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

Stem definition	Drug id	CAS RN
atropine derivatives	2677	186691-13-4

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: tiotropium bromide hydrate tiotropium respimat tiotropium bromide tiotropium bromide monohydrate spiriva tiotropiumbromide	A scopolamine derivative and CHOLINERGIC ANTAGONIST that functions as a BRONCHODILATOR AGENT. It is used in the treatment of CHRONIC OBSTRUCTIVE PULMONARY DISEASE. Molecular weight: 392.51 Formula: C19H22NO4S2 CLOGP: -1.91 LIPINSKI: 0 HAC: 5 HDO: 1 TPSA: 59.06 ALOGS: -4.44 ROTB: 5 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

tiotropium bromide hydrate
tiotropium
respimat
tiotropium bromide
tiotropium bromide monohydrate
spiriva
tiotropiumbromide

A scopolamine derivative and CHOLINERGIC ANTAGONIST that functions as a BRONCHODILATOR AGENT. It is used in the treatment of CHRONIC OBSTRUCTIVE PULMONARY DISEASE.

Molecular weight: 392.51
Formula: C19H22NO4S2
CLOGP: -1.91
LIPINSKI: 0
HAC: 5
HDO: 1
TPSA: 59.06
ALOGS: -4.44
ROTB: 5

Status: OFP

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

Drug dosage:

Dose	Unit	Route
10	mcg	Inhal.powder
5	mcg	Inhal.solution

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	3	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	74 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	0.00 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability)	2.50 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution)	32 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	12.60 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.28 %	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
Jan. 30, 2004	FDA	BOEHRINGER INGELHEIM

