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

Stem definition	Drug id	CAS RN
hypnotic tranquillizers	2873	43200-80-2

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: zopiclone zimovane imovane	S(+)-enantiomer of racemic zopiclone; azabicyclo(4.3.0)nonane; a nonbenzodiazepine; one of the so-called of Z drugs (zopiclone, eszopiclone, zolpidem, and zaleplon) for which there is some correlation with tumors; was term of zopiclone 2004-2007 Molecular weight: 388.81 Formula: C17H17ClN6O3 CLOGP: 1.25 LIPINSKI: 0 HAC: 9 HDO: 0 TPSA: 91.76 ALOGS: -2.64 ROTB: 3

Drug dosage:

Dose	Unit	Route
7.50	mg	O

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	1	Benet LZ, Broccatelli F, Oprea TI
S (Water solubility)	0.12 mg/mL	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	4.50 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	0.28 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
Vd (Volume of distribution)	1.30 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	3.30 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.20 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	5.20 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
Dec. 15, 2004	FDA	SUNOVION PHARMS INC

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
Intentional overdose	766.01	10.52	706	72419	64238	46548699
Intentional self-injury	598.47	10.52	407	72718	23759	46589178
Coma	555.34	10.52	564	72561	57785	46555152
Somnolence	291.63	10.52	710	72415	155811	46457126
Pneumonia aspiration	283.26	10.52	296	72829	31309	46581628
Poisoning deliberate	221.47	10.52	144	72981	7782	46605155
Toxicity to various agents	188.27	10.52	742	72383	211024	46401913
Lower respiratory tract infection	184.76	10.52	319	72806	54770	46558167
Suicide attempt	181.06	10.52	316	72809	54720	46558217
Product dose omission issue	162.71	10.52	33	73092	168487	46444450
Muscle spasticity	147.61	10.52	131	72994	11309	46601628
Drug ineffective	136.34	10.52	574	72551	677264	45935673
Akathisia	125.60	10.52	101	73024	7613	46605324
Body temperature increased	122.56	10.52	172	72953	24689	46588248
Ear pain	121.24	10.52	161	72964	21931	46591006
Confusional state	119.81	10.52	532	72593	159360	46453577
Depressed level of consciousness	118.97	10.52	243	72882	47326	46565611
Electrocardiogram QT prolonged	111.96	10.52	248	72877	51077	46561860
Hyponatraemia	108.19	10.52	377	72748	100955	46511982
Electric shock	105.07	10.52	43	73082	864	46612073
Death	102.00	10.52	235	72890	335313	46277624
Drug hypersensitivity	101.81	10.52	140	72985	243685	46369252
Overdose	97.49	10.52	366	72759	101613	46511324
Insomnia	88.26	10.52	499	72626	164425	46448512
Respiratory disorder	84.89	10.52	153	72972	27147	46585790
Hepatocellular injury	83.70	10.52	159	72966	29363	46583574
Suicidal ideation	81.50	10.52	233	72892	56149	46556788
Cardiac failure congestive	78.67	10.52	23	73102	91727	46521210
Antipsychotic drug level increased	74.79	10.52	52	73073	3140	46609797
Prescription form tampering	74.57	10.52	31	73094	649	46612288
Drug dependence	70.30	10.52	118	73007	19783	46593154
Altered state of consciousness	59.21	10.52	120	73005	23228	46589709
Night sweats	58.64	10.52	131	72994	27119	46585818
Intervertebral discitis	56.32	10.52	40	73085	2499	46610438
Post-traumatic stress disorder	55.52	10.52	48	73077	4000	46608937
Mydriasis	54.98	10.52	75	73050	10478	46602459
Alopecia	54.01	10.52	108	73017	162306	46450631
Injection site pain	53.83	10.52	53	73072	107099	46505838
Somnambulism	52.08	10.52	51	73074	4986	46607951
Drug intolerance	50.44	10.52	96	73029	146953	46465984
Disturbance in attention	50.11	10.52	135	72990	31425	46581512
Lupus vasculitis	49.98	10.52	21	73104	452	46612485
Depressed mood	48.43	10.52	138	72987	33181	46579756
Treatment failure	47.97	10.52	45	73080	93042	46519895
Mental status changes	47.71	10.52	3	73122	38085	46574852
Schizoaffective disorder	47.10	10.52	29	73096	1423	46611514
Hypothermia	46.76	10.52	75	73050	12108	46600829
Cholestasis	46.75	10.52	119	73006	26774	46586163
Agitation	46.51	10.52	191	72934	55224	46557713
