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

Stem definitionDrug idCAS RN
orexin receptor antagonists 4881 1030377-33-3

Description:

MoleculeDescription

Molfile Inchi Smiles

Synonyms:

  • MK 4305
  • suvorexant
  • belsomra
  • MK-4305
a highly selective antagonist for orexin receptors OX1R and OX2R, the orexin neuropeptide signaling system is a central promoter of wakefulness, blocking the binding of wake-promoting neuropeptides orexin A and orexin B to receptors OX1R and OX2R is thought to suppress wake drive
  • Molecular weight: 450.93
  • Formula: C23H23ClN6O2
  • CLOGP: 5.10
  • LIPINSKI: 0
  • HAC: 8
  • HDO: 0
  • TPSA: 80.29
  • ALOGS: -3.58
  • ROTB: 3
  • Status: ONP
    • Legend:
    OFP - off patent
    OFM - off market
    ONP - on patent

Drug dosage:

None

ADMET properties:

PropertyValueReference
Vd (Volume of distribution) 0.69 L/kg Lombardo F, Berellini G, Obach RS
CL (Clearance) 0.84 mL/min/kg Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma) 0.05 % Lombardo F, Berellini G, Obach RS
t_half (Half-life) 10.37 hours Lombardo F, Berellini G, Obach RS
BA (Bioavailability) 0.62 % Kawashima H, Watanabe R, Esaki T, Kuroda M, Nagao C, Natsume-Kitatani Y, Ohashi R, Komura H, Mizuguchi K

Predicted pharmacokinetic/toxicological properties (PK-AZ):

PropertyDescriptionValueUnitConfidenceSimilarity
azlogd74 LogD at pH 7.4 3.895 High 1
caco2-efflux Caco-2 efflux ratio (BA/AB) 1.059 High 1
caco2-intrinsic-papp Caco-2 intrinsic apparent permeability 62.661 10^-6 cm/s High 1
dh-clint Dog hepatocyte intrinsic clearance 39.628 uL/min/10^6 cells High 1
dppb Dog plasma protein binding (% unbound) 0.610 % High 1
fcs-ppb Fetal calf serum protein binding (% unbound) 1.630 % High 1
herg hERG pIC50 4.978 pIC50 High 1
hh-clint Human hepatocyte intrinsic clearance 45.499 uL/min/10^6 cells High 1
hlm-clint Human liver microsomal intrinsic clearance 210.378 uL/min/mg protein High 1
hppb Human plasma protein binding (% unbound) 0.780 % High 1
kinase-safety-class ACVR2B,EIF2AK3,GRK2,PDK1,PDK2,PDK4,PRKDC 7
mdck-mdr1-efflux MDCK-MDR1 efflux ratio 0.411 High 1
mh-clint Mouse hepatocyte intrinsic clearance 212.324 High 1
mppb Mouse plasma protein binding (% unbound) 0.940 High 1
nih-mdck-mdr1-efflux NIH MDCK-MDR1 efflux ratio 1.552 High 1
pfas-class PFAS structural alert (1 = True, 0 = False) 0
pppb Pig plasma protein binding (% unbound) 1.830 % High 1
rh-clint Rat hepatocyte intrinsic clearance 204.644 uL/min/10^6 cells High 1
rh-fuinc Rat hepatocyte fraction unbound in incubation 12.100 % High 1
rppb Rat plasma protein binding (% unbound) 1.090 % High 1
solubility-dd Solubility at pH 7.4 in DMSO 7.516 uM High 1

Approvals:

