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

Stem definition	Drug id	CAS RN
endothelin receptor antagonists	4809	441798-33-0

Description:

Molecule

Description

Molfile Inchi Smiles Synonyms: opsumit ACT-064992 macitentan

an endothelin receptor antagonist that prevents the binding of ET-1 to both ETA and ETB receptors, macitentan displays high affinity and sustained occupancy of the ET receptors in human pulmonary arterial smooth muscle cells Molecular weight: 588.28 Formula: C19H20Br2N6O4S CLOGP: 4.30 LIPINSKI: 1 HAC: 10 HDO: 2 TPSA: 128.22 ALOGS: -4.94 ROTB: 9 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Drug dosage:

Dose	Unit	Route
10	mg	O

ADMET properties:

None

Approvals:

Date	Agency	Company	Orphan
Dec. 20, 2013	EMA
Oct. 18, 2013	FDA	ACTELION PHARMS LTD

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
Pulmonary arterial hypertension	3112.68	15.18	1533	139451	24395	46520683
Dyspnoea	2825.32	15.18	5320	135664	510228	46034850
Fluid retention	2545.85	15.18	1701	139283	49345	46495733
Hospitalisation	2403.16	15.18	1786	139198	61599	46483479
Drug ineffective	1456.61	15.18	174	140810	677664	45867414
Death	1452.40	15.18	3150	137834	332398	46212680
Dyspnoea exertional	1285.11	15.18	1126	139858	49163	46495915
Pain in jaw	1156.55	15.18	945	140039	37427	46507651
Nasal congestion	1131.47	15.18	1028	139956	47085	46497993
Pulmonary hypertension	1088.05	15.18	888	140096	35105	46509973
Transfusion	1063.86	15.18	599	140385	12632	46532446
Right ventricular failure	912.65	15.18	582	140402	15511	46529567
Headache	896.63	15.18	3316	137668	475036	46070042
Fluid overload	774.02	15.18	648	140336	26537	46518541
Oxygen saturation decreased	736.64	15.18	974	140010	68190	46476888
Off label use	600.93	15.18	200	140784	379641	46165437
Oedema	581.83	15.18	856	140128	66215	46478863
Catheter management	548.72	15.18	233	140751	2562	46542516
Toxicity to various agents	531.57	15.18	26	140958	211740	46333338
Product dose omission issue	512.30	15.18	1384	139600	167136	46377942
Catheter site erythema	508.67	15.18	246	140738	3737	46541341
Rheumatoid arthritis	497.98	15.18	68	140916	240147	46304931
Pneumonia	475.02	15.18	2317	138667	374003	46171075
Lung transplant	457.15	15.18	207	140777	2685	46542393
Catheter site pain	455.88	15.18	225	140759	3581	46541497
Cough	450.30	15.18	1622	139362	228627	46316451
Oedema peripheral	436.39	15.18	1262	139722	158444	46386634
Drug hypersensitivity	436.11	15.18	101	140883	243724	46301354
Catheter site pruritus	428.82	15.18	177	140807	1802	46543276
Unevaluable event	424.57	15.18	606	140378	45569	46499509
Oxygen consumption increased	419.36	15.18	210	140774	3453	46541625
Drug interaction	401.25	15.18	66	140918	203028	46342050
Infusion site pain	398.20	15.18	292	140692	9815	46535263
Pulmonary oedema	388.96	15.18	614	140370	50491	46494587
Peripheral swelling	382.63	15.18	1197	139787	156874	46388204
Neutropenia	367.65	15.18	15	140969	143189	46401889
Catheterisation cardiac	332.73	15.18	186	140798	3861	46541217
Chest pain	325.63	15.18	1220	139764	175104	46369974
Flushing	316.04	15.18	640	140344	63974	46481104
Therapy change	315.89	15.18	195	140789	4895	46540183
Hypotension	305.40	15.18	1450	139534	231139	46313939
Condition aggravated	294.11	15.18	1489	139495	243563	46301515
Pulmonary arterial pressure increased	287.24	15.18	158	140826	3174	46541904
Dialysis	275.16	15.18	235	140749	9881	46535197
Maternal exposure during pregnancy	265.67	15.18	10	140974	102539	46442539
Febrile neutropenia	264.96	15.18	4	140980	94623	46450455
Treatment failure	264.76	15.18	3	140981	93084	46451994
Catheter site discharge	255.44	15.18	123	140861	1849	46543229
Scleroderma	253.88	15.18	164	140820	4465	46540613
Malaise	247.18	15.18	1778	139206	329454	46215624
Hypoxia	243.45	15.18	505	140479	51333	46493745
Therapy non-responder	235.87	15.18	436	140548	40716	46504362
Dizziness	233.94	15.18	1792	139192	338622	46206456
Vascular device infection	229.14	15.18	139	140845	3378	46541700
Therapeutic product effect decreased	229.12	15.18	4	140980	82597	46462481
Catheter placement	227.27	15.18	113	140871	1828	46543250
Alopecia	225.69	15.18	104	140880	162310	46382768
Catheter site rash	224.99	15.18	85	140899	669	46544409
Catheter site infection	221.13	15.18	152	140832	4601	46540477
Catheter site haemorrhage	218.61	15.18	123	140861	2586	46542492
Rash	218.37	15.18	470	140514	356042	46189036
Contraindicated product administered	217.24	15.18	5	140979	79942	46465136
Palpitations	217.05	15.18	707	140277	94552	46450526
Concomitant disease aggravated	214.16	15.18	183	140801	7699	46537379
Catheter site swelling	213.37	15.18	96	140888	1225	46543853
Transplant evaluation	212.20	15.18	90	140894	986	46544092
Diarrhoea	205.26	15.18	2582	138402	557020	45988058
Device related infection	198.98	15.18	280	140704	20761	46524317
Productive cough	192.82	15.18	454	140530	50261	46494817
Overdose	188.63	15.18	39	140945	101940	46443138
Therapeutic product effect incomplete	185.50	15.18	13	140971	78140	46466938
Exposure during pregnancy	183.19	15.18	50	140934	108162	46436916
Psoriasis	181.12	15.18	15	140969	78589	46466489
Malignant neoplasm progression	180.66	15.18	3	140981	64923	46480155
Leukopenia	179.30	15.18	6	140978	68337	46476741
Syncope	176.67	15.18	705	140279	104098	46440980
Product use in unapproved indication	176.61	15.18	30	140954	90243	46454835
Drug abuse	176.14	15.18	3	140981	63405	46481673
Device alarm issue	174.91	15.18	85	140899	1305	46543773
Hospice care	173.32	15.18	137	140847	5158	46539920
Cardiac failure congestive	168.34	15.18	634	140350	91116	46453962
Device leakage	165.36	15.18	134	140850	5231	46539847
Thrombocytopenia	165.31	15.18	88	140896	126493	46418585
Cardiac pacemaker insertion	164.35	15.18	115	140869	3584	46541494
Rehabilitation therapy	162.47	15.18	77	140907	1115	46543963
Intentional overdose	159.51	15.18	9	140975	64935	46480143
Abdominal distension	157.74	15.18	534	140450	72817	46472261
Injection site pain	154.49	15.18	65	140919	107087	46437991
