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

Stem definition	Drug id	CAS RN
beta-adrenoreceptor antagonists	4061	26839-75-8

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: timolol timolol maleate (-)-Timolol (S)-Timolol arutimol L-Timolol timolol maleate salt	A beta-adrenergic antagonist that is similar in action to PROPRANOLOL; the levo-isomer is more active. Timolol has been proposed as an anti-hypertensive, anti-arrhythmic, anti-angina, and anti-glaucoma agent. It is also used in the treatment of MIGRAINE DISORDERS and tremor. Molecular weight: 316.42 Formula: C13H24N4O3S CLOGP: 1.53 LIPINSKI: 0 HAC: 7 HDO: 2 TPSA: 79.74 ALOGS: -3.07 ROTB: 7 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

timolol
timolol maleate
(-)-Timolol
(S)-Timolol
arutimol
L-Timolol
timolol maleate salt

A beta-adrenergic antagonist that is similar in action to PROPRANOLOL; the levo-isomer is more active. Timolol has been proposed as an anti-hypertensive, anti-arrhythmic, anti-angina, and anti-glaucoma agent. It is also used in the treatment of MIGRAINE DISORDERS and tremor.

Molecular weight: 316.42
Formula: C13H24N4O3S
CLOGP: 1.53
LIPINSKI: 0
HAC: 7
HDO: 2
TPSA: 79.74
ALOGS: -3.07
ROTB: 7

Status: OFP

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

Drug dosage:

