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

Stem definitionDrug idCAS RN
beta-adrenoreceptor antagonists 4061 26839-75-8

Description:

MoleculeDescription

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:

DoseUnitRoute
20 mg O
20 mg P

ADMET properties:

PropertyValueReference
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 ┬ÁM/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:

DateAgencyCompanyOrphan
Aug. 17, 1978 FDA ATON

FDA Adverse Event Reporting System (Female)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Eye irritation 604.28 46.68 114 964 3398 2353609
Intraocular pressure increased 428.02 46.68 75 1003 1434 2355573
Ocular hyperaemia 319.76 46.68 69 1009 3987 2353020
Drug ineffective 281.45 46.68 132 946 101492 2255515
Eye pain 274.32 46.68 63 1015 4828 2352179
Product quality issue 224.60 46.68 63 1015 10766 2346241
Vision blurred 197.18 46.68 61 1017 14607 2342400
Eye pruritus 154.41 46.68 35 1043 2496 2354511
Bradycardia 144.41 46.68 44 1034 9937 2347070
Glaucoma 144.30 46.68 32 1046 2063 2354944
Visual acuity reduced 101.18 46.68 29 1049 5269 2351738
Dyspnoea 93.41 46.68 59 1019 78674 2278333
Hypersensitivity 90.55 46.68 39 1039 23554 2333453
Total lung capacity increased 88.87 46.68 11 1067 9 2356998
Dizziness 82.29 46.68 49 1029 58616 2298391
Eyelid margin crusting 79.71 46.68 13 1065 153 2356854
Product container issue 79.32 46.68 16 1062 647 2356360
Iris adhesions 79.31 46.68 12 1066 83 2356924
Incorrect dose administered 72.43 46.68 26 1052 9669 2347338
Eye discharge 68.45 46.68 15 1063 908 2356099
Dry eye 68.12 46.68 20 1058 3936 2353071
Hand deformity 66.02 46.68 15 1063 1071 2355936
No adverse event 65.37 46.68 24 1054 9504 2347503
Blood pressure systolic increased 63.99 46.68 17 1061 2322 2354685
Trabeculectomy 63.38 46.68 8 1070 9 2356998
Product dropper issue 61.92 46.68 10 1068 110 2356897
Eye swelling 61.80 46.68 19 1059 4371 2352636
Lacrimation increased 60.78 46.68 17 1061 2813 2354194
Sciatica 60.78 46.68 16 1062 2109 2354898
Visual impairment 60.46 46.68 24 1054 11731 2345276
Drug hypersensitivity 60.19 46.68 37 1041 46606 2310401
Frustration tolerance decreased 58.78 46.68 13 1065 820 2356187
Corneal oedema 57.35 46.68 11 1067 341 2356666
Respiration abnormal 56.53 46.68 12 1066 624 2356383
Cataract 56.25 46.68 19 1059 5889 2351118
Hypothermia 55.85 46.68 15 1063 2133 2354874
Intraocular pressure test abnormal 53.29 46.68 8 1070 52 2356955
Forced expiratory volume decreased 52.55 46.68 11 1067 534 2356473
Hypotony of eye 52.17 46.68 8 1070 61 2356946
Punctate keratitis 52.03 46.68 9 1069 154 2356853
Growth of eyelashes 50.05 46.68 8 1070 82 2356925
Foreign body sensation in eyes 48.95 46.68 10 1068 430 2356577
Keratopathy 48.30 46.68 8 1070 104 2356903
Vertigo 47.67 46.68 19 1059 9365 2347642
Hypotension 47.64 46.68 28 1050 32408 2324599
Obstructive airways disorder 47.34 46.68 12 1066 1361 2355646
Toxic anterior segment syndrome 46.76 46.68 9 1069 284 2356723

FDA Adverse Event Reporting System (Male)