Hallucination	45.81	10.52	177	72948	49774	46563163
Miosis	45.25	10.52	54	73071	6603	46606334
Drug interaction	44.44	10.52	500	72625	202594	46410343
Asphyxia	42.61	10.52	47	73078	5279	46607658
Maternal exposure during pregnancy	41.61	10.52	60	73065	102489	46510448
Disease progression	40.52	10.52	50	73075	91250	46521687
Fluid retention	39.88	10.52	15	73110	51031	46561906
Muscle injury	39.03	10.52	43	73082	4823	46608114
Abdominal discomfort	38.82	10.52	115	73010	151050	46461887
Inappropriate antidiuretic hormone secretion	38.79	10.52	75	73050	14027	46598910
Demyelination	38.48	10.52	46	73079	5634	46607303
Folliculitis	38.40	10.52	48	73077	6155	46606782
Nightmare	38.21	10.52	82	73043	16516	46596421
Tachycardia	36.97	10.52	275	72850	99347	46513590
Antipsychotic drug level above therapeutic	36.27	10.52	21	73104	920	46612017
Lactic acidosis	36.00	10.52	126	72999	33783	46579154
Sinus rhythm	35.95	10.52	18	73107	587	46612350
Synovitis	35.83	10.52	26	73099	61049	46551888
Fall	35.69	10.52	718	72407	328379	46284558
Dysarthria	35.30	10.52	134	72991	37364	46575573
Gastrooesophageal reflux disease	35.22	10.52	218	72907	74126	46538811
Temperature intolerance	35.08	10.52	51	73074	7556	46605381
Coordination abnormal	34.84	10.52	62	73063	10887	46602050
General physical health deterioration	34.51	10.52	304	72821	115465	46497472
Mania	33.98	10.52	61	73064	10785	46602152
Psychiatric symptom	33.10	10.52	38	73087	4459	46608478
Injection site erythema	32.77	10.52	41	73084	74386	46538551
Unevaluable event	32.21	10.52	16	73109	46159	46566778
Injection site reaction	31.29	10.52	18	73107	47831	46565106
Extrapyramidal disorder	31.08	10.52	60	73065	11208	46601729
Therapy cessation	30.82	10.52	3	73122	26626	46586311
Progressive multifocal leukoencephalopathy	30.79	10.52	60	73065	11286	46601651
Injection site bruising	30.41	10.52	9	73116	35627	46577310
Hyperhidrosis	30.05	10.52	241	72884	89067	46523870
Hallucination, visual	29.94	10.52	78	73047	17795	46595142
Drug level above therapeutic	29.88	10.52	32	73093	3477	46609460
Pemphigus	29.65	10.52	17	73108	45257	46567680
Sputum discoloured	29.27	10.52	63	73062	12715	46600222
Blood creatine increased	29.19	10.52	36	73089	4554	46608383
Therapy non-responder	29.10	10.52	14	73111	41138	46571799
Neutrophil count increased	28.97	10.52	67	73058	14186	46598751
Gallbladder adenocarcinoma	28.85	10.52	9	73116	78	46612859
Urticaria	28.41	10.52	296	72829	117596	46495341
Bezoar	28.39	10.52	21	73104	1398	46611539
Antidepressant drug level above therapeutic	28.19	10.52	13	73112	352	46612585
Toxicologic test abnormal	28.01	10.52	16	73109	683	46612254
Sepsis	27.83	10.52	114	73011	135900	46477037
Hospitalisation	27.82	10.52	35	73090	63350	46549587
White blood cells urine positive	27.44	10.52	33	73092	4067	46608870
Drug level increased	27.40	10.52	77	73048	18364	46594573
Broncholithiasis	27.36	10.52	9	73116	94	46612843
Eczema	27.25	10.52	82	73043	20318	46592619
Diaphragmatic rupture	27.16	10.52	11	73114	215	46612722
Cognitive disorder	27.00	10.52	122	73003	36761	46576176
Orthostatic hypotension	26.49	10.52	92	73033	24566	46588371
Psoriatic arthropathy	26.30	10.52	12	73113	36367	46576570
Red blood cells urine	25.99	10.52	13	73112	423	46612514
Myocardial infarction	25.90	10.52	73	73052	97455	46515482
Adverse drug reaction	25.87	10.52	19	73106	44343	46568594
Lupus nephritis	25.61	10.52	24	73101	2222	46610715
Balance disorder	25.59	10.52	181	72944	64340	46548597
Bronchial wall thickening	25.45	10.52	16	73109	815	46612122
Excessive eye blinking	24.87	10.52	14	73111	581	46612356
Disorientation	24.73	10.52	119	73006	36799	46576138
Injection site pruritus	24.53	10.52	16	73109	39727	46573210
Premature delivery	24.24	10.52	3	73122	22066	46590871
Agitation neonatal	24.18	10.52	13	73112	492	46612445
Wrong technique in product usage process	23.93	10.52	30	73095	54392	46558545
Product quality issue	23.90	10.52	13	73112	35635	46577302
Toxic skin eruption	23.84	10.52	57	73068	12330	46600607
Psoriasis	23.83	10.52	55	73070	78549	46534388
