Pyrexia	128.45	11.33	290	66036	319678	32127522
Febrile neutropenia	121.47	11.33	46	66280	119520	32327680
Anger	104.17	11.33	125	66201	11779	32435421
Fatigue	102.80	11.33	1129	65197	349572	32097628
Thrombocytopenia	100.16	11.33	93	66233	148206	32298994
Withdrawal syndrome	95.93	11.33	121	66205	12001	32435199
Acute kidney injury	90.68	11.33	302	66024	293166	32154034
Anaemia	88.49	11.33	204	66122	223420	32223780
Gastrointestinal tube insertion	84.65	11.33	46	66280	1356	32445844
Somnolence	74.97	11.33	413	65913	103384	32343816
Intentional self-injury	74.43	11.33	115	66211	13785	32433415
Neutropenia	73.63	11.33	110	66216	142065	32305135
Pancytopenia	69.23	11.33	51	66275	91184	32356016
Feeling abnormal	66.72	11.33	272	66054	60151	32387049
Fall	62.04	11.33	642	65684	195559	32251641
Disturbance in attention	61.37	11.33	144	66182	23609	32423591
Dyspnoea	59.93	11.33	463	65863	361582	32085618
Sepsis	58.72	11.33	150	66176	158684	32288516
Memory impairment	57.84	11.33	198	66128	40281	32406919
Multiple organ dysfunction syndrome	53.05	11.33	39	66287	69815	32377385
Hepatic enzyme increased	52.77	11.33	181	66145	36856	32410344
Leukopenia	51.89	11.33	29	66297	60093	32387107
Sexual dysfunction	51.71	11.33	64	66262	6225	32440975
Disease progression	51.25	11.33	61	66265	86801	32360399
Respiratory disorder neonatal	50.83	11.33	32	66294	1247	32445953
Platelet count decreased	49.84	11.33	99	66227	114492	32332708
Intentional overdose	48.89	11.33	191	66135	41410	32405790
Pleural effusion	48.19	11.33	54	66272	78938	32368262
Blood creatinine increased	48.17	11.33	76	66250	96056	32351144
Haemoglobin decreased	46.57	11.33	110	66216	119561	32327639
Renal failure	45.92	11.33	132	66194	134346	32312854
Loss of consciousness	45.64	11.33	307	66019	82400	32364800
Mucosal inflammation	45.30	11.33	7	66319	33427	32413773
Toxicity to various agents	44.67	11.33	557	65769	177484	32269716
Malignant neoplasm progression	43.31	11.33	58	66268	78438	32368762
Cardiac failure	40.89	11.33	78	66248	91595	32355605
Antidepressant drug level above therapeutic	40.86	11.33	15	66311	167	32447033
Therapy interrupted	40.70	11.33	65	66261	8013	32439187
Sedation	40.12	11.33	105	66221	18421	32428779
Migraine	38.56	11.33	87	66239	13898	32433302
Respiratory failure	38.22	11.33	103	66223	107079	32340121
Myoclonus	38.12	11.33	89	66237	14540	32432660
General physical health deterioration	37.27	11.33	116	66210	115143	32332057
Septic shock	37.02	11.33	52	66274	68937	32378263
Gastric bypass	36.73	11.33	16	66310	286	32446914
Urinary hesitation	35.57	11.33	33	66293	2308	32444892
Analgesic drug level above therapeutic	35.39	11.33	15	66311	250	32446950
Ascites	35.24	11.33	19	66307	40172	32407028
Road traffic accident	35.10	11.33	96	66230	17285	32429915
Pain	35.02	11.33	557	65769	186999	32260201
Urinary retention	34.96	11.33	155	66171	35542	32411658
Pneumonia	34.81	11.33	513	65813	354739	32092461
Haemorrhage	33.33	11.33	31	66295	49417	32397783
Balance disorder	33.26	11.33	164	66162	39295	32407905
Aggression	31.99	11.33	162	66164	39227	32407973
