darifenacin 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | 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: 4.28
  • 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 µM/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

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 2.616 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 5.821 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 14.421 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 18.155 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 8.200 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 19.350 % High 1
herg hERG pIC50 5.935 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 25.351 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 302.691 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 11.440 % High 1
kinase-safety-class ACVR2B,AKT2,AKT3,AXL,BRAF,BTK,CAMK2B,CAMK2D,CDK5,CDK9,EIF2AK3,EPHB4,ERBB2,GRK2,ITK,JAK3,MAP3K7,MAPK10,MAPK12,MAPK7,MAPKAPK2,MET,NTRK2,PDK2,PDK4,PIK3CB,PIM2,PRKDC,TEK,TGFBR1 30
kinase-selectivity-class AXL,EIF2AK3,GRK2,PDK4 4
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 7.228 High 1
mh-clint Mouse hepatocyte intrinsic clearance 121.899 High 1
mppb Mouse plasma protein binding (% unbound) 12.910 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 28.249 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pld-class Phospholipidosis risk class (1 = positive, 0 = negative) 1 High 1
pppb Pig plasma protein binding (% unbound) 22.070 % High 1
rh-clint Rat hepatocyte intrinsic clearance 146.555 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 43.360 % High 1
rppb Rat plasma protein binding (% unbound) 14.320 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 334.965 uM High 1

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
Pneumonia viral 513.45 35.03 107 3289 8716 90616335
Soft tissue disorder 417.90 35.03 80 3316 4210 90620841
Herpes zoster 388.37 35.03 142 3254 94502 90530549
Liver function test abnormal 260.03 35.03 90 3306 50755 90574296
Oral pain 227.40 35.03 73 3323 32610 90592441
Leukopenia 209.98 35.03 93 3303 100617 90524434
Asphyxia 201.96 35.03 48 3348 7055 90617996
Arteriosclerosis coronary artery 177.80 35.03 46 3350 9557 90615494
Arthritis 176.18 35.03 97 3299 167218 90457833
Peripheral swelling 161.92 35.03 129 3267 412977 90212074
Blood cholesterol increased 151.47 35.03 95 3301 207917 90417134
Fibromyalgia 149.68 35.03 94 3302 206175 90418876
Synovitis 131.15 35.03 104 3292 329648 90295403
Anaemia 112.61 35.03 98 3298 352704 90272347
Infection 87.16 35.03 86 3310 362008 90263043
Tenderness 83.32 35.03 33 3363 26835 90598216
Joint swelling 79.97 35.03 96 3300 503204 90121847
Therapeutic product effect incomplete 57.90 35.03 52 3344 193844 90431207
Drug ineffective 49.02 35.03 137 3259 1384161 89240890
Soft tissue swelling 48.05 35.03 11 3385 1367 90623684
Complement factor C4 decreased 37.99 35.03 7 3389 296 90624755
Complement factor C3 decreased 37.69 35.03 7 3389 309 90624742

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
Duplicate therapy error 47.77 43.92 7 400 289 42620639

FDA Adverse Event Reporting System (Geriatric)

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
Pneumonia viral 326.28 32.94 72 2801 11085 110575341
Soft tissue disorder 240.56 32.94 46 2827 3478 110582948
Herpes zoster 212.08 32.94 86 2787 108293 110478133
Asphyxia 191.30 32.94 49 2824 14166 110572260
Arteriosclerosis coronary artery 150.77 32.94 46 2827 25072 110561354
Liver function test abnormal 125.39 32.94 52 2821 68898 110517528
Oral pain 117.41 32.94 42 2831 37402 110549024
Arthritis 99.66 32.94 59 2814 167527 110418899
Fibromyalgia 95.99 32.94 58 2815 170851 110415575
Peripheral swelling 95.89 32.94 81 2792 403953 110182473
Leukopenia 95.36 32.94 55 2818 148736 110437690
Blood cholesterol increased 91.82 32.94 58 2815 184727 110401699
Synovitis 88.69 32.94 66 2807 274026 110312400
Tenderness 73.71 32.94 28 2845 29409 110557017
Therapeutic product effect incomplete 59.45 32.94 48 2825 223757 110362669
Joint swelling 51.01 32.94 60 2813 442785 110143641
Anaemia 46.95 32.94 64 2809 547022 110039404
Infection 46.62 32.94 52 2821 362148 110224278
Urinary tract infection 42.24 32.94 47 2826 326235 110260191
Complement factor C4 decreased 39.29 32.94 7 2866 356 110586070
Complement factor C3 decreased 38.95 32.94 7 2866 374 110586052
Soft tissue swelling 38.66 32.94 9 2864 1740 110584686
Duplicate therapy error 37.96 32.94 7 2866 432 110585994
Neuralgia 33.88 32.94 19 2854 48459 110537967
Arthralgia 33.79 32.94 67 2806 779565 109806861

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

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

Related Drugs by ATC class:

G04BD Drugs for urinary frequency and incontinence 13 drugs
emeproniumfesoterodineflavoxateimidafenacinmeladrazinemirabegronoxybutyninpropiverinesolifenacinterodilinetolterodinetrospium show all 13 →

Drug Use | Suggest Off label Use Form| |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




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

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
Beta-2 adrenergic receptor GPCR Ki 7.21 CHEMBL
D(2) dopamine receptor GPCR IC50 4.60 CHEMBL
Muscarinic acetylcholine receptor M1 GPCR Ki 8.30 CHEMBL
Muscarinic acetylcholine receptor M2 GPCR ANTAGONIST Ki 7.60 CHEMBL
Muscarinic acetylcholine receptor M4 GPCR Ki 8.10 CHEMBL
Muscarinic acetylcholine receptor M5 GPCR Ki 8.64 CHEMBL
Beta-1 adrenergic receptor GPCR IC50 6.50 CHEMBL
Muscarinic acetylcholine receptor M2 GPCR Ki 7.20 CHEMBL
Muscarinic acetylcholine receptor M3 GPCR Ki 8.60 CHEMBL