Malaise	23.79	10.52	683	72442	330549	46282388
Systemic lupus erythematosus	23.71	10.52	41	73084	65139	46547798
No adverse event	23.67	10.52	12	73113	34219	46578718
Adverse event	23.61	10.52	12	73113	34172	46578765
Urinary retention	23.60	10.52	92	73033	25969	46586968
Plasma cell myeloma	23.50	10.52	21	73104	44457	46568480
Drug reaction with eosinophilia and systemic symptoms	23.34	10.52	100	73025	29448	46583489
Coronary artery disease	23.08	10.52	12	73113	33740	46579197
Cerebrovascular accident	23.05	10.52	81	73044	100958	46511979
Aggression	22.84	10.52	83	73042	22661	46590276
Wrong rate	22.72	10.52	7	73118	58	46612879
Abortion spontaneous	22.59	10.52	21	73104	43625	46569312
Ataxia	22.52	10.52	60	73065	13870	46599067
Lymph node calcification	22.45	10.52	9	73116	171	46612766
Behaviour disorder	22.44	10.52	21	73104	1940	46610997
Full blood count decreased	22.14	10.52	4	73121	22207	46590730
Monocyte percentage increased	22.14	10.52	16	73109	1027	46611910
Hypocoagulable state	22.09	10.52	16	73109	1031	46611906
Hypersensitivity vasculitis	21.99	10.52	30	73095	4191	46608746
Malignant polyp	21.71	10.52	9	73116	187	46612750
Parkinsonism	21.53	10.52	42	73083	7906	46605031
Hypotension	21.48	10.52	496	72629	232093	46380844
Psychotic disorder	21.42	10.52	81	73044	22540	46590397
Urine leukocyte esterase positive	21.37	10.52	23	73102	2512	46610425
Hypersensitivity	21.20	10.52	143	72982	150178	46462759
Salivary hypersecretion	21.16	10.52	37	73088	6408	46606529
Poor feeding infant	20.99	10.52	9	73116	204	46612733
Procedural anxiety	20.97	10.52	12	73113	514	46612423
Pneumonia	20.94	10.52	440	72685	375880	46237057
Urine abnormality	20.87	10.52	34	73091	5560	46607377
Coma scale abnormal	20.85	10.52	32	73093	4974	46607963
Negative thoughts	20.65	10.52	14	73111	811	46612126
Learning disorder	20.42	10.52	11	73114	418	46612519
Loss of consciousness	20.35	10.52	259	72866	107979	46504958
Rash maculo-papular	20.25	10.52	92	73033	27782	46585155
Postmortem blood drug level abnormal	20.20	10.52	10	73115	318	46612619
Knee arthroplasty	20.15	10.52	6	73119	23659	46589278
Scratch	20.14	10.52	31	73094	4831	46608106
Delusion	19.95	10.52	50	73075	11138	46601799
Hand deformity	19.91	10.52	15	73110	34559	46578378
Peripheral circulatory failure	19.86	10.52	10	73115	330	46612607
Agranulocytosis	19.83	10.52	78	73047	22107	46590830
Fluid overload	19.60	10.52	9	73116	27176	46585761
Crystal urine present	19.47	10.52	16	73109	1243	46611694
Hypochloraemia	19.43	10.52	19	73106	1854	46611083
Psychotic symptom	19.41	10.52	14	73111	896	46612041
Myelocyte percentage increased	19.40	10.52	8	73117	164	46612773
Arthropathy	19.25	10.52	68	73057	84632	46528305
Hyperlipidaemia	19.23	10.52	3	73122	18536	46594401
Chest pain	19.19	10.52	180	72945	176144	46436793
Pulmonary hypertension	19.01	10.52	17	73108	35976	46576961
Oral herpes	18.83	10.52	70	73055	19320	46593617
Rheumatoid arthritis	18.80	10.52	264	72861	239951	46372986
Injury	18.61	10.52	25	73100	44002	46568935
Haemoglobin urine	18.51	10.52	7	73118	113	46612824
Respiratory failure	18.44	10.52	81	73044	94735	46518202
Distributive shock	18.43	10.52	11	73114	510	46612427
Distal intestinal obstruction syndrome	18.40	10.52	10	73115	387	46612550
Sleep disorder	18.39	10.52	131	72994	46664	46566273
Pharyngeal paraesthesia	18.37	10.52	15	73110	1155	46611782
Burnout syndrome	18.35	10.52	8	73117	189	46612748
Urine oxalate increased	18.16	10.52	8	73117	194	46612743
Rhabdomyolysis	18.06	10.52	120	73005	41789	46571148
Injection site swelling	17.97	10.52	22	73103	40305	46572632
Bulimia nervosa	17.97	10.52	11	73114	534	46612403
Band neutrophil percentage increased	17.86	10.52	8	73117	202	46612735
Exposure during pregnancy	17.84	10.52	98	73027	108114	46504823
Persecutory delusion	17.82	10.52	21	73104	2534	46610403
Tooth hypoplasia	17.80	10.52	6	73119	68	46612869
Adrenal insufficiency	17.76	10.52	53	73072	13071	46599866
Ill-defined disorder	17.63	10.52	86	73039	26741	46586196
Blister	17.57	10.52	125	73000	44506	46568431
Gait deviation	17.41	10.52	6	73119	73	46612864