Product use in unapproved indication	31.69	11.33	83	66243	87121	32360079
Major depression	31.27	11.33	42	66284	4429	32442771
Mania	31.24	11.33	64	66262	9568	32437632
Cytomegalovirus infection	30.93	11.33	7	66319	25457	32421743
Drug resistance	30.67	11.33	5	66321	22960	32424240
Cough	30.26	11.33	163	66163	138654	32308546
Dehydration	30.04	11.33	148	66178	128810	32318390
C-reactive protein increased	29.20	11.33	33	66293	48069	32399131
Disorientation	28.23	11.33	139	66187	33286	32413914
Metabolic acidosis	28.04	11.33	25	66301	40674	32406526
Abnormal dreams	27.89	11.33	57	66269	8507	32438693
Surgery	27.89	11.33	72	66254	12527	32434673
Amnesia	27.84	11.33	113	66213	24923	32422277
Atrial fibrillation	27.72	11.33	133	66193	116571	32330629
Self esteem decreased	27.62	11.33	16	66310	535	32446665
Renal impairment	27.36	11.33	96	66230	91876	32355324
Overdose	26.99	11.33	284	66042	86793	32360407
Disseminated intravascular coagulation	26.92	11.33	7	66319	23169	32424031
Yawning	26.65	11.33	16	66310	572	32446628
Hypokalaemia	26.24	11.33	45	66281	55049	32392151
Drug hypersensitivity	25.94	11.33	246	66080	73154	32374046
Agranulocytosis	25.59	11.33	8	66318	23469	32423731
Initial insomnia	24.83	11.33	31	66295	3041	32444159
Bone marrow failure	24.36	11.33	16	66310	30388	32416812
Toxic epidermal necrolysis	24.34	11.33	6	66320	20587	32426613
Feeling jittery	24.14	11.33	35	66291	3964	32443236
Homicidal ideation	23.21	11.33	28	66298	2652	32444548
Convulsive threshold lowered	22.70	11.33	14	66312	526	32446674
Hallucination	22.55	11.33	184	66142	52435	32394765
Myocardial infarction	22.46	11.33	157	66169	125519	32321681
Neuropathy peripheral	22.42	11.33	248	66078	76734	32370466
Erectile dysfunction	22.42	11.33	90	66236	19749	32427451
Fibromyalgia	22.35	11.33	28	66298	2756	32444444
White blood cell count decreased	22.20	11.33	103	66223	91095	32356105
Acute respiratory distress syndrome	22.04	11.33	12	66314	25241	32421959
Multiple sclerosis relapse	21.76	11.33	63	66263	11718	32435482
Agitation neonatal	21.70	11.33	18	66308	1084	32446116
International normalised ratio increased	21.61	11.33	42	66284	48993	32398207
Interstitial lung disease	21.29	11.33	65	66261	64936	32382264
Hallucination, auditory	20.73	11.33	57	66269	10293	32436907
Acute stress disorder	20.71	11.33	9	66317	160	32447040
Electric shock sensation	20.66	11.33	6	66320	29	32447171
Growth hormone deficiency	20.58	11.33	10	66316	232	32446968
Clonus	20.53	11.33	26	66300	2588	32444612
Peritonitis	20.40	11.33	10	66316	22320	32424880
Bradyphrenia	20.30	11.33	35	66291	4594	32442606
Hypotension	20.09	11.33	315	66011	215795	32231405
Acute myeloid leukaemia	20.08	11.33	7	66319	19167	32428033
Complex regional pain syndrome	19.95	11.33	13	66313	538	32446662
Dystonia	19.81	11.33	57	66269	10566	32436634
Neuralgia	19.69	11.33	61	66265	11774	32435426
Pneumocystis jirovecii pneumonia	19.57	11.33	7	66319	18863	32428337
Respiratory distress	19.47	11.33	26	66300	35220	32411980
Intentional product misuse	19.37	11.33	133	66193	35918	32411282