Dose	Unit	Route
20	mg	O
20	mg	P

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	1	Benet LZ, Broccatelli F, Oprea TI
S (Water solubility)	2.74 mg/mL	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	15 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	3.16 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability)	61 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution)	1.50 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	8.50 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.90 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	2.20 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
Aug. 17, 1978	FDA	ATON
March 25, 2020	PMDA	Senju Pharmaceutical Co., 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
Treatment failure	975.36	12.52	588	21958	92499	46571017
Intraocular pressure increased	647.82	12.52	199	22347	5758	46657758
Eye irritation	626.01	12.52	252	22294	16362	46647154
Glaucoma	529.91	12.52	221	22325	15700	46647816
Ocular hyperaemia	434.67	12.52	205	22341	19505	46644011
Eye pain	375.29	12.52	208	22338	27732	46635784
Eye pruritus	220.71	12.52	110	22436	11788	46651728
Vision blurred	173.63	12.52	203	22343	79505	46584011
Colitis microscopic	156.21	12.52	72	22474	6484	46657032
Visual acuity reduced	152.79	12.52	108	22438	22005	46641511
Foreign body sensation in eyes	127.80	12.52	44	22502	1832	46661684
Lacrimation increased	117.82	12.52	81	22465	15780	46647736
Product container issue	114.08	12.52	40	22506	1759	46661757
Choroidal effusion	104.40	12.52	27	22519	407	46663109
Hypersensitivity	98.12	12.52	221	22325	150100	46513416
Bradycardia	91.52	12.52	135	22411	66163	46597353
Iridocyclitis	88.07	12.52	34	22512	1966	46661550
Visual impairment	88.05	12.52	133	22413	66556	46596960
Cataract	87.87	12.52	109	22437	45306	46618210
Product delivery mechanism issue	87.66	12.52	22	22524	292	46663224
Eye discharge	86.77	12.52	44	22502	4884	46658632
Product quality issue	81.22	12.52	93	22453	35555	46627961
Total lung capacity increased	80.46	12.52	25	22521	749	46662767
Corneal disorder	78.74	12.52	30	22516	1673	46661843
Conjunctival hyperaemia	77.68	12.52	31	22515	1958	46661558
Skin reaction	76.83	12.52	54	22492	10892	46652624
Diverticulitis	76.63	12.52	87	22459	32952	46630564
Eye inflammation	69.97	12.52	35	22511	3774	46659742
Thyroid disorder	69.85	12.52	53	22493	12023	46651493
Corneal oedema	65.49	12.52	26	22520	1620	46661896
Choroidal detachment	62.03	12.52	15	22531	169	46663347
Eye swelling	60.88	12.52	61	22485	20042	46643474
Hypotony of eye	59.96	12.52	14	22532	134	46663382
Iris adhesions	58.06	12.52	16	22530	311	46663205
Completed suicide	55.09	12.52	4	22542	145916	46517600
Eyelid margin crusting	54.33	12.52	18	22528	665	46662851
Frustration tolerance decreased	54.20	12.52	33	22513	5224	46658292
Corneal opacity	53.59	12.52	18	22528	694	46662822
Ocular discomfort	53.15	12.52	27	22519	3008	46660508
Punctate keratitis	52.44	12.52	17	22529	586	46662930
Product packaging quantity issue	48.78	12.52	19	22527	1125	46662391
Intraocular pressure test abnormal	48.26	12.52	12	22534	153	46663363
Eye disorder	47.64	12.52	51	22495	18090	46645426
Cystoid macular oedema	46.64	12.52	20	22526	1516	46662000
Dry eye	46.58	12.52	65	22481	30257	46633259
Angle closure glaucoma	46.33	12.52	22	22524	2117	46661399
Corneal deposits	45.11	12.52	12	22534	203	46663313
Abnormal sensation in eye	41.33	12.52	19	22527	1699	46661817
Respiration abnormal	40.60	12.52	26	22520	4495	46659021
Forced expiratory volume decreased	40.11	12.52	27	22519	5077	46658439
Blindness	39.22	12.52	45	22501	17224	46646292
Eyelid irritation	38.41	12.52	12	22534	366	46663150
Conjunctivitis allergic	37.88	12.52	14	22532	717	46662799
Trabeculectomy	37.55	12.52	7	22539	18	46663498
Pulmonary thrombosis	37.41	12.52	30	22516	7372	46656144
Liquid product physical issue	36.74	12.52	13	22533	587	46662929
Ulcerative keratitis	36.12	12.52	19	22527	2274	46661242
Peak expiratory flow rate decreased	36.02	12.52	13	22533	622	46662894
Intraocular pressure decreased	35.89	12.52	9	22537	119	46663397
Lung diffusion test decreased	35.76	12.52	13	22533	635	46662881
Macular oedema	35.39	12.52	23	22523	4078	46659438
Uveitis	35.36	12.52	31	22515	8610	46654906
Sciatica	34.14	12.52	44	22502	18976	46644540
Erythema of eyelid	33.88	12.52	17	22529	1844	46661672
Open angle glaucoma	32.93	12.52	10	22536	277	46663239
Growth of eyelashes	32.85	12.52	9	22537	171	46663345
Keratopathy	32.30	12.52	10	22536	296	46663220
Swelling of eyelid	31.27	12.52	14	22532	1177	46662339
Normal tension glaucoma	30.07	12.52	7	22539	66	46663450
Serum procollagen type I N-terminal propeptide increased	29.98	12.52	6	22540	25	46663491
Procollagen type I C-terminal propeptide increased	29.98	12.52	6	22540	25	46663491
Febrile neutropenia	29.67	12.52	5	22541	94622	46568894
Vitreous opacities	29.54	12.52	9	22537	252	46663264
Hypopyon	29.46	12.52	12	22534	799	46662717
Exposure during pregnancy	29.29	12.52	8	22538	108204	46555312
Corneal degeneration	29.10	12.52	7	22539	77	46663439
Toxic anterior segment syndrome	28.89	12.52	16	22530	2121	46661395
Obstructive airways disorder	28.87	12.52	34	22512	13378	46650138
Vitreous floaters	28.86	12.52	22	22524	5023	46658493
Visual acuity reduced transiently	28.81	12.52	8	22538	160	46663356
Toxicity to various agents	28.78	12.52	36	22510	211730	46451786
Pain	28.57	12.52	126	22420	476822	46186694
Blepharitis	28.32	12.52	16	22530	2205	46661311