Platelet count decreased	17.37	10.52	89	73036	99935	46513002
Thrombosis	17.18	10.52	39	73086	56030	46556907
Obstructive airways disorder	17.06	10.52	53	73072	13359	46599578
Occult blood	17.04	10.52	13	73112	907	46612030
Epilepsy	16.98	10.52	78	73047	23660	46589277
Blood glucose increased	16.91	10.52	57	73068	71956	46540981
Housebound	16.90	10.52	8	73117	230	46612707
Psychomotor retardation	16.87	10.52	23	73102	3210	46609727
Libido increased	16.75	10.52	12	73113	760	46612177
Drug withdrawal syndrome	16.73	10.52	86	73039	27298	46585639
Bradycardia	16.69	10.52	168	72957	66130	46546807
Pemphigoid	16.56	10.52	31	73094	5660	46607277
Chronic kidney disease	16.48	10.52	24	73101	40847	46572090
Newborn persistent pulmonary hypertension	16.39	10.52	6	73119	88	46612849
Substance use disorder	16.38	10.52	5	73120	40	46612897
Pain in extremity	16.33	10.52	296	72829	258384	46354553
Urinary sediment present	16.21	10.52	17	73108	1803	46611134
Self-injurious ideation	16.20	10.52	19	73106	2281	46610656
Neuroleptic malignant syndrome	16.09	10.52	46	73079	11076	46601861
Glossodynia	16.06	10.52	28	73097	44345	46568592
Granulomatous liver disease	16.02	10.52	12	73113	814	46612123
Hypotonia	15.98	10.52	38	73087	8191	46604746
Cholinergic syndrome	15.97	10.52	9	73116	374	46612563
Ligament pain	15.84	10.52	7	73118	171	46612766
Loss of personal independence in daily activities	15.78	10.52	42	73083	57141	46555796
Therapeutic product effect incomplete	15.66	10.52	66	73059	78087	46534850
Heart rate decreased	15.63	10.52	94	73031	31629	46581308
Retinal depigmentation	15.62	10.52	8	73117	274	46612663
Wound	15.50	10.52	27	73098	42775	46570162
Victim of chemical submission	15.48	10.52	8	73117	279	46612658
Torsade de pointes	15.43	10.52	48	73077	12106	46600831
Calcium deficiency	15.43	10.52	12	73113	861	46612076
Sudden death	15.43	10.52	41	73084	9463	46603474
Tearfulness	15.25	10.52	25	73100	4110	46608827
Sopor	15.20	10.52	6	73119	19822	46593115
Muscle twitching	15.12	10.52	54	73071	14618	46598319
Pulmonary function test abnormal	15.08	10.52	14	73111	1281	46611656
Pressure of speech	14.90	10.52	10	73115	570	46612367
Ovarian germ cell cancer stage II	14.88	10.52	5	73120	56	46612881
Drug detoxification	14.86	10.52	7	73118	199	46612738
Postmortem blood drug level increased	14.72	10.52	9	73116	436	46612501
Platelet disorder	14.64	10.52	15	73110	1548	46611389
Diabetic hyperosmolar coma	14.63	10.52	9	73116	441	46612496
Chest wall mass	14.57	10.52	5	73120	60	46612877
Glucocorticoids increased	14.42	10.52	6	73119	126	46612811
Ureteric obstruction	14.35	10.52	16	73109	1818	46611119
Amyotrophy	14.33	10.52	6	73119	128	46612809
Post-traumatic neck syndrome	14.31	10.52	14	73111	1367	46611570
Hypokalaemia	14.22	10.52	205	72920	87819	46525118
Band neutrophil count increased	14.17	10.52	8	73117	334	46612603
Nail ridging	14.13	10.52	7	73118	223	46612714
Failed induction of labour	14.10	10.52	8	73117	337	46612600
Rales	14.10	10.52	40	73085	9591	46603346
Atelectasis	13.89	10.52	6	73119	18784	46594153
Gait disturbance	13.85	10.52	153	72972	145110	46467827
Neutrophil percentage increased	13.85	10.52	19	73106	2668	46610269
Myelocyte count increased	13.80	10.52	8	73117	351	46612586
Glomerular filtration rate decreased	13.77	10.52	45	73080	11649	46601288
Pruritus	13.76	10.52	486	72639	241866	46371071
Drug resistance	13.74	10.52	5	73120	17363	46595574
Respiratory acidosis	13.72	10.52	30	73095	6118	46606819
Rash scarlatiniform	13.60	10.52	6	73119	146	46612791
Blood creatine phosphokinase increased	13.56	10.52	82	73043	27642	46585295
Chemical submission	13.52	10.52	7	73118	245	46612692
Electrocardiogram repolarisation abnormality	13.44	10.52	13	73112	1252	46611685
Urinary tract obstruction	13.32	10.52	15	73110	1723	46611214
Concussion	13.23	10.52	32	73093	6971	46605966
Oedema	13.22	10.52	57	73068	67014	46545923
Hallucination, auditory	13.22	10.52	42	73083	10714	46602223
Social anxiety disorder	13.21	10.52	8	73117	381	46612556
Throat irritation	13.21	10.52	84	73041	28817	46584120