Infusion related reaction	19.28	11.33	40	66286	45559	32401641
Oedema peripheral	19.19	11.33	145	66181	113946	32333254
Haematuria	19.15	11.33	44	66282	48317	32398883
Somnambulism	19.09	11.33	28	66298	3204	32443996
Wrong drug	18.90	11.33	7	66319	80	32447120
Abnormal behaviour	18.85	11.33	105	66221	26361	32420839
Hypocalcaemia	18.65	11.33	12	66314	23042	32424158
Dysmetropsia	18.56	11.33	4	66322	3	32447197
Feeling guilty	18.46	11.33	10	66316	293	32446907
Rash maculo-papular	18.38	11.33	18	66308	28004	32419196
Cardiac failure congestive	18.27	11.33	100	66226	84752	32362448
Haemoptysis	18.25	11.33	25	66301	33500	32413700
Post concussion syndrome	18.23	11.33	7	66319	89	32447111
Tardive dyskinesia	18.23	11.33	37	66289	5494	32441706
Acute myocardial infarction	18.17	11.33	55	66271	55094	32392106
Sleep sex	18.02	11.33	4	66322	4	32447196
Drug reaction with eosinophilia and systemic symptoms	17.91	11.33	24	66302	32461	32414739
Angioedema	17.87	11.33	29	66297	36260	32410940
Delirium	17.79	11.33	152	66174	43894	32403306
Prescribed overdose	17.67	11.33	51	66275	9468	32437732
Therapy cessation	17.58	11.33	72	66254	15941	32431259
Psychotic disorder	17.52	11.33	93	66233	22927	32424273
Delirium tremens	17.50	11.33	12	66314	541	32446659
Neonatal tachypnoea	17.32	11.33	8	66318	165	32447035
Restless legs syndrome	17.32	11.33	44	66282	7580	32439620
Erythema	17.32	11.33	99	66227	83006	32364194
Affective disorder	17.21	11.33	28	66298	3505	32443695
Sleep-related eating disorder	17.11	11.33	10	66316	340	32446860
Neutrophil count decreased	17.01	11.33	45	66281	47094	32400106
Muscle spasticity	17	11.33	37	66289	5768	32441432
Compulsive shopping	16.91	11.33	11	66315	454	32446746
Pneumonitis	16.88	11.33	22	66304	30112	32417088
Paedophilia	16.76	11.33	4	66322	7	32447193
Steatohepatitis	16.65	11.33	10	66316	358	32446842
Hypersomnia	16.63	11.33	58	66268	11903	32435297
Colitis ulcerative	16.57	11.33	7	66319	17044	32430156
Drug tolerance	16.53	11.33	22	66304	2299	32444901
Rash	16.28	11.33	315	66011	209018	32238182
Gastrointestinal haemorrhage	16.28	11.33	107	66219	86775	32360425
Gait disturbance	16.19	11.33	242	66084	80166	32367034
Depression suicidal	16.16	11.33	17	66309	1385	32445815
Productive cough	16.11	11.33	28	66298	34088	32413112
Coronary artery disease	16.07	11.33	50	66276	49656	32397544
Pericardial effusion	16.00	11.33	14	66312	22988	32424212
Mental disorder	15.65	11.33	65	66261	14483	32432717
Lymphopenia	15.62	11.33	5	66321	14451	32432749
Orgasm abnormal	15.54	11.33	7	66319	136	32447064
Apathy	15.51	11.33	39	66287	6676	32440524
Liver function test abnormal	15.50	11.33	115	66211	31832	32415368
Blood lactate dehydrogenase increased	15.50	11.33	13	66313	21792	32425408
Epistaxis	15.48	11.33	60	66266	55795	32391405
Thinking abnormal	15.47	11.33	35	66291	5600	32441600
Speech sound disorder	15.44	11.33	7	66319	138	32447062
Dry mouth	15.43	11.33	93	66233	24026	32423174
Depressed mood	15.37	11.33	76	66250	18224	32428976
Hyperlipasaemia	15.11	11.33	11	66315	546	32446654
Nephropathy toxic	15.09	11.33	3	66323	11943	32435257
