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

Stem definitionDrug idCAS RN
muscarinic receptors antagonists 784 133099-04-4

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • enablex
  • darifenacin
  • darifenacin hydrobromide
  • emselex
a competitive muscarinic receptor antagonist with greater affinity for the M3 receptor than for the other known muscarinic receptors, M3 receptors are involved in contraction of human bladder and gastrointestinal smooth muscle, saliva production, and iris sphincter function
  • Molecular weight: 426.56
  • Formula: C28H30N2O2
  • CLOGP: 3.62
  • LIPINSKI: 0
  • HAC: 4
  • HDO: 1
  • TPSA: 55.56
  • ALOGS: -6.16
  • ROTB: 7

  • Status: OFP

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

Drug dosage:

DoseUnitRoute
7.50 mg O

ADMET properties:

PropertyValueReference
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine) 12.50 % Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose) 0.41 ┬ÁM/kg/day Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability) 17 % Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution) 2.60 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 12 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.02 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 3.60 hours Lombardo F, Berellini G, Obach RS

Approvals:

DateAgencyCompanyOrphan
Oct. 22, 2004 EMA Merus Labs Luxco S.a R.L.
Dec. 22, 2004 FDA WARNER CHILCOTT LLC

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
Asphyxia 213.39 38.51 32 239 972 2356842
Arteriosclerosis coronary artery 200.86 38.51 31 240 1142 2356672
Dry mouth 107.64 38.51 25 246 8228 2349586
Constipation 50.23 38.51 17 254 21612 2336202

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

Pharmacologic Action:

SourceCodeDescription
ATC G04BD10 GENITO URINARY SYSTEM AND SEX HORMONES
UROLOGICALS
UROLOGICALS
Drugs for urinary frequency and incontinence
FDA EPC N0000175700 Cholinergic Muscarinic Antagonist
FDA MoA N0000000125 Cholinergic Muscarinic Antagonists
MeSH PA D018678 Cholinergic Agents
MeSH PA D018680 Cholinergic Antagonists
MeSH PA D018727 Muscarinic Antagonists
MeSH PA D018377 Neurotransmitter Agents
CHEBI has role CHEBI:48876 muscarinic antagonist
CHEBI has role CHEBI:53784 antispasmodic drug
MeSH PA D064804 Urological Agents

Drug Use (View source of the data)

DiseaseRelationSNOMED_IDDOID
Urgent desire to urinate indication 75088002
Urge incontinence of urine indication 87557004
Bladder muscle dysfunction - overactive indication 236633002
Increased Urinary Frequency indication
Angioedema contraindication 41291007 DOID:1558
Hepatic failure contraindication 59927004
Ulcerative colitis contraindication 64766004 DOID:8577
Myasthenia gravis contraindication 91637004 DOID:437
Gastrointestinal obstruction contraindication 126765001
Acute constipation contraindication 197119006
Disease of liver contraindication 235856003 DOID:409
Bladder outflow obstruction contraindication 236645006
Retention of urine contraindication 267064002
Gastric retention contraindication 307227006
Angle-closure glaucoma contraindication 392291006 DOID:13550

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 8.6 Basic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])
Mechanism
action
Bioact sourceMoA source
Muscarinic acetylcholine receptor M3 GPCR ANTAGONIST Kd 9.52 CHEMBL CHEMBL
Muscarinic acetylcholine receptor M1 GPCR Ki 8.30 CHEMBL
Muscarinic acetylcholine receptor M4 GPCR Ki 8.10 CHEMBL
Muscarinic acetylcholine receptor M5 GPCR Ki 8.64 CHEMBL
Beta-2 adrenergic receptor GPCR Ki 7.21 CHEMBL
Beta-1 adrenergic receptor GPCR IC50 6.50 CHEMBL
Muscarinic acetylcholine receptor M2 GPCR ANTAGONIST Ki 7.60 CHEMBL
D(2) dopamine receptor GPCR IC50 4.60 CHEMBL
Muscarinic acetylcholine receptor M3 GPCR Ki 8.60 CHEMBL
Muscarinic acetylcholine receptor M2 GPCR Ki 7.20 CHEMBL

External reference:

IDSource
C1310721 UMLSCUI
D01699 KEGG_DRUG
416385001 SNOMEDCT_US
136198 RXNORM
416140008 SNOMEDCT_US
19114 MMSL
d05422 MMSL
4024903 VANDF
008802 NDDF
APG9819VLM UNII
7153 INN_ID
133099-07-7 SECONDARY_CAS_RN
CHEMBL1346 ChEMBL_ID
DB00496 DRUGBANK_ID
C101207 MESH_SUPPLEMENTAL_RECORD_UI
CHEBI:391960 CHEBI
321 IUPHAR_LIGAND_ID
CHEMBL1200935 ChEMBL_ID
444031 PUBCHEM_CID