Vitreous haemorrhage	28.26	12.52	15	22531	1829	46661687
Forced vital capacity decreased	28.17	12.52	12	22534	895	46662621
Conjunctival ulcer	27.49	12.52	6	22540	41	46663475
Incorrect dose administered	27.46	12.52	65	22481	45485	46618031
Corneal epithelium defect	26.97	12.52	9	22537	340	46663176
Eye allergy	26.89	12.52	10	22536	521	46662995
Flat anterior chamber of eye	25.55	12.52	6	22540	59	46663457
Eyelid oedema	25.24	12.52	28	22518	10329	46653187
Conjunctivitis	25.09	12.52	34	22512	15390	46648126
Vitamin B12 decreased	25.02	12.52	16	22530	2759	46660757
Corneal erosion	25.01	12.52	8	22538	264	46663252
Eyelid disorder	24.89	12.52	12	22534	1194	46662322
Fall	24.70	12.52	255	22291	328842	46334674
Dry mouth	24.50	12.52	70	22476	54856	46608660
Retinal detachment	24.36	12.52	20	22526	5080	46658436
Product physical consistency issue	24.33	12.52	9	22537	462	46663054
Nausea	24.33	12.52	214	22332	687240	45976276
Bronchitis	23.90	12.52	108	22438	105871	46557645
Chronotropic incompetence	23.81	12.52	6	22540	81	46663435
Photophobia	23.56	12.52	32	22514	14512	46649004
Thermal burns of eye	21.47	12.52	6	22540	123	46663393
Visual field defect	21.31	12.52	20	22526	6063	46657453
Eye colour change	21.19	12.52	7	22539	256	46663260
Corneal endothelial cell loss	21.01	12.52	4	22542	12	46663504
Abdominal pain	20.47	12.52	51	22495	229980	46433536
Foreign body in eye	20.23	12.52	6	22540	153	46663363
Retinal disorder	19.92	12.52	11	22535	1450	46662066
Hallucination, visual	19.90	12.52	33	22513	17840	46645676
Product deposit	19.87	12.52	6	22540	163	46663353
Superficial injury of eye	19.87	12.52	6	22540	163	46663353
Ocular hypertension	19.79	12.52	9	22537	785	46662731
Rabbit syndrome	19.78	12.52	7	22539	316	46663200
Corneal infiltrates	19.76	12.52	6	22540	166	46663350
Retinopathy haemorrhagic	19.56	12.52	4	22542	19	46663497
Symblepharon	19.48	12.52	5	22541	73	46663443
Rheumatoid arthritis	19.30	12.52	56	22490	240159	46423357
Systemic lupus erythematosus	19.24	12.52	4	22542	65176	46598340
Pyrexia	19.16	12.52	95	22451	348707	46314809
Conjunctival oedema	19.03	12.52	8	22538	577	46662939
Intraocular pressure fluctuation	18.63	12.52	4	22542	25	46663491
Corneal decompensation	18.50	12.52	4	22542	26	46663490
Reaction to preservatives	18.42	12.52	6	22540	210	46663306
Blood pressure systolic increased	18.36	12.52	42	22504	28745	46634771
Synovitis	18.33	12.52	68	22478	61007	46602509
Eye operation	18.18	12.52	11	22535	1721	46661795
Ocular pemphigoid	18.12	12.52	4	22542	29	46663487
Endophthalmitis	18.10	12.52	14	22532	3264	46660252
Product packaging issue	17.85	12.52	9	22537	987	46662529
Malignant glaucoma	17.83	12.52	3	22543	3	46663513
Blindness unilateral	17.60	12.52	17	22529	5340	46658176
Atrioventricular block complete	17.53	12.52	20	22526	7607	46655909
Corneal neovascularisation	17.47	12.52	5	22541	112	46663404
Product packaging difficult to open	17.35	12.52	4	22542	36	46663480
Keratic precipitates	17.35	12.52	5	22541	115	46663401
Thyroxine decreased	17.23	12.52	7	22539	463	46663053
Glaucoma surgery	17.16	12.52	4	22542	38	46663478
Iris neovascularisation	17.16	12.52	4	22542	38	46663478
Eyelid exfoliation	17.11	12.52	5	22541	121	46663395
Suicide attempt	17.05	12.52	3	22543	55033	46608483
Haemangioma congenital	16.95	12.52	7	22539	483	46663033
Product dispensing issue	16.80	12.52	4	22542	42	46663474
Corneal perforation	16.73	12.52	7	22539	499	46663017
Ophthalmic herpes simplex	16.63	12.52	6	22540	287	46663229
Bronchopulmonary disease	16.62	12.52	3	22543	6	46663510
Achromotrichia acquired	16.62	12.52	3	22543	6	46663510
C-reactive protein increased	16.56	12.52	64	22482	58526	46604990
Hypertension	16.07	12.52	155	22391	196201	46467315
Anterior chamber cell	15.87	12.52	7	22539	568	46662948
Keratolysis exfoliativa acquired	15.75	12.52	3	22543	9	46663507
Photopsia	15.74	12.52	14	22532	3962	46659554
Eyelid ptosis	15.55	12.52	17	22529	6171	46657345
Vitreal cells	15.55	12.52	4	22542	59	46663457
Retinal vascular occlusion	15.44	12.52	6	22540	353	46663163
Retinal vascular disorder	15.27	12.52	5	22541	178	46663338
Blepharal pigmentation	15.13	12.52	4	22542	66	46663450
Eyelid injury	15.09	12.52	3	22543	12	46663504
Metamorphopsia	14.97	12.52	8	22538	989	46662527
Conjunctival follicles	14.89	12.52	3	22543	13	46663503
Seborrhoeic keratosis	14.89	12.52	10	22536	1872	46661644
Hypotonia	14.71	12.52	19	22527	8210	46655306
Abdominal discomfort	14.65	12.52	32	22514	151133	46512383
Psoriasis	14.64	12.52	10	22536	78594	46584922
Keratitis	14.58	12.52	11	22535	2472	46661044
Corneal thickening	14.23	12.52	3	22543	17	46663499
Infusion related reaction	13.95	12.52	17	22529	101191	46562325
Dacryocystitis	13.94	12.52	3	22543	19	46663497
Instillation site reaction	13.75	12.52	6	22540	474	46663042
Accidental exposure to product	13.71	12.52	31	22515	21050	46642466
Iris hyperpigmentation	13.68	12.52	3	22543	21	46663495
Sinus bradycardia	13.44	12.52	24	22522	13758	46649758
Eyelid pain	13.31	12.52	5	22541	268	46663248
Drug ineffective	13.25	12.52	424	22122	677414	45986102
Counterfeit product administered	13.22	12.52	3	22543	25	46663491
Eczema eyelids	13.20	12.52	4	22542	110	46663406
Vitritis	13.11	12.52	7	22539	864	46662652
Subretinal fluid	12.88	12.52	5	22541	293	46663223
Iritis	12.86	12.52	10	22536	2351	46661165
Product use complaint	12.85	12.52	9	22537	1803	46661713
Foot amputation	12.69	12.52	5	22541	305	46663211
Toxic epidermal necrolysis	12.57	12.52	31	22515	22247	46641269