Axillary pain	15.04	11.33	9	66317	320	32446880
Urethral discharge	15.03	11.33	4	66322	13	32447187
Neoplasm progression	14.88	11.33	11	66315	19647	32427553
Cholestasis	14.87	11.33	20	66306	27013	32420187
Neonatal hyponatraemia	14.79	11.33	6	66320	89	32447111
Drug screen positive	14.73	11.33	29	66297	4212	32442988
Paranoia	14.70	11.33	52	66274	10747	32436453
Ventricular hypoplasia	14.67	11.33	6	66320	91	32447109
Cerebral infarction	14.62	11.33	21	66305	27593	32419607
Seizure	14.57	11.33	295	66031	103559	32343641
Retrograde ejaculation	14.47	11.33	9	66317	343	32446857
Treatment failure	14.42	11.33	37	66289	39126	32408074
Muscle twitching	14.36	11.33	45	66281	8739	32438461
Bradycardia	13.98	11.33	87	66239	71475	32375725
Bipolar disorder	13.92	11.33	27	66299	3879	32443321
Blood urea increased	13.91	11.33	28	66298	32245	32414955
Cardiogenic shock	13.86	11.33	13	66313	20649	32426551
Narcissistic personality disorder	13.83	11.33	4	66322	19	32447181
Suicidal behaviour	13.78	11.33	16	66310	1455	32445745
Angina pectoris	13.77	11.33	27	66299	31399	32415801
Libido decreased	13.73	11.33	30	66296	4688	32442512
Rhabdomyolysis	13.55	11.33	81	66245	67184	32380016
Psychopathic personality	13.52	11.33	3	66323	3	32447197
Tubulointerstitial nephritis	13.51	11.33	12	66314	19565	32427635
Pulmonary fibrosis	13.51	11.33	9	66317	16965	32430235
Loss of employment	13.50	11.33	10	66316	510	32446690
Homicide	13.42	11.33	13	66313	960	32446240
Influenza like illness	13.34	11.33	98	66228	27042	32420158
Stomatitis	13.33	11.33	40	66286	40189	32407011
Pulmonary embolism	13.28	11.33	108	66218	83551	32363649
Chills	13.23	11.33	99	66227	77985	32369215
Selective eating disorder	13.21	11.33	17	66309	1719	32445481
Helplessness	13.21	11.33	5	66321	61	32447139
Ureteric haemorrhage	13.16	11.33	6	66320	120	32447080
Anaphylactic reaction	13.15	11.33	26	66300	30146	32417054
Lung disorder	13.13	11.33	31	66295	33723	32413477
Facial spasm	13.02	11.33	7	66319	202	32446998
Palmar-plantar erythrodysaesthesia syndrome	13.01	11.33	8	66318	15741	32431459
Lymphadenopathy	13.00	11.33	22	66304	27060	32420140
Chest injury	12.99	11.33	16	66310	1548	32445652
Myelodysplastic syndrome	12.99	11.33	13	66313	20025	32427175
Restlessness	12.90	11.33	91	66235	24790	32422410
Dyspnoea exertional	12.73	11.33	39	66287	38922	32408278
Brief psychotic disorder with marked stressors	12.68	11.33	7	66319	213	32446987
Hypoxia	12.60	11.33	59	66267	52073	32395127
Concussion	12.60	11.33	19	66307	2228	32444972
Melaena	12.58	11.33	33	66293	34632	32412568
Tumour lysis syndrome	12.57	11.33	7	66319	14540	32432660
Ileus	12.44	11.33	9	66317	16256	32430944
Stiff person syndrome	12.40	11.33	6	66320	138	32447062
Reflexes abnormal	12.32	11.33	8	66318	329	32446871
Haematochezia	12.28	11.33	40	66286	39168	32408032
Hyperreflexia	12.25	11.33	22	66304	2982	32444218
Autonomic dysreflexia	12.16	11.33	5	66321	77	32447123
Hyperglycaemia	12.14	11.33	39	66287	38352	32408848
Alanine aminotransferase increased	12.05	11.33	226	66100	78253	32368947