Infusion site erythema	153.90	15.18	150	140834	7492	46537586
Dyspnoea at rest	153.50	15.18	109	140875	3479	46541599
Stomatitis	152.06	15.18	15	140969	68282	46476796
Musculoskeletal stiffness	151.98	15.18	53	140931	97940	46447138
Cardiac failure	151.27	15.18	558	140426	79390	46465688
Infusion site infection	147.71	15.18	77	140907	1382	46543696
Acute kidney injury	143.28	15.18	312	140672	235543	46309535
Oxygen therapy	140.92	15.18	81	140903	1776	46543302
Catheter site irritation	139.10	15.18	53	140931	428	46544650
Cardiac operation	137.76	15.18	91	140893	2575	46542503
Disease progression	137.21	15.18	593	140391	90707	46454371
Epistaxis	136.37	15.18	466	140518	63839	46481239
Paracentesis	134.82	15.18	63	140921	882	46544196
Infusion site discharge	131.92	15.18	54	140930	537	46544541
Suicide attempt	131.04	15.18	9	140975	55027	46490051
Ascites	130.96	15.18	320	140664	36264	46508814
Device infusion issue	128.73	15.18	64	140920	1035	46544043
Infusion site swelling	128.35	15.18	119	140865	5580	46539498
Chest discomfort	127.84	15.18	576	140408	89693	46455385
Blood pressure increased	125.98	15.18	118	140866	126548	46418530
Injection site erythema	124.80	15.18	35	140949	74392	46470686
Dermatitis contact	123.23	15.18	137	140847	7986	46537092
Injection site reaction	122.75	15.18	5	140979	47844	46497234
Cardiac disorder	122.73	15.18	350	140634	43508	46501570
Anaphylactic reaction	122.72	15.18	10	140974	53102	46491976
Depression	122.56	15.18	203	140781	169901	46375177
Urticaria	121.81	15.18	106	140878	117786	46427292
Nasopharyngitis	121.62	15.18	839	140145	153159	46391919
Emergency care	119.71	15.18	56	140928	786	46544292
White blood cell count decreased	119.53	15.18	98	140886	112133	46432945
Arthropathy	119.50	15.18	53	140931	84647	46460431
Pericardial effusion	118.87	15.18	248	140736	25295	46519783
Electrocardiogram QT prolonged	117.66	15.18	10	140974	51315	46493763
Product use issue	116.10	15.18	71	140913	94573	46450505
Internal haemorrhage	116.09	15.18	101	140883	4354	46540724
Wrong technique in product usage process	113.52	15.18	15	140969	54407	46490671
Rhabdomyolysis	112.39	15.18	3	140981	41906	46503172
Brain natriuretic peptide increased	112.35	15.18	101	140883	4549	46540529
Seizure	110.63	15.18	125	140859	122929	46422149
Abortion spontaneous	110.50	15.18	5	140979	43641	46501437
Hypertension	110.14	15.18	271	140713	196085	46348993
Neutrophil count decreased	109.86	15.18	5	140979	43421	46501657
Influenza	109.19	15.18	546	140438	88724	46456354
Aspiration pleural cavity	108.74	15.18	52	140932	769	46544309
Hyponatraemia	108.50	15.18	88	140896	101244	46443834
Suicidal ideation	107.51	15.18	20	140964	56362	46488716
Central venous catheterisation	106.61	15.18	70	140914	1960	46543118
Presyncope	104.10	15.18	229	140755	24225	46520853
Disease complication	102.75	15.18	80	140904	2945	46542133
Osteoarthritis	102.45	15.18	30	140954	61995	46483083
Pancytopenia	101.30	15.18	66	140918	84992	46460086
Glossodynia	100.75	15.18	9	140975	44364	46500714
Plasma cell myeloma	98.40	15.18	10	140974	44468	46500610
Feeling abnormal	97.89	15.18	680	140304	124380	46420698
Packed red blood cell transfusion	97.86	15.18	68	140916	2095	46542983
Acute respiratory failure	97.06	15.18	248	140736	28890	46516188
Psoriatic arthropathy	96.10	15.18	3	140981	36376	46508702
Infusion site haemorrhage	95.21	15.18	67	140917	2107	46542971
Confusional state	94.97	15.18	214	140770	159678	46385400
Coma	94.96	15.18	29	140955	58320	46486758
N-terminal prohormone brain natriuretic peptide increased	94.76	15.18	61	140923	1650	46543428
Joint swelling	94.05	15.18	228	140756	165845	46379233
Respiratory failure	93.65	15.18	547	140437	94269	46450809
Drug intolerance	90.47	15.18	193	140791	146856	46398222
Device dislocation	90.36	15.18	202	140782	21600	46523478
Catheter site inflammation	89.85	15.18	43	140941	637	46544441
Mineral supplementation	89.56	15.18	41	140943	546	46544532
Hypersensitivity	89.42	15.18	201	140783	150120	46394958
Intentional product misuse	89.25	15.18	17	140967	47111	46497967
Dyspepsia	88.14	15.18	425	140559	68047	46477031
Product quality issue	87.34	15.18	5	140979	35643	46509435
Deep vein thrombosis	87.00	15.18	68	140916	79705	46465373
Dizziness postural	86.43	15.18	102	140882	6344	46538734
Catheter site related reaction	86.32	15.18	44	140940	752	46544326
Angioedema	84.10	15.18	10	140974	39332	46505746
Hepatic enzyme increased	82.70	15.18	75	140909	81712	46463366
Weight increased	82.70	15.18	809	140175	163664	46381414
Depressed level of consciousness	82.32	15.18	21	140963	47548	46497530
Walking distance test abnormal	81.62	15.18	37	140947	481	46544597
Intentional product use issue	81.03	15.18	29	140955	52751	46492327
Pulmonary veno-occlusive disease	80.28	15.18	44	140940	877	46544201
Sinus congestion	79.01	15.18	142	140842	12967	46532111
Seasonal allergy	78.53	15.18	143	140841	13191	46531887
Abdominal cavity drainage	78.50	15.18	33	140951	353	46544725
Bradycardia	78.19	15.18	52	140932	66246	46478832
Device occlusion	77.94	15.18	93	140891	5852	46539226
Adverse event	77.11	15.18	253	140731	33931	46511147
Myalgia	76.47	15.18	634	140350	122454	46422624
Bone marrow failure	76.43	15.18	3	140981	29666	46515412
Endarterectomy	75.82	15.18	26	140958	149	46544929
Renal disorder	75.65	15.18	214	140770	26472	46518606
Atrial septal defect repair	75.39	15.18	28	140956	209	46544869
Terminal state	75.24	15.18	59	140925	2195	46542883
Pulmonary endarterectomy	73.70	15.18	24	140960	114	46544964
Rhinorrhoea	73.41	15.18	312	140672	47353	46497725
Hepatocellular injury	72.76	15.18	4	140980	29518	46515560
Exercise tolerance decreased	72.55	15.18	79	140905	4498	46540580
Pulmonary pain	71.89	15.18	51	140933	1625	46543453
Lung disorder	71.83	15.18	290	140694	43014	46502064
C-reactive protein increased	71.77	15.18	44	140940	58546	46486532
Liver transplant	71.61	15.18	59	140925	2358	46542720
Catheter site vesicles	70.94	15.18	28	140956	251	46544827
Blood pressure decreased	70.85	15.18	351	140633	56808	46488270