DateAgencyCompanyOrphan
Aug. 13, 2014 FDA MERCK SHARP DOHME

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
Drug ineffective 489.04 19.09 554 6300 1383744 89237849
Nightmare 198.39 19.09 71 6783 21654 90599939
Abnormal dreams 162.88 19.09 52 6802 11205 90610388
Somnolence 145.98 19.09 123 6731 208961 90412632
Sleep paralysis 140.73 19.09 28 6826 870 90620723
Wrong technique in product usage process 104.74 19.09 66 6788 71505 90550088
Poor quality sleep 93.87 19.09 43 6811 24650 90596943
No adverse event 87.89 19.09 58 6796 67924 90553669
Feeling abnormal 80.55 19.09 80 6774 167155 90454438
Hallucination 79.79 19.09 54 6800 65905 90555688
Product dose omission issue 78.26 19.09 103 6751 291584 90330009
Initial insomnia 64.99 19.09 25 6829 9285 90612308
Product packaging quantity issue 62.27 19.09 16 6838 1586 90620007
Altered state of consciousness 56.16 19.09 33 6821 31499 90590094
Product blister packaging issue 43.70 19.09 9 6845 333 90621260
Middle insomnia 42.10 19.09 22 6832 16729 90604864
Suicidal ideation 33.06 19.09 34 6820 73821 90547772
Inappropriate schedule of product administration 31.26 19.09 47 6807 149886 90471707
Restlessness 31.16 19.09 24 6830 35696 90585897
Therapeutic product effect incomplete 29.87 19.09 53 6801 193843 90427750
Intentional overdose 29.62 19.09 36 6818 93798 90527795
Agitation 28.43 19.09 30 6824 67068 90554525
Completed suicide 28.17 19.09 44 6810 145014 90476579
Overdose 26.76 19.09 45 6809 157664 90463929
Poor quality product administered 25.27 19.09 10 6844 3998 90617595
Anxiety 24.89 19.09 65 6789 309707 90311886
Sleep terror 24.23 19.09 10 6844 4454 90617139
Somnambulism 24.14 19.09 11 6843 6217 90615376
Parkinsonism 23.16 19.09 14 6840 14051 90607542
Swelling 21.68 19.09 3 6851 419055 90202538
Hallucination, auditory 21.52 19.09 14 6840 15961 90605632
Abnormal sleep-related event 21.14 19.09 6 6848 865 90620728
Renal impairment 20.49 19.09 32 6822 105389 90516204
Headache 20.48 19.09 123 6731 862623 89758970
Circumstance or information capable of leading to medication error 19.97 19.09 9 6845 4958 90616635
Product quality issue 19.65 19.09 27 6827 79298 90542295
Cardiac failure 19.58 19.09 32 6822 109464 90512129
Fall 19.49 19.09 80 6774 481730 90139863
Hangover 19.38 19.09 7 6847 2182 90619411
Delirium 19.34 19.09 31 6823 104328 90517265
Palpitations 19.30 19.09 36 6818 136692 90484901
Therapeutic product effect delayed 19.23 19.09 8 6846 3633 90617960
Suicide attempt 19.18 19.09 26 6828 75373 90546220

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
Drug ineffective 294.26 20.64 340 4090 629857 41987048
Nightmare 118.84 20.64 56 4374 24956 42591949
Abnormal dreams 92.02 20.64 34 4396 8237 42608668
Poor quality sleep 73.68 20.64 30 4400 9410 42607495
Somnolence 67.47 20.64 78 4352 141027 42475878
Delirium 59.84 20.64 47 4383 52472 42564433
Hepatic function abnormal 58.43 20.64 46 4384 51521 42565384
Wrong technique in product usage process 54.80 20.64 41 4389 42594 42574311
Sleep paralysis 46.33 20.64 10 4420 336 42616569
Interstitial lung disease 45.42 20.64 48 4382 78414 42538491
No adverse event 44.60 20.64 35 4395 38986 42577919
Product packaging quantity issue 37.11 20.64 11 4419 1342 42615563
Middle insomnia 35.50 20.64 17 4413 7816 42609089
Overdose 31.14 20.64 46 4384 105218 42511687
Altered state of consciousness 30.76 20.64 25 4405 29234 42587671
Hangover 30.11 20.64 9 4421 1129 42615776
Therapeutic product effect incomplete 28.55 20.64 36 4394 70903 42546002
Oesophageal dilatation 26.56 20.64 6 4424 249 42616656
Feeling abnormal 24.33 20.64 33 4397 69753 42547152
Therapeutic product effect delayed 23.54 20.64 8 4422 1517 42615388
Initial insomnia 22.16 20.64 10 4420 4020 42612885
Sleep disorder 21.92 20.64 26 4404 48069 42568836
Liver disorder 20.71 20.64 23 4407 39621 42577284