Death	12.05	11.33	648	65678	381869	32065331
Dyskinesia	12.04	11.33	86	66240	23517	32423683
Central nervous system stimulation	11.99	11.33	3	66323	7	32447193
Drug withdrawal syndrome neonatal	11.93	11.33	24	66302	3540	32443660
Alcoholism	11.90	11.33	24	66302	3548	32443652
Asthma	11.79	11.33	48	66278	44017	32403183
Gastric ulcer	11.77	11.33	9	66317	15800	32431400
Drug screen false positive	11.75	11.33	11	66315	778	32446422
Mitral valve incompetence	11.68	11.33	8	66318	14863	32432337
Deep vein thrombosis	11.66	11.33	79	66247	63634	32383566
Pseudomonas infection	11.63	11.33	5	66321	12051	32435149
Abdominal pain	11.61	11.33	225	66101	149304	32297896
Hyperkalaemia	11.55	11.33	89	66237	69661	32377539
Mood altered	11.37	11.33	42	66284	8862	32438338
Loss of proprioception	11.37	11.33	7	66319	262	32446938
Crying	11.34	11.33	32	66294	5864	32441336
Abdominal compartment syndrome	11.33	11.33	12	66314	985	32446215

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
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
FDA EPC	N0000175749	Serotonin and Norepinephrine Reuptake Inhibitor
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 serotonin transporter	Transporter	P31645	SC6A4_HUMAN	INHIBITOR	Ki	9.62		CHEMBL	CHEMBL
Sodium-dependent noradrenaline transporter	Transporter	P23975	SC6A2_HUMAN	INHIBITOR	Ki	8.22		CHEMBL	CHEMBL
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
5-hydroxytryptamine receptor 2B	GPCR	P41595	5HT2B_HUMAN		Ki	5.68		PDSP
5-hydroxytryptamine receptor 2C	GPCR	P28335	5HT2C_HUMAN	ANTAGONIST	Ki	6		IUPHAR
5-hydroxytryptamine receptor 6	GPCR	P50406	5HT6R_HUMAN	ANTAGONIST	Ki	6.40		IUPHAR
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 1B	GPCR	P28222	5HT1B_HUMAN		Ki	5.40		PDSP
5-hydroxytryptamine receptor 1D	GPCR	P28221	5HT1D_HUMAN		Ki	5.52		PDSP
Sodium-dependent dopamine transporter	Transporter	Q01959	SC6A3_HUMAN		Ki	6.62		CHEMBL
5-hydroxytryptamine receptor 1F	GPCR	P30939	5HT1F_HUMAN		Ki	5.35		PDSP
5-hydroxytryptamine receptor 1E	GPCR	P28566	5HT1E_HUMAN		Ki	5.43		PDSP
Serine hydroxymethyltransferase, mitochondrial	Enzyme	P34897	GLYM_HUMAN		IC50	5.16		CHEMBL
Sodium-dependent serotonin transporter	Transporter		SC6A4_RAT		Ki	10.09		CHEMBL
Sodium-dependent dopamine transporter	Transporter		SC6A3_RAT		IC50	6.43		CHEMBL
Transporter	Transporter		Q63380_RAT		Ki	8.52		CHEMBL

External reference:

ID	Source
D01179	KEGG_DRUG
136434-34-9	SECONDARY_CAS_RN
4021477	VANDF
C0245561	UMLSCUI
CHEBI:31526	CHEBI
29E	PDB_CHEM_ID
CHEMBL1175	ChEMBL_ID
CHEMBL1200328	ChEMBL_ID
DB00476	DRUGBANK_ID
D000068736	MESH_DESCRIPTOR_UI
60835	PUBCHEM_CID
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	31722-168	CAPSULE, DELAYED RELEASE	20 mg	ORAL	ANDA	31 sections
Duloxetine	HUMAN PRESCRIPTION DRUG LABEL	1	31722-169	CAPSULE, DELAYED RELEASE	30 mg	ORAL	ANDA	31 sections
Duloxetine	HUMAN PRESCRIPTION DRUG LABEL	1	31722-170	CAPSULE, DELAYED RELEASE	60 mg	ORAL	ANDA	31 sections
Duloxetine	Human Prescription Drug Label	1	31722-581	CAPSULE, DELAYED RELEASE	20 mg	ORAL	ANDA	30 sections