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
Intraocular pressure increased	763.49	13.52	221	15094	4899	29932264
Treatment failure	760.66	13.52	365	14950	34314	29902849
Eye irritation	436.98	13.52	148	15167	5548	29931615
Ocular hyperaemia	279.08	13.52	121	15194	8922	29928241
Eye pain	242.39	13.52	119	15196	11670	29925493
Visual acuity reduced	198.55	13.52	115	15200	15731	29921432
Glaucoma	188.62	13.52	81	15234	5827	29931336
Vision blurred	150.62	13.52	143	15172	41673	29895490
Corneal oedema	120.17	13.52	39	15276	1273	29935890
Cataract	105.04	13.52	88	15227	21747	29915416
Eye pruritus	97.00	13.52	45	15270	3882	29933281
Choroidal detachment	82.96	13.52	22	15293	346	29936817
Product delivery mechanism issue	82.49	13.52	18	15297	115	29937048
Visual impairment	81.93	13.52	89	15226	30349	29906814
Bradycardia	81.44	13.52	131	15184	65395	29871768
Corneal deposits	80.76	13.52	19	15296	177	29936986
Blindness	79.43	13.52	59	15256	12250	29924913
Eye discharge	73.40	13.52	29	15286	1684	29935479
Intraocular pressure decreased	73.36	13.52	16	15299	102	29937061
Hypotony of eye	71.21	13.52	16	15299	119	29937044
Lacrimation increased	69.94	13.52	44	15271	6972	29930191
Ocular discomfort	69.34	13.52	26	15289	1309	29935854
Toxic anterior segment syndrome	66.05	13.52	26	15289	1495	29935668
Ocular hypertension	62.97	13.52	21	15294	747	29936416
Hyphaema	62.46	13.52	18	15297	390	29936773
Product container issue	61.37	13.52	21	15294	809	29936354
Ocular surface disease	60.42	13.52	13	15302	77	29937086
Corneal disorder	57.88	13.52	20	15295	794	29936369
Blepharitis	57.36	13.52	21	15294	988	29936175
Open angle glaucoma	57.34	13.52	15	15300	223	29936940
Product quality issue	56.00	13.52	58	15257	18716	29918447
Anterior chamber disorder	55.96	13.52	13	15302	114	29937049
Foreign body sensation in eyes	53.05	13.52	17	15298	532	29936631
Choroidal effusion	52.42	13.52	13	15302	154	29937009
Visual field defect	52.36	13.52	31	15284	4405	29932758
Uveitis	51.23	13.52	33	15282	5444	29931719
Blindness unilateral	50.16	13.52	29	15286	3943	29933220
Punctate keratitis	48.20	13.52	14	15301	312	29936851
Intraocular pressure test abnormal	45.42	13.52	10	15305	67	29937096
Product packaging quantity issue	45.26	13.52	16	15299	680	29936483
Glaucoma surgery	43.53	13.52	8	15307	17	29937146
Corneal neovascularisation	42.17	13.52	9	15306	51	29937112
Cystoid macular oedema	41.72	13.52	15	15300	670	29936493
Conjunctival hyperaemia	41.01	13.52	21	15294	2246	29934917
Erythema of eyelid	39.13	13.52	14	15301	616	29936547
Iridocyclitis	37.47	13.52	17	15298	1392	29935771
Completed suicide	36.77	13.52	4	15311	99488	29837675
Eye swelling	36.75	13.52	33	15282	8931	29928232
Retinal detachment	36.60	13.52	26	15289	5034	29932129
Visual acuity tests abnormal	36.54	13.52	8	15307	52	29937111
Corneal opacity	36.47	13.52	13	15302	566	29936597
Ulcerative keratitis	34.55	13.52	16	15299	1373	29935790
Anterior chamber inflammation	33.77	13.52	10	15305	239	29936924
Dry eye	33.02	13.52	27	15288	6441	29930722
Eye inflammation	32.05	13.52	16	15299	1621	29935542
Corneal degeneration	31.69	13.52	6	15309	16	29937147
Retinal haemorrhage	31.18	13.52	23	15292	4720	29932443
Drug abuse	31.10	13.52	3	15312	82069	29855094
Angle closure glaucoma	29.96	13.52	12	15303	722	29936441
Thunderclap headache	29.77	13.52	7	15308	65	29937098
Eyelids pruritus	28.62	13.52	7	15308	78	29937085
Endophthalmitis	27.79	13.52	19	15296	3461	29933702
Eyelid oedema	27.75	13.52	22	15293	5023	29932140
Optic nerve injury	27.22	13.52	7	15308	97	29937066
Floppy iris syndrome	27.21	13.52	9	15306	312	29936851
Photophobia	26.97	13.52	23	15292	5813	29931350
Vitreous floaters	26.59	13.52	18	15297	3226	29933937
Conjunctivitis allergic	26.28	13.52	10	15305	524	29936639
Accidental exposure to product	26.19	13.52	29	15286	10086	29927077
Anterior chamber cell	25.76	13.52	9	15306	369	29936794
Flat anterior chamber of eye	24.85	13.52	6	15309	63	29937100
Eyelid irritation	24.68	13.52	6	15309	65	29937098
Conjunctival oedema	24.65	13.52	9	15306	420	29936743
Trabeculectomy	24.48	13.52	5	15310	22	29937141
Corneal pigmentation	24.08	13.52	4	15311	3	29937160
Cataract nuclear	23.33	13.52	9	15306	490	29936673
Eye disorder	23.25	13.52	24	15291	7710	29929453
Hypersensitivity	21.84	13.52	69	15246	53959	29883204
Instillation site pain	21.61	13.52	6	15309	113	29937050
Eye infection	21.47	13.52	15	15300	2827	29934336
Reversible cerebral vasoconstriction syndrome	21.23	13.52	7	15308	240	29936923
Abnormal sensation in eye	20.96	13.52	9	15306	646	29936517
Macular degeneration	20.91	13.52	13	15302	2015	29935148
Eyelid margin crusting	20.32	13.52	6	15309	142	29937021
Atrioventricular block second degree	20.13	13.52	15	15300	3125	29934038
Photocoagulation	19.89	13.52	4	15311	16	29937147
Growth of eyelashes	19.88	13.52	5	15310	63	29937100
Keratitis interstitial	19.51	13.52	4	15311	18	29937145
Corneal infection	19.51	13.52	4	15311	18	29937145
Corneal epithelium defect	19.15	13.52	7	15308	328	29936835
Ureteral disorder	19.06	13.52	6	15309	177	29936986
Superficial injury of eye	19.00	13.52	4	15311	21	29937142
Pupillary reflex impaired	18.85	13.52	11	15304	1521	29935642
Iris adhesions	18.33	13.52	6	15309	201	29936962
Iritis	17.76	13.52	10	15305	1292	29935871
Cutis laxa	17.59	13.52	5	15310	103	29937060
Retinal disorder	17.42	13.52	9	15306	980	29936183
Macular oedema	17.38	13.52	13	15302	2725	29934438
Sinus bradycardia	16.75	13.52	25	15290	11670	29925493
Liquid product physical issue	16.45	13.52	6	15309	279	29936884
Incorrect dose administered	16.19	13.52	44	15271	31642	29905521
Corneal endotheliitis	16.13	13.52	3	15312	7	29937156
Retinal vein occlusion	16.09	13.52	10	15305	1549	29935614
Alanine aminotransferase increased	16.05	13.52	9	15306	74267	29862896
Cataract operation	16.02	13.52	9	15306	1158	29936005
Optic nerve cupping	15.38	13.52	4	15311	58	29937105
Scleral hyperaemia	15.32	13.52	4	15311	59	29937104
Eyelid pain	14.79	13.52	4	15311	68	29937095
Eyelid disorder	14.66	13.52	6	15309	382	29936781
Hyperaemia	14.64	13.52	8	15307	975	29936188
Coronavirus infection	14.58	13.52	13	15302	3485	29933678
Macular fibrosis	14.55	13.52	6	15309	389	29936774
Cerebellar stroke	14.43	13.52	5	15310	200	29936963
Night blindness	14.43	13.52	5	15310	200	29936963
Ectropion	14.32	13.52	4	15311	77	29937086
Toxicity to various agents	14.18	13.52	45	15270	177138	29760025
Electrolyte depletion	14.13	13.52	5	15310	213	29936950
Intraocular pressure fluctuation	14.06	13.52	3	15312	17	29937146
Madarosis	14.00	13.52	5	15310	219	29936944
Iris neovascularisation	13.91	13.52	3	15312	18	29937145
Corneal infiltrates	13.87	13.52	5	15310	225	29936938