External reference:

IDSource
D01699 KEGG_DRUG
133099-07-7 SECONDARY_CAS_RN
136198 RXNORM
C0529351 UMLSCUI
CHEBI:391960 CHEBI
A1CIW PDB_CHEM_ID
CHEMBL1346 ChEMBL_ID
CHEMBL1200935 ChEMBL_ID
DB00496 DRUGBANK_ID
C101207 MESH_SUPPLEMENTAL_RECORD_UI
444031 PUBCHEM_CID
321 IUPHAR_LIGAND_ID
7153 INN_ID
APG9819VLM UNII
19114 MMSL
64038 MMSL
d05422 MMSL
008802 NDDF
008812 NDDF
416140008 SNOMEDCT_US
416385001 SNOMEDCT_US
426766002 SNOMEDCT_US
4024903 VANDF
APG9819VLM INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Darifenacin HUMAN PRESCRIPTION DRUG LABEL 1 13668-202 TABLET, EXTENDED RELEASE 7.50 mg ORAL ANDA 25 sections
Darifenacin HUMAN PRESCRIPTION DRUG LABEL 1 13668-203 TABLET, EXTENDED RELEASE 15 mg ORAL ANDA 25 sections
Darifenacin Human Prescription Drug Label 1 16571-767 TABLET, FILM COATED, EXTENDED RELEASE 7.50 mg ORAL ANDA 26 sections
Darifenacin Human Prescription Drug Label 1 16571-768 TABLET, FILM COATED, EXTENDED RELEASE 15 mg ORAL ANDA 26 sections
Darifenacin Human Prescription Drug Label 1 33342-276 TABLET, EXTENDED RELEASE 7.50 mg ORAL ANDA 26 sections
Darifenacin Human Prescription Drug Label 1 33342-277 TABLET, EXTENDED RELEASE 15 mg ORAL ANDA 26 sections
DARIFENACIN Human Prescription Drug Label 1 46708-223 TABLET, EXTENDED RELEASE 7.50 mg ORAL ANDA 26 sections
DARIFENACIN Human Prescription Drug Label 1 46708-224 TABLET, EXTENDED RELEASE 15 mg ORAL ANDA 26 sections
Darifenacin Human Prescription Drug Label 1 52605-067 TABLET, EXTENDED RELEASE 7.50 mg ORAL ANDA 27 sections
Darifenacin Human Prescription Drug Label 1 52605-068 TABLET, EXTENDED RELEASE 15 mg ORAL ANDA 27 sections
Enablex HUMAN PRESCRIPTION DRUG LABEL 1 54868-5363 TABLET, EXTENDED RELEASE 15 mg ORAL NDA 25 sections
Enablex HUMAN PRESCRIPTION DRUG LABEL 1 54868-5704 TABLET, EXTENDED RELEASE 7.50 mg ORAL NDA 25 sections
DARIFENACIN Human Prescription Drug Label 1 62332-223 TABLET, EXTENDED RELEASE 7.50 mg ORAL ANDA 26 sections
DARIFENACIN Human Prescription Drug Label 1 62332-224 TABLET, EXTENDED RELEASE 15 mg ORAL ANDA 26 sections
Darifenacin Human Prescription Drug Label 1 65862-861 TABLET, FILM COATED, EXTENDED RELEASE 7.50 mg ORAL ANDA 26 sections
Darifenacin Human Prescription Drug Label 1 65862-862 TABLET, FILM COATED, EXTENDED RELEASE 15 mg ORAL ANDA 26 sections
Darifenacin HUMAN PRESCRIPTION DRUG LABEL 1 69097-431 TABLET, EXTENDED RELEASE 7.50 mg ORAL ANDA 25 sections
Darifenacin HUMAN PRESCRIPTION DRUG LABEL 1 69097-431 TABLET, EXTENDED RELEASE 7.50 mg ORAL ANDA 25 sections
Darifenacin HUMAN PRESCRIPTION DRUG LABEL 1 69097-432 TABLET, EXTENDED RELEASE 15 mg ORAL ANDA 25 sections
Darifenacin HUMAN PRESCRIPTION DRUG LABEL 1 69097-432 TABLET, EXTENDED RELEASE 15 mg ORAL ANDA 25 sections
Darifenacin 7.5 mg HUMAN PRESCRIPTION DRUG LABEL 1 70700-182 TABLET, EXTENDED RELEASE 7.50 mg ORAL ANDA 25 sections
Darifenacin 15 mg HUMAN PRESCRIPTION DRUG LABEL 1 70700-183 TABLET, EXTENDED RELEASE 15 mg ORAL ANDA 25 sections
darifenacin HUMAN PRESCRIPTION DRUG LABEL 1 70754-161 TABLET, FILM COATED, EXTENDED RELEASE 7.50 mg ORAL ANDA 28 sections
darifenacin HUMAN PRESCRIPTION DRUG LABEL 1 70754-162 TABLET, FILM COATED, EXTENDED RELEASE 15 mg ORAL ANDA 28 sections
Darifenacin HUMAN PRESCRIPTION DRUG LABEL 1 72162-2570 TABLET, EXTENDED RELEASE 7.50 mg ORAL ANDA 25 sections
Darifenacin HUMAN PRESCRIPTION DRUG LABEL 1 72162-2571 TABLET, EXTENDED RELEASE 15 mg ORAL ANDA 25 sections