MedDRA adverse event termLikelihood ratioLikelihood ratio thresholdPatients taking drug having adverse eventPatients taking drug not having adverse eventPatients not taking drug having adverse eventPatients not taking drug not having adverse event
Intraocular pressure increased 463.85 54.58 78 619 1103 1744981
Eye irritation 323.40 54.58 59 638 1344 1744740
Bradycardia 191.58 54.58 56 641 10478 1735606
Eye pain 171.77 54.58 38 659 2293 1743791
Ocular hyperaemia 166.05 54.58 36 661 1974 1744110
Visual acuity reduced 132.53 54.58 34 663 3854 1742230
Corneal deposits 122.88 54.58 18 679 90 1745994
Drug ineffective 121.39 54.58 66 631 63735 1682349
Product quality issue 104.14 54.58 31 666 6062 1740022
Vision blurred 98.32 54.58 32 665 8391 1737693
Eye pruritus 85.79 54.58 18 679 832 1745252
Blindness 78.49 54.58 21 676 2775 1743309
Anterior chamber disorder 71.77 54.58 10 687 32 1746052
Glaucoma 70.09 54.58 16 681 1095 1744989
Corneal oedema 69.85 54.58 13 684 320 1745764
Product container issue 69.58 54.58 13 684 327 1745757
Lacrimation increased 66.10 54.58 16 681 1412 1744672
Intraocular pressure test abnormal 63.86 54.58 9 688 32 1746052
Hyphaema 63.10 54.58 10 687 90 1745994
Thunderclap headache 57.11 54.58 7 690 4 1746080

Pharmacologic Action:

SourceCodeDescription
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 agents1)
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 agents1)
MeSH PA D018663 Adrenergic Agents
MeSH PA D018674 Adrenergic Antagonists
MeSH PA D000319 Adrenergic beta-Antagonists
CHEBI has role CHEBI:35674 antihypertensive agent
CHEBI has role CHEBI:38070 anti-arrhythmia drug
CHEBI has role CHEBI:35530 beta-adrenergic antagonist
CHEBI has role CHEBI:39456 antiglaucoma drug
MeSH PA D000889 Anti-Arrhythmia Agents
MeSH PA D000959 Antihypertensive Agents
MeSH PA D002317 Cardiovascular Agents
MeSH PA D018377 Neurotransmitter Agents

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
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
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 levelDissociation constantType (acidic/basic)
pKa1 9.15 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 0.5% BASE COMBIGAN ALLERGAN N021398 Oct. 30, 2007 RX SOLUTION/DROPS OPHTHALMIC 7030149 April 19, 2022 REDUCTION OF ELEVATED INTRAOCULAR PRESSURE (IOP) IN PATIENTS WITH GLAUCOMA OR OCULAR HYPERTENSION WHO REQUIRE ADJUNCTIVE OR REPLACEMENT THERAPY DUE TO INADEQUATELY CONTROLLED IOP. DOSE IS ONE DROP OF COMBIGAN IN THE AFFECTED EYE TWICE DAILY