Strabismus	13.15	10.52	15	73110	1747	46611190
Device dislocation	13.15	10.52	9	73116	21793	46591144
Sensory level abnormal	13.09	10.52	6	73119	160	46612777
Clostridium difficile infection	13.08	10.52	12	73113	25091	46587846
Nausea	12.99	10.52	915	72210	686539	45926398
Tumour marker abnormal	12.96	10.52	6	73119	164	46612773
Soft tissue injury	12.92	10.52	11	73114	898	46612039
Pancreatic carcinoma recurrent	12.88	10.52	5	73120	87	46612850
Restlessness	12.81	10.52	76	73049	25448	46587489
Eye irritation	12.78	10.52	5	73120	16609	46596328
Lip blister	12.75	10.52	16	73109	2059	46610878
Biliary sepsis	12.70	10.52	9	73116	560	46612377
Panic attack	12.67	10.52	64	73061	20178	46592759
Thyroid adenoma	12.66	10.52	6	73119	173	46612764
Hostility	12.63	10.52	13	73112	1349	46611588
Osteonecrosis	12.61	10.52	13	73112	25731	46587206
Anaphylactic reaction	12.50	10.52	42	73083	53070	46559867
Vaginal haemorrhage	12.46	10.52	13	73112	25591	46587346
White blood cell count decreased	12.44	10.52	114	73011	112117	46500820
Bladder dilatation	12.44	10.52	10	73115	753	46612184
Device issue	12.39	10.52	8	73117	19972	46592965
Menopause	12.37	10.52	16	73109	2123	46610814
Dyspnoea exertional	12.36	10.52	39	73086	50250	46562687
Gallbladder disorder	12.30	10.52	6	73119	17492	46595445
Completed suicide	12.26	10.52	158	72967	145762	46467175
Specific gravity urine decreased	12.22	10.52	8	73117	437	46612500
Respiratory depression	12.22	10.52	43	73082	11557	46601380
Suicidal behaviour	12.15	10.52	17	73108	2431	46610506
Thirst decreased	12.14	10.52	6	73119	190	46612747
Personality change	12.13	10.52	26	73099	5232	46607705
Water intoxication	11.96	10.52	8	73117	453	46612484
Enanthema	11.96	10.52	8	73117	453	46612484
Subdural haematoma	11.86	10.52	46	73079	12951	46599986
Procedural pain	11.86	10.52	3	73122	13176	46599761
Withdrawal syndrome	11.82	10.52	58	73067	18076	46594861
Infusion site scar	11.81	10.52	6	73119	202	46612735
Hepatitis fulminant	11.78	10.52	20	73105	3382	46609555
Oropharyngeal blistering	11.68	10.52	10	73115	822	46612115
Camptocormia	11.51	10.52	6	73119	213	46612724
Body mass index decreased	11.49	10.52	7	73118	337	46612600
Developmental hip dysplasia	11.45	10.52	12	73113	1271	46611666
Sinusitis	11.43	10.52	275	72850	129493	46483444
Gamma-glutamyltransferase increased	11.41	10.52	87	73038	31653	46581284
Eosinophil count decreased	11.41	10.52	13	73112	1513	46611424
Anticonvulsant drug level above therapeutic	11.39	10.52	8	73117	491	46612446
Drug diversion	11.38	10.52	10	73115	851	46612086
Neoplasm malignant	11.36	10.52	12	73113	23487	46589450
Dysphagia	11.30	10.52	177	72948	77135	46535802
Acute kidney injury	11.25	10.52	464	72661	235391	46377546
Incoherent	11.21	10.52	23	73102	4489	46608448
Agoraphobia	11.13	10.52	7	73118	357	46612580
Tri-iodothyronine free decreased	11.12	10.52	6	73119	229	46612708
Meningitis herpes	11.12	10.52	6	73119	229	46612708
Cardiogenic shock	11.11	10.52	53	73072	16331	46596606
Urethral haemorrhage	11.10	10.52	4	73121	56	46612881
Pelvic prolapse	11.08	10.52	8	73117	513	46612424
Melaena	11.06	10.52	78	73047	27694	46585243
Potentiating drug interaction	10.95	10.52	21	73104	3902	46609035
Haematemesis	10.95	10.52	80	73045	28726	46584211
Lymphocyte percentage decreased	10.89	10.52	17	73108	2682	46610255
Poor quality sleep	10.82	10.52	50	73075	15203	46597734
Lower limb fracture	10.82	10.52	3	73122	12395	46600542
COVID-19	10.77	10.52	8	73117	18567	46594370
Neurotoxicity	10.76	10.52	4	73121	13713	46599224
Atrial fibrillation	10.73	10.52	107	73018	103483	46509454
Cardiac valve disease	10.73	10.52	21	73104	3963	46608974
Condition aggravated	10.71	10.52	297	72828	244755	46368182
Bradypnoea	10.70	10.52	18	73107	3021	46609916
Deep vein thrombosis	10.69	10.52	77	73048	79696	46533241
Negativism	10.65	10.52	7	73118	385	46612552
Foetal death	10.62	10.52	34	73091	8709	46604228
Illness anxiety disorder	10.59	10.52	5	73120	143	46612794
Parophthalmia	10.57	10.52	6	73119	253	46612684
Bronchopulmonary aspergillosis allergic	10.54	10.52	9	73116	737	46612200