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
Drug ineffective 542.55 17.28 670 9342 1519870 109059417
Nightmare 265.87 17.28 108 9904 38755 110540532
Abnormal dreams 186.18 17.28 62 9950 12718 110566569
Somnolence 167.50 17.28 168 9844 297281 110282006
Sleep paralysis 152.70 17.28 31 9981 887 110578400
Poor quality sleep 129.23 17.28 59 9953 28018 110551269
Wrong technique in product usage process 113.30 17.28 80 9932 87268 110492019
Hallucination 83.59 17.28 71 9941 101361 110477926
Feeling abnormal 80.08 17.28 90 9922 180621 110398666
Altered state of consciousness 79.89 17.28 55 9957 57571 110521716
Hepatic function abnormal 74.59 17.28 63 9949 89232 110490055
Delirium 68.08 17.28 72 9940 134953 110444334
Initial insomnia 68.00 17.28 28 9984 10361 110568926
Interstitial lung disease 64.46 17.28 71 9941 139263 110440024
Middle insomnia 63.88 17.28 33 9979 20469 110558818
Overdose 41.19 17.28 75 9937 233719 110345568
Hangover 39.88 17.28 13 9999 2489 110576798
Product packaging quantity issue 39.77 17.28 12 10000 1787 110577500
Suicidal ideation 38.55 17.28 45 9967 93892 110485395
Therapeutic product effect incomplete 38.42 17.28 71 9941 223734 110355553
Somnambulism 37.67 17.28 16 9996 6389 110572898
Therapeutic product effect delayed 36.00 17.28 14 9998 4465 110574822
Inappropriate schedule of product administration 35.45 17.28 65 9947 203572 110375715
Cerebral infarction 32.25 17.28 31 9981 51807 110527480
Restlessness 31.94 17.28 32 9980 56227 110523060
Pneumonia aspiration 30.18 17.28 37 9975 81196 110498091
Cardiac failure 26.68 17.28 55 9957 187571 110391716
Suicide attempt 24.64 17.28 38 9974 103356 110475931
Infusion related reaction 24.23 17.28 3 10009 381159 110198128
Intentional overdose 23.94 17.28 43 9969 132458 110446829
Product dose omission issue 22.37 17.28 72 9940 321710 110257577
Radiation pneumonitis 22.34 17.28 10 10002 4526 110574761
Stoma site hypergranulation 22.24 17.28 6 10006 598 110578689
Oesophageal dilatation 22.12 17.28 6 10006 611 110578676
Underdose 22.08 17.28 28 9984 63526 110515761
Renal impairment 21.97 17.28 51 9961 188394 110390893
Parkinsonism 21.33 17.28 17 9995 22170 110557117
Agitation 20.82 17.28 37 9975 113014 110466273
Sleep disorder 20.20 17.28 51 9961 198593 110380694
Completed suicide 19.42 17.28 57 9955 242324 110336963
Immune-mediated hepatic disorder 19.36 17.28 9 10003 4441 110574846
Cholangitis 18.96 17.28 14 9998 16321 110562966
Pneumonia bacterial 18.83 17.28 17 9995 26244 110553043
Loss of consciousness 18.52 17.28 49 9963 196257 110383030
Drug hypersensitivity 18.49 17.28 9 10003 454081 110125206
Circumstance or information capable of leading to medication error 17.98 17.28 9 10003 5224 110574063
Femoral neck fracture 17.41 17.28 12 10000 12555 110566732