EQ 0.5% BASE COMBIGAN ALLERGAN N021398 Oct. 30, 2007 RX SOLUTION/DROPS OPHTHALMIC 7320976 April 19, 2022 REDUCTION OF ELEVATED INTRAOCULAR PRESSURE (IOP) IN PATIENTS WITH GLAUCOMA OR OCULAR HYPERTENSION WHO REQUIRE ADJUNCTIVE OR REPLACEMENT THERAPY DUE TO INADEQUATELY CONTROLLED IOP. DOSE IS ONE DROP OF COMBIGAN IN THE AFFECTED EYE TWICE DAILY
EQ 0.5% BASE COMBIGAN ALLERGAN N021398 Oct. 30, 2007 RX SOLUTION/DROPS OPHTHALMIC 7642258 April 19, 2022 REDUCTION OF ELEVATED INTRAOCULAR PRESSURE IN PATIENTS WITH GLAUCOMA OR OCULAR HYPERTENSION WHO REQUIRE ADJUNCTIVE OR REPLACEMENT THERAPY DUE TO INADEQUATELY CONTROLLED IOP
EQ 0.5% BASE COMBIGAN ALLERGAN N021398 Oct. 30, 2007 RX SOLUTION/DROPS OPHTHALMIC 8133890 April 19, 2022 REDUCTION OF ELEVATED INTRAOCULAR PRESSURE IN PATIENTS WITH GLAUCOMA OR OCULAR HYPERTENSION
EQ 0.5% BASE COMBIGAN ALLERGAN N021398 Oct. 30, 2007 RX SOLUTION/DROPS OPHTHALMIC 8354409 April 19, 2022 REDUCTION OF INTRAOCULAR PRESSURE IN PATIENTS WITH ELEVATED INTRAOCULAR PRESSURE OR GLAUCOMA
EQ 0.5% BASE COMBIGAN ALLERGAN N021398 Oct. 30, 2007 RX SOLUTION/DROPS OPHTHALMIC 8748425 April 19, 2022 REDUCTION OF ELEVATED INTRAOCULAR PRESSURE
EQ 0.5% BASE COMBIGAN ALLERGAN N021398 Oct. 30, 2007 RX SOLUTION/DROPS OPHTHALMIC 9474751 April 19, 2022 REDUCTION OF ELEVATED INTRAOCULAR PRESSURE
EQ 0.5% BASE COMBIGAN ALLERGAN N021398 Oct. 30, 2007 RX SOLUTION/DROPS OPHTHALMIC 9770453 April 19, 2022 REDUCTION OF ELEVATED INTRAOCULAR PRESSURE (IOP) IN PATIENTS WITH GLAUCOMA OR OCULAR HYPERTENSION, WITH COMPARABLE EFFICACY, AND A REDUCTION IN SPECIFIED ADVERSE EVENTS, COMPARED TO BRIMONIDINE 0.2% TID
EQ 0.5% BASE COMBIGAN ALLERGAN N021398 Oct. 30, 2007 RX SOLUTION/DROPS OPHTHALMIC 9907801 April 19, 2022 REDUCTION OF ELEVATED INTRAOCULAR PRESSURE (IOP) IN PATIENTS WITH GLAUCOMA OR OCULAR HYPERTENSION, WITH A REDUCTION IN SPECIFIED ADVERSE EVENTS, COMPARED TO BRIMONIDINE 0.2% TID
EQ 0.5% BASE COMBIGAN ALLERGAN N021398 Oct. 30, 2007 RX SOLUTION/DROPS OPHTHALMIC 9907802 April 19, 2022 REDUCTION OF ELEVATED INTRAOCULAR PRESSURE (IOP) IN PATIENTS WITH GLAUCOMA OR OCULAR HYPERTENSION, WITH COMPARABLE EFFICACY TO BRIMONIDINE 0.2% TID