Hallucination	70.85	15.18	31	140953	49920	46495158
Infusion site warmth	70.54	15.18	45	140939	1198	46543880
Paraesthesia	69.85	15.18	157	140827	117280	46427798
Nausea	68.97	15.18	2629	138355	684825	45860253
Injury	67.91	15.18	24	140960	44003	46501075
Injection site pruritus	67.90	15.18	18	140966	39725	46505353
Heart rate increased	67.79	15.18	422	140562	74369	46470709
Stent placement	66.42	15.18	67	140917	3489	46541589
Cognitive disorder	66.34	15.18	15	140969	36868	46508210
Pain in extremity	65.47	15.18	1121	139863	257559	46287519
Neuropathy peripheral	64.91	15.18	109	140875	90784	46454294
Blood creatine phosphokinase increased	64.65	15.18	5	140979	27719	46517359
Transplant	64.59	15.18	34	140950	623	46544455
Right ventricular dilatation	64.41	15.18	38	140946	876	46544202
Haemoglobin decreased	64.16	15.18	633	140351	128316	46416762
Impaired healing	64.01	15.18	16	140968	36727	46508351
Injection site swelling	63.91	15.18	21	140963	40306	46504772
Metabolic acidosis	63.59	15.18	19	140965	38761	46506317
Hypoglycaemia	63.58	15.18	43	140941	54306	46490772
Pulmonary arterial pressure abnormal	62.59	15.18	30	140954	446	46544632
Chemotherapy	62.33	15.18	43	140941	1309	46543769
Blood iron decreased	61.57	15.18	116	140868	10981	46534097
Blood cholesterol increased	61.39	15.18	22	140962	39991	46505087
Cardioversion	61.17	15.18	40	140944	1112	46543966
Cardiac ablation	60.31	15.18	41	140943	1218	46543860
Cholestasis	59.60	15.18	6	140978	26887	46518191
Illness	59.59	15.18	121	140863	12103	46532975
Pulmonary embolism	59.15	15.18	152	140832	108433	46436645
Atrial flutter	58.88	15.18	102	140882	9046	46536032
Left ventricular failure	58.85	15.18	74	140910	4916	46540162
Blood potassium decreased	58.49	15.18	249	140735	37814	46507264
Product supply issue	57.96	15.18	35	140949	843	46544235
Right ventricular dysfunction	57.85	15.18	43	140941	1475	46543603
Chronic obstructive pulmonary disease	57.85	15.18	334	140650	57299	46487779
Infusion site irritation	57.72	15.18	29	140955	480	46544598
Decreased appetite	57.26	15.18	862	140122	192974	46352104
Dysarthria	56.88	15.18	21	140963	37477	46507601
Hypocalcaemia	56.78	15.18	7	140977	26778	46518300
Therapeutic response decreased	56.27	15.18	30	140954	43115	46501963
Emotional distress	56.22	15.18	12	140972	30695	46514383
Pulmonary arterial wedge pressure increased	56.10	15.18	24	140960	269	46544809
Gout	56.06	15.18	113	140871	11243	46533835
Generalised tonic-clonic seizure	55.31	15.18	8	140976	27114	46517964
Toxic epidermal necrolysis	54.96	15.18	3	140981	22275	46522803
Stevens-Johnson syndrome	54.90	15.18	4	140980	23293	46521785
Diagnostic procedure	54.85	15.18	18	140966	88	46544990
Haemoptysis	54.79	15.18	189	140795	26000	46519078
Nasal dryness	54.76	15.18	60	140924	3440	46541638
Oropharyngeal pain	54.33	15.18	397	140587	73771	46471307
Sinus disorder	53.12	15.18	139	140845	16424	46528654
Angioplasty	53.07	15.18	38	140946	1229	46543849
Infusion site induration	53.02	15.18	32	140952	770	46544308
Biopsy	52.56	15.18	25	140959	365	46544713
Arthralgia	52.53	15.18	780	140204	363823	46181255
Catheter site warmth	52.37	15.18	21	140963	197	46544881
Inappropriate schedule of product administration	52.16	15.18	72	140912	64941	46480137
Hepatotoxicity	51.89	15.18	7	140977	25002	46520076
Hyperkalaemia	51.85	15.18	46	140938	50663	46494415
Hyperhidrosis	51.79	15.18	121	140863	89187	46455891
Agranulocytosis	51.74	15.18	4	140980	22181	46522897
Lymphocyte count decreased	51.15	15.18	8	140976	25581	46519497
Swollen tongue	50.39	15.18	13	140971	29219	46515859
Pericardial drainage	50.25	15.18	21	140963	221	46544857
Biopsy lung	49.38	15.18	19	140965	158	46544920
Blood pressure systolic increased	49.25	15.18	13	140971	28774	46516304
Somnolence	48.86	15.18	275	140709	156246	46388832
Hypercalcaemia	48.51	15.18	4	140980	21042	46524036
Bone disorder	48.50	15.18	3	140981	20030	46525048
Delirium	48.38	15.18	26	140958	37202	46507876
Drug dependence	48.12	15.18	3	140981	19898	46525180
Extra dose administered	48.03	15.18	65	140919	4642	46540436
Orthopnoea	47.97	15.18	73	140911	5807	46539271
Catheter site scab	47.88	15.18	19	140965	173	46544905
Psychotic disorder	47.73	15.18	6	140978	22615	46522463
Drug withdrawal syndrome	47.55	15.18	12	140972	27372	46517706
Hepatitis	47.28	15.18	19	140965	32196	46512882
Pulmonary congestion	47.26	15.18	124	140860	14675	46530403
Osteonecrosis	47.25	15.18	10	140974	25734	46519344
Pleural effusion	47.14	15.18	419	140565	82533	46462545
Pruritus	47.12	15.18	486	140498	241866	46303212
Respiration abnormal	47.00	15.18	63	140921	4458	46540620
Asthma	46.94	15.18	132	140852	91410	46453668
Agitation	46.88	15.18	59	140925	55356	46489722
Lactic acidosis	46.59	15.18	22	140962	33887	46511191
Concomitant disease progression	46.48	15.18	44	140940	2118	46542960
Blood glucose increased	46.38	15.18	92	140892	71921	46473157
Hyperglycaemia	46.30	15.18	24	140960	35047	46510031
Epilepsy	46.16	15.18	8	140976	23730	46521348
Mouth ulceration	46.13	15.18	12	140972	26820	46518258
Red blood cell sedimentation rate increased	46.11	15.18	7	140977	22882	46522196
Aggression	45.71	15.18	7	140977	22737	46522341
Medical device change	45.55	15.18	22	140962	333	46544745
Catheterisation cardiac abnormal	43.94	15.18	19	140965	219	46544859
Respiratory tract congestion	43.92	15.18	110	140874	12654	46532424
Fibromyalgia	43.80	15.18	28	140956	36435	46508643
Anaemia	43.53	15.18	1045	139939	254734	46290344
Cytomegalovirus infection	43.09	15.18	3	140981	18141	46526937
Medical procedure	42.78	15.18	18	140966	193	46544885
Medication error	42.55	15.18	20	140964	30891	46514187
Multiple allergies	42.08	15.18	78	140906	7293	46537785
Basal cell carcinoma	41.88	15.18	6	140978	20481	46524597
Blood count abnormal	41.83	15.18	134	140850	17744	46527334
Premature delivery	41.70	15.18	8	140976	22061	46523017
Oxygen saturation abnormal	41.50	15.18	46	140938	2672	46542406
Drug level increased	41.16	15.18	4	140980	18437	46526641
Mobility decreased	41.13	15.18	75	140909	60519	46484559