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
Incorrect route of product administration	6957.90	11.69	2455	124239	24997	63337331
Asthma	3325.81	11.69	2430	124264	125131	63237197
Dyspnoea	1950.79	11.69	4145	122549	657168	62705160
Wheezing	1880.59	11.69	1543	125151	94052	63268276
Obstructive airways disorder	1540.63	11.69	775	125919	19924	63342404
Chronic obstructive pulmonary disease	1234.03	11.69	1013	125681	61673	63300655
Sleep disorder due to a general medical condition	979.69	11.69	481	126213	11707	63350621
Full blood count abnormal	935.65	11.69	653	126041	31064	63331264
Productive cough	915.27	11.69	858	125836	62350	63299978
Cough	891.79	11.69	1866	124828	290877	63071451
Forced expiratory volume decreased	709.40	11.69	293	126401	4675	63357653
Sputum discoloured	655.91	11.69	408	126286	15939	63346389
Product quality issue	635.90	11.69	546	126148	35319	63327009
Pneumonia	540.56	11.69	2065	124629	454702	62907626
Sedation complication	487.39	11.69	318	126376	13504	63348824
Creatinine renal clearance decreased	462.72	11.69	328	126366	15980	63346348
Therapeutic product effect incomplete	435.35	11.69	844	125850	124212	63238116
Orthostatic hypotension	383.63	11.69	415	126279	35745	63326583
Chest discomfort	380.02	11.69	740	125954	109229	63253099
Contraindicated product administered	369.53	11.69	15	126679	217633	63144695
Sedation	336.26	11.69	401	126293	38408	63323920
Blood calcium decreased	335.31	11.69	334	126360	26117	63336211
Synovitis	323.76	11.69	11	126683	186907	63175421
Loss of personal independence in daily activities	319.56	11.69	641	126053	96649	63265679
Systemic lupus erythematosus	308.54	11.69	30	126664	208888	63153440
Treatment failure	290.23	11.69	30	126664	199013	63163315
Dyspnoea exertional	289.81	11.69	469	126225	59833	63302495
Off label use	283.41	11.69	576	126118	673886	62688442
Drug intolerance	283.09	11.69	131	126563	308530	63053798
Middle insomnia	279.65	11.69	219	126475	12424	63349904
Balance disorder	267.42	11.69	548	126146	83874	63278454
Hand deformity	267.24	11.69	12	126682	159445	63202883
Arthropathy	262.30	11.69	72	126622	234720	63127608
Cognitive disorder	261.29	11.69	429	126265	55386	63306942
Maternal exposure during pregnancy	260.28	11.69	60	126634	220002	63142326
Completed suicide	257.93	11.69	7	126687	145666	63216662
Dysphonia	235.16	11.69	375	126319	47239	63315089
Alopecia	234.04	11.69	198	126496	337338	63024990
Bronchitis	231.54	11.69	659	126035	124276	63238052
Blood immunoglobulin E increased	231.43	11.69	125	126569	3724	63358604
Eosinophil count increased	226.07	11.69	182	126512	10746	63351582
Pulmonary mass	225.17	11.69	251	126443	22345	63339983
Glossodynia	221.23	11.69	44	126650	178832	63183496
Pericarditis	220.14	11.69	10	126684	131569	63230759
Reversible airways obstruction	214.41	11.69	94	126600	1748	63360580
Abdominal discomfort	214.27	11.69	195	126499	320690	63041638
Respiratory tract infection	208.00	11.69	329	126365	41154	63321174
Exposure during pregnancy	203.74	11.69	33	126661	155514	63206814
Joint swelling	201.61	11.69	214	126480	327452	63034876
Upper-airway cough syndrome	198.55	11.69	172	126522	11246	63351082
Depressed level of consciousness	197.76	11.69	404	126290	61674	63300654
Anti-cyclic citrullinated peptide antibody positive	190.66	11.69	10	126684	116202	63246126
Nasal congestion	190.19	11.69	411	126283	65249	63297079
Rheumatoid arthritis	188.30	11.69	139	126555	253680	63108648
Lung neoplasm malignant	186.94	11.69	213	126481	19420	63342908
Nasal polyps	172.51	11.69	122	126572	5917	63356411
Hepatic enzyme increased	171.67	11.69	95	126599	202233	63160095
Total lung capacity increased	170.29	11.69	86	126608	2224	63360104
Wound	169.72	11.69	57	126637	163206	63199122
Asthmatic crisis	162.10	11.69	77	126617	1736	63360592
Vital capacity decreased	159.44	11.69	75	126619	1653	63360675
Infusion related reaction	159.32	11.69	153	126541	245368	63116960
Bronchial secretion retention	158.25	11.69	87	126607	2686	63359642
Bronchiectasis	156.87	11.69	177	126517	15965	63346363
Forced vital capacity decreased	155.25	11.69	64	126630	1015	63361313
Secretion discharge	152.31	11.69	153	126541	12078	63350250
Therapeutic product effect decreased	149.55	11.69	101	126593	193086	63169242
Rales	149.32	11.69	154	126540	12543	63349785
Throat clearing	146.67	11.69	79	126615	2340	63359988
Discomfort	138.50	11.69	81	126613	167293	63195035
Emphysema	138.37	11.69	138	126556	10800	63351528
Breath sounds abnormal	134.33	11.69	136	126558	10837	63351491
Arthralgia	133.04	11.69	635	126059	569075	62793253
Helicobacter infection	132.57	11.69	15	126679	92770	63269558
Restrictive pulmonary disease	127.00	11.69	65	126629	1730	63360598
Asthma-chronic obstructive pulmonary disease overlap syndrome	126.90	11.69	68	126626	1993	63360335
Swelling	126.73	11.69	222	126472	275156	63087172
Hypoventilation	122.01	11.69	90	126604	4664	63357664
Neutropenia	121.93	11.69	102	126592	174903	63187425
Sputum culture positive	120.95	11.69	67	126627	2100	63360228
Nasal obstruction	120.49	11.69	62	126632	1669	63360659
Respiratory tract congestion	119.19	11.69	162	126532	17670	63344658
Eosinophilia	118.94	11.69	184	126510	22572	63339756
Folliculitis	118.72	11.69	5	126689	70312	63292016
Peak expiratory flow rate decreased	113.77	11.69	44	126650	585	63361743
Eosinophilic granulomatosis with polyangiitis	112.11	11.69	64	126630	2128	63360200
Bronchial wall thickening	111.06	11.69	56	126638	1443	63360885
Influenza	108.99	11.69	468	126226	108254	63254074
Total lung capacity decreased	107.01	11.69	62	126632	2121	63360207
Product use issue	106.76	11.69	172	126522	220348	63141980
Psoriatic arthropathy	104.11	11.69	27	126667	91493	63270835
Intentional overdose	103.43	11.69	13	126681	74139	63288189
Irritable bowel syndrome	102.40	11.69	20	126674	82392	63279936
Haemoptysis	101.14	11.69	195	126499	28531	63333797
Rash	100.65	11.69	681	126013	560190	62802138
Lung diffusion test abnormal	99.48	11.69	34	126660	309	63362019
Impaired healing	99.44	11.69	40	126654	102502	63259826
Eosinophil count abnormal	98.82	11.69	39	126655	549	63361779
Fall	98.23	11.69	1205	125489	391129	62971199
Blister	97.59	11.69	70	126624	129744	63232584
Intentional product use issue	97.41	11.69	68	126626	127824	63234504
Musculoskeletal stiffness	97.09	11.69	136	126558	184482	63177846
Respiration abnormal	96.38	11.69	89	126605	6328	63356000
Bronchopulmonary aspergillosis allergic	94.71	11.69	58	126636	2200	63360128
Constipation	94.27	11.69	769	125925	224174	63138154
Rhinitis allergic	93.13	11.69	116	126578	11611	63350717
Pulmonary function test decreased	93.01	11.69	71	126623	3876	63358452
Febrile neutropenia	91.52	11.69	62	126632	118387	63243941
Gastrooesophageal reflux disease	90	11.69	404	126290	95235	63267093
Drug ineffective	89.73	11.69	1508	125186	1043257	62319071
Sleep apnoea syndrome	89.68	11.69	187	126507	28946	63333382
Gastrointestinal disorder	89.55	11.69	78	126616	131161	63231167
Sensitivity to weather change	89.14	11.69	90	126604	7147	63355181
Rhinitis	87.98	11.69	111	126583	11255	63351073
Lung opacity	85.89	11.69	62	126632	3106	63359222
Lung diffusion test decreased	85.74	11.69	37	126657	661	63361667
White blood cell count decreased	85.23	11.69	91	126603	139013	63223315
Prolonged expiration	84.31	11.69	42	126652	1054	63361274
Vocal cord dysfunction	83.42	11.69	34	126660	523	63361805
Upper respiratory tract infection	81.30	11.69	352	126342	81695	63280633
Thrombocytopenia	80.82	11.69	110	126584	151047	63211281
Malaise	80.12	11.69	1219	125475	414735	62947593
Impaired quality of life	79.93	11.69	117	126577	13666	63348662
Multiple allergies	79.81	11.69	117	126577	13685	63348643
Mobility decreased	79.79	11.69	463	126231	120696	63241632
Respiratory rate increased	79.36	11.69	116	126578	13532	63348796
C-reactive protein abnormal	78.75	11.69	3	126691	46093	63316235
Oropharyngeal pain	78.55	11.69	385	126309	94102	63268226
Diarrhoea	77.07	11.69	987	125707	714379	62647949
Bronchospasm	77.04	11.69	130	126564	17150	63345178
Heart rate increased	76.21	11.69	381	126313	93857	63268471
Lung disorder	75.14	11.69	284	126410	61977	63300351
Oxygen saturation decreased	73.67	11.69	361	126333	88224	63274104
Dust allergy	72.58	11.69	33	126661	671	63361657
Cardiac murmur	72.34	11.69	115	126579	14437	63347891
Drug hypersensitivity	71.31	11.69	348	126346	310339	63051989
Liver injury	70.48	11.69	17	126677	60503	63301825
Blood cholesterol increased	70.28	11.69	51	126643	93981	63268347
Choking	67.92	11.69	91	126603	9788	63352540
Drug abuse	67.56	11.69	30	126664	72488	63289840
Blood pressure systolic increased	67.27	11.69	228	126466	47169	63315159
Lung hyperinflation	66.74	11.69	38	126656	1257	63361071
Hypercapnia	64.09	11.69	66	126628	5365	63356963
Hyper IgE syndrome	62.53	11.69	27	126667	483	63361845
Factor V Leiden mutation	59.66	11.69	21	126673	210	63362118
Respiratory gas exchange disorder	58.60	11.69	24	126670	374	63361954
Pregnancy	57.88	11.69	4	126690	36832	63325496
Pancytopenia	57.61	11.69	65	126629	96868	63265460
Sarcoidosis	57.43	11.69	71	126623	7051	63355277
Infective exacerbation of chronic obstructive airways disease	57.14	11.69	34	126660	1223	63361105
Seasonal allergy	57.07	11.69	128	126566	20822	63341506
Asthma exercise induced	56.65	11.69	22	126672	296	63362032
Platelet count decreased	55.75	11.69	91	126603	116031	63246297
Spirometry abnormal	55.04	11.69	20	126674	221	63362107
Smoke sensitivity	54.95	11.69	24	126670	442	63361886
Aphonia	54.88	11.69	83	126611	9980	63352348
Oesophageal spasm	54.20	11.69	47	126647	3076	63359252
Sinus disorder	53.93	11.69	138	126556	24415	63337913
Blood test abnormal	53.67	11.69	105	126589	15524	63346804
Rubber sensitivity	52.89	11.69	41	126653	2290	63360038
Rib deformity	52.19	11.69	20	126674	259	63362069
Nausea	52.03	11.69	1304	125390	853167	62509161
Lower respiratory tract infection	51.46	11.69	445	126249	131862	63230466
Pain	51.28	11.69	1108	125586	739520	62622808
Malignant neoplasm progression	51.10	11.69	53	126641	82068	63280260
Broncholithiasis	50.44	11.69	19	126675	234	63362094
Respiratory disorder	50.27	11.69	182	126512	38900	63323428
Allergy to animal	49.71	11.69	31	126663	1215	63361113
Increased upper airway secretion	49.55	11.69	48	126646	3624	63358704
Therapy non-responder	49.51	11.69	47	126647	75854	63286474
Hypoxia	49.22	11.69	243	126451	59549	63302779
Lymph node calcification	48.81	11.69	20	126674	312	63362016
Skin candida	48.58	11.69	34	126660	1621	63360707
Seizure	48.27	11.69	122	126572	132512	63229816
Alanine aminotransferase increased	48.25	11.69	83	126611	103687	63258641
Suicide attempt	48.24	11.69	31	126663	60887	63301441
Abortion spontaneous	48.10	11.69	17	126677	47178	63315150
Knee arthroplasty	48.06	11.69	24	126670	54182	63308146
Disease progression	47.77	11.69	109	126585	122649	63239679
Hip arthroplasty	47.14	11.69	18	126676	47628	63314700
Humidity intolerance	47.14	11.69	20	126674	342	63361986
Mycobacterium avium complex infection	46.71	11.69	43	126651	3045	63359283
Acute respiratory failure	46.41	11.69	163	126531	34322	63328006
Sputum purulent	45.79	11.69	28	126666	1059	63361269
Product physical issue	45.67	11.69	53	126641	4927	63357401
Pulmonary function test abnormal	45.51	11.69	34	126660	1796	63360532
Heart sounds	45.43	11.69	27	126667	969	63361359
Perfume sensitivity	45.23	11.69	25	126669	780	63361548
C-reactive protein increased	44.73	11.69	75	126619	94632	63267696
Oesophageal pain	43.71	11.69	45	126649	3656	63358672
Chest pain	43.44	11.69	638	126056	215321	63147007
Lower respiratory tract congestion	43.29	11.69	40	126654	2846	63359482
Hypotension	42.79	11.69	773	125921	271831	63090497
Bronchitis chronic	42.75	11.69	48	126646	4305	63358023
Eczema	42.06	11.69	151	126543	32140	63330188
Drug-induced liver injury	41.83	11.69	14	126680	40208	63322120
Degenerative bone disease	41.75	11.69	15	126679	160	63362168
Paroxysmal extreme pain disorder	41.50	11.69	13	126681	87	63362241
Red blood cell sedimentation rate increased	41.27	11.69	18	126676	43964	63318364
Idiopathic intracranial hypertension	40.85	11.69	39	126655	2892	63359436
Status asthmaticus	39.92	11.69	24	126670	880	63361448
Multiple sclerosis relapse	39.31	11.69	24	126670	48454	63313874
Occupational asthma	39.25	11.69	14	126680	146	63362182
Throat irritation	39.19	11.69	164	126530	37483	63324845
Throat tightness	39.15	11.69	124	126570	24763	63337565
Oedema peripheral	38.94	11.69	562	126132	188949	63173379
Stomatitis	38.78	11.69	144	126550	138581	63223747
Frustration tolerance decreased	38.62	11.69	58	126636	6930	63355398
Laryngeal stenosis	38.48	11.69	25	126669	1053	63361275
Rhinorrhoea	38.31	11.69	243	126451	65334	63296994
Respiratory failure	38.25	11.69	340	126354	101518	63260810
Aspartate aminotransferase increased	37.74	11.69	77	126617	90200	63272128
Adverse event	37.28	11.69	48	126646	67511	63294817
Condition aggravated	37.08	11.69	572	126122	401645	62960683
Chronic respiratory disease	36.90	11.69	14	126680	176	63362152
Cholestasis	36.86	11.69	7	126687	29427	63332901
Coma	36.27	11.69	45	126649	64319	63298009
Viral infection	36.07	11.69	154	126540	35509	63326819
Blood pressure increased	35.87	11.69	487	126207	161575	63200753
Confusional arousal	35.54	11.69	14	126680	196	63362132
Fatigue	35.41	11.69	1432	125262	886596	62475732
Liver disorder	35.30	11.69	33	126661	53654	63308674
Vision blurred	35.11	11.69	308	126386	91616	63270712
Nasal discharge discolouration	35.08	11.69	32	126662	2239	63360089
Psoriasis	34.82	11.69	76	126618	86881	63275447
Blood calcium increased	34.79	11.69	65	126629	9285	63353043
Bronchomalacia	34.19	11.69	14	126680	218	63362110
Pneumothorax spontaneous	33.90	11.69	21	126673	813	63361515
Drug ineffective for unapproved indication	33.48	11.69	13	126681	34050	63328278
Expiratory reserve volume decreased	33.39	11.69	9	126685	32	63362296