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

SourceCodeDescription
ATC N05CJ01 NERVOUS SYSTEM
PSYCHOLEPTICS
HYPNOTICS AND SEDATIVES
Orexin receptor antagonists
MeSH PA D000068776 Sleep Aids, Pharmaceutical
MeSH PA D000068796 Orexin Receptor Antagonists
MeSH PA D002491 Central Nervous System Agents
MeSH PA D002492 Central Nervous System Depressants
MeSH PA D006993 Hypnotics and Sedatives
MeSH PA D018377 Neurotransmitter Agents
FDA MoA N0000185503 P-Glycoprotein Inhibitors
FDA MoA N0000190114 Cytochrome P450 3A Inhibitors
FDA MoA N0000190998 Orexin Receptor Antagonists
FDA EPC N0000191000 Orexin Receptor Antagonist
CHEBI has role CHEBI:35488 central nervous system depressant
CHEBI has role CHEBI:83296 orexin receptor antagonist

Related Drugs by ATC class:

N05CJ Orexin receptor antagonists 2 drugs
daridorexantlemborexant

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

DiseaseRelationSNOMED_IDDOID
Insomnia indication 193462001
Narcolepsy contraindication 60380001 DOID:8986




🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 0.96 Basic

Orange Book patent data (new drug applications)

Formulation strengthTrade nameApplicantApplication numberApproval dateTypeDose formRoutePatent numberPatent expiration datePatent use
10MG BELSOMRA MERCK SHARP DOHME N204569 Aug. 13, 2014 RX TABLET ORAL 7951797 Nov. 20, 2029 TREATMENT OF INSOMNIA
15MG BELSOMRA MERCK SHARP DOHME N204569 Aug. 13, 2014 RX TABLET ORAL 7951797 Nov. 20, 2029 TREATMENT OF INSOMNIA
20MG BELSOMRA MERCK SHARP DOHME N204569 Aug. 13, 2014 RX TABLET ORAL 7951797 Nov. 20, 2029 TREATMENT OF INSOMNIA
5MG BELSOMRA MERCK SHARP DOHME N204569 Aug. 13, 2014 RX TABLET ORAL 7951797 Nov. 20, 2029 TREATMENT OF INSOMNIA

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

TargetClassPharosUniProtActionTypeActivity value
(-log[M])		Mechanism
action		Bioact sourceMoA source
Orexin receptor type 1 GPCR ANTAGONIST Ki 9.26 SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
Orexin receptor type 2 GPCR ANTAGONIST Ki 9.46 SCIENTIFIC LITERATURE SCIENTIFIC LITERATURE
Orexin receptor type 2 GPCR Ki 8.06 CHEMBL
Orexin receptor type 1 GPCR Ki 8.77 CHEMBL
Orexin receptor type 2 GPCR ANTAGONIST Ki 9 IUPHAR

External reference:

IDSource
081L192FO9 UNII
D10082 KEGG_DRUG
4033910 VUID
N0000191283 NUI
4033910 VANDF
C3179535 UMLSCUI
CHEBI:82698 CHEBI
SUV PDB_CHEM_ID
CHEMBL1083659 ChEMBL_ID
24965990 PUBCHEM_CID
DB09034 DRUGBANK_ID
9435 INN_ID
C551624 MESH_SUPPLEMENTAL_RECORD_UI
2890 IUPHAR_LIGAND_ID
1547099 RXNORM
227824 MMSL
30487 MMSL
d08281 MMSL
015650 NDDF
708714001 SNOMEDCT_US
715609002 SNOMEDCT_US
081L192FO9 INXIGHT DRUGS

Pharmaceutical products:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
BELSOMRA HUMAN PRESCRIPTION DRUG LABEL 1 0006-0005 TABLET, FILM COATED 5 mg ORAL NDA 36 sections
BELSOMRA HUMAN PRESCRIPTION DRUG LABEL 1 0006-0033 TABLET, FILM COATED 10 mg ORAL NDA 36 sections
BELSOMRA HUMAN PRESCRIPTION DRUG LABEL 1 0006-0325 TABLET, FILM COATED 15 mg ORAL NDA 36 sections
BELSOMRA HUMAN PRESCRIPTION DRUG LABEL 1 0006-0335 TABLET, FILM COATED 20 mg ORAL NDA 36 sections