Wrong dose	41.06	15.18	27	140957	758	46544320
Catheter site discolouration	40.85	15.18	15	140969	108	46544970
Hernia repair	40.62	15.18	31	140953	1107	46543971
Premature baby	40.24	15.18	4	140980	18108	46526970
Dependence on oxygen therapy	39.92	15.18	20	140964	329	46544749
Infusion site pruritus	39.36	15.18	48	140936	3090	46541988
Pancreatitis acute	39.32	15.18	13	140971	24859	46520219
Skin lesion	38.80	15.18	16	140968	26697	46518381
Pericarditis	38.73	15.18	12	140972	23915	46521163
Cardiac output increased	38.65	15.18	15	140969	128	46544950
Head discomfort	38.59	15.18	92	140892	10259	46534819
Metastases to bone	38.46	15.18	4	140980	17472	46527606
Peritonitis	38.11	15.18	8	140976	20706	46524372
Hypokalaemia	38.07	15.18	137	140847	87887	46457191
Liver function test abnormal	37.77	15.18	51	140933	46436	46498642
Drug eruption	37.71	15.18	9	140975	21320	46523758
Choking	37.42	15.18	80	140904	8296	46536782
Encephalopathy	37.41	15.18	28	140956	33561	46511517
Polypectomy	37.33	15.18	23	140961	575	46544503
Cerebral infarction	37.32	15.18	12	140972	23354	46521724
Cardio-respiratory arrest	37.26	15.18	78	140906	59791	46485287
Drug-induced liver injury	37.16	15.18	15	140969	25353	46519725
Device connection issue	37.16	15.18	24	140960	653	46544425
Accidental exposure to product	37.07	15.18	9	140975	21072	46524006
Chronic respiratory failure	36.56	15.18	35	140949	1709	46543369
Dyskinesia	36.43	15.18	21	140963	28904	46516174
Ischaemic stroke	36.36	15.18	4	140980	16718	46528360
Infusion site discolouration	36.28	15.18	22	140962	534	46544544
Eosinophilia	36.24	15.18	7	140977	19210	46525868
Jugular vein distension	36.07	15.18	26	140958	850	46544228
Visual acuity reduced	35.95	15.18	11	140973	22102	46522976
Bronchitis	35.92	15.18	483	140501	105496	46439582
Hypoaesthesia	35.92	15.18	211	140773	118658	46426420
Heart valve replacement	35.72	15.18	21	140963	481	46544597
Diabetic ketoacidosis	35.71	15.18	6	140978	18204	46526874
Tremor	35.62	15.18	204	140780	115435	46429643
Hepatic steatosis	35.57	15.18	14	140970	24028	46521050
Withdrawal syndrome	35.50	15.18	6	140978	18128	46526950
Complication associated with device	35.46	15.18	115	140869	15326	46529752
Erythema	35.40	15.18	269	140715	142551	46402527
Blister	35.22	15.18	50	140934	44581	46500497
Hypoacusis	35.22	15.18	141	140843	20828	46524250
Pregnancy	35.19	15.18	19	140965	27118	46517960
Pyelonephritis	35.17	15.18	3	140981	15354	46529724
Abnormal behaviour	35.10	15.18	10	140974	21048	46524030
Nocturnal dyspnoea	34.91	15.18	27	140957	984	46544094
Pneumocystis jirovecii pneumonia	34.86	15.18	3	140981	15245	46529833
Hallucination, visual	34.80	15.18	6	140978	17867	46527211
Osteopenia	34.59	15.18	5	140979	16956	46528122
Pancreatitis	34.31	15.18	49	140935	43578	46501500
Coronary artery disease	34.05	15.18	31	140953	33721	46511357
No adverse event	33.87	15.18	32	140952	34199	46510879
Acute myocardial infarction	33.80	15.18	28	140956	31896	46513182
Swelling	33.78	15.18	546	140438	123965	46421113
Acute myeloid leukaemia	33.74	15.18	4	140980	15774	46529304
Skin exfoliation	33.53	15.18	30	140954	32908	46512170
Cor pulmonale	33.38	15.18	35	140949	1908	46543170
Metastases to liver	33.21	15.18	9	140975	19576	46525502
Cardiac failure high output	32.79	15.18	16	140968	248	46544830
Mood swings	32.67	15.18	5	140979	16247	46528831
Product prescribing error	32.54	15.18	10	140974	20037	46525041
Hepatic cirrhosis	32.44	15.18	113	140871	15619	46529459
Lymphopenia	32.40	15.18	4	140980	15289	46529789
Myoclonus	32.34	15.18	3	140981	14349	46530729
Altered state of consciousness	32.30	15.18	15	140969	23333	46521745
Oxygen consumption	32.14	15.18	12	140972	91	46544987
Endotracheal intubation	31.95	15.18	36	140948	2129	46542949
Spinal osteoarthritis	31.77	15.18	3	140981	14148	46530930
Osteoporosis	31.55	15.18	46	140938	40562	46504516
Catheter removal	31.37	15.18	17	140967	331	46544747
Paranasal sinus discomfort	30.99	15.18	39	140945	2593	46542485
Ejection fraction decreased	30.87	15.18	8	140976	17929	46527149
Heart and lung transplant	30.86	15.18	12	140972	103	46544975
Biopsy liver	30.78	15.18	18	140966	408	46544670
Sinus bradycardia	30.74	15.18	3	140981	13779	46531299
Foot deformity	30.43	15.18	5	140979	15420	46529658
Tracheostomy	30.43	15.18	20	140964	561	46544517
Cardiac failure acute	30.33	15.18	72	140912	8006	46537072
Biopsy bone marrow	30.31	15.18	16	140968	295	46544783
Hypertensive crisis	30.27	15.18	3	140981	13612	46531466
Device related sepsis	29.97	15.18	43	140941	3244	46541834
Catheter site nodule	29.97	15.18	10	140974	52	46545026
Catheter site dermatitis	29.66	15.18	10	140974	54	46545024
Disturbance in attention	29.50	15.18	31	140953	31529	46513549
Injection site rash	29.31	15.18	6	140978	15807	46529271
Proteinuria	29.23	15.18	7	140977	16546	46528532
Diplopia	29.21	15.18	11	140973	19394	46525684
Dysphagia	29.18	15.18	127	140857	77185	46467893
Cholecystectomy	29.11	15.18	76	140908	8966	46536112
Poisoning	28.84	15.18	4	140980	13990	46531088
Therapeutic response unexpected	28.79	15.18	6	140978	15610	46529468
Tubulointerstitial nephritis	28.72	15.18	5	140979	14783	46530295
Type 2 diabetes mellitus	28.71	15.18	12	140972	19863	46525215
Blood lactate dehydrogenase increased	28.63	15.18	13	140971	20487	46524591
Rash erythematous	28.60	15.18	37	140947	34313	46510765
Platelet transfusion	28.57	15.18	21	140963	708	46544370
Colitis ulcerative	28.51	15.18	9	140975	17723	46527355
Catheter site erosion	28.24	15.18	10	140974	64	46545014
Balance disorder	28.17	15.18	100	140884	64421	46480657
Localised oedema	28.14	15.18	53	140931	5016	46540062
Chest tube insertion	27.94	15.18	9	140975	41	46545037
Cardiac flutter	27.92	15.18	42	140942	3307	46541771
Haematuria	27.89	15.18	24	140960	26834	46518244
Femur fracture	27.68	15.18	43	140941	36954	46508124
Respiratory arrest	27.57	15.18	37	140947	33779	46511299
Carbon dioxide increased	27.38	15.18	25	140959	1149	46543929
Anxiety	27.27	15.18	386	140598	181571	46363507
Upper respiratory tract congestion	27.26	15.18	31	140953	1852	46543226