Nasal mucosal disorder	33.23	11.69	17	126677	452	63361876
Bronchial obstruction	33.09	11.69	26	126668	1481	63360847
Carcinoid tumour pulmonary	32.92	11.69	17	126677	461	63361867
Joint range of motion decreased	32.50	11.69	12	126682	32416	63329912
Intentional self-injury	32.40	11.69	6	126688	25681	63336647
Product use in unapproved indication	32.19	11.69	217	126477	178863	63183465
Nasopharyngitis	31.84	11.69	697	125997	253560	63108768
Post procedural hypothyroidism	31.70	11.69	14	126680	265	63362063
Cardio-respiratory arrest	31.66	11.69	44	126650	59915	63302413
Painful respiration	31.45	11.69	33	126661	2741	63359587
Neurosensory hypoacusis	30.93	11.69	13	126681	217	63362111
Prescribed overdose	30.46	11.69	15	126679	34138	63328190
Drug reaction with eosinophilia and systemic symptoms	29.97	11.69	15	126679	33821	63328507
Chest X-ray abnormal	29.90	11.69	41	126653	4508	63357820
Hypoaesthesia	29.79	11.69	205	126489	168188	63194140
Forced expiratory flow decreased	29.74	11.69	10	126684	86	63362242
Neoplasm progression	29.58	11.69	18	126676	36410	63325918
Increased bronchial secretion	29.49	11.69	26	126668	1740	63360588
Neuropathy peripheral	29.21	11.69	122	126572	113545	63248783
Dry throat	28.97	11.69	50	126644	6715	63355613
Paraesthesia	28.81	11.69	189	126505	156777	63205551
Respiratory distress	28.66	11.69	139	126555	33812	63328516
Multiple organ dysfunction syndrome	28.63	11.69	43	126651	56709	63305619
Decreased bronchial secretion	28.51	11.69	9	126685	62	63362266
Mite allergy	27.80	11.69	17	126677	643	63361685
Premature delivery	27.46	11.69	13	126681	30268	63332060
Leukopenia	27.41	11.69	72	126622	77218	63285110
CFTR gene mutation	27.08	11.69	10	126684	116	63362212
Weight decreased	26.89	11.69	733	125961	276065	63086263
Oesophageal dilatation	26.87	11.69	14	126680	387	63361941
Dry mouth	26.75	11.69	255	126439	77608	63284720
Hepatic function abnormal	26.65	11.69	21	126673	37121	63325207
Body temperature decreased	26.44	11.69	95	126599	20224	63342104
Intentional product misuse	26.28	11.69	51	126643	60866	63301462
Cytomegalovirus infection	26.20	11.69	5	126689	20947	63341381
Polymyalgia rheumatica	26.18	11.69	35	126659	3756	63358572
HIV infection	26.16	11.69	14	126680	409	63361919
Infection	26.10	11.69	312	126382	228861	63133467
Septic shock	26.04	11.69	59	126635	66570	63295758
Palmar-plantar erythrodysaesthesia syndrome	25.77	11.69	7	126687	23008	63339320
Pneumonia viral	25.73	11.69	52	126642	7870	63354458
Multiple drug therapy	25.70	11.69	34	126660	3612	63358716
Muscle spasticity	25.61	11.69	6	126688	21788	63340540
Glossitis	25.30	11.69	31	126663	3051	63359277
Diabetes mellitus	25.07	11.69	194	126500	55616	63306712
Peak expiratory flow rate abnormal	25.05	11.69	9	126685	96	63362232
Rhonchi	24.60	11.69	28	126666	2548	63359780
Perineal fistula	24.40	11.69	7	126687	33	63362295
Breath sounds	24.33	11.69	9	126685	105	63362223
Inflammation	23.91	11.69	84	126610	82189	63280139
Total lung capacity abnormal	23.67	11.69	8	126686	70	63362258
Night sweats	23.65	11.69	38	126656	48776	63313552
FEV1/FVC ratio decreased	23.59	11.69	9	126685	115	63362213
Exposure to allergen	23.49	11.69	12	126682	318	63362010
Hypersensitivity	23.41	11.69	427	126267	292258	63070070
Device dislocation	23.37	11.69	11	126683	25694	63336634
Injury	23.21	11.69	72	126622	73175	63289153
Peripheral swelling	23.19	11.69	382	126312	265560	63096768
Lymphocyte count decreased	23.14	11.69	16	126678	30241	63332087
Aspirin-exacerbated respiratory disease	23.09	11.69	17	126677	878	63361450
Bone marrow failure	23.06	11.69	15	126679	29275	63333053
Increased viscosity of bronchial secretion	23.05	11.69	12	126682	331	63361997
Functional residual capacity decreased	23.00	11.69	8	126686	77	63362251
Schizophrenia	22.96	11.69	57	126637	9895	63352433
Forced expiratory volume abnormal	22.91	11.69	8	126686	78	63362250
Sputum culture	22.57	11.69	11	126683	263	63362065
Illness	22.29	11.69	171	126523	48888	63313440
Dyslipidaemia	22.22	11.69	47	126647	7346	63354982
Pharyngeal oedema	22.16	11.69	69	126625	13652	63348676
Drug resistance	22.13	11.69	9	126685	22924	63339404
Functional residual capacity increased	21.97	11.69	8	126686	89	63362239
Foetal exposure during pregnancy	21.78	11.69	19	126675	31943	63330385
Acute myeloid leukaemia	21.64	11.69	4	126690	17143	63345185
Hepatocellular injury	21.58	11.69	14	126680	27367	63334961
Electrocardiogram QT prolonged	21.46	11.69	55	126639	59475	63302853
Respiratory depression	21.26	11.69	68	126626	13647	63348681
Depressive symptom	21.19	11.69	33	126661	4069	63358259
Osteoarthritis	21.13	11.69	108	126586	95235	63267093
Hypomania	21.10	11.69	42	126652	6288	63356040
Prescribed underdose	21.03	11.69	17	126677	29672	63332656
Foot deformity	20.94	11.69	15	126679	27838	63334490
Laboratory test abnormal	20.89	11.69	14	126680	26898	63335430
Lip dry	20.88	11.69	3	126691	15467	63346861
Blood creatine phosphokinase increased	20.84	11.69	18	126676	30412	63331916
Aspiration	20.81	11.69	58	126636	10793	63351535
Pulmonary pain	20.78	11.69	30	126664	3460	63358868
Hepatic cytolysis	20.77	11.69	3	126691	15404	63346924
Neutrophil count decreased	20.42	11.69	52	126642	56354	63305974
Nocturnal dyspnoea	20.40	11.69	18	126676	1206	63361122
Plasma cell myeloma	20.34	11.69	25	126669	35880	63326448
Lipohypertrophy	20.31	11.69	14	126680	651	63361677
Deep vein thrombosis	20.27	11.69	92	126602	83708	63278620
Disturbance in attention	20.18	11.69	28	126666	38161	63324167
Drug withdrawal syndrome	19.99	11.69	15	126679	27179	63335149
Oral candidiasis	19.72	11.69	94	126600	22704	63339624
Drug eruption	19.62	11.69	17	126677	28677	63333651
Skin ulcer	19.48	11.69	35	126659	43010	63319318
Blood immunoglobulin E decreased	19.21	11.69	7	126687	78	63362250
Confusional state	19.16	11.69	344	126350	236036	63126292
Cerebral infarction	19.13	11.69	12	126682	23881	63338447
Swollen tongue	19.12	11.69	127	126567	34673	63327655
Hypoacusis	19.05	11.69	97	126597	24054	63338274
Mononeuropathy multiplex	19.01	11.69	10	126684	282	63362046
Female sterilisation	18.91	11.69	13	126681	602	63361726
Nasal oedema	18.88	11.69	19	126675	1503	63360825
Metastases to liver	18.75	11.69	12	126682	23627	63338701
Peripheral venous disease	18.71	11.69	4	126690	15473	63346855
Ageusia	18.56	11.69	65	126629	13663	63348665
Eye infection bacterial	18.55	11.69	9	126685	213	63362115
Atrial flutter	18.51	11.69	52	126642	9720	63352608
Chronic sinusitis	18.41	11.69	62	126632	12781	63349547
Lupus-like syndrome	18.40	11.69	4	126690	15291	63347037
Chronic respiratory failure	18.32	11.69	21	126673	1926	63360402
Foetal malnutrition	18.04	11.69	7	126687	94	63362234
Sinus polyp degeneration	18.01	11.69	6	126688	50	63362278
Abdominal pain	17.95	11.69	447	126247	293009	63069319
Croup infectious	17.86	11.69	12	126682	535	63361793
Encephalopathy	17.84	11.69	31	126663	38589	63323739
Fungal endocarditis	17.77	11.69	9	126685	234	63362094
Anaphylactic reaction	17.76	11.69	206	126488	65894	63296434
Exercise tolerance decreased	17.76	11.69	36	126658	5461	63356867
Hepatic cirrhosis	17.72	11.69	14	126680	24720	63337608
Crystal arthropathy	17.69	11.69	10	126684	326	63362002
Caesarean section	17.59	11.69	6	126688	17026	63345302
Forced expiratory volume increased	17.53	11.69	5	126689	23	63362305
Urinary retention	17.52	11.69	112	126582	30189	63332139
Social problem	17.42	11.69	14	126680	824	63361504
Cardiogenic shock	17.37	11.69	7	126687	17925	63344403
Laryngectomy	17.35	11.69	5	126689	24	63362304
Rib fracture	17.30	11.69	90	126604	22507	63339821
Lymphoedema	17.25	11.69	57	126637	11635	63350693
Shock	17.17	11.69	13	126681	23450	63338878
Candida infection	17.14	11.69	106	126588	28245	63334083
Heavy menstrual bleeding	17.11	11.69	7	126687	17766	63344562
Mouth injury	17.03	11.69	15	126679	1002	63361326
Carbon dioxide increased	17.01	11.69	17	126677	1333	63360995
Injection site reaction	16.84	11.69	60	126634	58464	63303864
Vaginal haemorrhage	16.80	11.69	18	126676	27469	63334859
Ascites	16.80	11.69	35	126659	40693	63321635
Amnesia	16.66	11.69	56	126638	55529	63306799
Tooth disorder	16.59	11.69	19	126675	28138	63334190
Acute hepatic failure	16.42	11.69	8	126686	18319	63344009
Wrist fracture	16.40	11.69	62	126632	13525	63348803
Status epilepticus	16.38	11.69	5	126689	15228	63347100
Rash maculo-papular	16.25	11.69	24	126670	31872	63330456
Haemoglobin decreased	16.20	11.69	199	126495	145286	63217042
Pulmonary thrombosis	16.18	11.69	46	126648	8656	63353672
Vomiting	16.15	11.69	933	125761	558684	62803644
Drug level increased	16.13	11.69	13	126681	22723	63339605
Dyspnoea at rest	15.99	11.69	29	126665	4050	63358278
Pulmonary congestion	15.93	11.69	73	126621	17345	63344983
Immune-mediated pancreatitis	15.78	11.69	7	126687	134	63362194
Hepatitis	15.74	11.69	35	126659	39753	63322575
Product prescribing error	15.71	11.69	98	126596	26191	63336137
Occult blood	15.69	11.69	16	126678	1285	63361043
Sciatica	15.45	11.69	28	126666	34296	63328032
Pyrexia	15.32	11.69	775	125919	469703	62892625
Polycystic ovaries	15.30	11.69	30	126664	4441	63357887
Nervousness	15.22	11.69	110	126584	30869	63331459
Toxic epidermal necrolysis	15.03	11.69	17	126677	25317	63337011
Respiratory tract irritation	14.98	11.69	10	126684	441	63361887
Inhalation therapy	14.98	11.69	5	126689	42	63362286
Mucosal inflammation	14.95	11.69	46	126648	46882	63315446
Colitis ulcerative	14.95	11.69	18	126676	26073	63336255
Interstitial lung disease	14.95	11.69	68	126626	61840	63300488
Jaundice cholestatic	14.89	11.69	40	126654	7284	63355044
Full blood count decreased	14.86	11.69	18	126676	26006	63336322
Cytokine release syndrome	14.85	11.69	5	126689	14309	63348019
Acute respiratory distress syndrome	14.85	11.69	15	126679	23519	63338809
Injection site erythema	14.82	11.69	101	126593	83073	63279255
Magnesium metabolism disorder	14.77	11.69	5	126689	44	63362284
Musculoskeletal discomfort	14.76	11.69	73	126621	17894	63344434
Bronchospasm paradoxical	14.74	11.69	6	126688	92	63362236
Respiratory tract inflammation	14.53	11.69	11	126683	593	63361735
Premature baby	14.53	11.69	12	126682	20723	63341605
Muscular weakness	14.52	11.69	165	126529	122188	63240140
Dyskinesia	14.50	11.69	26	126668	31976	63330352
Cardiac failure congestive	14.43	11.69	262	126432	92171	63270157
Blood lactate dehydrogenase increased	14.28	11.69	15	126679	23101	63339227
Exostosis	14.26	11.69	9	126685	17853	63344475
Adenocarcinoma	14.23	11.69	23	126671	2927	63359401
Frequent bowel movements	14.16	11.69	15	126679	23007	63339321
Overdose	14.13	11.69	154	126540	114924	63247404
Cytopenia	14.02	11.69	3	126691	11598	63350730
Ear discomfort	13.94	11.69	41	126653	7865	63354463
Aphasia	13.91	11.69	28	126666	32972	63329356
Appetite disorder	13.91	11.69	39	126655	7282	63355046
Muscle rigidity	13.85	11.69	3	126691	11497	63350831
Colitis	13.80	11.69	50	126644	48478	63313850
Sinus congestion	13.75	11.69	72	126622	18051	63344277
Hypophosphataemia	13.72	11.69	3	126691	11423	63350905
Enterobiasis	13.70	11.69	5	126689	56	63362272
Impaired work ability	13.68	11.69	9	126685	17466	63344862
Premature labour	13.63	11.69	4	126690	12500	63349828
Bacterial disease carrier	13.63	11.69	15	126679	1316	63361012
Adverse drug reaction	13.62	11.69	98	126596	79616	63282712
Caffeine allergy	13.59	11.69	4	126690	21	63362307
Right ventricular systolic pressure	13.58	11.69	3	126691	3	63362325
Arthritis	13.50	11.69	157	126537	115764	63246564
Infective aneurysm	13.42	11.69	9	126685	400	63361928
Pulmonary arterial hypertension	13.39	11.69	84	126610	22493	63339835
Skin lesion	13.36	11.69	106	126588	30615	63331713
Monocytopenia	13.32	11.69	5	126689	61	63362267
Forced vital capacity abnormal	13.28	11.69	4	126690	23	63362305
Serotonin syndrome	13.27	11.69	23	126671	28659	63333669
Brain hypoxia	13.26	11.69	10	126684	536	63361792
Rheumatoid nodule	13.21	11.69	9	126685	17146	63345182
Peritonitis	13.21	11.69	9	126685	17145	63345183
Musculoskeletal disorder	13.21	11.69	13	126681	20631	63341697
Grip strength decreased	13.18	11.69	15	126679	22272	63340056
Myocardial infarction	13.17	11.69	276	126418	99617	63262711
Pneumonia aspiration	13.16	11.69	31	126663	34509	63327819
Metabolic acidosis	13.10	11.69	46	126648	45023	63317305
Blood alkaline phosphatase increased	13.07	11.69	43	126651	42924	63319404
Pancreatitis	13.00	11.69	52	126642	49003	63313325
Sepsis	12.99	11.69	221	126473	152902	63209426
Complication associated with device	12.95	11.69	9	126685	16969	63345359
Osteomyelitis	12.85	11.69	20	126674	26000	63336328
Lung diffusion disorder	12.69	11.69	5	126689	70	63362258
Overweight	12.64	11.69	25	126669	3726	63358602
Chronic gastrointestinal bleeding	12.56	11.69	6	126688	137	63362191
Coronavirus test positive	12.50	11.69	11	126683	734	63361594
Scratch	12.50	11.69	35	126659	6530	63355798
Oxygen saturation abnormal	12.47	11.69	24	126670	3505	63358823
Hallucination, auditory	12.43	11.69	5	126689	12819	63349509
Sputum retention	12.39	11.69	10	126684	592	63361736
Poisoning	12.24	11.69	6	126688	13694	63348634
Haematocrit decreased	12.23	11.69	39	126655	39301	63323027
Airway remodelling	12.20	11.69	5	126689	78	63362250
Fibromuscular dysplasia	12.20	11.69	7	126687	235	63362093
Pain of skin	12.18	11.69	4	126690	11630	63350698
Ejection fraction decreased	12.18	11.69	16	126678	22316	63340012
Bone density decreased	12.17	11.69	7	126687	14605	63347723
Aspergillus test positive	12.16	11.69	8	126686	344	63361984
Anaemia	12.07	11.69	471	126223	292959	63069369
Pulmonary eosinophilia	12.06	11.69	8	126686	349	63361979
Synovial cyst	12.01	11.69	3	126691	10430	63351898
General physical health deterioration	11.98	11.69	308	126386	201094	63161234
Autoimmune disorder	11.96	11.69	10	126684	17167	63345161
Musculoskeletal pain	11.93	11.69	122	126572	92155	63270173
Laryngitis	11.92	11.69	66	126628	16901	63345427
Panniculitis	11.77	11.69	4	126690	11381	63350947