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Beta-1 adrenergic receptor GPCR ANTAGONIST Ki 9 WOMBAT-PK CHEMBL
Beta-2 adrenergic receptor GPCR ANTAGONIST Ki 9.70 WOMBAT-PK CHEMBL
5-hydroxytryptamine receptor 1A GPCR Ki 5.81 DRUG MATRIX
Beta-3 adrenergic receptor GPCR Ki 6.47 DRUG MATRIX
Beta-2 adrenergic receptor GPCR Kd 9.78 CHEMBL
5-hydroxytryptamine receptor 1A GPCR Ki 6.21 CHEMBL
Beta-1 adrenergic receptor GPCR Kd 9.44 CHEMBL

External reference:

IDSource
4019949 VUID
N0000148034 NUI
C0040233 UMLSCUI
D00378 KEGG_DRUG
85591001 SNOMEDCT_US
4019949 VANDF
10600 RXNORM
372880004 SNOMEDCT_US
d00139 MMSL
004741 NDDF
817W3C6175 UNII
91524-16-2 SECONDARY_CAS_RN
CHEMBL499 ChEMBL_ID
DB00373 DRUGBANK_ID
TIM PDB_CHEM_ID
CHEBI:60787 CHEBI
33624 PUBCHEM_CID
CHEMBL1200870 ChEMBL_ID
D013999 MESH_DESCRIPTOR_UI
565 IUPHAR_LIGAND_ID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
COMBIGAN HUMAN PRESCRIPTION DRUG LABEL 2 0023-9211 SOLUTION/ DROPS 5 mg OPHTHALMIC NDA 17 sections
Timoptic in Ocudose HUMAN PRESCRIPTION DRUG LABEL 1 0187-1496 SOLUTION 6.80 mg OPHTHALMIC NDA 12 sections
Timoptic in Ocudose HUMAN PRESCRIPTION DRUG LABEL 1 0187-1498 SOLUTION 3.40 mg OPHTHALMIC NDA 12 sections
Timolol Maleate HUMAN PRESCRIPTION DRUG LABEL 1 0378-0055 TABLET 5 mg ORAL ANDA 11 sections
Timolol Maleate HUMAN PRESCRIPTION DRUG LABEL 1 0378-0221 TABLET 10 mg ORAL ANDA 11 sections
Timolol Maleate HUMAN PRESCRIPTION DRUG LABEL 1 0378-0715 TABLET 20 mg ORAL ANDA 11 sections
Dorzolamide Hydrochloride-Timolol Maleate HUMAN PRESCRIPTION DRUG LABEL 2 0527-1763 SOLUTION 5 mg OPHTHALMIC ANDA 13 sections
Timolol Maleate HUMAN PRESCRIPTION DRUG LABEL 1 13811-618 TABLET 5 mg ORAL ANDA 11 sections
Timolol Maleate HUMAN PRESCRIPTION DRUG LABEL 1 13811-619 TABLET 10 mg ORAL ANDA 11 sections
Timolol Maleate HUMAN PRESCRIPTION DRUG LABEL 1 13811-620 TABLET 20 mg ORAL ANDA 11 sections
Timolol Maleate HUMAN PRESCRIPTION DRUG LABEL 1 17478-288 SOLUTION/ DROPS 5 mg OPHTHALMIC ANDA 12 sections
Timolol Maleate HUMAN PRESCRIPTION DRUG LABEL 1 17478-289 SOLUTION/ DROPS 2.50 mg OPHTHALMIC ANDA 12 sections
Timolol Maleate HUMAN PRESCRIPTION DRUG LABEL 1 17478-365 SOLUTION/ DROPS 2.50 mg OPHTHALMIC ANDA 11 sections
Timolol Maleate HUMAN PRESCRIPTION DRUG LABEL 1 17478-366 SOLUTION/ DROPS 5 mg OPHTHALMIC ANDA 11 sections
Dorzolamide HCl and Timolol Maleate HUMAN PRESCRIPTION DRUG LABEL 2 17478-514 SOLUTION/ DROPS 5 mg OPHTHALMIC ANDA 18 sections
COSOPT PF HUMAN PRESCRIPTION DRUG LABEL 2 17478-604 SOLUTION/ DROPS 5 mg OPHTHALMIC NDA 18 sections
COSOPT HUMAN PRESCRIPTION DRUG LABEL 2 17478-605 SOLUTION/ DROPS 5 mg OPHTHALMIC NDA 17 sections
Istalol HUMAN PRESCRIPTION DRUG LABEL 1 24208-004 SOLUTION/ DROPS 5 mg OPHTHALMIC NDA 17 sections
Dorzolamide Hydrochloride and Timolol Maleate HUMAN PRESCRIPTION DRUG LABEL 2 24208-486 SOLUTION/ DROPS 5 mg OPHTHALMIC ANDA 17 sections
Timoptic HUMAN PRESCRIPTION DRUG LABEL 1 24208-812 SOLUTION 2.50 mg OPHTHALMIC NDA 12 sections
Timoptic HUMAN PRESCRIPTION DRUG LABEL 1 24208-813 SOLUTION 5 mg OPHTHALMIC NDA 12 sections
Timoptic-XE HUMAN PRESCRIPTION DRUG LABEL 1 24208-814 SOLUTION 2.50 mg OPHTHALMIC NDA 13 sections
Timoptic-XE HUMAN PRESCRIPTION DRUG LABEL 1 24208-816 SOLUTION 5 mg OPHTHALMIC NDA 13 sections
Timolol Maleate HUMAN PRESCRIPTION DRUG LABEL 1 24208-818 SOLUTION 2.50 mg OPHTHALMIC NDA authorized generic 13 sections
Timolol Maleate HUMAN PRESCRIPTION DRUG LABEL 1 24208-819 SOLUTION 5 mg OPHTHALMIC NDA authorized generic 13 sections
Timoptic HUMAN PRESCRIPTION DRUG LABEL 1 25010-814 SOLUTION 2.50 mg OPHTHALMIC NDA 12 sections
Timoptic HUMAN PRESCRIPTION DRUG LABEL 1 25010-815 SOLUTION 5 mg OPHTHALMIC NDA 12 sections
Dorzolamide Hydrochloride and Timolol Maleate HUMAN PRESCRIPTION DRUG LABEL 2 50090-1247 SOLUTION/ DROPS 5 mg OPHTHALMIC ANDA 16 sections
TIMOLOL MALEATE HUMAN PRESCRIPTION DRUG LABEL 1 50090-1852 SOLUTION/ DROPS 5 mg OPHTHALMIC ANDA 12 sections
Dorzolamide HCl and Timolol Maleate HUMAN PRESCRIPTION DRUG LABEL 2 50090-2867 SOLUTION 5 mg OPHTHALMIC ANDA 18 sections