Pharmacologic Action:

Source	Code	Description
ATC	C07AA06	CARDIOVASCULAR SYSTEM BETA BLOCKING AGENTS BETA BLOCKING AGENTS Beta blocking agents, non-selective
ATC	S01ED01	SENSORY ORGANS OPHTHALMOLOGICALS ANTIGLAUCOMA PREPARATIONS AND MIOTICS Beta blocking agents
ATC	C07BA06	CARDIOVASCULAR SYSTEM BETA BLOCKING AGENTS BETA BLOCKING AGENTS AND THIAZIDES Beta blocking agents, non-selective, and thiazides
ATC	C07DA06	CARDIOVASCULAR SYSTEM BETA BLOCKING AGENTS BETA BLOCKING AGENTS, THIAZIDES AND OTHER DIURETICS Beta blocking agents, non-selective, thiazides and other diuretics
ATC	S01ED51	SENSORY ORGANS OPHTHALMOLOGICALS ANTIGLAUCOMA PREPARATIONS AND MIOTICS Beta blocking agents
MeSH PA	D018663	Adrenergic Agents
MeSH PA	D018674	Adrenergic Antagonists
MeSH PA	D000319	Adrenergic beta-Antagonists
MeSH PA	D000889	Anti-Arrhythmia Agents
MeSH PA	D000959	Antihypertensive Agents
MeSH PA	D002317	Cardiovascular Agents
MeSH PA	D018377	Neurotransmitter Agents
CHEBI has role	CHEBI:35530	beta-adrenoceptor antagonists
CHEBI has role	CHEBI:35674	antihypertensive
CHEBI has role	CHEBI:38070	antiarrhythmic agent
CHEBI has role	CHEBI:39456	antiglaucoma agent