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
Incorrect route of product administration	2981.69	11.25	1193	86964	13652	34855122
Asthma	2661.74	11.25	1534	86623	41122	34827652
Wheezing	1794.87	11.25	1181	86976	40221	34828553
Dyspnoea	1522.15	11.25	3083	85074	373699	34495075
Obstructive airways disorder	1165.41	11.25	631	87526	14863	34853911
Chronic obstructive pulmonary disease	1077.74	11.25	931	87226	47987	34820787
Full blood count abnormal	955.53	11.25	592	87565	18076	34850698
Sleep disorder due to a general medical condition	766.20	11.25	336	87821	4885	34863889
Productive cough	706.25	11.25	656	87501	37157	34831617
Therapeutic product effect incomplete	705.32	11.25	748	87409	49793	34818981
Cough	656.24	11.25	1275	86882	148865	34719909
Loss of personal independence in daily activities	473.14	11.25	497	87660	32682	34836092
Sputum discoloured	405.20	11.25	250	87907	7562	34861212
Forced expiratory volume decreased	380.74	11.25	178	87979	3025	34865749
Chest discomfort	339.81	11.25	542	87615	53988	34814786
Bronchiectasis	339.67	11.25	244	87913	9557	34859217
Dyspnoea exertional	301.54	11.25	453	87704	42826	34825948
Product quality issue	267.71	11.25	269	87888	16766	34852008
Pneumonia	251.63	11.25	1667	86490	360960	34507814
Nasal congestion	231.24	11.25	288	87869	22769	34846005
Off label use	226.27	11.25	449	87708	419075	34449699
Toxicity to various agents	223.92	11.25	113	88044	200249	34668525
Emphysema	220.93	11.25	187	87970	9338	34859436
Breath sounds abnormal	219.59	11.25	163	87994	6718	34862056
Asthma-chronic obstructive pulmonary disease overlap syndrome	218.98	11.25	92	88065	1195	34867579
Pulmonary function test decreased	217.62	11.25	143	88014	4832	34863942
Pulmonary function test abnormal	186.92	11.25	103	88054	2507	34866267
Middle insomnia	183.89	11.25	146	88011	6656	34862118
Lower respiratory tract infection	166.89	11.25	292	87865	31345	34837429
Drug abuse	163.11	11.25	27	88130	99069	34769705
Bronchial wall thickening	159.41	11.25	75	88082	1293	34867481
Nasal polyps	147.59	11.25	87	88070	2416	34866358
Completed suicide	140.49	11.25	37	88120	98131	34770643
Bronchial obstruction	138.87	11.25	72	88085	1544	34867230
Bronchial secretion retention	133.61	11.25	69	88088	1467	34867307
Dust allergy	128.66	11.25	57	88100	849	34867925
Nasal obstruction	127.15	11.25	52	88105	628	34868146
Blood immunoglobulin E increased	125.73	11.25	79	88078	2467	34866307
Benign prostatic hyperplasia	123.36	11.25	167	87990	14328	34854446
Obstruction	120.98	11.25	79	88078	2640	34866134
Lung hyperinflation	119.43	11.25	54	88103	846	34867928
Febrile neutropenia	117.91	11.25	103	88054	136746	34732028
Respiratory disorder	117.81	11.25	190	87967	19074	34849700
Eosinophil count increased	114.28	11.25	124	88033	8448	34860326
Spirometry abnormal	110.76	11.25	48	88109	676	34868098
Eosinophil count abnormal	109.90	11.25	38	88119	276	34868498
Right atrial hypertrophy	105.87	11.25	48	88109	757	34868017
Chronic sinusitis	98.43	11.25	65	88092	2214	34866560
Neutropenia	97.45	11.25	153	88004	156625	34712149
Diarrhoea	94.90	11.25	586	87571	389326	34479448
Sinus pain	94.51	11.25	43	88114	684	34868090
Bronchial hyperreactivity	94.51	11.25	57	88100	1652	34867122
Vital capacity decreased	94.42	11.25	36	88121	356	34868418
Urinary retention	92.90	11.25	250	87907	36038	34832736
Respiratory rate increased	91.90	11.25	119	88038	9775	34858999
Upper-airway cough syndrome	89.02	11.25	73	88084	3485	34865289
Pulmonary mass	87.56	11.25	133	88024	12679	34856095
Bronchitis	86.07	11.25	267	87890	41696	34827078
Mycotic allergy	85.53	11.25	38	88119	570	34868204
Mite allergy	83.38	11.25	39	88118	663	34868111
Congenital hiatus hernia	82.42	11.25	41	88116	803	34867971
Right ventricular hypertrophy	81.84	11.25	50	88107	1484	34867290
Conjunctivitis allergic	80.57	11.25	45	88112	1125	34867649
Gastrooesophageal reflux disease	80.29	11.25	244	87913	37680	34831094
Blood test abnormal	77.87	11.25	92	88065	6879	34861895
Lung disorder	76.06	11.25	226	87931	34470	34834304
Allergy to animal	75.53	11.25	31	88126	378	34868396
Bronchospasm	74.18	11.25	112	88045	10619	34858155
Lung neoplasm malignant	69.90	11.25	143	88014	17252	34851522
Foetal exposure during pregnancy	65.82	11.25	9	88148	38092	34830682
Respiratory failure	65.78	11.25	484	87673	108088	34760686
Disease progression	64.73	11.25	108	88049	107969	34760805
Aortic valve stenosis	64.59	11.25	54	88103	2649	34866125
Oxygen saturation decreased	63.78	11.25	287	87870	53531	34815243
Product use in unapproved indication	63.60	11.25	125	88032	117374	34751400
Thrombocytopenia	63.51	11.25	193	87964	156054	34712720
Dyspnoea at rest	62.98	11.25	62	88095	3766	34865008
Chest X-ray abnormal	62.82	11.25	66	88091	4332	34864442
Mycobacterium avium complex infection	61.74	11.25	51	88106	2460	34866314
Eosinophilia	61.50	11.25	175	87982	26047	34842727
Hypoxia	60.99	11.25	288	87869	54807	34813967
Vocal cord dysfunction	59.75	11.25	21	88136	161	34868613
Bronchopulmonary aspergillosis allergic	59.30	11.25	34	88123	895	34867879
Reversible airways obstruction	57.57	11.25	27	88130	462	34868312
White blood cell count decreased	57.50	11.25	95	88062	95350	34773424
Platelet count decreased	56.82	11.25	137	88020	119580	34749194
Asthmatic crisis	56.79	11.25	27	88130	477	34868297
Forced vital capacity decreased	56.60	11.25	31	88126	745	34868029
Intentional product use issue	56.51	11.25	41	88116	59775	34808999
Haemoptysis	56.07	11.25	205	87952	34801	34833973
Intentional overdose	56.07	11.25	20	88137	43654	34825120
Rhinorrhoea	55.12	11.25	166	87991	25502	34843272
Eosinophil count	55.07	11.25	19	88138	137	34868637
Rhinitis perennial	54.38	11.25	23	88134	304	34868470
Multiple organ dysfunction syndrome	54.21	11.25	68	88089	76498	34792276
Sputum purulent	54.15	11.25	26	88131	470	34868304
Sensitivity to weather change	52.95	11.25	39	88118	1587	34867187
Neuropathy peripheral	51.92	11.25	81	88076	83182	34785592
Pancytopenia	51.68	11.25	101	88056	95056	34773718
Vomiting	51.19	11.25	390	87767	247231	34621543
Alanine aminotransferase increased	50.98	11.25	78	88079	80737	34788037
Lung consolidation	49.90	11.25	68	88089	5868	34862906
Sputum increased	49.82	11.25	44	88113	2326	34866448
Throat irritation	49.80	11.25	93	88064	10492	34858282
Dry mouth	49.45	11.25	178	87979	29987	34838787
Diastolic dysfunction	48.85	11.25	69	88088	6158	34862616
Influenza	48.82	11.25	251	87906	49415	34819359
Nausea	48.35	11.25	587	87570	339321	34529453
Malaise	46.64	11.25	692	87465	185133	34683641
Sepsis	45.90	11.25	240	87917	166321	34702453
Seizure	45.89	11.25	125	88032	104732	34764042
Nasopharyngitis	44.11	11.25	315	87842	69653	34799121
Suffocation feeling	44.00	11.25	24	88133	572	34868202
Respiratory tract congestion	43.75	11.25	65	88092	6074	34862700
Drug resistance	42.76	11.25	7	88150	25920	34842854
Restrictive pulmonary disease	41.76	11.25	30	88127	1174	34867600
Peak expiratory flow rate decreased	41.70	11.25	15	88142	124	34868650
Sleep apnoea syndrome	41.37	11.25	129	88028	20192	34848582
Aspartate aminotransferase increased	41.25	11.25	67	88090	67716	34801058
Cytomegalovirus infection	41.06	11.25	8	88149	26127	34842647
Dysphonia	40.92	11.25	141	88016	23242	34845532
Heart rate increased	39.98	11.25	226	87931	46117	34822657
Sinusitis	39.83	11.25	208	87949	41194	34827580
Total lung capacity abnormal	39.73	11.25	15	88142	144	34868630
Respiratory symptom	39.06	11.25	34	88123	1763	34867011
Normochromic normocytic anaemia	38.93	11.25	51	88106	4236	34864538
Fractured coccyx	38.67	11.25	15	88142	156	34868618
Eosinophilic granulomatosis with polyangiitis	38.05	11.25	35	88122	1952	34866822
Forced expiratory flow decreased	38.00	11.25	15	88142	164	34868610
Intentional product misuse	37.24	11.25	36	88121	45575	34823199
Mucosal inflammation	37.09	11.25	26	88131	38596	34830178
Infusion related reaction	36.64	11.25	48	88109	53009	34815765
Hypoventilation	36.39	11.25	44	88113	3370	34865404
Obesity	36.29	11.25	92	88065	12786	34855988
Brain natriuretic peptide abnormal	36.21	11.25	18	88139	352	34868422
Intervertebral disc degeneration	36.14	11.25	61	88096	6356	34862418
Seasonal allergy	35.68	11.25	62	88095	6613	34862161
Blood pressure systolic increased	35.56	11.25	133	88024	22819	34845955
Pancreatitis	35.01	11.25	28	88129	38863	34829911
Decreased activity	34.99	11.25	49	88108	4338	34864436
Body temperature decreased	34.55	11.25	91	88066	12943	34855831
Pickwickian syndrome	34.48	11.25	11	88146	60	34868714
Throat clearing	34.26	11.25	17	88140	331	34868443
Osteopenia	34.07	11.25	51	88106	4798	34863976
Cytokine release syndrome	33.90	11.25	8	88149	22869	34845905
Leukopenia	33.87	11.25	67	88090	62789	34805985
Serotonin syndrome	33.74	11.25	5	88152	19928	34848846
Impaired quality of life	33.69	11.25	56	88101	5762	34863012
Treatment failure	33.54	11.25	41	88116	46656	34822118
Stomatitis	33.06	11.25	35	88122	42479	34826295
Lung opacity	32.98	11.25	35	88122	2324	34866450
Lung diffusion test decreased	32.51	11.25	20	88137	601	34868173
Malignant melanoma in situ	32.24	11.25	30	88127	1698	34867076
Osteoporosis	32.12	11.25	87	88070	12581	34856193
Respiratory tract infection	32.03	11.25	116	88041	19596	34849178
Septic shock	31.89	11.25	85	88072	71749	34797025
Dyspnoea paroxysmal nocturnal	31.85	11.25	28	88129	1471	34867303
Atrial fibrillation	31.53	11.25	458	87699	121935	34746839
Mycobacterial infection	31.04	11.25	34	88123	2340	34866434
Oxygen saturation increased	30.71	11.25	15	88142	282	34868492
Bone marrow failure	30.40	11.25	18	88139	29235	34839539
Drug hypersensitivity	30.22	11.25	103	88054	80426	34788348
Dysarthria	30.12	11.25	26	88131	34756	34834018
Pyrexia	29.55	11.25	628	87529	332385	34536389
Drug reaction with eosinophilia and systemic symptoms	29.42	11.25	24	88133	32988	34835786
Granulomatous rosacea	29.41	11.25	12	88145	144	34868630
Aptyalism	29.23	11.25	16	88141	384	34868390
N-terminal prohormone brain natriuretic peptide abnormal	29.20	11.25	13	88144	196	34868578
Psoriatic arthropathy	29.19	11.25	7	88150	19791	34848983
Cardiac failure	29.11	11.25	355	87802	90893	34777881
Nocturnal dyspnoea	28.96	11.25	18	88139	551	34868223
Eye disorder	28.89	11.25	70	88087	9458	34859316
Malignant neoplasm progression	28.88	11.25	119	88038	87927	34780847
Pulmonary arterial pressure abnormal	28.73	11.25	13	88144	204	34868570
Adjustment disorder	28.71	11.25	24	88133	1177	34867597
Therapy non-responder	28.50	11.25	34	88123	39112	34829662
Suicide attempt	28.45	11.25	34	88123	39082	34829692
Somnolence	28.44	11.25	164	87993	110952	34757822
Factitious disorder	28.38	11.25	9	88148	48	34868726
Prostatic adenoma	27.95	11.25	12	88145	165	34868609
Prolonged expiration	27.69	11.25	13	88144	223	34868551
Hypercholesterolaemia	27.24	11.25	65	88092	8697	34860077
Hepatocellular injury	27.12	11.25	11	88146	22200	34846574
Pleural thickening	27.04	11.25	15	88142	370	34868404
Drug ineffective for unapproved indication	26.98	11.25	13	88144	23702	34845072
Drug-induced liver injury	26.91	11.25	20	88137	28812	34839962
Pulmonary congestion	26.75	11.25	86	88071	13679	34855095
Adverse drug reaction	26.56	11.25	21	88136	29321	34839453
Sputum abnormal	25.97	11.25	16	88141	482	34868292
Renal impairment	25.54	11.25	137	88020	94376	34774398
Discomfort	25.50	11.25	105	88052	18833	34849941
Orthopnoea	25.47	11.25	46	88111	5057	34863717
Hypochromic anaemia	25.04	11.25	20	88137	919	34867855
Hepatic function abnormal	25.02	11.25	46	88111	44317	34824457
Decreased gait velocity	24.82	11.25	11	88146	164	34868610
Choking	24.77	11.25	45	88112	4970	34863804
Snoring	24.67	11.25	36	88121	3310	34865464
Hepatic enzyme increased	24.36	11.25	38	88119	39042	34829732
Lower respiratory tract congestion	24.25	11.25	22	88135	1205	34867569
Rhinitis allergic	24.23	11.25	34	88123	3016	34865758
Acute respiratory failure	24.19	11.25	147	88010	30781	34837993
Rhinitis	24.16	11.25	51	88106	6287	34862487
Nasal disorder	24.15	11.25	27	88130	1901	34866873
COVID-19	24.09	11.25	107	88050	77443	34791331
Hepatic haematoma	23.51	11.25	14	88143	396	34868378
Lacrimal disorder	23.35	11.25	13	88144	323	34868451
Rales	23.21	11.25	66	88091	9817	34858957
Confusional state	23.15	11.25	242	87915	143918	34724856
Proteinuria	23.14	11.25	9	88148	18633	34850141
Ascites	23.10	11.25	52	88105	46519	34822255
Gout	23.03	11.25	103	88054	19150	34849624
Cardiogenic shock	22.92	11.25	20	88137	26598	34842176
Multiple sclerosis relapse	22.92	11.25	3	88154	13130	34855644
Pain	22.77	11.25	371	87786	204304	34664470
Coma	22.66	11.25	51	88106	45627	34823147
Sarcopenia	22.48	11.25	14	88143	430	34868344
Convulsive threshold lowered	22.40	11.25	15	88142	523	34868251
Haemophilus infection	22.40	11.25	21	88136	1200	34867574
Nasal oedema	22.18	11.25	13	88144	357	34868417
Electrocardiogram QRS complex abnormal	22.11	11.25	13	88144	359	34868415
Pneumothorax	21.99	11.25	101	88056	18991	34849783
Sputum retention	21.97	11.25	14	88143	448	34868326
Vascular shunt	21.97	11.25	7	88150	38	34868736
Overdose	21.92	11.25	137	88020	90922	34777852
Oropharyngeal pain	21.91	11.25	159	87998	35326	34833448
Left ventricular dilatation	21.89	11.25	17	88140	750	34868024
Rash	21.83	11.25	413	87744	222339	34646435
Acute respiratory distress syndrome	21.78	11.25	20	88137	25949	34842825
Electrocardiogram QT prolonged	21.75	11.25	44	88113	40908	34827866
Bronchiolitis	21.74	11.25	33	88124	3143	34865631
Type 2 diabetes mellitus	21.67	11.25	89	88068	15943	34852831
Infective exacerbation of chronic obstructive airways disease	21.62	11.25	25	88132	1826	34866948
Aphonia	21.62	11.25	34	88123	3339	34865435
Oropharyngeal discomfort	21.58	11.25	33	88124	3163	34865611
Blood thyroid stimulating hormone abnormal	21.55	11.25	13	88144	377	34868397
Joint injury	21.29	11.25	61	88096	9112	34859662
Cholestasis	21.16	11.25	22	88135	26926	34841848
Sneezing	20.94	11.25	43	88114	5199	34863575
Poisoning	20.85	11.25	3	88154	12223	34856551
Total lung capacity decreased	20.65	11.25	18	88139	935	34867839
Encephalopathy	20.47	11.25	36	88121	35283	34833491
Hypopnoea	20.43	11.25	27	88130	2262	34866512
Anaemia	20.37	11.25	441	87716	232894	34635880
Flour sensitivity	20.32	11.25	6	88151	24	34868750
Acute kidney injury	20.30	11.25	600	87557	304388	34564386
Hepatic failure	20.20	11.25	35	88122	34496	34834278
Neutrophil count decreased	20.10	11.25	64	88093	51040	34817734
Lymphopenia	20.09	11.25	8	88149	16327	34852447
Tachyarrhythmia	19.92	11.25	34	88123	3574	34865200
Choking sensation	19.91	11.25	19	88138	1110	34867664
Cardio-respiratory arrest	19.85	11.25	72	88085	55201	34813573
Diaphragmatic disorder	19.77	11.25	20	88137	1255	34867519
C-reactive protein increased	19.74	11.25	70	88087	54028	34814746
Hyperkaliuria	19.61	11.25	8	88149	96	34868678
Bronchitis chronic	19.29	11.25	21	88136	1435	34867339
Product use issue	19.16	11.25	88	88069	63128	34805646
Panic reaction	19.07	11.25	21	88136	1454	34867320
Joint swelling	18.98	11.25	82	88075	59808	34808966
Hyperglycaemia	18.84	11.25	45	88112	39435	34829339
Weight decreased	18.63	11.25	579	87578	175722	34693052
Drug level increased	18.55	11.25	17	88140	22079	34846695
Haemoglobin decreased	18.47	11.25	205	87952	120567	34748207
Pneumothorax spontaneous	18.35	11.25	14	88143	601	34868173
Atheroembolism	18.23	11.25	11	88146	319	34868455
Cardiac failure congestive	18.14	11.25	303	87854	82967	34785807
Primary hypogonadism	18.11	11.25	7	88150	72	34868702
Respiratory tract haemorrhage	18.03	11.25	19	88138	1251	34867523
Sinus congestion	17.88	11.25	42	88115	5563	34863211
Bradycardia	17.88	11.25	114	88043	75304	34793470
Blood alkaline phosphatase increased	17.87	11.25	32	88125	31143	34837631
Cytopenia	17.80	11.25	5	88152	12718	34856056
Cough decreased	17.79	11.25	5	88152	16	34868758
Transaminases increased	17.77	11.25	25	88132	26798	34841976
Hepatotoxicity	17.49	11.25	17	88140	21468	34847306
Musculoskeletal stiffness	17.30	11.25	60	88097	46620	34822154
Hangover	17.25	11.25	17	88140	1034	34867740
Rib fracture	17.20	11.25	77	88080	14323	34854451
Increased upper airway secretion	17.17	11.25	22	88135	1788	34866986
Renal failure	17.16	11.25	229	87928	130328	34738446
Rheumatoid arthritis	17.15	11.25	45	88112	38193	34830581
Psychotic disorder	17.00	11.25	22	88135	24430	34844344
Dyskinesia	16.82	11.25	19	88138	22394	34846380
Hernia pain	16.79	11.25	10	88147	283	34868491
Eosinophilic pneumonia chronic	16.73	11.25	10	88147	285	34868489
Illness	16.65	11.25	73	88084	13456	34855318
Increased viscosity of bronchial secretion	16.56	11.25	9	88148	213	34868561
Blood bilirubin increased	16.47	11.25	46	88111	38250	34830524
Hypoacusis	16.44	11.25	83	88074	16218	34852556
Upper respiratory tract congestion	16.40	11.25	15	88142	830	34867944
Blood creatine phosphokinase increased	16.40	11.25	58	88099	44799	34823975
Dehydration	16.35	11.25	230	87927	129739	34739035
Bronchospasm paradoxical	16.04	11.25	6	88151	56	34868718
FEV1/FVC ratio decreased	16.00	11.25	7	88150	101	34868673
Bone deformity	15.95	11.25	6	88151	57	34868717
Pseudomonas bronchitis	15.87	11.25	5	88152	26	34868748
Nephrolithiasis	15.76	11.25	33	88124	30300	34838474
Peritonitis	15.73	11.25	11	88146	16354	34852420
Drug interaction	15.64	11.25	442	87715	225504	34643270
Laboratory test abnormal	15.61	11.25	17	88140	20374	34848400
Agitation	15.61	11.25	83	88074	57316	34811458
Mastication disorder	15.57	11.25	18	88139	1315	34867459
Appendicitis	15.54	11.25	9	88148	14798	34853976
Hyperbilirubinaemia	15.31	11.25	12	88145	16831	34851943
Mesothelioma	15.23	11.25	11	88146	434	34868340
Lung hernia	15.17	11.25	6	88151	66	34868708
Neoplasm progression	15.15	11.25	22	88135	23278	34845496
FEV1/FVC ratio abnormal	15.13	11.25	5	88152	31	34868743
Cardiac failure chronic	15.10	11.25	49	88108	7830	34860944
Carbon dioxide increased	15.04	11.25	16	88141	1065	34867709
Blood creatinine increased	15.00	11.25	160	87997	94816	34773958
Intentional self-injury	14.99	11.25	8	88149	13763	34855011
Atelectasis	14.98	11.25	86	88071	17641	34851133
Large cell lung cancer metastatic	14.96	11.25	4	88153	10	34868764
Multiple allergies	14.90	11.25	27	88130	2976	34865798
Lower respiratory tract infection viral	14.83	11.25	10	88147	353	34868421
Blood pressure increased	14.82	11.25	308	87849	87794	34780980
Laryngitis	14.60	11.25	23	88134	2262	34866512
Tubulointerstitial nephritis	14.53	11.25	19	88138	21005	34847769
Sedation	14.50	11.25	19	88138	20987	34847787
Forced expiratory volume abnormal	14.50	11.25	5	88152	36	34868738
Rhonchi	14.49	11.25	21	88136	1919	34866855
Tumour lysis syndrome	14.47	11.25	13	88144	17046	34851728
Ischaemic cardiomyopathy	14.36	11.25	42	88115	6347	34862427
Delusion	14.26	11.25	7	88150	12628	34856146
Abscess	14.19	11.25	6	88151	11811	34856963
Smoke sensitivity	14.03	11.25	7	88150	138	34868636
Umbilical hernia	13.79	11.25	34	88123	4643	34864131
Deep vein thrombosis	13.79	11.25	102	88055	65146	34803628
Eosinophilic bronchitis	13.77	11.25	8	88149	216	34868558
Magnetic resonance imaging heart	13.75	11.25	4	88153	15	34868759
Liver function test increased	13.73	11.25	10	88147	14555	34854219
Blood lactate dehydrogenase increased	13.72	11.25	23	88134	22967	34845807
Hypothermia	13.66	11.25	5	88152	10743	34858031
Paraneoplastic rash	13.63	11.25	6	88151	88	34868686
Exercise tolerance decreased	13.48	11.25	36	88121	5162	34863612
Congenital megaureter	13.46	11.25	7	88150	151	34868623
Pulmonary artery dilatation	13.41	11.25	8	88149	227	34868547
Apnoeic attack	13.38	11.25	10	88147	416	34868358
Lactic acidosis	13.36	11.25	44	88113	34728	34834046
Abdominal symptom	13.32	11.25	11	88146	530	34868244
Blood glucose increased	13.30	11.25	106	88051	66612	34802162
Hepatitis	13.29	11.25	25	88132	23879	34844895
Aplastic anaemia	13.26	11.25	4	88153	9712	34859062
Xanthelasma	13.21	11.25	6	88151	95	34868679
Status asthmaticus	13.14	11.25	9	88148	326	34868448
Eye swelling	13.13	11.25	55	88102	9940	34858834
Nasal septum deviation	13.10	11.25	15	88142	1084	34867690
Respiratory depression	13.05	11.25	13	88144	16232	34852542
Lichenoid keratosis	13.02	11.25	23	88134	2485	34866289
Pulmonary arterial hypertension	13.00	11.25	50	88107	8689	34860085
Fatigue	13.00	11.25	784	87373	369869	34498905
Upper respiratory tract infection	12.97	11.25	134	88023	32925	34835849
Idiopathic pulmonary fibrosis	12.97	11.25	28	88129	3506	34865268
Renal injury	12.94	11.25	6	88151	11189	34857585
Intercostal neuralgia	12.88	11.25	3	88154	3	34868771
Right ventricular failure	12.86	11.25	50	88107	8734	34860040
Acute hepatic failure	12.83	11.25	10	88147	14064	34854710
Humidity intolerance	12.83	11.25	4	88153	20	34868754
Blood immunoglobulin E abnormal	12.83	11.25	4	88153	20	34868754
Transplant rejection	12.76	11.25	5	88152	10306	34858468
Tracheal disorder	12.75	11.25	7	88150	169	34868605
No adverse event	12.72	11.25	24	88133	22903	34845871
Expiratory reserve volume decreased	12.72	11.25	5	88152	54	34868720
Total lung capacity	12.66	11.25	4	88153	21	34868753
Hypotension	12.58	11.25	445	87712	221204	34647570
Device related infection	12.51	11.25	15	88142	17222	34851552
Respiratory gas exchange disorder	12.47	11.25	10	88147	462	34868312
Nervous system disorder	12.43	11.25	11	88146	14532	34854242
Precancerous condition	12.40	11.25	5	88152	58	34868716
Suicidal ideation	12.37	11.25	56	88101	40332	34828442
Concomitant disease aggravated	12.36	11.25	37	88120	5664	34863110
Paraesthesia	12.31	11.25	103	88054	64069	34804705
Nasal inflammation	12.26	11.25	8	88149	267	34868507
Lipohypertrophy	12.18	11.25	8	88149	270	34868504
Drug intolerance	12.17	11.25	94	88063	59476	34809298
Increased bronchial secretion	12.11	11.25	19	88138	1862	34866912
Immune thrombocytopenia	12.07	11.25	4	88153	9148	34859626
Posterior reversible encephalopathy syndrome	12.04	11.25	5	88152	9949	34858825
Oxygen consumption increased	12.02	11.25	16	88141	1350	34867424
Oxygen therapy	12.01	11.25	13	88144	883	34867891
Shock	11.99	11.25	27	88130	24152	34844622
Aortic aneurysm	11.96	11.25	41	88116	6738	34862036
Hypoalbuminaemia	11.95	11.25	8	88149	12166	34856608
Blood albumin decreased	11.93	11.25	10	88147	13562	34855212
Febrile bone marrow aplasia	11.91	11.25	3	88154	8206	34860568
Viral myelitis	11.90	11.25	5	88152	65	34868709
Abdominal pain	11.84	11.25	318	87839	163300	34705474
Altered state of consciousness	11.82	11.25	25	88132	22868	34845906
Drug eruption	11.79	11.25	20	88137	19878	34848896
Systolic dysfunction	11.76	11.25	23	88134	2685	34866089
Diabetic ketoacidosis	11.75	11.25	17	88140	18015	34850759
Myositis	11.75	11.25	8	88149	12062	34856712
Neurotoxicity	11.72	11.25	17	88140	17993	34850781
Decreased appetite	11.63	11.25	325	87832	166067	34702707
Necrotising ulcerative gingivostomatitis	11.56	11.25	5	88152	70	34868704
Hepatic encephalopathy	11.51	11.25	12	88145	14673	34854101
Hallucination, auditory	11.47	11.25	8	88149	11909	34856865
Basal cell carcinoma	11.43	11.25	20	88137	19638	34849136
Temperature intolerance	11.31	11.25	26	88131	3396	34865378
Hypohidrosis	11.30	11.25	7	88150	213	34868561
Hydronephrosis	11.28	11.25	6	88151	10340	34858434
Nasal discomfort	11.26	11.25	17	88140	1611	34867163