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
Coma	286.96	11.32	315	40983	40134	29871046
Depression	259.99	11.32	455	40843	89982	29821198
Drug interaction	239.53	11.32	709	40589	198859	29712321
Poisoning deliberate	235.74	11.32	129	41169	5775	29905405
Intentional overdose	220.94	11.32	279	41019	41202	29869978
Somnolence	158.27	11.32	386	40912	96377	29814803
Suicide attempt	128.52	11.32	202	41096	36495	29874685
Intentional self-injury	125.87	11.32	122	41176	13410	29897770
Overdose	109.73	11.32	309	40989	84028	29827152
Confusional state	108.88	11.32	420	40878	134414	29776766
Hypothermia	101.90	11.32	93	41205	9474	29901706
Toxicity to various agents	99.62	11.32	495	40803	176688	29734492
Electrocardiogram QT prolonged	97.19	11.32	176	41122	35659	29875521
Hepatocellular injury	88.86	11.32	140	41158	25331	29885849
Suicidal ideation	76.71	11.32	160	41138	35954	29875226
Prescription form tampering	76.43	11.32	29	41269	541	29910639
Drug dependence	74.21	11.32	117	41181	21178	29890002
Miosis	70.23	11.32	69	41229	7707	29903473
Neuroleptic malignant syndrome	68.88	11.32	98	41200	16197	29894983
Product dose omission issue	60.96	11.32	25	41273	91606	29819574
Cardiac failure congestive	59.53	11.32	21	41277	84386	29826794
Agitation	57.84	11.32	185	41113	53888	29857292
Blood mercury abnormal	54.65	11.32	17	41281	168	29911012
Withdrawal syndrome	54.08	11.32	72	41226	11178	29900002
Cholestasis	53.50	11.32	111	41187	24839	29886341
Housebound	53.26	11.32	17	41281	184	29910996
5-hydroxyindolacetic acid in urine increased	52.53	11.32	17	41281	193	29910987
Fall	49.83	11.32	424	40874	181448	29729732
Low density lipoprotein decreased	49.28	11.32	25	41273	956	29910224
Hyperthermia	47.57	11.32	64	41234	10035	29901145
Drug ineffective	41.58	11.32	287	41011	340100	29571080
Death	40.86	11.32	307	40991	356976	29554204
Bradypnoea	40.69	11.32	28	41270	1893	29909287
Disease progression	38.65	11.32	32	41266	79842	29831338
Myocardial infarction	38.13	11.32	72	41226	125553	29785627
Mental status changes	36.96	11.32	4	41294	37075	29874105
Agranulocytosis	36.25	11.32	88	41210	21854	29889326
Pneumonia aspiration	35.70	11.32	124	41174	37656	29873524
Macrophages increased	35.19	11.32	12	41286	162	29911018
Dysarthria	35.05	11.32	107	41191	30383	29880797
Thrombosis	34.38	11.32	8	41290	42223	29868957
Cerebral artery thrombosis	34.38	11.32	16	41282	505	29910675
Drug hypersensitivity	32.48	11.32	28	41270	68491	29842689
Altered state of consciousness	31.97	11.32	79	41219	19840	29891340
Insomnia	31.21	11.32	228	41070	93108	29818072
Pneumonia	31.12	11.32	303	40995	334003	29577177
Dystonic tremor	31.02	11.32	10	41288	112	29911068
Restlessness	30.50	11.32	84	41214	22515	29888665
Burnout syndrome	30.25	11.32	10	41288	122	29911058
Tremor	29.89	11.32	192	41106	75171	29836009
Disturbance in attention	29.61	11.32	82	41216	22047	29889133
Coma scale abnormal	28.72	11.32	29	41269	3347	29907833
Akathisia	28.70	11.32	38	41260	5866	29905314
Muscle rigidity	28.56	11.32	51	41247	10210	29900970
General physical health deterioration	28.35	11.32	235	41063	99709	29811471
Purpura	28.34	11.32	50	41248	9917	29901263
Gamma-glutamyltransferase increased	28.31	11.32	97	41201	29253	29881927
Neutrophil count increased	28.08	11.32	64	41234	15259	29895921
Faecaloma	27.26	11.32	32	41266	4373	29906807
Implant site extravasation	27.20	11.32	13	41285	436	29910744
Bradycardia	26.63	11.32	168	41130	65358	29845822
Drug monitoring procedure incorrectly performed	26.58	11.32	10	41288	182	29910998
Toxic skin eruption	25.98	11.32	51	41247	10964	29900216
Hepatic neoplasm	25.74	11.32	21	41277	1838	29909342
Dystonia	25.37	11.32	47	41251	9680	29901500
Disorientation	25.36	11.32	98	41200	31320	29879860
Brain scan abnormal	25.32	11.32	14	41284	639	29910541
Epilepsy	25.29	11.32	73	41225	20096	29891084
Sedation	25.29	11.32	64	41234	16309	29894871
Serum ferritin abnormal	25.22	11.32	10	41288	211	29910969
Extrapyramidal disorder	24.61	11.32	49	41249	10644	29900536
Respiratory failure	24.54	11.32	65	41233	100577	29810603
Restless legs syndrome	24.26	11.32	38	41260	6834	29904346
Electrocardiogram abnormal	24.25	11.32	35	41263	5857	29905323
Injection site pain	24.16	11.32	6	41292	30304	29880876
Puncture site haematoma	23.91	11.32	9	41289	164	29911016
Accessory spleen	23.76	11.32	9	41289	167	29911013
Contraindicated product administered	23.20	11.32	64	41234	17167	29894013
Bladder dilatation	22.90	11.32	17	41281	1295	29909885
Plasma cell myeloma	22.81	11.32	24	41274	53438	29857742
Antiphospholipid antibodies positive	22.43	11.32	10	41288	285	29910895
Dyspnoea	21.83	11.32	326	40972	332969	29578211
Depressed mood	21.70	11.32	62	41236	16967	29894213
Coronary artery disease	21.57	11.32	22	41276	49690	29861490
Malaise	21.40	11.32	336	40962	166626	29744554
Aggression	21.26	11.32	104	41194	36803	29874377
Loss of consciousness	21.11	11.32	184	41114	79191	29831989
Alcohol poisoning	21.09	11.32	26	41272	3738	29907442
Blepharospasm	20.81	11.32	14	41284	912	29910268
Diarrhoea	20.79	11.32	330	40968	333773	29577407
Paraneoplastic rash	20.63	11.32	7	41291	93	29911087
Blood ethanol increased	20.29	11.32	10	41288	359	29910821
Dextrocardia	20.16	11.32	8	41290	169	29911011
Cough	20.05	11.32	97	41201	125545	29785635
Logorrhoea	19.78	11.32	19	41279	2063	29909117
Loss of personal independence in daily activities	19.75	11.32	70	41228	21465	29889715