Acne	27.25	15.18	13	140971	19906	46525172
Biopsy lymph gland	27.18	15.18	8	140976	25	46545053
Dialysis related complication	27.11	15.18	10	140974	73	46545005
Hyperlipidaemia	27.09	15.18	11	140973	18528	46526550
Myelodysplastic syndrome	27.06	15.18	7	140977	15704	46529374
Disseminated intravascular coagulation	26.62	15.18	12	140972	18993	46526085
Systemic lupus erythematosus	26.52	15.18	104	140880	65076	46480002
Device physical property issue	26.51	15.18	27	140957	1422	46543656
Wound	26.43	15.18	56	140928	42746	46502332
Diet noncompliance	26.38	15.18	14	140970	261	46544817
Lower respiratory tract infection	26.38	15.18	82	140902	55007	46490071
Urinary retention	26.21	15.18	24	140960	26037	46519041
Dizziness exertional	26.17	15.18	15	140969	327	46544751
Cardiomyopathy	26.12	15.18	8	140976	16065	46529013
Ventilation perfusion mismatch	26.10	15.18	13	140971	211	46544867
Abdominal pain upper	26.00	15.18	598	140386	144707	46400371
Oral herpes	26.00	15.18	13	140971	19377	46525701
Myocardial infarction	25.94	15.18	180	140804	97348	46447730
Muscular weakness	25.68	15.18	167	140817	91677	46453401
Unevaluable investigation	25.67	15.18	8	140976	32	46545046
Joint range of motion decreased	25.55	15.18	7	140977	15117	46529961
Thrombectomy	25.49	15.18	12	140972	171	46544907
Medical device implantation	25.41	15.18	18	140966	572	46544506
Systemic scleroderma	25.36	15.18	21	140963	845	46544233
Palliative care	25.32	15.18	14	140970	284	46544794
Echocardiogram abnormal	25.23	15.18	22	140962	951	46544127
Drug ineffective for unapproved indication	25.22	15.18	9	140975	16404	46528674
Hip surgery	25.15	15.18	34	140950	2426	46542652
Infusion site vesicles	24.93	15.18	15	140969	359	46544719
Lip swelling	24.82	15.18	24	140960	25371	46519707
Critical illness	24.75	15.18	11	140973	136	46544942
Pulmonary vascular resistance abnormality	24.74	15.18	8	140976	37	46545041
Pulmonary artery aneurysm	24.74	15.18	8	140976	37	46545041
Cancer surgery	24.65	15.18	16	140968	439	46544639
Pericardial excision	24.51	15.18	7	140977	19	46545059
Iron deficiency anaemia	24.47	15.18	110	140874	17096	46527982
Infusion site abscess	24.42	15.18	12	140972	189	46544889
Sinus tachycardia	24.17	15.18	18	140966	21631	46523447
Right ventricular systolic pressure increased	24.09	15.18	17	140967	537	46544541
Heart valve operation	23.99	15.18	11	140973	147	46544931
Metastases to central nervous system	23.62	15.18	3	140981	11218	46533860
Aphasia	23.55	15.18	31	140953	28536	46516542
Treatment noncompliance	23.41	15.18	162	140822	29569	46515509
Discomfort	23.40	15.18	68	140916	46602	46498476
Secretion discharge	23.32	15.18	71	140913	9148	46535930
Cerebrovascular accident	23.31	15.18	194	140790	100845	46444233
Platelet count increased	23.12	15.18	8	140976	14866	46530212
Tenderness	23.12	15.18	11	140973	16870	46528208
Body temperature decreased	23.04	15.18	6	140978	13403	46531675
Transaminases increased	23.02	15.18	30	140954	27731	46517347
Haematoma	22.95	15.18	38	140946	31834	46513244
Dry eye	22.92	15.18	35	140949	30287	46514791
Right-to-left cardiac shunt	22.86	15.18	11	140973	165	46544913
Blood triglycerides increased	22.84	15.18	4	140980	11779	46533299
Bursitis	22.80	15.18	16	140968	19826	46525252
Joint stiffness	22.78	15.18	29	140955	27079	46517999
Pulmonary arterial pressure decreased	22.77	15.18	9	140975	81	46544997
Hypervolaemia	22.68	15.18	27	140957	1695	46543383
Catheter site extravasation	22.65	15.18	12	140972	223	46544855
Colonoscopy	22.64	15.18	23	140961	1208	46543870
Heart transplant	22.63	15.18	15	140969	427	46544651
Speech disorder	22.60	15.18	47	140937	36120	46508958
Brain natriuretic peptide abnormal	22.58	15.18	14	140970	354	46544724
Gastrointestinal tube insertion	22.53	15.18	22	140962	1101	46543977
Respiratory depression	22.35	15.18	4	140980	11596	46533482
Catheter site induration	22.35	15.18	8	140976	53	46545025
Hallucination, auditory	22.34	15.18	3	140981	10753	46534325
Application site pruritus	22.33	15.18	42	140942	3971	46541107
Arteriovenous malformation	22.29	15.18	23	140961	1230	46543848
Hypercholesterolaemia	22.17	15.18	4	140980	11526	46533552
Paranasal sinus hypersecretion	22.14	15.18	37	140947	3187	46541891
Jaundice	22.09	15.18	33	140951	28812	46516266
Paranoia	21.90	15.18	3	140981	10594	46534484
Breast cancer metastatic	21.88	15.18	7	140977	13671	46531407
CREST syndrome	21.87	15.18	14	140970	375	46544703
Cardiovascular disorder	21.83	15.18	5	140979	12182	46532896
Dysgeusia	21.79	15.18	57	140927	40434	46504644
Mydriasis	21.78	15.18	3	140981	10550	46534528
Catheter culture positive	21.72	15.18	10	140974	135	46544943
Tendonitis	21.64	15.18	8	140976	14269	46530809
Neutrophil count increased	21.58	15.18	8	140976	14245	46530833
Cor pulmonale chronic	21.53	15.18	11	140973	189	46544889
Spinal operation	21.48	15.18	50	140934	5490	46539588
Fear	21.45	15.18	11	140973	16161	46528917
Lymphadenopathy	21.37	15.18	43	140941	33445	46511633
Infusion site discomfort	21.32	15.18	17	140967	648	46544430
Atrial fibrillation	21.30	15.18	435	140549	103155	46441923
Delusion	21.25	15.18	4	140980	11184	46533894
Anhedonia	21.19	15.18	3	140981	10332	46534746
Ear congestion	21.13	15.18	26	140958	1689	46543389
Vitamin D deficiency	21.11	15.18	4	140980	11130	46533948
Drug therapy	21.09	15.18	6	140978	16	46545062
Cardiac monitoring	21.09	15.18	6	140978	16	46545062
Exostosis	20.99	15.18	3	140981	10260	46534818
Muscle twitching	20.97	15.18	9	140975	14663	46530415
Injection site haemorrhage	20.91	15.18	19	140965	20690	46524388
Sickle cell anaemia	20.86	15.18	16	140968	576	46544502
Gastrointestinal surgery	20.73	15.18	11	140973	205	46544873
Carpal tunnel syndrome	20.72	15.18	11	140973	15848	46529230
Pulmonary artery dilatation	20.63	15.18	11	140973	207	46544871
Pharyngeal oedema	20.48	15.18	9	140975	14462	46530616
Head injury	20.45	15.18	136	140848	24500	46520578
Injection site warmth	20.41	15.18	8	140976	13764	46531314
Irritability	20.39	15.18	35	140949	28911	46516167
Mania	20.35	15.18	4	140980	10842	46534236