FDA Adverse Event Reporting System (Geriatric)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Asthma	4621.32	10.88	3163	173275	131932	79436018
Wheezing	2884.70	10.88	2247	174191	114417	79453533
Dyspnoea	2514.81	10.88	5703	170735	851322	78716628
Obstructive airways disorder	2329.97	10.88	1214	175224	30245	79537705
Incorrect route of product administration	2202.29	10.88	1211	175227	33718	79534232
Chronic obstructive pulmonary disease	1749.38	10.88	1475	174963	83944	79484006
Full blood count abnormal	1649.24	10.88	1059	175379	39415	79528535
Productive cough	1458.27	10.88	1350	175088	86981	79480969
Cough	1319.12	10.88	2660	173778	364129	79203821
Sleep disorder due to a general medical condition	1154.97	10.88	585	175853	13692	79554258
Forced expiratory volume decreased	998.71	10.88	439	175999	7375	79560575
Sputum discoloured	947.94	10.88	594	175844	21149	79546801
Product quality issue	675.37	10.88	577	175861	33363	79534587
Pneumonia	623.54	10.88	2996	173442	657250	78910700
Therapeutic product effect incomplete	620.42	10.88	1119	175319	140526	79427424
Chest discomfort	592.44	10.88	1081	175357	136963	79430987
Dyspnoea exertional	555.67	10.88	816	175622	86257	79481693
Loss of personal independence in daily activities	492.53	10.88	844	175594	101736	79466214
Sedation complication	448.49	10.88	330	176108	15339	79552611
Bronchiectasis	444.13	10.88	380	176058	22006	79545944
Off label use	440.29	10.88	839	175599	906376	78661574
Middle insomnia	436.61	10.88	328	176110	15741	79552209
Creatinine renal clearance decreased	429.81	10.88	348	176090	18654	79549296
Completed suicide	410.76	10.88	36	176402	245731	79322219
Nasal congestion	374.15	10.88	635	175803	75917	79492033
Breath sounds abnormal	334.87	10.88	280	176158	15704	79552246
Synovitis	292.29	10.88	9	176429	150725	79417225
Blood immunoglobulin E increased	290.27	10.88	174	176264	5708	79562242
Asthma-chronic obstructive pulmonary disease overlap syndrome	290.04	10.88	142	176296	3079	79564871
Eosinophil count increased	286.79	10.88	264	176174	16841	79551109
Emphysema	274.12	10.88	252	176186	16048	79551902
Blood calcium decreased	270.76	10.88	343	176095	31476	79536474
Nasal polyps	267.19	10.88	179	176259	7148	79560802
Orthostatic hypotension	266.64	10.88	460	175978	55704	79512246
Pulmonary function test decreased	265.19	10.88	181	176257	7456	79560494
Upper-airway cough syndrome	264.12	10.88	214	176224	11479	79556471
Bronchitis	263.41	10.88	759	175679	129885	79438065
Bronchial secretion retention	263.11	10.88	144	176294	3960	79563990
Bronchial wall thickening	251.57	10.88	121	176317	2520	79565430
Sedation	238.48	10.88	419	176019	51476	79516474
Balance disorder	233.77	10.88	609	175829	98248	79469702
Reversible airways obstruction	232.78	10.88	108	176330	2068	79565882
Pulmonary mass	229.84	10.88	302	176136	28732	79539218
Cognitive disorder	211.71	10.88	474	175964	69452	79498498
Pulmonary function test abnormal	208.16	10.88	124	176314	4020	79563930
Drug abuse	205.70	10.88	53	176385	162638	79405312
Treatment failure	203.54	10.88	62	176376	170424	79397526
Nasal obstruction	202.66	10.88	98	176340	2066	79565884
Drug intolerance	197.64	10.88	176	176262	263943	79304007
Dysphonia	194.47	10.88	405	176033	56467	79511483
Respiratory tract infection	192.00	10.88	368	176070	48321	79519629
Hand deformity	191.90	10.88	9	176429	103910	79464040
Forced vital capacity decreased	187.98	10.88	87	176351	1656	79566294
Neutropenia	184.39	10.88	219	176219	287491	79280459
Febrile neutropenia	183.80	10.88	145	176293	230854	79337096
Contraindicated product administered	183.23	10.88	60	176378	157478	79410472
Arthropathy	181.87	10.88	82	176356	177029	79390921
Vital capacity decreased	178.45	10.88	85	176353	1731	79566219
Lung neoplasm malignant	176.47	10.88	260	176178	27532	79540418
Asthmatic crisis	176.34	10.88	87	176351	1919	79566031
Systemic lupus erythematosus	172.51	10.88	30	176408	121119	79446831
Eosinophilia	170.60	10.88	336	176102	45009	79522941
Dust allergy	169.82	10.88	78	176360	1458	79566492
Influenza	168.23	10.88	649	175789	128957	79438993
Maternal exposure during pregnancy	167.83	10.88	47	176391	136491	79431459
Respiratory rate increased	165.30	10.88	221	176217	21379	79546571
Lower respiratory tract infection	165.22	10.88	644	175794	128576	79439374
Alopecia	163.85	10.88	162	176276	231193	79336757
Hypoventilation	162.71	10.88	132	176306	7092	79560858
Throat clearing	161.56	10.88	90	176348	2564	79565386
Total lung capacity increased	159.50	10.88	85	176353	2213	79565737
Respiratory tract congestion	158.62	10.88	208	176230	19746	79548204
Spirometry abnormal	156.16	10.88	64	176374	895	79567055
Joint swelling	154.60	10.88	250	176188	288396	79279554
Pericarditis	152.44	10.88	24	176414	104212	79463738
Rheumatoid arthritis	151.07	10.88	143	176295	208327	79359623
Infusion related reaction	150.98	10.88	172	176266	230065	79337885
Rales	147.51	10.88	201	176237	19800	79548150
Restrictive pulmonary disease	147.14	10.88	84	176354	2511	79565439
Intentional overdose	147.06	10.88	28	176410	105932	79462018
Hepatic enzyme increased	144.77	10.88	115	176323	182495	79385455
Respiratory disorder	144.74	10.88	312	176126	44544	79523406
Bronchial obstruction	144.73	10.88	85	176353	2683	79565267
Exposure during pregnancy	144.08	10.88	25	176413	101107	79466843
Lung hyperinflation	143.98	10.88	74	176364	1785	79566165
Gastrooesophageal reflux disease	143.52	10.88	532	175906	103714	79464236
Eosinophil count abnormal	142.65	10.88	56	176382	695	79567255
Sensitivity to weather change	142.33	10.88	128	176310	7919	79560031
Sleep apnoea syndrome	140.50	10.88	273	176165	36205	79531745
Bronchopulmonary aspergillosis allergic	139.36	10.88	86	176352	2975	79564975
Vocal cord dysfunction	138.82	10.88	52	176386	563	79567387
Peak expiratory flow rate decreased	137.06	10.88	53	176385	630	79567320
Helicobacter infection	135.68	10.88	4	176434	69700	79498250
Intentional product use issue	134.77	10.88	85	176353	152027	79415923
Blood test abnormal	133.68	10.88	180	176258	17530	79550420
Haemoptysis	130.30	10.88	343	176095	55656	79512294
Bronchospasm	129.11	10.88	212	176226	24647	79543303
Secretion discharge	127.88	10.88	162	176276	14860	79553090
Therapeutic product effect decreased	122.74	10.88	109	176329	163754	79404196
Thrombocytopenia	122.17	10.88	252	176186	265007	79302943
Eosinophilic granulomatosis with polyangiitis	120.61	10.88	84	176354	3576	79564374
Oxygen saturation decreased	118.96	10.88	583	175855	128464	79439486
Depressed level of consciousness	117.32	10.88	474	175964	96178	79471772
Multiple allergies	115.81	10.88	129	176309	10331	79557619
Mite allergy	113.07	10.88	55	176383	1175	79566775
Glossodynia	112.23	10.88	44	176394	103293	79464657
Lung diffusion test decreased	109.78	10.88	55	176383	1255	79566695
Psoriatic arthropathy	109.54	10.88	20	176418	77979	79489971
White blood cell count decreased	108.54	10.88	155	176283	188133	79379817
Malaise	107.78	10.88	1600	174838	488269	79079681
Right atrial hypertrophy	107.26	10.88	46	176392	725	79567225
Benign prostatic hyperplasia	106.50	10.88	130	176308	11482	79556468
Seasonal allergy	104.89	10.88	154	176284	16252	79551698
Heart rate increased	104.63	10.88	536	175902	120188	79447762
Wound	104.17	10.88	64	176374	116115	79451835
Diarrhoea	103.65	10.88	1351	175087	879138	78688812
Blood pressure systolic increased	100.81	10.88	352	176086	66634	79501316
Hypoxia	99.88	10.88	473	175965	102770	79465180
Lung disorder	98.50	10.88	396	176042	80161	79487789
Abdominal discomfort	97.96	10.88	260	176178	250467	79317483
Arthralgia	97.72	10.88	803	175635	571000	78996950
Folliculitis	95.53	10.88	7	176431	55373	79512577
Obstruction	94.99	10.88	80	176358	4530	79563420
Nausea	93.37	10.88	1524	174914	955672	78612278
Pancytopenia	92.05	10.88	140	176298	165605	79402345
Lung diffusion test abnormal	91.78	10.88	34	176404	356	79567594
Prolonged expiration	91.01	10.88	48	176390	1223	79566727
Allergy to animal	90.89	10.88	50	176388	1389	79566561
Respiration abnormal	89.60	10.88	98	176340	7690	79560260
Nasopharyngitis	89.16	10.88	906	175532	252975	79314975
Disease progression	88.40	10.88	171	176267	184191	79383759
Alanine aminotransferase increased	87.73	10.88	140	176298	162430	79405520
Right ventricular hypertrophy	87.51	10.88	51	176387	1586	79566364
Total lung capacity decreased	87.24	10.88	63	176375	2842	79565108
Mobility decreased	86.80	10.88	514	175924	121661	79446289
Rash	86.19	10.88	841	175597	577517	78990433
Congenital hiatus hernia	85.36	10.88	40	176398	784	79567166
Irritable bowel syndrome	85.19	10.88	17	176421	62224	79505726
Bronchial hyperreactivity	84.68	10.88	63	176375	2977	79564973
Fall	83.95	10.88	1530	174908	486099	79081851
Product use issue	83.92	10.88	215	176223	209607	79358343
Rhinorrhoea	83.64	10.88	362	176076	75712	79492238
Drug hypersensitivity	83.28	10.88	359	176079	298557	79269393
Conjunctivitis allergic	82.59	10.88	50	176388	1670	79566280
Platelet count decreased	82.14	10.88	194	176244	194470	79373480
Toxicity to various agents	81.88	10.88	571	175867	420969	79146981
Chest X-ray abnormal	81.80	10.88	94	176344	7789	79560161
Oropharyngeal pain	80.23	10.88	464	175974	108889	79459061
Musculoskeletal stiffness	79.07	10.88	168	176270	174840	79393110
Impaired healing	78.98	10.88	48	176390	87607	79480343
Seizure	78.23	10.88	190	176248	188644	79379306
Product use in unapproved indication	76.45	10.88	290	176148	250069	79317881
Rhinitis allergic	75.32	10.88	113	176325	12156	79555794
Aspartate aminotransferase increased	75.17	10.88	119	176319	138522	79429428
Rhinitis	73.83	10.88	124	176314	14683	79553267
Multiple organ dysfunction syndrome	73.30	10.88	95	176343	120151	79447799
Sputum culture positive	72.57	10.88	63	176375	3718	79564232
Drug ineffective	72.43	10.88	1831	174607	1079082	78488868
Constipation	71.58	10.88	948	175490	282102	79285848
Blister	71.19	10.88	96	176342	119380	79448570
Cardiac murmur	69.12	10.88	125	176313	15699	79552251
Respiratory failure	69.03	10.88	657	175781	180254	79387696
Drug-induced liver injury	68.79	10.88	30	176408	66087	79501863
Gastrointestinal disorder	68.06	10.88	103	176335	122102	79445848
Intentional product misuse	68.05	10.88	66	176372	95099	79472851
Choking	68.03	10.88	107	176331	11994	79555956
Chronic sinusitis	67.52	10.88	111	176327	12915	79555035
Suicide attempt	67.24	10.88	51	176387	82881	79485069
Stomatitis	66.19	10.88	141	176297	146616	79421334
Lower respiratory tract congestion	65.65	10.88	61	176377	3936	79564014
Upper respiratory tract infection	65.03	10.88	384	176054	90784	79477166
Mycotic allergy	64.92	10.88	41	176397	1478	79566472
Lung opacity	64.61	10.88	68	176370	5106	79562844
Forced expiratory flow decreased	63.65	10.88	24	176414	265	79567685
Swelling	61.73	10.88	258	176180	216453	79351497
C-reactive protein increased	61.56	10.88	120	176318	128907	79439043
Infective exacerbation of chronic obstructive airways disease	60.87	10.88	50	176388	2734	79565216
Therapy non-responder	60.41	10.88	69	176369	92236	79475714
Body temperature decreased	60.17	10.88	182	176256	31963	79535987
Cytomegalovirus infection	59.73	10.88	11	176427	42633	79525317
Neuropathy peripheral	59.45	10.88	141	176297	141164	79426786
Dyspnoea at rest	59.40	10.88	77	176361	7225	79560725
Rhinitis perennial	58.92	10.88	24	176414	330	79567620
C-reactive protein abnormal	58.76	10.88	17	176421	48350	79519600
Smoke sensitivity	58.00	10.88	28	176410	588	79567362
Malignant neoplasm progression	57.77	10.88	135	176303	135855	79432095
Rubber sensitivity	57.30	10.88	40	176398	1709	79566241
Impaired quality of life	57.02	10.88	109	176329	14277	79553673
Hyper IgE syndrome	56.94	10.88	27	176411	544	79567406
Liver injury	56.86	10.88	27	176411	56587	79511363
Sputum purulent	56.63	10.88	36	176402	1313	79566637
Blood cholesterol increased	56.52	10.88	61	176377	83659	79484291
Hypercapnia	55.86	10.88	83	176355	8852	79559098
Humidity intolerance	55.69	10.88	24	176414	383	79567567
Drug reaction with eosinophilia and systemic symptoms	55.38	10.88	37	176401	64207	79503743
Multiple sclerosis relapse	55.36	10.88	17	176421	46516	79521434
Drug ineffective for unapproved indication	55.32	10.88	22	176416	51216	79516734
Overdose	55.16	10.88	215	176223	183991	79383959
Coma	54.92	10.88	86	176352	100563	79467387
Cardio-respiratory arrest	54.33	10.88	98	176340	108412	79459538
Blood pressure increased	53.44	10.88	708	175730	210652	79357298
Drug resistance	52.85	10.88	14	176424	42199	79525751
Acute respiratory failure	52.70	10.88	266	176172	59275	79508675
Septic shock	52.08	10.88	122	176316	122679	79445271
Eosinophil count	51.16	10.88	17	176421	125	79567825
Cholestasis	50.59	10.88	26	176412	52083	79515867
Weight decreased	50.43	10.88	1083	175355	354115	79213835
Rib deformity	49.97	10.88	19	176419	215	79567735
Total lung capacity abnormal	49.81	10.88	19	176419	217	79567733
Leukopenia	49.22	10.88	116	176322	116397	79451553
Perfume sensitivity	48.62	10.88	28	176410	851	79567099
Pregnancy	47.46	10.88	3	176435	26848	79541102
Hepatocellular injury	47.33	10.88	23	176415	47570	79520380
Status asthmaticus	46.94	10.88	29	176409	1005	79566945
Throat irritation	46.66	10.88	197	176241	40749	79527201
Broncholithiasis	45.81	10.88	18	176420	224	79567726
Aphonia	45.73	10.88	82	176356	10230	79557720
Vomiting	44.91	10.88	1126	175312	664702	78903248
Red blood cell sedimentation rate increased	44.49	10.88	23	176415	45919	79522031
Knee arthroplasty	44.40	10.88	20	176418	43228	79524722
Oesophageal spasm	44.19	10.88	46	176392	3410	79564540
Respiratory gas exchange disorder	44.14	10.88	26	176412	825	79567125
Mucosal inflammation	43.74	10.88	62	176376	75518	79492432
Heart sounds	43.62	10.88	27	176411	939	79567011
Hepatic function abnormal	43.28	10.88	59	176379	73048	79494902
Sarcoidosis	43.16	10.88	71	176367	8264	79559686
Cytokine release syndrome	43.10	10.88	13	176425	35985	79531965
Mycobacterium avium complex infection	43.00	10.88	52	176386	4548	79563402
Lymph node calcification	42.54	10.88	20	176418	395	79567555
Pneumothorax spontaneous	42.45	10.88	31	176407	1423	79566527
Nasal discharge discolouration	42.43	10.88	39	176399	2482	79565468
Eczema	42.40	10.88	191	176247	40627	79527323
Bone marrow failure	41.98	10.88	31	176407	51076	79516874
Bronchiolitis	41.88	10.88	49	176389	4139	79563811
Sepsis	41.62	10.88	388	176050	269040	79298910
Serotonin syndrome	41.48	10.88	24	176414	45003	79522947
Nasal mucosal disorder	41.08	10.88	19	176419	361	79567589
Sinus disorder	40.93	10.88	126	176312	22338	79545612
Premature delivery	40.38	10.88	3	176435	23464	79544486
Neoplasm progression	40.36	10.88	33	176405	51649	79516301
Aortic valve stenosis	40.25	10.88	54	176384	5240	79562710
Intentional self-injury	40.11	10.88	11	176427	32408	79535542
Electrocardiogram QT prolonged	39.78	10.88	88	176350	90298	79477652
FEV1/FVC ratio decreased	39.55	10.88	16	176422	216	79567734
Oesophageal pain	39.39	10.88	48	176390	4231	79563719
Frustration tolerance decreased	38.98	10.88	64	176374	7438	79560512
Oedema peripheral	38.98	10.88	779	175659	251509	79316441
Mycobacterial infection	38.50	10.88	44	176394	3624	79564326
Lung consolidation	38.22	10.88	70	176368	8877	79559073
Sputum increased	38.08	10.88	49	176389	4564	79563386
Cardiogenic shock	37.68	10.88	23	176415	41891	79526059
Hip arthroplasty	37.55	10.88	16	176422	35740	79532210
Inflammation	37.50	10.88	96	176342	93657	79474293
Psoriasis	37.19	10.88	90	176348	89497	79478453
Confusional state	37.17	10.88	488	175950	317509	79250441
Decreased activity	37.11	10.88	68	176370	8626	79559324
Pulmonary congestion	37.01	10.88	138	176300	26962	79540988
Respiratory symptom	36.62	10.88	49	176389	4742	79563208
Skin candida	36.52	10.88	33	176405	2054	79565896
Posterior reversible encephalopathy syndrome	36.34	10.88	7	176431	26274	79541676
Idiopathic intracranial hypertension	36.12	10.88	40	176398	3182	79564768
Laryngeal stenosis	35.92	10.88	25	176413	1063	79566887
Acute respiratory distress syndrome	35.85	10.88	27	176411	44040	79523910
Pyrexia	35.83	10.88	1187	175251	677522	78890428
Liver disorder	35.71	10.88	66	176372	72351	79495599
Paraesthesia	35.57	10.88	236	176202	176087	79391863
Increased upper airway secretion	35.48	10.88	45	176393	4132	79563818
Nocturnal dyspnoea	35.12	10.88	29	176409	1597	79566353
Rhonchi	35.10	10.88	44	176394	3992	79563958
Neurotoxicity	35.04	10.88	14	176424	32504	79535446
Carcinoid tumour pulmonary	34.79	10.88	17	176421	367	79567583
Diastolic dysfunction	34.64	10.88	75	176363	10736	79557214
Illness	34.51	10.88	198	176240	46313	79521637
Poisoning	34.38	10.88	7	176431	25265	79542685
Viral infection	33.82	10.88	186	176252	42830	79525120
Ascites	33.72	10.88	73	176365	75489	79492461
Dyspnoea paroxysmal nocturnal	32.79	10.88	32	176406	2196	79565754
Renal impairment	32.42	10.88	210	176228	157573	79410377
Snoring	32.38	10.88	50	176388	5516	79562434
Dysarthria	32.15	10.88	63	176375	67559	79500391
Drug eruption	31.95	10.88	30	176408	43905	79524045
Joint range of motion decreased	31.73	10.88	17	176421	33265	79534685
Decreased bronchial secretion	31.42	10.88	10	176428	63	79567887
Adverse event	31.39	10.88	53	176385	60161	79507789
Discomfort	31.31	10.88	157	176281	125460	79442490
Sinus pain	31.29	10.88	40	176398	3702	79564248
Neutrophil count decreased	31.20	10.88	105	176333	93854	79474096
Encephalopathy	31.00	10.88	64	176374	67333	79500617
Increased viscosity of bronchial secretion	31.00	10.88	18	176420	556	79567394
Dyskinesia	30.92	10.88	32	176406	44741	79523209
Brain natriuretic peptide abnormal	30.33	10.88	20	176418	777	79567173
Exercise tolerance decreased	30.29	10.88	64	176374	9007	79558943
Drug level increased	30.12	10.88	26	176412	39625	79528325
Increased bronchial secretion	30.11	10.88	37	176401	3290	79564660
Abortion spontaneous	29.74	10.88	14	176424	29493	79538457
Nasal oedema	29.66	10.88	27	176411	1697	79566253
Chest pain	29.57	10.88	826	175612	281478	79286472
Nasal disorder	29.50	10.88	39	176399	3730	79564220
Blood creatine phosphokinase increased	29.36	10.88	64	176374	66026	79501924
Throat tightness	29.29	10.88	131	176307	27776	79540174
Oropharyngeal discomfort	29.27	10.88	55	176383	7111	79560839
Acute hepatic failure	29.27	10.88	15	176423	30098	79537852
Expiratory reserve volume decreased	29.04	10.88	10	176428	83	79567867
Blood alkaline phosphatase increased	28.83	10.88	61	176377	63603	79504347
Pain	28.52	10.88	1270	175168	702532	78865418