Substance abuse	19.60	11.32	35	41263	7005	29904175
Optic nerve cupping	19.59	11.32	6	41292	56	29911124
Blood creatine phosphokinase increased	19.44	11.32	115	41183	43733	29867447
Foetal alcohol syndrome	18.84	11.32	8	41290	202	29910978
Hospitalisation	18.79	11.32	20	41278	44299	29866881
Gastrointestinal haemorrhage	18.77	11.32	56	41242	83390	29827790
Normochromic normocytic anaemia	18.45	11.32	25	41273	3945	29907235
Conjunctival hyperaemia	18.42	11.32	19	41279	2248	29908932
Spinal cord haemorrhage	18.16	11.32	9	41289	327	29910853
Cell death	18.12	11.32	19	41279	2292	29908888
Depressed level of consciousness	18.09	11.32	102	41196	38120	29873060
Therapy non-responder	18.06	11.32	9	41289	29444	29881736
Pemphigoid	17.93	11.32	35	41263	7493	29903687
Anxiety	17.85	11.32	196	41102	89675	29821505
Clumsiness	17.81	11.32	15	41283	1372	29909808
Speech disorder	17.81	11.32	74	41224	24438	29886742
Drug intolerance	17.70	11.32	115	41183	45176	29866004
Adverse drug reaction	17.65	11.32	5	41293	23140	29888040
Eosinophil percentage increased	17.16	11.32	10	41288	505	29910675
Obsessive thoughts	17.16	11.32	11	41287	660	29910520
Pain	17.06	11.32	154	41144	172487	29738693
Sensorimotor disorder	17.05	11.32	9	41289	374	29910806
Peripheral swelling	16.81	11.32	37	41261	61037	29850143
Femoral artery aneurysm	16.44	11.32	7	41291	178	29911002
Product quality issue	16.43	11.32	3	41295	18771	29892409
Blood pressure systolic increased	16.41	11.32	52	41246	15058	29896122
Parkinsonism	16.35	11.32	33	41265	7236	29903944
Erythrosis	16.20	11.32	5	41293	48	29911132
Tachycardia	16.13	11.32	164	41134	73575	29837605
Implant site infection	16.13	11.32	12	41286	917	29910263
Lymphocyte percentage decreased	16.08	11.32	17	41281	2069	29909111
Vascular purpura	15.99	11.32	15	41283	1582	29909598
Reading disorder	15.94	11.32	8	41290	299	29910881
Mean cell haemoglobin concentration increased	15.91	11.32	8	41290	300	29910880
Band neutrophil percentage increased	15.86	11.32	6	41292	111	29911069
Jaundice cholestatic	15.84	11.32	25	41273	4526	29906654
Neutrophil percentage increased	15.83	11.32	16	41282	1848	29909332
Dermatitis psoriasiform	15.73	11.32	13	41285	1158	29910022
Asthenia	15.67	11.32	213	41085	221077	29690103
Congenital hand malformation	15.40	11.32	9	41289	457	29910723
Nausea	15.36	11.32	303	40995	296654	29614526
Arteriovenous fistula	15.29	11.32	10	41288	621	29910559
Urine leukocyte esterase positive	15.26	11.32	8	41290	328	29910852
Hypoglycaemia	15.04	11.32	121	41177	50860	29860320
Psychotic disorder	14.89	11.32	64	41234	21451	29889729
Homicide	14.87	11.32	12	41286	1034	29910146
Laboratory test abnormal	14.81	11.32	3	41295	17439	29893741
Respiratory depression	14.77	11.32	42	41256	11461	29899719
Sudden death	14.76	11.32	51	41247	15441	29895739
Neuropathy peripheral	14.65	11.32	49	41249	70426	29840754
Somnambulism	14.58	11.32	20	41278	3194	29907986
Capillary fragility	14.50	11.32	5	41293	70	29911110
Spleen congestion	14.41	11.32	8	41290	368	29910812
Musculoskeletal pain	14.22	11.32	13	41285	30927	29880253
Drug resistance	14.20	11.32	5	41293	20128	29891052
Rhabdomyolysis	14.19	11.32	142	41156	63438	29847742
Rash maculo-papular	14.19	11.32	71	41227	25347	29885833
pH urine increased	14.12	11.32	5	41293	76	29911104
Opiates positive	14.01	11.32	7	41291	259	29910921
Respiratory arrest	13.80	11.32	12	41286	29246	29881934
Tooth injury	13.73	11.32	10	41288	740	29910440
Delirium febrile	13.72	11.32	4	41294	31	29911149
Prothrombin level decreased	13.59	11.32	12	41286	1170	29910010
Drug therapy enhancement	13.48	11.32	3	41295	6	29911174
Intra-abdominal fluid collection	13.45	11.32	12	41286	1186	29909994
Haemorrhage	13.45	11.32	27	41271	46052	29865128
Mania	13.33	11.32	35	41263	9119	29902061
Expired product administered	13.23	11.32	18	41280	2851	29908329
General symptom	12.87	11.32	10	41288	816	29910364
Myoclonus	12.83	11.32	44	41254	13268	29897912
Pyrexia	12.76	11.32	309	40989	294180	29617000
Therapeutic response decreased	12.73	11.32	9	41289	24340	29886840
Poverty of thought content	12.64	11.32	4	41294	42	29911138
Dyssomnia	12.47	11.32	4	41294	44	29911136
Areflexia	12.45	11.32	17	41281	2702	29908478
Blood urea increased	12.39	11.32	15	41283	31366	29879814
Adrenocortical insufficiency acute	12.32	11.32	12	41286	1325	29909855
Abdominal compartment syndrome	12.30	11.32	10	41288	871	29910309
Hyponatraemia	12.18	11.32	144	41154	67058	29844122
Sinusitis	12.07	11.32	17	41281	33328	29877852
Chronic kidney disease	12.07	11.32	21	41277	37817	29873363
Cytomegalovirus infection	12.05	11.32	9	41289	23665	29887515
Staphylococcal impetigo	11.95	11.32	3	41295	12	29911168
Hypercapnia	11.94	11.32	20	41278	3804	29907376
Exhibitionism	11.94	11.32	4	41294	51	29911129
Paranoia	11.93	11.32	36	41262	10152	29901028
Band neutrophil count increased	11.86	11.32	6	41292	228	29910952
Acute respiratory failure	11.72	11.32	11	41287	25839	29885341
Hypomania	11.71	11.32	15	41283	2241	29908939
COVID-19	11.68	11.32	5	41293	17873	29893307
Fatigue	11.67	11.32	345	40953	320328	29590852
Psychomotor skills impaired	11.62	11.32	14	41284	1965	29909215
Muscle spasms	11.57	11.32	48	41250	64790	29846390
Asphyxia	11.46	11.32	24	41274	5401	29905779
Bradyphrenia	11.44	11.32	20	41278	3937	29907243
Intentional device misuse	11.40	11.32	6	41292	248	29910932
Myocarditis	11.38	11.32	35	41263	9976	29901204