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Ocular hypertension	indication	4210003	DOID:9282
Hypertensive disorder	indication	38341003	DOID:10763
Open-angle glaucoma	indication	84494001	DOID:1067
Myocardial Reinfarction Prevention	indication
Migraine Prevention	indication
Malignant glaucoma	off-label use	10100008
Aphakic glaucoma	off-label use	15374009
Secondary glaucoma	off-label use	95717004
Angina pectoris	off-label use	194828000
Angle-closure glaucoma	off-label use	392291006	DOID:13550
Mitral valve prolapse	off-label use	409712001
Stalled wound	off-label use	789507005
Anuria	contraindication	2472002	DOID:2983
Bronchospasm	contraindication	4386001
Hypercholesterolemia	contraindication	13644009
Secondary angle-closure glaucoma	contraindication	21571006
Complete atrioventricular block	contraindication	27885002
Hypovolemia	contraindication	28560003
Orthostatic hypotension	contraindication	28651003
Acute cerebrovascular insufficiency	contraindication	29322000
Dehydration	contraindication	34095006
Hyperthyroidism	contraindication	34486009	DOID:7998
Depressive disorder	contraindication	35489007
Hyperuricemia	contraindication	35885006	DOID:1920
Anaphylaxis	contraindication	39579001
Hypokalemia	contraindication	43339004
Sinus bradycardia	contraindication	49710005
General anesthesia	contraindication	50697003
Thromboangiitis obliterans	contraindication	52403007	DOID:12918
Systemic lupus erythematosus	contraindication	55464009	DOID:9074
Sympathectomy	contraindication	57071006
Acute nephropathy	contraindication	58574008
Cerebrovascular disease	contraindication	62914000	DOID:6713
Hypercalcemia	contraindication	66931009	DOID:12678
Hyperparathyroidism	contraindication	66999008	DOID:13543
Hypochloremic alkalosis	contraindication	70134007
Hepatic coma	contraindication	72836002	DOID:12550
Diabetes mellitus	contraindication	73211009	DOID:9351
Pulmonary emphysema	contraindication	87433001
Cardiogenic shock	contraindication	89138009
Hyponatremia	contraindication	89627008
Gout	contraindication	90560007	DOID:13189
Kidney disease	contraindication	90708001	DOID:557
Myasthenia gravis	contraindication	91637004	DOID:437
Acute disease of cardiovascular system	contraindication	128487001
Hypomagnesemia	contraindication	190855004
Partial atrioventricular block	contraindication	195039008
Decompensated cardiac failure	contraindication	195111005
Acute pancreatitis	contraindication	197456007	DOID:2913
Disease of liver	contraindication	235856003	DOID:409
Hypoglycemic disorder	contraindication	237630007
Raynaud's phenomenon	contraindication	266261006
Neonatal hyperbilirubinemia	contraindication	281610001
Pregnancy, function	contraindication	289908002
Severe chronic obstructive pulmonary disease	contraindication	313299006
Right ventricular failure	contraindication	367363000
Azotemia	contraindication	445009001