Blood lactate dehydrogenase increased	28.19	10.88	27	176411	39143	79528807
Product physical issue	27.79	10.88	40	176398	4145	79563805
Sinus congestion	27.74	10.88	102	176336	19794	79548156
Injection site erythema	27.63	10.88	85	176353	78112	79489838
Blood calcium increased	27.62	10.88	67	176371	10333	79557617
Respiratory distress	27.49	10.88	222	176216	58117	79509833
N-terminal prohormone brain natriuretic peptide abnormal	27.41	10.88	13	176425	262	79567688
Bronchomalacia	27.32	10.88	13	176425	264	79567686
Granulomatous rosacea	27.16	10.88	12	176426	204	79567746
Muscle spasticity	27.11	10.88	7	176431	21468	79546482
Blood immunoglobulin E decreased	27.05	10.88	10	176428	104	79567846
Respiratory arrest	27.03	10.88	54	176384	57496	79510454
Atrial fibrillation	26.96	10.88	600	175838	197286	79370664
Hypoaesthesia	26.95	10.88	260	176178	179092	79388858
Pancreatitis	26.83	10.88	71	176367	68504	79499446
Sputum retention	26.74	10.88	21	176417	1076	79566874
Neurosensory hypoacusis	26.44	10.88	12	176426	218	79567732
Deep vein thrombosis	26.36	10.88	158	176280	120761	79447189
Lipohypertrophy	26.16	10.88	19	176419	865	79567085
Oxygen saturation increased	25.99	10.88	16	176422	551	79567399
Hepatic cytolysis	25.69	10.88	14	176424	27137	79540813
Amnesia	25.66	10.88	64	176374	62993	79504957
Forced expiratory volume abnormal	25.55	10.88	10	176428	123	79567827
Rib fracture	25.54	10.88	126	176312	27821	79540129
Decreased gait velocity	25.39	10.88	11	176427	178	79567772
Normochromic normocytic anaemia	25.21	10.88	54	176384	7673	79560277
Transplant rejection	25.19	10.88	6	176432	19431	79548519
Device dislocation	25.15	10.88	13	176425	25957	79541993
Gout	25.10	10.88	115	176323	24634	79543316
Malignant melanoma in situ	25.04	10.88	29	176409	2423	79565527
Shock	24.92	10.88	36	176402	43512	79524438
Exposure to allergen	24.76	10.88	13	176425	328	79567622
Thrombotic microangiopathy	24.66	10.88	7	176431	20162	79547788
Functional residual capacity increased	24.49	10.88	9	176429	92	79567858
Haemoglobin decreased	24.44	10.88	345	176093	221774	79346176
Klebsiella infection	24.43	10.88	3	176435	15717	79552233
Skin ulcer	24.42	10.88	52	176386	54098	79513852
Bronchitis chronic	24.32	10.88	39	176399	4443	79563507
Hyperbilirubinaemia	24.15	10.88	12	176426	24506	79543444
Suffocation feeling	24.01	10.88	24	176414	1696	79566254
Pneumothorax	23.99	10.88	125	176313	28198	79539752
Cardiac arrest	23.98	10.88	254	176184	171842	79396108
Somnolence	23.95	10.88	378	176060	238603	79329347
Carbon dioxide increased	23.73	10.88	27	176411	2213	79565737
Orthopnoea	23.73	10.88	62	176376	10011	79557939
Product prescribing error	23.59	10.88	175	176263	44638	79523312
Metastases to liver	23.48	10.88	17	176421	28297	79539653
Toxic epidermal necrolysis	23.46	10.88	39	176399	44542	79523408
CFTR gene mutation	23.42	10.88	9	176429	105	79567845
Sarcopenia	23.41	10.88	14	176424	457	79567493
Haemophilus infection	23.38	10.88	27	176411	2249	79565701
Cytopenia	23.27	10.88	8	176430	20375	79547575
Lactic acidosis	23.10	10.88	79	176359	70280	79497670
Prostatic adenoma	23.05	10.88	9	176429	110	79567840
Peritonitis	23.03	10.88	17	176421	28019	79539931
Convulsive threshold lowered	22.81	10.88	18	176420	929	79567021
Rash maculo-papular	22.75	10.88	57	176381	56021	79511929
Proteinuria	22.70	10.88	23	176415	32479	79535471
Colitis ulcerative	22.69	10.88	26	176412	34716	79533234
Drug interaction	22.60	10.88	723	175715	414460	79153490
Acute myeloid leukaemia	22.56	10.88	21	176417	30864	79537086
Nasal septum deviation	22.30	10.88	24	176414	1849	79566101
Eosinophilic pneumonia chronic	22.18	10.88	14	176424	504	79567446
Hallucination, auditory	22.15	10.88	9	176429	20684	79547266
Functional residual capacity decreased	22.01	10.88	8	176430	79	79567871
Laboratory test abnormal	21.79	10.88	18	176420	28030	79539920
Tumour lysis syndrome	21.71	10.88	13	176425	23926	79544024
Lymphocyte count decreased	21.67	10.88	45	176393	47244	79520706
Prescribed underdose	21.64	10.88	20	176418	29494	79538456
Poor quality device used	21.63	10.88	26	176412	2259	79565691
Fractured coccyx	21.60	10.88	18	176420	1004	79566946
Hepatitis	21.57	10.88	58	176380	55669	79512281
Condition aggravated	21.56	10.88	898	175540	500226	79067724
Osteoporosis	21.35	10.88	198	176240	53914	79514036
Oral candidiasis	21.25	10.88	125	176313	29503	79538447
Eye swelling	21.18	10.88	115	176323	26353	79541597
Breath sounds	21.15	10.88	9	176429	139	79567811
Hypothermia	21.13	10.88	12	176426	22734	79545216
Gamma-glutamyltransferase increased	21.10	10.88	57	176381	54623	79513327
Sinusitis	21.01	10.88	574	175864	194927	79373023
Haematocrit decreased	20.71	10.88	68	176370	61244	79506706
Aplastic anaemia	20.49	10.88	7	176431	17898	79550052
Peak expiratory flow rate abnormal	20.47	10.88	8	176430	98	79567852
Sputum culture	20.46	10.88	10	176428	216	79567734
Left ventricular dilatation	20.44	10.88	18	176420	1083	79566867
Factitious disorder	20.42	10.88	9	176429	152	79567798
Cardiac failure congestive	20.42	10.88	435	176003	141967	79425983
Bone erosion	20.38	10.88	7	176431	17840	79550110
Palmar-plantar erythrodysaesthesia syndrome	20.37	10.88	26	176412	33108	79534842
Blood immunoglobulin E abnormal	20.35	10.88	6	176432	28	79567922
Exostosis	20.34	10.88	6	176432	16852	79551098
Eosinophilic bronchitis	20.33	10.88	13	176425	479	79567471
Anaemia	20.31	10.88	792	175646	444223	79123727
Vascular shunt	20.24	10.88	7	176431	59	79567891
Sputum abnormal	20.19	10.88	19	176419	1246	79566704
Multiple drug therapy	20.13	10.88	34	176404	4044	79563906
Device related infection	19.97	10.88	28	176410	34266	79533684
Bronchospasm paradoxical	19.95	10.88	9	176429	161	79567789
Lacrimal disorder	19.93	10.88	13	176425	496	79567454
Pulmonary arterial hypertension	19.91	10.88	119	176319	28247	79539703
Injection site reaction	19.74	10.88	59	176379	54726	79513224
Abdominal pain	19.64	10.88	685	175753	388884	79179066
Epstein-Barr virus infection	19.59	10.88	4	176434	14412	79553538
FEV1/FVC ratio abnormal	19.54	10.88	6	176432	33	79567917
Lip dry	19.51	10.88	5	176433	15413	79552537
Akathisia	19.50	10.88	3	176435	13256	79554694
Aptyalism	19.42	10.88	15	176423	750	79567200
Nasal mucosal discolouration	19.39	10.88	6	176432	34	79567916
Hypochromic anaemia	19.31	10.88	27	176411	2724	79565226
Atheroembolism	19.14	10.88	11	176427	333	79567617
Hypoacusis	18.98	10.88	123	176315	30027	79537923
Tooth disorder	18.97	10.88	18	176420	26215	79541735
Aortic aneurysm	18.89	10.88	51	176387	8395	79559555
Mononeuropathy multiplex	18.87	10.88	12	176426	438	79567512
Lung diffusion disorder	18.73	10.88	9	176429	187	79567763
Joint injury	18.61	10.88	126	176312	31209	79536741
Musculoskeletal discomfort	18.53	10.88	90	176348	19745	79548205
Urinary tract infection	18.50	10.88	464	175974	274048	79293902
Diaphragmatic disorder	18.38	10.88	21	176417	1729	79566221
Vaginal haemorrhage	18.22	10.88	13	176425	21804	79546146
Hyperglycaemia	18.04	10.88	87	176351	70248	79497702
Vision blurred	18.04	10.88	332	176106	105566	79462384
Plasma cell myeloma	18.03	10.88	59	176379	53200	79514750
Device issue	18.02	10.88	20	176418	27088	79540862
Right ventricular systolic pressure	17.99	10.88	5	176433	18	79567932
Diabetic ketoacidosis	17.82	10.88	30	176408	34092	79533858
Respiratory tract inflammation	17.75	10.88	15	176423	853	79567097
Physiotherapy chest	17.70	10.88	4	176434	4	79567946
Pulmonary arterial pressure abnormal	17.65	10.88	14	176424	728	79567222
Flour sensitivity	17.58	10.88	5	176433	20	79567930
Gingival bleeding	17.55	10.88	7	176431	16269	79551681
Sinus polyp degeneration	17.40	10.88	6	176432	50	79567900
Ageusia	17.40	10.88	78	176360	16554	79551396
Myelodysplastic syndrome	17.39	10.88	25	176413	30276	79537674
Electrocardiogram QRS complex abnormal	17.35	10.88	13	176425	621	79567329
Abnormal behaviour	17.25	10.88	34	176404	36387	79531563
Immune thrombocytopenia	17.11	10.88	9	176429	17796	79550154
Urinary retention	17.01	10.88	196	176242	56434	79511516
Colitis	16.93	10.88	94	176344	73213	79494737
Inhalation therapy	16.90	10.88	6	176432	55	79567895
Peripheral venous disease	16.90	10.88	7	176431	15902	79552048
Heavy menstrual bleeding	16.88	10.88	5	176433	14006	79553944
Restlessness	16.80	10.88	50	176388	46442	79521508
Taste disorder	16.74	10.88	7	176431	15816	79552134
Polycystic ovaries	16.69	10.88	30	176408	3749	79564201
Pulmonary pain	16.64	10.88	33	176405	4440	79563510
COVID-19	16.61	10.88	247	176191	157427	79410523
Pneumocystis jirovecii pneumonia	16.59	10.88	29	176409	32479	79535471
Prescribed overdose	16.57	10.88	37	176401	37846	79530104
Hydronephrosis	16.51	10.88	9	176429	17445	79550505
Hyperkaliuria	16.48	10.88	8	176430	170	79567780
Therapy partial responder	16.42	10.88	9	176429	17388	79550562
Musculoskeletal disorder	16.37	10.88	14	176424	21434	79546516
Pneumonia viral	16.34	10.88	51	176387	9107	79558843
Frequent bowel movements	16.34	10.88	25	176413	29514	79538436
Metastases to bone	16.26	10.88	18	176420	24409	79543541
Lung hernia	16.18	10.88	6	176432	63	79567887
Hepatic cirrhosis	16.18	10.88	33	176405	34873	79533077
Osteomyelitis	16.16	10.88	30	176408	32835	79535115
Hypoalbuminaemia	16.13	10.88	14	176424	21283	79546667
Caesarean section	15.99	10.88	4	176434	12531	79555419
Mental status changes	15.94	10.88	85	176353	66874	79501076
Umbilical hernia	15.89	10.88	38	176400	5807	79562143
Eye infection bacterial	15.87	10.88	10	176428	359	79567591
Hepatic haematoma	15.83	10.88	14	176424	847	79567103
Hernia pain	15.80	10.88	11	176427	468	79567482
Pathogen resistance	15.74	10.88	6	176432	14336	79553614
Aspiration	15.74	10.88	87	176351	20071	79547879
Dry throat	15.73	10.88	45	176393	7661	79560289
Acute kidney injury	15.72	10.88	965	175473	518439	79049511
Panniculitis	15.68	10.88	4	176434	12367	79555583
Aphasia	15.66	10.88	52	176386	46680	79521270
Osteoarthritis	15.59	10.88	121	176317	87188	79480762
Hemiparesis	15.54	10.88	32	176406	33701	79534249
Hepatic failure	15.54	10.88	76	176362	61136	79506814
Full blood count decreased	15.51	10.88	22	176416	26797	79541153
Large cell lung cancer metastatic	15.47	10.88	4	176434	10	79567940
Uveitis	15.46	10.88	9	176429	16821	79551129
Joint stiffness	15.42	10.88	43	176395	40787	79527163
Mydriasis	15.42	10.88	10	176428	17633	79550317
Brain oedema	15.34	10.88	20	176418	25243	79542707
Hypomania	15.34	10.88	44	176394	7500	79560450
Diffuse large B-cell lymphoma	15.26	10.88	4	176434	12145	79555805
Cough decreased	15.20	10.88	4	176434	11	79567939
Perennial allergy	15.20	10.88	4	176434	11	79567939
Agranulocytosis	15.17	10.88	50	176388	44980	79522970
Enterobiasis	15.14	10.88	5	176433	36	79567914
Drug withdrawal syndrome	15.11	10.88	34	176404	34684	79533266
Peripheral sensory neuropathy	15.08	10.88	5	176433	13028	79554922
Eye disorder	15.03	10.88	96	176342	23316	79544634
Renal tubular necrosis	15.03	10.88	20	176418	25019	79542931
Drug tolerance decreased	14.98	10.88	5	176433	12973	79554977
Disseminated intravascular coagulation	14.88	10.88	36	176402	35806	79532144
Adverse drug reaction	14.86	10.88	86	176352	66306	79501644
Hypertransaminasaemia	14.84	10.88	4	176434	11920	79556030
Impaired work ability	14.83	10.88	13	176425	19668	79548282
Extrapyramidal disorder	14.78	10.88	17	176421	22662	79545288
Tubulointerstitial nephritis	14.64	10.88	40	176398	38195	79529755
Decreased appetite	14.62	10.88	614	175824	341804	79226146
Upper respiratory tract congestion	14.61	10.88	23	176415	2580	79565370
Muscular weakness	14.54	10.88	259	176179	160470	79407480
Cardiac failure	14.53	10.88	447	175991	154395	79413555
Altered state of consciousness	14.52	10.88	49	176389	43773	79524177
Injury	14.50	10.88	106	176332	77390	79490560
Fluid retention	14.49	10.88	226	176212	69583	79498367
Respiratory tract haemorrhage	14.48	10.88	19	176419	1804	79566146
Bacteraemia	14.40	10.88	32	176406	32792	79535158
Paraneoplastic rash	14.38	10.88	6	176432	88	79567862
Jaundice	14.27	10.88	65	176373	53284	79514666
Torsade de pointes	14.26	10.88	13	176425	19299	79548651
Lung carcinoma cell type unspecified recurrent	14.26	10.88	9	176429	324	79567626
Arthritis	14.25	10.88	174	176264	114706	79453244
Disorientation	14.22	10.88	81	176357	62695	79505255
No adverse event	14.17	10.88	39	176399	37153	79530797
Magnesium metabolism disorder	14.17	10.88	5	176433	45	79567905
Fatigue	14.13	10.88	1822	174616	927905	78640045
Nervousness	14.06	10.88	124	176314	33291	79534659
Dizziness exertional	14.02	10.88	11	176427	563	79567387
Hypophosphataemia	14.01	10.88	14	176424	19899	79548051
Blood uric acid increased	13.99	10.88	6	176432	13354	79554596
Metabolic acidosis	13.98	10.88	116	176322	82413	79485537
Transient ischaemic attack	13.92	10.88	178	176260	52517	79515433
Progressive multifocal leukoencephalopathy	13.91	10.88	15	176423	20585	79547365
Cerebral infarction	13.86	10.88	53	176385	45623	79522327
Blood phosphorus increased	13.80	10.88	3	176435	10344	79557606
Rheumatoid nodule	13.78	10.88	11	176427	17427	79550523
Autoimmune disorder	13.74	10.88	10	176428	16602	79551348
Laryngitis	13.73	10.88	71	176367	15968	79551982
Nasal inflammation	13.72	10.88	12	176426	715	79567235
Pickwickian syndrome	13.71	10.88	10	176428	458	79567492
Bradycardia	13.71	10.88	214	176224	135343	79432607
Dry mouth	13.64	10.88	272	176166	87747	79480203
Affect lability	13.60	10.88	4	176434	11255	79556695
Enterococcal infection	13.52	10.88	9	176429	15651	79552299
Painful respiration	13.48	10.88	26	176412	3427	79564523
Hypercalcaemia	13.41	10.88	42	176396	38388	79529562
Encephalitis	13.41	10.88	8	176430	14752	79553198
Febrile bone marrow aplasia	13.40	10.88	6	176432	13014	79554936
Pneumonitis	13.39	10.88	199	176239	60661	79507289
Sciatica	13.30	10.88	34	176404	33188	79534762
Generalised tonic-clonic seizure	13.29	10.88	51	176387	43859	79524091
Eosinophilic otitis media	13.28	10.88	3	176435	3	79567947
Fractional exhaled nitric oxide increased	13.28	10.88	3	176435	3	79567947
Synovial cyst	13.26	10.88	3	176435	10062	79557888
Pulmonary toxicity	13.21	10.88	6	176432	12908	79555042
Respiratory tract irritation	13.19	10.88	11	176427	614	79567336
Caffeine allergy	13.18	10.88	4	176434	21	79567929
Idiopathic pulmonary fibrosis	13.17	10.88	29	176409	4199	79563751
Forced expiratory volume increased	13.12	10.88	5	176433	57	79567893
Herpes zoster	13.12	10.88	137	176301	92946	79475004
Status epilepticus	13.09	10.88	22	176416	25019	79542931
Ischaemic cardiomyopathy	12.95	10.88	42	176396	7653	79560297
Coagulopathy	12.81	10.88	39	176399	35967	79531983
Foot deformity	12.72	10.88	21	176417	24053	79543897
Colitis microscopic	12.69	10.88	4	176434	10764	79557186
Blood thyroid stimulating hormone abnormal	12.68	10.88	13	176425	947	79567003
Use of accessory respiratory muscles	12.66	10.88	10	176428	517	79567433
Rash papular	12.66	10.88	18	176420	21898	79546052
Brain hypoxia	12.64	10.88	13	176425	950	79567000
Tachyarrhythmia	12.63	10.88	39	176399	6923	79561027
Red blood cell count decreased	12.61	10.88	75	176363	57438	79510512
Immune-mediated pancreatitis	12.60	10.88	8	176430	291	79567659
Mastication disorder	12.58	10.88	22	176416	2691	79565259
Intestinal perforation	12.55	10.88	12	176426	17414	79550536
Underdose	12.46	10.88	35	176403	33116	79534834
Lymphopenia	12.44	10.88	31	176407	30526	79537424
Skin necrosis	12.40	10.88	13	176425	18074	79549876
Squamous cell carcinoma of lung	12.37	10.88	20	176418	2294	79565656
Laryngectomy	12.33	10.88	4	176434	27	79567923
Cardiac failure chronic	12.24	10.88	53	176385	11082	79556868
Intervertebral disc degeneration	12.24	10.88	68	176370	15717	79552233
Small airways disease	12.21	10.88	4	176434	28	79567922
Toxic encephalopathy	12.20	10.88	5	176433	11435	79556515
Ataxia	12.18	10.88	23	176415	25016	79542934
Blood glucose increased	12.14	10.88	180	176258	114795	79453155
Memory impairment	12.12	10.88	174	176264	111560	79456390
Bacterial disease carrier	12.11	10.88	16	176422	1530	79566420
Chronic respiratory failure	12.10	10.88	23	176415	2999	79564951
Lymphoedema	12.09	10.88	57	176381	12356	79555594
Hepatitis acute	12.04	10.88	10	176428	15532	79552418
Ankylosing spondylitis	11.98	10.88	6	176432	12199	79555751
Benign breast neoplasm	11.98	10.88	12	176426	850	79567100
Forced vital capacity abnormal	11.97	10.88	4	176434	30	79567920
Accidental overdose	11.96	10.88	46	176392	39535	79528415
Menopausal symptoms	11.94	10.88	18	176420	1945	79566005
Anal abscess	11.91	10.88	3	176435	9352	79558598
Non-small cell lung cancer	11.89	10.88	36	176402	6324	79561626
Aspirin-exacerbated respiratory disease	11.87	10.88	14	176424	1193	79566757
Hypotension	11.76	10.88	1129	175309	439188	79128762
Abnormal loss of weight	11.73	10.88	43	176395	8333	79559617
Grip strength decreased	11.63	10.88	19	176419	21850	79546100
Hyperammonaemia	11.59	10.88	5	176433	11088	79556862
Metabolic disorder	11.56	10.88	3	176435	9167	79558783
Exposure to toxic agent	11.53	10.88	3	176435	9155	79558795
Pyelonephritis	11.52	10.88	17	176421	20371	79547579
Pulmonary artery dilatation	11.48	10.88	9	176429	460	79567490
Metastases to lung	11.43	10.88	14	176424	18149	79549801
Hepatic necrosis	11.42	10.88	3	176435	9097	79558853
Croup infectious	11.39	10.88	11	176427	745	79567205
Fibromuscular dysplasia	11.37	10.88	7	176431	241	79567709
Poisoning deliberate	11.34	10.88	15	176423	18813	79549137
Anxiety	11.33	10.88	665	175773	247847	79320103
Sensory disturbance	11.31	10.88	10	176428	15067	79552883
Hyposmia	11.28	10.88	11	176427	754	79567196
Choking sensation	11.28	10.88	26	176412	3880	79564070
Hallucination, visual	11.26	10.88	36	176402	32693	79535257
Crepitations	11.26	10.88	48	176390	9969	79557981
Graft versus host disease	11.23	10.88	10	176428	15016	79552934
Lung adenocarcinoma stage II	11.21	10.88	3	176435	9	79567941
Major depression	11.20	10.88	3	176435	8977	79558973
Breast neoplasm	11.20	10.88	12	176426	920	79567030
Occupational exposure to air contaminants	11.20	10.88	6	176432	158	79567792
Cholecystitis chronic	11.11	10.88	4	176434	9902	79558048
Oxygen consumption increased	11.07	10.88	30	176408	4949	79563001
Wrist fracture	11.07	10.88	54	176384	11867	79556083
Anhedonia	11.04	10.88	10	176428	14888	79553062
Lip blister	11.01	10.88	21	176417	2746	79565204
Serum ferritin increased	11.01	10.88	4	176434	9843	79558107
Schizophrenia	10.98	10.88	65	176373	15375	79552575
Xanthelasma	10.96	10.88	6	176432	165	79567785
Pneumonectomy	10.91	10.88	5	176433	93	79567857
Lower gastrointestinal haemorrhage	10.90	10.88	67	176371	16058	79551892