Device breakage	20.31	15.18	70	140914	9622	46535456
Diabetes mellitus	20.29	15.18	80	140904	49985	46495093
Vasculitis	20.26	15.18	8	140976	13703	46531375
Thrombosis in device	20.20	15.18	34	140950	2945	46542133
Sensory disturbance	20.13	15.18	6	140978	12261	46532817
Renal tubular necrosis	20.12	15.18	4	140980	10755	46534323
Portopulmonary hypertension	20.06	15.18	9	140975	114	46544964
Abdominal pain	20.03	15.18	535	140449	229496	46315582
Injection site discharge	19.83	15.18	13	140971	363	46544715
Cardiac septal defect	19.80	15.18	12	140972	291	46544787
Blood pressure abnormal	19.60	15.18	81	140903	12136	46532942
Acute right ventricular failure	19.46	15.18	10	140974	174	46544904
Dialysis device insertion	19.45	15.18	6	140978	23	46545055
Living in residential institution	19.43	15.18	13	140971	376	46544702
Gastrointestinal haemorrhage	19.39	15.18	335	140649	77038	46468040
Infusion site rash	19.37	15.18	19	140965	956	46544122
Catheter site bruise	19.37	15.18	12	140972	303	46544775
Oral pain	19.35	15.18	28	140956	24769	46520309
Body height decreased	19.33	15.18	3	140981	9649	46535429
Congestive hepatopathy	19.32	15.18	30	140954	2428	46542650
Hypophagia	19.24	15.18	37	140947	29269	46515809
Joint dislocation	19.23	15.18	5	140979	11181	46533897
Liver ablation	19.22	15.18	4	140980	0	46545078
Immune tolerance induction	19.22	15.18	4	140980	0	46545078
Intervertebral disc degeneration	19.14	15.18	8	140976	13244	46531834
Live birth	18.98	15.18	4	140980	10326	46534752
Bronchospasm	18.94	15.18	12	140972	15695	46529383
Drug titration	18.91	15.18	5	140979	9	46545069
Gastroenteritis viral	18.82	15.18	106	140878	18013	46527065
Clostridium difficile infection	18.73	15.18	135	140849	24968	46520110
Medical device site haemorrhage	18.69	15.18	6	140978	27	46545051
Coordination abnormal	18.62	15.18	5	140979	10944	46534134
Laboratory test abnormal	18.62	15.18	25	140959	22822	46522256
Nervous system disorder	18.54	15.18	13	140971	16116	46528962
Drug titration error	18.47	15.18	15	140969	587	46544491
Mechanical ventilation	18.44	15.18	21	140963	1257	46543821
Hypothermia	18.18	15.18	7	140977	12176	46532902
Obstructive airways disorder	17.97	15.18	9	140975	13403	46531675
Right ventricular enlargement	17.75	15.18	11	140973	278	46544800
Labelled drug-drug interaction medication error	17.73	15.18	3	140981	9058	46536020
Drain placement	17.71	15.18	7	140977	63	46545015
Ecchymosis	17.67	15.18	5	140979	10571	46534507
Breast cancer	17.65	15.18	74	140910	45444	46499634
Oesophageal motility disorder	17.51	15.18	11	140973	285	46544793
Diabetes mellitus inadequate control	17.50	15.18	9	140975	13205	46531873
Retching	17.48	15.18	82	140902	12975	46532103
Viral infection	17.30	15.18	153	140831	30082	46514996
Brain oedema	17.29	15.18	8	140976	12470	46532608
Circulatory collapse	17.28	15.18	24	140960	21600	46523478
Catheter site dryness	17.27	15.18	6	140978	36	46545042
Myopathy	17.25	15.18	3	140981	8878	46536200
General physical health deterioration	17.18	15.18	246	140738	115523	46429555
Walking disability	17.16	15.18	21	140963	1357	46543721
Arthritis	17.14	15.18	150	140834	77166	46467912
Nightmare	17.03	15.18	15	140969	16583	46528495
Conjunctivitis	16.99	15.18	13	140971	15411	46529667
Respiratory syncytial virus infection	16.98	15.18	42	140942	4793	46540285
Cataract operation	16.98	15.18	38	140946	4065	46541013
Biopsy kidney	16.87	15.18	8	140976	116	46544962
Oxygen saturation increased	16.81	15.18	8	140976	117	46544961
Cardiac pacemaker replacement	16.78	15.18	11	140973	307	46544771
Sluggishness	16.74	15.18	41	140943	4650	46540428
Upper-airway cough syndrome	16.73	15.18	57	140927	7790	46537288
Adverse drug reaction	16.66	15.18	73	140911	44289	46500789
Blood bilirubin increased	16.58	15.18	167	140817	34017	46511061
Tooth disorder	16.57	15.18	28	140956	23275	46521803
Skin necrosis	16.51	15.18	3	140981	8601	46536477
Cardiac septal defect repair	16.46	15.18	4	140980	4	46545074
Full blood count decreased	16.44	15.18	26	140958	22185	46522893
Hypomagnesaemia	16.44	15.18	26	140958	22184	46522894
Throat irritation	16.41	15.18	146	140838	28755	46516323
Rales	16.36	15.18	65	140919	9566	46535512
Suture related complication	16.35	15.18	9	140975	181	46544897
Hemiparesis	16.32	15.18	22	140962	20047	46525031
Acute left ventricular failure	16.28	15.18	16	140968	807	46544271
Disorientation	16.26	15.18	57	140927	36861	46508217
Fluid intake restriction	16.24	15.18	5	140979	19	46545059
Petechiae	16.24	15.18	9	140975	12661	46532417
Metastases to lung	16.20	15.18	6	140978	10690	46534388
Life support	16.20	15.18	10	140974	251	46544827
Inflammation	16.14	15.18	84	140900	48697	46496381
Ear discomfort	16.11	15.18	51	140933	6710	46538368
Transient ischaemic attack	15.97	15.18	53	140931	34850	46510228
Fatigue	15.97	15.18	2084	138900	606613	45938465
Eczema	15.95	15.18	23	140961	20377	46524701
Spinal stenosis	15.95	15.18	9	140975	12534	46532544
Right atrial enlargement	15.94	15.18	7	140977	84	46544994
Acute respiratory distress syndrome	15.91	15.18	26	140958	21896	46523182
Leukocytosis	15.84	15.18	29	140955	23369	46521709
Haemolytic anaemia	15.81	15.18	5	140979	9837	46535241
Large intestinal polypectomy	15.79	15.18	9	140975	194	46544884
Oesophagogastroduodenoscopy	15.69	15.18	6	140978	49	46545029
Product storage error	15.67	15.18	8	140976	11784	46533294
Gastrointestinal endoscopic therapy	15.66	15.18	5	140979	22	46545056
Bronchial artery embolisation	15.58	15.18	4	140980	6	46545072
Infusion site inflammation	15.55	15.18	9	140975	200	46544878
Immune thrombocytopenia	15.54	15.18	3	140981	8238	46536840
Arteriosclerosis	15.54	15.18	5	140979	9728	46535350
Feeding tube user	15.48	15.18	5	140979	23	46545055
Bronchoscopy	15.48	15.18	6	140978	51	46545027
Mixed connective tissue disease	15.46	15.18	11	140973	352	46544726
Endoscopy	15.39	15.18	10	140974	275	46544803
Dysentery	15.37	15.18	15	140969	750	46544328
Arteriosclerosis coronary artery	15.32	15.18	3	140981	8153	46536925
Infusion site dryness	15.20	15.18	4	140980	7	46545071