Pharmacologic Action:

Source	Code	Description
ATC	N05CF01	NERVOUS SYSTEM PSYCHOLEPTICS HYPNOTICS AND SEDATIVES Benzodiazepine related drugs
MeSH PA	D002491	Central Nervous System Agents
MeSH PA	D002492	Central Nervous System Depressants
MeSH PA	D006993	Hypnotics and Sedatives
CHEBI has role	CHEBI:35488	cns depressants
CHEBI has role	CHEBI:35717	sedatives

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Insomnia	indication	193462001
Suicidal thoughts	contraindication	6471006
Asthenia	contraindication	13791008
Alcohol intoxication	contraindication	25702006
Depressive disorder	contraindication	35489007
Hepatic failure	contraindication	59927004
Sleep automatism	contraindication	247962006
Severe chronic obstructive pulmonary disease	contraindication	313299006

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	7.95	Basic
pKa2	2.26	Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
GABA-A receptor alpha-5/beta-3/gamma-2	Ion channel	P18507 P28472 P31644	GBRA5_HUMAN GBRB3_HUMAN GBRG2_HUMAN	POSITIVE MODULATOR	Ki	7.28		WOMBAT-PK	DRUG LABEL
GABA A receptor alpha-3/beta-2/gamma-2	Ion channel	P18507 P34903 P47870	GBRA3_HUMAN GBRB2_HUMAN GBRG2_HUMAN	POSITIVE MODULATOR	Ki	6.58		WOMBAT-PK	DRUG LABEL
GABA A receptor alpha-3/beta-2/gamma-3	Ion channel	P34903 P47870 Q99928	GBRA3_HUMAN GBRB2_HUMAN GBRG3_HUMAN	POSITIVE MODULATOR	Ki	6.49		WOMBAT-PK	DRUG LABEL
GABA-A receptor alpha-1/beta-2/gamma-3	Ion channel	P14867 P47870 Q99928	GBRA1_HUMAN GBRB2_HUMAN GBRG3_HUMAN	POSITIVE MODULATOR	Ki	7.15		WOMBAT-PK	DRUG LABEL
GABA A receptor alpha-5/beta-2/gamma-2	Ion channel	P18507 P31644 P47870	GBRA5_HUMAN GBRB2_HUMAN GBRG2_HUMAN	POSITIVE MODULATOR	Ki	7.28		WOMBAT-PK	DRUG LABEL
GABA A receptor alpha-5/beta-2/gamma-3	Ion channel	P31644 P47870 Q99928	GBRA5_HUMAN GBRB2_HUMAN GBRG3_HUMAN	POSITIVE MODULATOR	Ki	6.75		WOMBAT-PK	DRUG LABEL
GABA-A receptor alpha-1/beta-2/gamma-2	Ion channel	P14867 P18507 P47870	GBRA1_HUMAN GBRB2_HUMAN GBRG2_HUMAN	POSITIVE MODULATOR	Ki	7.18		WOMBAT-PK	DRUG LABEL
GABA A receptor alpha-5/beta-3/gamma-3	Ion channel	P28472 P31644 Q99928	GBRA5_HUMAN GBRB3_HUMAN GBRG3_HUMAN	POSITIVE MODULATOR	Ki	6.75		WOMBAT-PK	DRUG LABEL
GABA-A receptor; anion channel	Ion channel		GBRA1_RAT GBRA2_RAT GBRA3_RAT GBRA4_RAT GBRA5_RAT GBRA6_RAT GBRB1_RAT GBRB2_RAT GBRB3_RAT GBRD_RAT GBRE_RAT GBRG1_RAT GBRG2_RAT GBRG3_RAT GBRP_RAT Q91ZM7_RAT		IC50	7.54		CHEMBL

External reference:

ID	Source
D01372	KEGG_DRUG
C0592282	UMLSCUI
CHEBI:53762	CHEBI
ZPC	PDB_CHEM_ID
CHEMBL135400	ChEMBL_ID
C515050	MESH_SUPPLEMENTAL_RECORD_UI
4462	INN_ID
03A5ORL08Q	UNII
5735	PUBCHEM_CID
7430	IUPHAR_LIGAND_ID
DB01198	DRUGBANK_ID
152527	RXNORM
003775	NDDF
321174005	SNOMEDCT_US
395929002	SNOMEDCT_US

Pharmaceutical products:

None