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	R03AL06	RESPIRATORY SYSTEM DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES ADRENERGICS, INHALANTS Adrenergics in combination with anticholinergics incl. triple combinations with corticosteroids
ATC	R03AL10	RESPIRATORY SYSTEM DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES ADRENERGICS, INHALANTS Adrenergics in combination with anticholinergics incl. triple combinations with corticosteroids
ATC	R03BB04	RESPIRATORY SYSTEM DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES OTHER DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES, INHALANTS Anticholinergics
ATC	R03BB54	RESPIRATORY SYSTEM DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES OTHER DRUGS FOR OBSTRUCTIVE AIRWAY DISEASES, INHALANTS Anticholinergics
FDA MoA	N0000175370	Cholinergic Antagonists
FDA EPC	N0000175574	Anticholinergic
MeSH PA	D018927	Anti-Asthmatic Agents
MeSH PA	D001993	Bronchodilator Agents
MeSH PA	D018678	Cholinergic Agents
MeSH PA	D018680	Cholinergic Antagonists
MeSH PA	D018377	Neurotransmitter Agents
MeSH PA	D010276	Parasympatholytics
MeSH PA	D018373	Peripheral Nervous System Agents
MeSH PA	D019141	Respiratory System Agents
CHEBI has role	CHEBI:35523	bronchodilator
CHEBI has role	CHEBI:48876	muscarinic antagonists