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
Pulmonary arterial hypertension	1466.39	20.31	532	40733	8769	29902444
Fluid retention	1150.10	20.31	599	40666	24399	29886814
Dyspnoea	1012.85	20.31	1707	39558	331588	29579625
Hospitalisation	863.37	20.31	612	40653	43707	29867506
Death	809.27	20.31	1613	39652	355670	29555543
Pulmonary hypertension	592.23	20.31	353	40912	18683	29892530
Right ventricular failure	578.81	20.31	262	41003	7774	29903439
Pain in jaw	506.56	20.31	273	40992	11883	29899330
Dyspnoea exertional	431.55	20.31	371	40894	35059	29876154
Transfusion	431.32	20.31	209	41056	7252	29903961
Headache	370.01	20.31	790	40475	181516	29729697
Oxygen saturation decreased	325.48	20.31	348	40917	43092	29868121
Nasal congestion	318.99	20.31	238	41027	18328	29892885
Fluid overload	295.54	20.31	230	41035	18862	29892351
Oedema	295.23	20.31	329	40936	42664	29868549
Drug ineffective	247.55	20.31	81	41184	340306	29570907
Peripheral swelling	245.45	20.31	358	40907	60716	29850497
Drug interaction	232.66	20.31	10	41255	199558	29711655
Lung transplant	230.36	20.31	90	41175	1826	29909387
Toxicity to various agents	216.56	20.31	6	41259	177177	29734036
Condition aggravated	204.20	20.31	529	40736	137337	29773876
Oxygen consumption increased	203.90	20.31	74	41191	1214	29909999
Catheter management	201.09	20.31	67	41198	840	29910373
Oedema peripheral	165.79	20.31	415	40850	105417	29805796
Neutropenia	162.22	20.31	3	41262	128537	29782676
Catheterisation cardiac	158.21	20.31	72	41193	2159	29909054
Product dose omission issue	157.00	20.31	372	40893	91259	29819954
Catheter site erythema	143.23	20.31	56	41209	1138	29910075
Therapy non-responder	141.09	20.31	188	41077	29265	29881948
Flushing	133.29	20.31	183	41082	29309	29881904
Concomitant disease aggravated	126.15	20.31	82	41183	5047	29906166
Transplant evaluation	120.96	20.31	40	41225	489	29910724
Dialysis	119.39	20.31	108	41157	10888	29900325
Infusion site pain	117.29	20.31	62	41203	2588	29908625
Unevaluable event	115.63	20.31	178	41087	31607	29879606
Catheter site pain	110.42	20.31	45	41220	1023	29910190
Off label use	104.36	20.31	114	41151	249176	29662037
Weight increased	100.05	20.31	277	40988	74636	29836577
Hypoxia	98.32	20.31	209	41056	47645	29863568
Acute kidney injury	97.19	20.31	142	41123	273700	29637513
Thrombocytopenia	96.81	20.31	34	41231	137010	29774203
Catheter site pruritus	93.76	20.31	29	41236	281	29910932
Pulmonary arterial pressure increased	92.32	20.31	40	41225	1064	29910149
Pain in extremity	89.61	20.31	344	40921	109877	29801336
Drug abuse	89.59	20.31	6	41259	82066	29829147
Cough	89.28	20.31	376	40889	125266	29785947
Oxygen therapy	87.41	20.31	34	41231	681	29910532
Swelling	85.60	20.31	167	41098	35808	29875405
Malaise	85.32	20.31	454	40811	166508	29744705
Therapy change	85.25	20.31	50	41215	2559	29908654
Brain natriuretic peptide increased	83.60	20.31	58	41207	3977	29907236
Catheter site rash	82.91	20.31	24	41241	181	29911032
Pneumonia	79.80	20.31	755	40510	333551	29577662
Catheter site discharge	77.26	20.31	29	41236	525	29910688
Overdose	74.85	20.31	13	41252	84324	29826889
Pulmonary oedema	73.51	20.31	177	41088	43798	29867415
Dizziness	71.43	20.31	486	40779	194423	29716790
Aspiration pleural cavity	69.69	20.31	30	41235	785	29910428
Abdominal distension	68.02	20.31	176	41089	45533	29865680
Pancytopenia	67.48	20.31	17	41248	85035	29826178
Catheter site irritation	67.20	20.31	18	41247	98	29911115
Catheter placement	66.34	20.31	28	41237	697	29910516
Liver transplant	64.53	20.31	43	41222	2759	29908454
Productive cough	62.85	20.31	132	41133	29821	29881392
Leukopenia	61.59	20.31	4	41261	56155	29855058
Hypotension	58.05	20.31	473	40792	200092	29711121
Product use in unapproved indication	57.93	20.31	15	41250	73678	29837535
Disease complication	57.73	20.31	39	41226	2560	29908653
Paracentesis	56.42	20.31	21	41244	371	29910842
Syncope	56.31	20.31	249	41016	84654	29826559
Diarrhoea	56.17	20.31	704	40561	333399	29577814
Adverse event	55.88	20.31	86	41179	15255	29895958
Endarterectomy	53.08	20.31	16	41249	141	29911072
Rash	53.08	20.31	116	41149	191773	29719440
Cardiac pacemaker insertion	51.36	20.31	36	41229	2509	29908704
Packed red blood cell transfusion	51.24	20.31	30	41235	1530	29909683
Hyperkalaemia	50.82	20.31	14	41251	65996	29845217
Confusional state	50.61	20.31	67	41198	134767	29776446
Disease progression	50.52	20.31	231	41034	79643	29831570
Abdominal discomfort	50.50	20.31	165	41100	48626	29862587
Plasma cell myeloma	50.23	20.31	7	41258	53455	29857758
Drug hypersensitivity	50.07	20.31	16	41249	68503	29842710
Device dislocation	49.92	20.31	47	41218	4984	29906229
Vascular device infection	49.65	20.31	31	41234	1778	29909435
Cardiac operation	48.96	20.31	35	41230	2517	29908696
Nasopharyngitis	47.18	20.31	183	41082	58666	29852547
Hospice care	46.89	20.31	43	41222	4409	29906804
Sinus congestion	46.63	20.31	44	41221	4678	29906535
Pulmonary veno-occlusive disease	46.61	20.31	19	41246	432	29910781
Chronic obstructive pulmonary disease	45.96	20.31	154	41111	45972	29865241
Emergency care	45.76	20.31	15	41250	178	29911035
Lung operation	45.32	20.31	12	41253	62	29911151
Catheter site haemorrhage	44.48	20.31	31	41234	2141	29909072
Infusion site infection	44.15	20.31	17	41248	331	29910882
Acute respiratory failure	43.12	20.31	104	41161	25746	29885467
Chest pain	42.79	20.31	293	40972	117334	29793879
Cardiac failure	42.59	20.31	227	41038	83191	29828022
Cardiac ablation	41.61	20.31	19	41246	574	29910639
Walking distance test abnormal	41.40	20.31	13	41252	133	29911080
Cardiac disorder	41.36	20.31	135	41130	39758	29871455
Acute myocardial infarction	41.17	20.31	11	41254	52928	29858285
Seizure	41.11	20.31	45	41220	98430	29812783
Hallucination	40.48	20.31	9	41256	49050	29862163
Feeling abnormal	40.32	20.31	170	41095	56586	29854627
Pulmonary endarterectomy	40.31	20.31	11	41254	65	29911148
Hypertension	39.97	20.31	66	41199	121288	29789925
Infusion site erythema	39.70	20.31	26	41239	1620	29909593
Neuropathy peripheral	39.61	20.31	24	41241	70451	29840762
Deep vein thrombosis	39.38	20.31	17	41248	60484	29850729
Intentional product use issue	38.78	20.31	3	41262	36437	29874776
Device leakage	37.59	20.31	35	41230	3659	29907554
Atrial septal defect repair	37.00	20.31	11	41254	92	29911121
Abdominal cavity drainage	36.80	20.31	15	41250	341	29910872
Blood iron decreased	36.78	20.31	36	41229	4004	29907209
Psoriasis	36.72	20.31	7	41258	42499	29868714
Exercise tolerance decreased	36.65	20.31	35	41230	3777	29907436
White blood cell count decreased	36.56	20.31	37	41228	83910	29827303
Epistaxis	35.56	20.31	156	41109	52825	29858388
Cardiac failure congestive	35.41	20.31	218	41047	84189	29827024
Metabolic acidosis	34.96	20.31	5	41260	37456	29873757
Ascites	34.96	20.31	119	41146	35802	29875411
Stomatitis	34.74	20.31	5	41260	37274	29873939
Bradycardia	34.53	20.31	24	41241	65502	29845711
Dizziness exertional	34.48	20.31	11	41254	119	29911094
Internal haemorrhage	34.06	20.31	36	41229	4386	29906827
Device alarm issue	33.85	20.31	18	41247	760	29910453
Respiratory failure	33.84	20.31	246	41019	100396	29810817
Palpitations	33.36	20.31	112	41153	33461	29877752
Myocardial infarction	33.02	20.31	78	41187	125547	29785666
Stent placement	32.91	20.31	36	41229	4560	29906653
Delirium	32.44	20.31	8	41257	40623	29870590
Catheter site infection	32.23	20.31	27	41238	2454	29908759
Rehabilitation therapy	32.16	20.31	16	41249	587	29910626
Aggression	32.05	20.31	6	41259	36901	29874312
Wrong technique in product usage process	31.96	20.31	3	41262	31152	29880061
Rhinorrhoea	30.94	20.31	80	41185	20674	29890539
Terminal state	30.75	20.31	31	41234	3573	29907640
Coronary artery disease	30.74	20.31	15	41250	49697	29861516
Hernia repair	30.50	20.31	19	41246	1085	29910128
Device infusion issue	30.44	20.31	15	41250	539	29910674
Suture insertion	30.43	20.31	8	41257	40	29911173
Pyrexia	30.28	20.31	260	41005	294229	29616984
Hyperglycaemia	29.98	20.31	6	41259	35194	29876019
Heart rate increased	29.88	20.31	119	41146	38602	29872611
Hyperhidrosis	29.86	20.31	29	41236	67061	29844152
Rheumatoid arthritis	29.42	20.31	10	41255	41187	29870026
Platelet count decreased	29.42	20.31	64	41201	106065	29805148
Intentional product misuse	29.34	20.31	6	41259	34661	29876552
Biopsy liver	28.68	20.31	10	41255	145	29911068
Haemoptysis	28.54	20.31	101	41164	30977	29880236
Complication associated with device	28.11	20.31	37	41228	5683	29905530
Catheter site warmth	27.89	20.31	7	41258	28	29911185
Blood pressure increased	27.72	20.31	35	41230	71893	29839320
Catheter site swelling	27.66	20.31	11	41254	234	29910979
Dizziness postural	27.53	20.31	36	41229	5494	29905719
Infusion site haemorrhage	26.75	20.31	13	41252	453	29910760
Hypoglycaemia	26.43	20.31	19	41246	50962	29860251
Catheter removal	25.81	20.31	10	41255	198	29911015
Oxygen saturation abnormal	25.56	20.31	17	41248	1087	29910126
Lung disorder	25.32	20.31	98	41167	31371	29879842
Abnormal behaviour	24.92	20.31	3	41262	25620	29885593
Influenza	24.85	20.31	122	41143	43276	29867937
Device related infection	24.76	20.31	65	41200	16950	29894263
Hyponatraemia	24.57	20.31	34	41231	67168	29844045
Therapeutic product effect incomplete	24.53	20.31	8	41257	33826	29877387
Cardiac index increased	24.11	20.31	6	41259	23	29911190
Cholestasis	24.07	20.31	3	41262	24947	29886266
Gout	24.03	20.31	65	41200	17250	29893963
Suicidal ideation	23.73	20.31	10	41255	36104	29875109
Right ventricular dysfunction	23.70	20.31	15	41250	881	29910332
Diuretic therapy	23.53	20.31	6	41259	26	29911187
Agitation	23.34	20.31	24	41241	54049	29857164
Myalgia	23.28	20.31	183	41082	76484	29834729
Dyspepsia	23.22	20.31	93	41172	30236	29880977
Scleroderma	22.74	20.31	17	41248	1310	29909903
Urticaria	22.72	20.31	25	41240	54581	29856632
N-terminal prohormone brain natriuretic peptide increased	22.52	20.31	17	41248	1329	29909884
Chemotherapy	22.11	20.31	12	41253	528	29910685
Presyncope	22.01	20.31	60	41205	15996	29895217
Heart and lung transplant	22.00	20.31	7	41258	75	29911138
Cardioversion	21.67	20.31	14	41251	852	29910361
Depressed level of consciousness	21.49	20.31	13	41252	38209	29873004
Cerebral infarction	21.43	20.31	5	41260	26368	29884845
Spontaneous intrahepatic portosystemic venous shunt	21.03	20.31	5	41260	15	29911198
Heart valve operation	20.99	20.31	6	41259	43	29911170
Pneumonitis	20.79	20.31	6	41259	27448	29883765