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Enablex HUMAN PRESCRIPTION DRUG LABEL 1 0430-0170 TABLET, EXTENDED RELEASE 7.50 mg ORAL NDA 17 sections
Enablex HUMAN PRESCRIPTION DRUG LABEL 1 0430-0171 TABLET, EXTENDED RELEASE 15 mg ORAL NDA 17 sections
Darifenacin HUMAN PRESCRIPTION DRUG LABEL 1 0591-4375 TABLET, EXTENDED RELEASE 7.50 mg ORAL NDA 17 sections
Darifenacin HUMAN PRESCRIPTION DRUG LABEL 1 0591-4380 TABLET, EXTENDED RELEASE 15 mg ORAL NDA 17 sections
Darifenacin Hydrobromide HUMAN PRESCRIPTION DRUG LABEL 1 10370-170 TABLET, EXTENDED RELEASE 7.50 mg ORAL ANDA 18 sections
Darifenacin Hydrobromide HUMAN PRESCRIPTION DRUG LABEL 1 10370-171 TABLET, EXTENDED RELEASE 15 mg ORAL ANDA 18 sections
Darifenacin HUMAN PRESCRIPTION DRUG LABEL 1 13668-202 TABLET, EXTENDED RELEASE 7.50 mg ORAL ANDA 16 sections
Darifenacin HUMAN PRESCRIPTION DRUG LABEL 1 13668-203 TABLET, EXTENDED RELEASE 15 mg ORAL ANDA 16 sections
Darifenacin HUMAN PRESCRIPTION DRUG LABEL 1 33342-276 TABLET, EXTENDED RELEASE 7.50 mg ORAL ANDA 18 sections
Darifenacin HUMAN PRESCRIPTION DRUG LABEL 1 33342-277 TABLET, EXTENDED RELEASE 15 mg ORAL ANDA 18 sections
DARIFENACIN HUMAN PRESCRIPTION DRUG LABEL 1 46708-223 TABLET, EXTENDED RELEASE 7.50 mg ORAL ANDA 17 sections
DARIFENACIN HUMAN PRESCRIPTION DRUG LABEL 1 46708-224 TABLET, EXTENDED RELEASE 15 mg ORAL ANDA 17 sections
Enablex HUMAN PRESCRIPTION DRUG LABEL 1 54868-5363 TABLET, EXTENDED RELEASE 15 mg ORAL NDA 12 sections
Enablex HUMAN PRESCRIPTION DRUG LABEL 1 54868-5704 TABLET, EXTENDED RELEASE 7.50 mg ORAL NDA 12 sections
darifenacin HUMAN PRESCRIPTION DRUG LABEL 1 59746-516 TABLET, EXTENDED RELEASE 7.50 mg ORAL ANDA 18 sections
darifenacin HUMAN PRESCRIPTION DRUG LABEL 1 59746-517 TABLET, EXTENDED RELEASE 15 mg ORAL ANDA 18 sections
Darifenacin Hydrobromide HUMAN PRESCRIPTION DRUG LABEL 1 60429-850 TABLET, EXTENDED RELEASE 7.50 mg ORAL ANDA 18 sections
Darifenacin Hydrobromide HUMAN PRESCRIPTION DRUG LABEL 1 60429-851 TABLET, EXTENDED RELEASE 15 mg ORAL ANDA 18 sections
DARIFENACIN HUMAN PRESCRIPTION DRUG LABEL 1 62332-223 TABLET, EXTENDED RELEASE 7.50 mg ORAL ANDA 18 sections
DARIFENACIN HUMAN PRESCRIPTION DRUG LABEL 1 62332-224 TABLET, EXTENDED RELEASE 15 mg ORAL ANDA 18 sections
Darifenacin HUMAN PRESCRIPTION DRUG LABEL 1 65862-861 TABLET, FILM COATED, EXTENDED RELEASE 7.50 mg ORAL ANDA 17 sections
Darifenacin HUMAN PRESCRIPTION DRUG LABEL 1 65862-862 TABLET, FILM COATED, EXTENDED RELEASE 15 mg ORAL ANDA 17 sections
Darifenacin HUMAN PRESCRIPTION DRUG LABEL 1 69097-431 TABLET, EXTENDED RELEASE 7.50 mg ORAL ANDA 18 sections
Darifenacin HUMAN PRESCRIPTION DRUG LABEL 1 69097-432 TABLET, EXTENDED RELEASE 15 mg ORAL ANDA 18 sections