ambrisentan indications/contra

Stem definitionDrug idCAS RN
endothelin receptor antagonists 4337 177036-94-1

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • LU208075
  • LU 208075
  • ambrisentan
  • letairis
  • volibris
an endothelin receptor antagonist that is selective for the endothelin type-A (ETA) receptor
  • Molecular weight: 378.43
  • Formula: C22H22N2O4
  • CLOGP: 3.75
  • LIPINSKI: 0
  • HAC: 6
  • HDO: 1
  • TPSA: 81.54
  • ALOGS: -3.88
  • ROTB: 7

Drug dosage:

DoseUnitRoute
7.50 mg O

Approvals:

DateAgencyCompanyOrphan
June 15, 2007 FDA GILEAD

FDA Adverse Event Reporting System

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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
Dyspnoea 9098.07 53.89 3541 20876 99393 3262049
Fluid retention 3847.53 53.89 1017 23400 7141 3354301
Nasal congestion 3679.41 53.89 964 23453 6503 3354939
Oedema 3648.15 53.89 1109 23308 13571 3347871
Headache 3202.18 53.89 1670 22747 90310 3271132
Oedema peripheral 3025.12 53.89 1195 23222 33166 3328276
Death 2837.77 53.89 1841 22576 150483 3210959
Peripheral swelling 2644.54 53.89 889 23528 15243 3346199
Unevaluable event 2122.92 53.89 716 23701 12360 3349082
Pulmonary arterial hypertension 2044.29 53.89 539 23878 3701 3357741
Dizziness 1830.69 53.89 1090 23327 75422 3286020
Pulmonary hypertension 1811.20 53.89 538 23879 5972 3355470
Swelling 1612.71 53.89 646 23771 18398 3343044
Pneumonia 1553.85 53.89 952 23465 69191 3292251
Fatigue 1352.15 53.89 1027 23390 106213 3255229
Malaise 1294.21 53.89 826 23591 64351 3297091
Right ventricular failure 1194.42 53.89 322 24095 2421 3359021
Cough 1127.37 53.89 635 23782 39223 3322219
Diarrhoea 968.66 53.89 837 23580 103511 3257931
Nausea 957.25 53.89 914 23503 128731 3232711
Chest pain 956.34 53.89 573 23844 39702 3321740
Fluid overload 955.77 53.89 290 24127 3461 3357981
Flushing 914.11 53.89 396 24021 13717 3347725
Syncope 880.75 53.89 465 23952 25168 3336274
Hypotension 869.37 53.89 582 23835 48932 3312510
Pain in jaw 826.83 53.89 292 24125 5766 3355676
Cardiac failure congestive 820.18 53.89 467 23950 29355 3332087
Respiratory failure 815.33 53.89 427 23990 22714 3338728
Nasopharyngitis 810.56 53.89 418 23999 21529 3339913
Palpitations 773.22 53.89 387 24030 18696 3342746

Pharmacologic Action:

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SourceCodeDescription
ATC C02KX02 CARDIOVASCULAR SYSTEM
ANTIHYPERTENSIVES
OTHER ANTIHYPERTENSIVES
Antihypertensives for pulmonary arterial hypertension
FDA EPC N0000175581 Endothelin Receptor Antagonist
FDA MoA N0000175364 Endothelin Receptor Antagonists
MeSH PA D000959 Antihypertensive Agents
MeSH PA D002317 Cardiovascular Agents

Drug Use (View source of the data)

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DiseaseRelationSNOMED_IDDOID
Pulmonary arterial hypertension indication 11399002
Body fluid retention contraindication 43498006
Chronic heart failure contraindication 48447003
Oligozoospermia contraindication 88311004
Pulmonary veno-occlusive disease contraindication 89420002 DOID:5453
Liver function tests abnormal contraindication 166603001
Edema contraindication 267038008
Anemia contraindication 271737000 DOID:2355
Pregnancy, function contraindication 289908002
Breastfeeding (mother) contraindication 413712001

Acid dissociation constants calculated using MoKa v3.0.0

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Dissociation levelDissociation constantType (acidic/basic)
pKa1 3.3 acidic
pKa2 2.68 Basic

Orange Book patent data (new drug applications)