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	9.15	Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
EQ 0.25% BASE	TIMOLOL MALEATE	ALEMBIC PHARMS LTD	A212942	Oct. 22, 2020	RX	SOLUTION, GEL FORMING/DROPS	OPHTHALMIC	May 24, 2021	COMPETITIVE GENERIC THERAPY
EQ 0.5% BASE	TIMOLOL MALEATE	ALEMBIC PHARMS LTD	A212942	Oct. 22, 2020	RX	SOLUTION, GEL FORMING/DROPS	OPHTHALMIC	May 24, 2021	COMPETITIVE GENERIC THERAPY

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Beta-1 adrenergic receptor	GPCR	P08588	ADRB1_HUMAN	ANTAGONIST	Ki	9	WOMBAT-PK	CHEMBL
Beta-2 adrenergic receptor	GPCR	P07550	ADRB2_HUMAN	ANTAGONIST	Ki	9.70	WOMBAT-PK	CHEMBL
5-hydroxytryptamine receptor 1A	GPCR	P08908	5HT1A_HUMAN		Ki	5.81	DRUG MATRIX
Beta-3 adrenergic receptor	GPCR	P13945	ADRB3_HUMAN		Ki	6.47	DRUG MATRIX
Beta-2 adrenergic receptor	GPCR		ADRB2_CAVPO		Kd	9.78	CHEMBL
5-hydroxytryptamine receptor 1A	GPCR		5HT1A_RAT		Ki	6.21	CHEMBL
Beta-1 adrenergic receptor	GPCR		B0FL73_CAVPO		Kd	9.44	CHEMBL

External reference:

