safinamide 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | PK/Tox | Related Drugs | BioActivity |

Stem definitionDrug idCAS RN
4921 133865-89-1

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • EMD-1195686
  • safinamide
  • xadago
  • EMD 1195686
  • safinamide mesylate
  • safinamide mesilate
  • safinamide methanesulfonate
Safinamide acts through both dopaminergic and non-dopaminergic mechanisms of action. Safinamide is a highly selective and reversible MAO-B inhibitor causing an increase in extracellular levels of dopamine in the striatum. Safinamide is associated with state-dependent inhibition of voltage-gated sodium (Na+) channels, and modulation of stimulated release of glutamate. To what extent the nondopaminergic effects contribute to the overall effect has not been established.
  • Molecular weight: 302.35
  • Formula: C17H19FN2O2
  • CLOGP: 2.49
  • LIPINSKI: 0
  • HAC: 4
  • HDO: 2
  • TPSA: 64.35
  • ALOGS: -4.49
  • ROTB: 7
  • Status: OFP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

DoseUnitRoute
75 mg O

ADMET properties:

PropertyValueReference
Vd (Volume of distribution) 2.19 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 1.17 mL/min/kg Lombardo F, Berellini G, Obach RS
t_half (Half-life) 21.67 hours Lombardo F, Berellini G, Obach RS
S (Water solubility) 80 mg/mL Bocci G, Oprea TI, Benet LZ
BDDCS (Biopharmaceutical Drug Disposition Classification System) 1 Bocci G, Oprea TI, Benet LZ
BA (Bioavailability) 86 %

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 2.156 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 1.452 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 28.708 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 3.846 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 12.730 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 25.090 % High 1
herg hERG pIC50 4.697 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 1.641 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 3.724 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 15.940 % High 1
kinase-safety-class ACVR2B,AXL,BRAF,BTK,CAMK2D,CDK5,CDK9,EIF2AK3,ERBB2,GRK2,ITK,MAPK10,MET,NTRK2,PDK1,PDK2,PDK4,PIK3CB,PRKDC,TEK,TGFBR1 21
kinase-selectivity-class AXL,EIF2AK3,GRK2,MAP2K6 4
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 5.248 High 1
mh-clint Mouse hepatocyte intrinsic clearance 11.803 High 1
mppb Mouse plasma protein binding (% unbound) 9.640 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 13.062 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 22.150 % High 1
rh-clint Rat hepatocyte intrinsic clearance 28.314 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 60.380 % High 1
rppb Rat plasma protein binding (% unbound) 10.800 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 734.514 uM High 1

Approvals:

DateAgencyCompanyOrphan
Sept. 20, 2019 PMDA Meiji Seika Pharma Co., Ltd.
March 21, 2017 FDA NEWRON PHARMS US INC
Dec. 18, 2014 EMA Zambon SpA

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
Dyskinesia 158.15 43.61 41 776 36493 90591137
On and off phenomenon 150.27 43.61 25 792 2518 90625112
Parkinsonism hyperpyrexia syndrome 82.86 43.61 11 806 231 90627399
Freezing phenomenon 73.95 43.61 13 804 1799 90625831
Fall 60.86 43.61 43 774 481767 90145863
Hallucination 54.70 43.61 21 796 65938 90561692

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
Hallucination 126.59 39.52 53 1346 57454 42562482
Freezing phenomenon 113.32 39.52 23 1376 1866 42618070
Dyskinesia 104.65 39.52 37 1362 25353 42594583
On and off phenomenon 99.40 39.52 23 1376 3444 42616492
Bradykinesia 70.00 39.52 19 1380 5417 42614519
Reduced facial expression 53.79 39.52 12 1387 1521 42618415
Akinesia 53.14 39.52 13 1386 2459 42617477
Muscle rigidity 51.22 39.52 18 1381 12041 42607895
Device dislocation 50.44 39.52 16 1383 7815 42612121
Duplicate therapy error 45.74 39.52 8 1391 288 42619648
Tremor 40.76 39.52 30 1369 96899 42523037
Hyperkinesia 39.89 39.52 10 1389 2088 42617848
Delirium tremens 39.68 39.52 8 1391 624 42619312

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
On and off phenomenon 220.25 35.93 42 2022 4382 110582853
Dyskinesia 210.94 35.93 65 1999 51381 110535854
Hallucination 164.16 35.93 64 2000 101368 110485867
Freezing phenomenon 162.97 35.93 30 2034 2579 110584656
Bradykinesia 81.58 35.93 22 2042 10766 110576469
Reduced facial expression 76.97 35.93 17 2047 3634 110583601
Parkinsonism hyperpyrexia syndrome 64.51 35.93 11 2053 607 110586628
Hallucination, visual 63.91 35.93 25 2039 39580 110547655
Hyperkinesia 62.58 35.93 14 2050 3170 110584065
Muscle rigidity 60.33 35.93 21 2043 24010 110563225
Hypokinesia 58.38 35.93 20 2044 21806 110565429
Akinesia 55.32 35.93 13 2051 3654 110583581
Dystonia 51.39 35.93 19 2045 25786 110561449
Fall 50.53 35.93 59 2005 603423 109983812
Tremor 49.22 35.93 36 2028 202196 110385039
Duplicate therapy error 47.10 35.93 8 2056 431 110586804
Delirium tremens 42.81 35.93 8 2056 743 110586492
Therapeutic response shortened 41.88 35.93 17 2047 29566 110557669
Serum serotonin increased 41.25 35.93 7 2057 375 110586860
Gait disturbance 41.10 35.93 37 2027 278171 110309064