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

Disease	Relation	SNOMED_ID	DOID
Chronic bronchitis	indication	63480004	DOID:6132
Pulmonary emphysema	indication	87433001
Asthma	indication	195967001	DOID:2841
Bronchospasm Prevention with COPD	indication
Chronic Obstructive Pulmonary Disease with Bronchospasms	indication
Impaired renal function disorder	contraindication	197663003
Bladder outflow obstruction	contraindication	236645006
Benign prostatic hyperplasia	contraindication	266569009
Retention of urine	contraindication	267064002
Angle-closure glaucoma	contraindication	392291006	DOID:13550
Cardiovascular event risk	contraindication	395112001

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	13.97	acidic

Orange Book patent data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Patent number	Patent expiration date	Patent use
EQ 0.0025MG BASE/INH;EQ 0.0025MG BASE/INH	STIOLTO RESPIMAT	BOEHRINGER INGELHEIM	N206756	May 21, 2015	RX	SPRAY, METERED	INHALATION	8044046	Nov. 10, 2023	TREATMENT OF COPD
EQ 0.0025MG BASE/INH;EQ 0.0025MG BASE/INH	STIOLTO RESPIMAT	BOEHRINGER INGELHEIM	N206756	May 21, 2015	RX	SPRAY, METERED	INHALATION	7220742	May 12, 2025	TREATMENT OF RESPIRATORY COMPLAINTS
EQ 0.0025MG BASE/INH;EQ 0.0025MG BASE/INH	STIOLTO RESPIMAT	BOEHRINGER INGELHEIM	N206756	May 21, 2015	RX	SPRAY, METERED	INHALATION	8034809	May 12, 2025	TREATMENT OF COPD
EQ 0.018MG BASE/INH	SPIRIVA	BOEHRINGER INGELHEIM	N021395	Jan. 30, 2004	RX	POWDER	INHALATION	8022082	Jan. 19, 2026	ADMINISTRATION OF AN INHALABLE POWDER COMPRISING TIOTROPIUM VIA DEVICE

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Muscarinic acetylcholine receptor M3	GPCR	P20309	ACM3_HUMAN	ANTAGONIST	Ki	11.10	WOMBAT-PK	CHEMBL
Muscarinic acetylcholine receptor M2	GPCR	P08172	ACM2_HUMAN		Ki	11	WOMBAT-PK
Muscarinic acetylcholine receptor M4	GPCR	P08173	ACM4_HUMAN		Ki	11	WOMBAT-PK
Muscarinic acetylcholine receptor M5	GPCR	P08912	ACM5_HUMAN		Ki	11	WOMBAT-PK
Muscarinic acetylcholine receptor M1	GPCR	P11229	ACM1_HUMAN		Ki	11	WOMBAT-PK
Muscarinic acetylcholine receptor M2	GPCR		ACM2_RAT		Ki	9.82	CHEMBL
Muscarinic acetylcholine receptor M1	GPCR		ACM1_RAT		Ki	9.80	CHEMBL
Muscarinic acetylcholine receptor M3	GPCR		ACM3_RAT		Ki	9.52	CHEMBL

External reference:

ID	Source
4021416	VUID
N0000148830	NUI
411207-31-3	SECONDARY_CAS_RN
4021416	VANDF
CHEBI:90959	CHEBI
0HK	PDB_CHEM_ID
CHEMBL3545181	ChEMBL_ID
CHEMBL1900528	ChEMBL_ID
CHEMBL1182657	ChEMBL_ID
367	IUPHAR_LIGAND_ID
DB01409	DRUGBANK_ID
1298831	RXNORM
17045	MMSL
31060	MMSL
45574	MMSL
d04829	MMSL
009712	NDDF
009713	NDDF
407730002	SNOMEDCT_US
409169006	SNOMEDCT_US
425812008	SNOMEDCT_US
734451000	SNOMEDCT_US
C1306772	UMLSCUI
D000069447	MESH_DESCRIPTOR_UI
5487426	PUBCHEM_CID
0EB439235F	UNII

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Spiriva HandiHaler	HUMAN PRESCRIPTION DRUG LABEL	1	0597-0075	CAPSULE	18 ug	ORAL	NDA	30 sections
Stiolto Respimat	HUMAN PRESCRIPTION DRUG LABEL	2	0597-0155	SPRAY, METERED	3.12 ug	RESPIRATORY (INHALATION)	NDA	31 sections
Stiolto Respimat	HUMAN PRESCRIPTION DRUG LABEL	2	0597-0155	SPRAY, METERED	3.12 ug	RESPIRATORY (INHALATION)	NDA	31 sections
Spiriva HandiHaler	HUMAN PRESCRIPTION DRUG LABEL	1	50090-4248	CAPSULE	18 ug	ORAL	NDA	29 sections
Spiriva HandiHaler	HUMAN PRESCRIPTION DRUG LABEL	1	50090-4248	CAPSULE	18 ug	ORAL	NDA	29 sections
Spiriva	HUMAN PRESCRIPTION DRUG LABEL	1	50090-4414	CAPSULE	18 ug	ORAL	NDA	29 sections
Spiriva	HUMAN PRESCRIPTION DRUG LABEL	1	54868-5109	CAPSULE	18 ug	ORAL	NDA	29 sections
Tiotropium Bromide	HUMAN PRESCRIPTION DRUG LABEL	1	68180-964	CAPSULE	18 ug	ORAL	ANDA	24 sections