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Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
10MG LETAIRIS GILEAD N022081 June 15, 2007 RX TABLET ORAL 8377933 Dec. 11, 2027 FOR THE TREATMENT OF PULMONARY HYPERTENSION (PAH) IN COMBINATION WITH TADALAFIL
10MG LETAIRIS GILEAD N022081 June 15, 2007 RX TABLET ORAL 9474752 Dec. 11, 2027 FOR THE TREATMENT OF PULMONARY HYPERTENSION (PAH) IN COMBINATION WITH TADALAFIL
5MG LETAIRIS GILEAD N022081 June 15, 2007 RX TABLET ORAL 8377933 Dec. 11, 2027 FOR THE TREATMENT OF PULMONARY HYPERTENSION (PAH) IN COMBINATION WITH TADALAFIL
5MG LETAIRIS GILEAD N022081 June 15, 2007 RX TABLET ORAL 9474752 Dec. 11, 2027 FOR THE TREATMENT OF PULMONARY HYPERTENSION (PAH) IN COMBINATION WITH TADALAFIL
10MG LETAIRIS GILEAD N022081 June 15, 2007 RX TABLET ORAL 9549926 Oct. 14, 2031 FOR THE TREATMENT OF PULMONARY ARTERIAL HYPERTENSION (PAH) IN COMBINATION WITH TADALAFIL, WHEREIN THE WEIGHT RATIO OF AMBRISENTAN TO TADALAFIL IS ABOUT 1:2 TO ABOUT 1:3
5MG LETAIRIS GILEAD N022081 June 15, 2007 RX TABLET ORAL 9549926 Oct. 14, 2031 FOR THE TREATMENT OF PULMONARY ARTERIAL HYPERTENSION (PAH) IN COMBINATION WITH TADALAFIL, WHEREIN THE WEIGHT RATIO OF AMBRISENTAN TO TADALAFIL IS ABOUT 1:2 TO ABOUT 1:3

Orange Book exclusivity data (new drug applications)

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Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRouteExclusivity dateDescription
10MG LETAIRIS GILEAD N022081 June 15, 2007 RX TABLET ORAL Oct. 2, 2018 REVISED INDICATION TO INCLUDE LANGUAGE ABOUT THE BENEFITS OF USING LETAIRIS IN COMBINATION WITH TADALAFIL TO REDUCE THE RISK OF DISEASE PROGRESSION AND HOSPITALIZATION FOR WORSENING PAH AND TO IMPROVE EXERCISE ABILITY, BASED ON THE AMBITION STUDY
5MG LETAIRIS GILEAD N022081 June 15, 2007 RX TABLET ORAL Oct. 2, 2018 REVISED INDICATION TO INCLUDE LANGUAGE ABOUT THE BENEFITS OF USING LETAIRIS IN COMBINATION WITH TADALAFIL TO REDUCE THE RISK OF DISEASE PROGRESSION AND HOSPITALIZATION FOR WORSENING PAH AND TO IMPROVE EXERCISE ABILITY, BASED ON THE AMBITION STUDY

Bioactivity Summary:

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TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Endothelin-1 receptor GPCR ANTAGONIST Ki 9.65 WOMBAT-PK DRUG LABEL
Endothelin B receptor GPCR ANTAGONIST Ki 6.98 WOMBAT-PK

External reference:

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IDSource
3951 IUPHAR_LIGAND_ID
4026238 VUID
N0000179774 NUI
C1176329 UMLSCUI
D07077 KEGG_DRUG
CHEMBL1111 ChEMBL_ID
DB06403 DRUGBANK_ID
358274 RXNORM
23940 MMSL
d06841 MMSL
4026238 VANDF
427735003 SNOMEDCT_US
428159003 SNOMEDCT_US
N0000179774 NDFRT
N0000176107 NDFRT
012216 NDDF
6918493 PUBCHEM_CID
HW6NV07QEC UNII
8128 INN_ID
C467894 MESH_SUPPLEMENTAL_RECORD_UI
CHEBI:135949 CHEBI

Pharmaceutical products:

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ProductCategoryIngredientsNDCFormQuantityRoute MarketingLabel
Letairis HUMAN PRESCRIPTION DRUG LABEL 1 61958-0801 TABLET, FILM COATED 5 mg ORAL NDA 20 sections
Letairis HUMAN PRESCRIPTION DRUG LABEL 1 61958-0802 TABLET, FILM COATED 10 mg ORAL NDA 20 sections