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC N04BD03 NERVOUS SYSTEM
ANTI-PARKINSON DRUGS
DOPAMINERGIC AGENTS
Monoamine oxidase B inhibitors
FDA MoA N0000175761 Monoamine Oxidase-B Inhibitors
FDA EPC N0000175762 Monoamine Oxidase Type B Inhibitor
FDA MoA N0000190113 Breast Cancer Resistance Protein Inhibitors
CHEBI has role CHEBI:48407 antiparkinson drug
CHEBI has role CHEBI:231911 renoprotective agent

Related Drugs by ATC class:

N04BD Monoamine oxidase B inhibitors 2 drugs
rasagilineselegiline

Drug Use | Suggest Off label Use Form| |View source of the data|

DiseaseRelationSNOMED_IDDOID
Parkinson's disease indication 49049000 DOID:14330




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 12.92 acidic
pKa2 7.54 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
EQ 100MG BASE XADAGO MDD US N207145 March 21, 2017 RX TABLET ORAL 8278485 June 8, 2027 ADJUNCTIVE TREATMENT TO LEVODOPA/CARBIDOPA IN PATIENTS WITH PARKINSONS DISEASE EXPERIENCING OFF EPISODES
EQ 50MG BASE XADAGO MDD US N207145 March 21, 2017 RX TABLET ORAL 8278485 June 8, 2027 ADJUNCTIVE TREATMENT TO LEVODOPA/CARBIDOPA IN PATIENTS WITH PARKINSONS DISEASE EXPERIENCING OFF EPISODES
EQ 100MG BASE XADAGO MDD US N207145 March 21, 2017 RX TABLET ORAL 8076515 Dec. 10, 2028 ADJUNCTIVE TREATMENT TO LEVODOPA/CARBIDOPA IN PATIENTS WITH PARKINSONS DISEASE EXPERIENCING OFF EPISODES
EQ 50MG BASE XADAGO MDD US N207145 March 21, 2017 RX TABLET ORAL 8076515 Dec. 10, 2028 ADJUNCTIVE TREATMENT TO LEVODOPA/CARBIDOPA IN PATIENTS WITH PARKINSONS DISEASE EXPERIENCING OFF EPISODES
EQ 100MG BASE XADAGO MDD US N207145 March 21, 2017 RX TABLET ORAL 8283380 March 21, 2031 ADJUNCTIVE TREATMENT TO LEVODOPA/CARBIDOPA IN PATIENTS WITH PARKINSONS DISEASE EXPERIENCING OFF EPISODES
EQ 50MG BASE XADAGO MDD US N207145 March 21, 2017 RX TABLET ORAL 8283380 March 21, 2031 ADJUNCTIVE TREATMENT TO LEVODOPA/CARBIDOPA IN PATIENTS WITH PARKINSONS DISEASE EXPERIENCING OFF EPISODES

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Amine oxidase [flavin-containing] B Enzyme INHIBITOR Ki 6.35 SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
Amine oxidase [flavin-containing] A Enzyme IC50 4.35 CHEMBL
Sodium channel protein type 9 subunit alpha Ion channel IC50 4.48 CHEMBL
Sigma non-opioid intracellular receptor 1 Membrane receptor IC50 7.71 CHEMBL
Amine oxidase [flavin-containing] A Enzyme IC50 5.55 CHEMBL
Sodium channel alpha subunits; brain (Types I, II, III) Ion channel IC50 5.09 CHEMBL
Amine oxidase [flavin-containing] B Enzyme IC50 7.59 CHEMBL

External reference:

IDSource
90ENL74SIG UNII
D10158 KEGG_DRUG
202825-46-5 SECONDARY_CAS_RN
4036707 VANDF
C1098261 UMLSCUI
CHEBI:134718 CHEBI
SAG PDB_CHEM_ID
CHEMBL396778 ChEMBL_ID
131682 PUBCHEM_CID
DB06654 DRUGBANK_ID
CHEMBL48582 ChEMBL_ID
8013 INN_ID
C092797 MESH_SUPPLEMENTAL_RECORD_UI
8291 IUPHAR_LIGAND_ID
1922448 RXNORM
241367 MMSL
d08444 MMSL
016557 NDDF
016558 NDDF
1217565003 SNOMEDCT_US
718852000 SNOMEDCT_US
763521008 SNOMEDCT_US
90ENL74SIG INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
Xadago HUMAN PRESCRIPTION DRUG LABEL 1 27505-110 TABLET, FILM COATED 50 mg ORAL NDA 31 sections
Xadago HUMAN PRESCRIPTION DRUG LABEL 1 27505-110 TABLET, FILM COATED 50 mg ORAL NDA 31 sections
Xadago HUMAN PRESCRIPTION DRUG LABEL 1 27505-111 TABLET, FILM COATED 100 mg ORAL NDA 31 sections
Xadago HUMAN PRESCRIPTION DRUG LABEL 1 27505-111 TABLET, FILM COATED 100 mg ORAL NDA 31 sections