ID	Source
4019949	VUID
N0000148034	NUI
D00378	KEGG_DRUG
91524-16-2	SECONDARY_CAS_RN
4017930	VANDF
4019949	VANDF
C0040233	UMLSCUI
CHEBI:9599	CHEBI
TIM	PDB_CHEM_ID
33624	PUBCHEM_CID
CHEMBL499	ChEMBL_ID
CHEMBL1200870	ChEMBL_ID
D013999	MESH_DESCRIPTOR_UI
DB00373	DRUGBANK_ID
817W3C6175	UNII
565	IUPHAR_LIGAND_ID
10600	RXNORM
5585	MMSL
6436	MMSL
d00139	MMSL
001856	NDDF
004741	NDDF
372880004	SNOMEDCT_US
75359005	SNOMEDCT_US
85591001	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
COMBIGAN	HUMAN PRESCRIPTION DRUG LABEL	2	0023-9211	SOLUTION/ DROPS	5 mg	OPHTHALMIC	NDA	26 sections
Timoptic in Ocudose	HUMAN PRESCRIPTION DRUG LABEL	1	0187-1496	SOLUTION	6.80 mg	OPHTHALMIC	NDA	20 sections
Timoptic in Ocudose	HUMAN PRESCRIPTION DRUG LABEL	1	0187-1498	SOLUTION	3.40 mg	OPHTHALMIC	NDA	20 sections
Timolol Maleate	HUMAN PRESCRIPTION DRUG LABEL	1	0378-0055	TABLET	5 mg	ORAL	ANDA	22 sections
Timolol Maleate	HUMAN PRESCRIPTION DRUG LABEL	1	0378-0221	TABLET	10 mg	ORAL	ANDA	22 sections
Timolol Maleate	HUMAN PRESCRIPTION DRUG LABEL	1	0378-0715	TABLET	20 mg	ORAL	ANDA	22 sections
Dorzolamide Hydrochloride-Timolol Maleate	HUMAN PRESCRIPTION DRUG LABEL	2	0527-1763	SOLUTION	5 mg	OPHTHALMIC	ANDA	25 sections
Timolol Maleate	HUMAN PRESCRIPTION DRUG LABEL	1	13811-618	TABLET	5 mg	ORAL	ANDA	14 sections
Timolol Maleate	HUMAN PRESCRIPTION DRUG LABEL	1	13811-619	TABLET	10 mg	ORAL	ANDA	14 sections
Timolol Maleate	HUMAN PRESCRIPTION DRUG LABEL	1	13811-620	TABLET	20 mg	ORAL	ANDA	14 sections
DORZOLAMIDE HYDROCHLORIDE TIMOLOL MALETAE	Human Prescription Drug Label	2	14445-405	SOLUTION/ DROPS	5 mg	OPHTHALMIC	ANDA	24 sections
Timolol Maleate	HUMAN PRESCRIPTION DRUG LABEL	1	17478-189	SOLUTION/ DROPS	5 mg	OPHTHALMIC	ANDA	25 sections
Timolol Maleate	HUMAN PRESCRIPTION DRUG LABEL	1	17478-288	SOLUTION/ DROPS	5 mg	OPHTHALMIC	ANDA	23 sections
Timolol Maleate	HUMAN PRESCRIPTION DRUG LABEL	1	17478-289	SOLUTION/ DROPS	2.50 mg	OPHTHALMIC	ANDA	23 sections
Timolol Maleate	HUMAN PRESCRIPTION DRUG LABEL	1	17478-365	SOLUTION/ DROPS	2.50 mg	OPHTHALMIC	ANDA	22 sections
Timolol Maleate	HUMAN PRESCRIPTION DRUG LABEL	1	17478-366	SOLUTION/ DROPS	5 mg	OPHTHALMIC	ANDA	22 sections
Dorzolamide HCl and Timolol Maleate	HUMAN PRESCRIPTION DRUG LABEL	2	17478-514	SOLUTION/ DROPS	5 mg	OPHTHALMIC	ANDA	28 sections
COSOPT PF	HUMAN PRESCRIPTION DRUG LABEL	2	17478-604	SOLUTION/ DROPS	5 mg	OPHTHALMIC	NDA	26 sections
COSOPT	HUMAN PRESCRIPTION DRUG LABEL	2	17478-605	SOLUTION/ DROPS	5 mg	OPHTHALMIC	NDA	28 sections
Istalol	HUMAN PRESCRIPTION DRUG LABEL	1	24208-004	SOLUTION/ DROPS	5 mg	OPHTHALMIC	NDA	24 sections
Dorzolamide Hydrochloride and Timolol Maleate	HUMAN PRESCRIPTION DRUG LABEL	2	24208-486	SOLUTION/ DROPS	5 mg	OPHTHALMIC	ANDA	25 sections
Timolol Maleate	HUMAN PRESCRIPTION DRUG LABEL	1	24208-496	SOLUTION	6.80 mg	OPHTHALMIC	NDA authorized generic	12 sections
Timoptic	HUMAN PRESCRIPTION DRUG LABEL	1	24208-812	SOLUTION	2.50 mg	OPHTHALMIC	NDA	25 sections
Timoptic	HUMAN PRESCRIPTION DRUG LABEL	1	24208-813	SOLUTION	5 mg	OPHTHALMIC	NDA	25 sections
Timoptic-XE	HUMAN PRESCRIPTION DRUG LABEL	1	24208-814	SOLUTION	2.50 mg	OPHTHALMIC	NDA	23 sections
Timoptic-XE	HUMAN PRESCRIPTION DRUG LABEL	1	24208-816	SOLUTION	5 mg	OPHTHALMIC	NDA	23 sections
Timolol Maleate	HUMAN PRESCRIPTION DRUG LABEL	1	24208-818	SOLUTION	2.50 mg	OPHTHALMIC	NDA authorized generic	23 sections
Timolol Maleate	HUMAN PRESCRIPTION DRUG LABEL	1	24208-819	SOLUTION	5 mg	OPHTHALMIC	NDA authorized generic	23 sections
Dorzolamide Hydrochloride and Timolol Maleate ophthalmic Solution	HUMAN PRESCRIPTION DRUG LABEL	2	42571-147	SOLUTION/ DROPS	6.80 mg	OPHTHALMIC	ANDA	24 sections
TIMOLOL MALEATE	HUMAN PRESCRIPTION DRUG LABEL	1	45865-121	SOLUTION/ DROPS	5 mg	OPHTHALMIC	ANDA	21 sections