Pharmacologic Action:

Source	Code	Description
ATC	C02KX04	CARDIOVASCULAR SYSTEM ANTIHYPERTENSIVES OTHER ANTIHYPERTENSIVES Antihypertensives for pulmonary arterial hypertension
FDA MoA	N0000175364	Endothelin Receptor Antagonists
FDA EPC	N0000175581	Endothelin Receptor Antagonist
MeSH PA	D065130	Endothelin A Receptor Antagonists
MeSH PA	D065131	Endothelin B Receptor Antagonists
MeSH PA	D065128	Endothelin Receptor Antagonists
CHEBI has role	CHEBI:35674	antihypertensive
CHEBI has role	CHEBI:51451	era
CHEBI has role	CHEBI:71031	orphan drugs

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Pulmonary arterial hypertension	indication	11399002
Pregnancy, function	contraindication	289908002

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	5.83	acidic
pKa2	10.58	acidic
pKa3	2.37	Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Endothelin-1 receptor	GPCR	P25101	EDNRA_HUMAN	ANTAGONIST	IC50	9.30		SCIENTIFIC LITERATURE	SCIENTIFIC LITERATURE
Endothelin B receptor	GPCR	P24530	EDNRB_HUMAN	ANTAGONIST	IC50	6.41		SCIENTIFIC LITERATURE	SCIENTIFIC LITERATURE

External reference:

ID	Source
D10135	KEGG_DRUG
4032833	VANDF
C2606557	UMLSCUI
CHEBI:76607	CHEBI
CHEMBL2103873	ChEMBL_ID
16004692	PUBCHEM_CID
DB08932	DRUGBANK_ID
C533860	MESH_SUPPLEMENTAL_RECORD_UI
7352	IUPHAR_LIGAND_ID
9018	INN_ID
Z9K9Y9WMVL	UNII
1442132	RXNORM
206622	MMSL
29714	MMSL
d08126	MMSL
015242	NDDF
710283008	SNOMEDCT_US
715555005	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
OPSUMIT	HUMAN PRESCRIPTION DRUG LABEL	1	66215-501	TABLET, FILM COATED	10 mg	ORAL	NDA	32 sections