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

Stem definition	Drug id	CAS RN
	4881	1030377-33-3

Description:

Molecule	Description
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: 4.79 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

Molecule

Description

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: 4.79
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:

Property	Value	Reference
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

Approvals:

Date	Agency	Company	Orphan
Aug. 13, 2014	FDA	MERCK SHARP DOHME

FDA Adverse Event Reporting System (Female)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Drug ineffective	554.93	23.13	512	4512	816733	52527309
Nightmare	167.70	23.13	63	4961	17688	53326354
Insomnia	146.70	23.13	129	4895	186943	53157099
Abnormal dreams	143.01	23.13	49	4975	10552	53333490
Somnolence	116.27	23.13	108	4916	167626	53176416
Sleep paralysis	115.70	23.13	23	5001	567	53343475
Poor quality sleep	92.98	23.13	41	4983	17282	53326760
Wrong technique in product usage process	87.68	23.13	60	4964	59972	53284070
No adverse event	81.52	23.13	49	4975	39216	53304826
Product dose omission issue	78.10	23.13	93	4931	191527	53152515
Feeling abnormal	74.67	23.13	77	4947	135224	53208818
Initial insomnia	58.64	23.13	21	5003	5134	53338908
Product packaging quantity issue	57.40	23.13	15	5009	1274	53342768
Middle insomnia	49.98	23.13	23	5001	10685	53333357
Product blister packaging issue	46.20	23.13	9	5015	199	53343843
Hallucination	45.75	23.13	39	4985	53799	53290243
Therapeutic product effect incomplete	39.69	23.13	46	4978	91738	53252304
Sleep terror	38.49	23.13	10	5014	830	53343212
Sleep disorder	36.99	23.13	36	4988	58834	53285208
Altered state of consciousness	36.62	23.13	25	4999	24811	53319231
Inappropriate schedule of product administration	31.48	23.13	37	4987	74841	53269201
Suicidal ideation	25.59	23.13	30	4994	60481	53283561
Headache	24.87	23.13	108	4916	536713	52807329
Product quality issue	23.92	23.13	23	5001	37000	53307042
Circumstance or information capable of leading to medication error	23.79	23.13	10	5014	3744	53340298

FDA Adverse Event Reporting System (Male)

MedDRA adverse event term	Likelihood ratio	Likelihood ratio threshold	Patients taking drug having adverse event	Patients taking drug not having adverse event	Patients not taking drug having adverse event	Patients not taking drug not having adverse event
Drug ineffective	419.90	24.01	317	2758	383160	32127291
Nightmare	139.99	24.01	51	3024	13115	32497336
Poor quality sleep	84.73	24.01	31	3044	8043	32502408
Abnormal dreams	82.95	24.01	31	3044	8533	32501918
Somnolence	81.92	24.01	72	3003	103725	32406726
Wrong technique in product usage process	65.66	24.01	41	3034	35018	32475433
Insomnia	55.05	24.01	57	3018	100291	32410160
Sleep paralysis	53.25	24.01	10	3065	180	32510271
Hepatic function abnormal	47.56	24.01	37	3038	44803	32465648
No adverse event	46.71	24.01	27	3048	20026	32490425
Delirium	41.69	24.01	34	3041	44012	32466439
Sleep disorder	39.55	24.01	27	3048	26725	32483726
Therapeutic product effect incomplete	39.31	24.01	32	3043	41309	32469142
Middle insomnia	36.84	24.01	16	3059	6468	32503983
Hangover	35.79	24.01	10	3065	1089	32509362
Interstitial lung disease	32.16	24.01	35	3040	64966	32445485
Oesophageal dilatation	30.30	24.01	6	3069	144	32510307
Initial insomnia	29.28	24.01	11	3064	3061	32507390
Product packaging quantity issue	29.07	24.01	8	3067	823	32509628
Feeling abnormal	28.95	24.01	32	3043	60391	32450060

Pharmacologic Action:

Source	Code	Description
ATC	N05CM19	NERVOUS SYSTEM PSYCHOLEPTICS HYPNOTICS AND SEDATIVES Other hypnotics and sedatives
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
MeSH PA	D000068796	Orexin Receptor Antagonists
MeSH PA	D000068776	Sleep Aids, Pharmaceutical
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	CNS depressants
CHEBI has role	CHEBI:83296	orexin receptor antagonists

Drug Use (View source of the data)

Disease	Relation	SNOMED_ID	DOID
Insomnia	indication	193462001
Narcolepsy	contraindication	60380001	DOID:8986

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	0.96	Basic

Orange Book patent data (new drug applications)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Patent number	Patent expiration date	Patent 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)

Formulation strength	Trade name	Applicant	Application number	Approval date	Type	Dose form	Route	Exclusivity date	Description
10MG	BELSOMRA	MERCK SHARP DOHME	N204569	Aug. 13, 2014	RX	TABLET	ORAL	Jan. 29, 2023	INFORMATION ADDED TO THE LABELING TO DESCRIBE STUDY P061, A RANDOMIZED, PLACEBO-CONTROLLED, PARALLEL GROUP, MULTI-SITE, DOUBLE-BLIND STUDY TO EVALUATE SAFETY AND EFFICACY OF SUVOREXANT FOR THE TREATMENT OF INSOMNIA IN SUBJECTS WITH ALZHEIMERS DISEASE
15MG	BELSOMRA	MERCK SHARP DOHME	N204569	Aug. 13, 2014	RX	TABLET	ORAL	Jan. 29, 2023	INFORMATION ADDED TO THE LABELING TO DESCRIBE STUDY P061, A RANDOMIZED, PLACEBO-CONTROLLED, PARALLEL GROUP, MULTI-SITE, DOUBLE-BLIND STUDY TO EVALUATE SAFETY AND EFFICACY OF SUVOREXANT FOR THE TREATMENT OF INSOMNIA IN SUBJECTS WITH ALZHEIMERS DISEASE
20MG	BELSOMRA	MERCK SHARP DOHME	N204569	Aug. 13, 2014	RX	TABLET	ORAL	Jan. 29, 2023	INFORMATION ADDED TO THE LABELING TO DESCRIBE STUDY P061, A RANDOMIZED, PLACEBO-CONTROLLED, PARALLEL GROUP, MULTI-SITE, DOUBLE-BLIND STUDY TO EVALUATE SAFETY AND EFFICACY OF SUVOREXANT FOR THE TREATMENT OF INSOMNIA IN SUBJECTS WITH ALZHEIMERS DISEASE
5MG	BELSOMRA	MERCK SHARP DOHME	N204569	Aug. 13, 2014	RX	TABLET	ORAL	Jan. 29, 2023	INFORMATION ADDED TO THE LABELING TO DESCRIBE STUDY P061, A RANDOMIZED, PLACEBO-CONTROLLED, PARALLEL GROUP, MULTI-SITE, DOUBLE-BLIND STUDY TO EVALUATE SAFETY AND EFFICACY OF SUVOREXANT FOR THE TREATMENT OF INSOMNIA IN SUBJECTS WITH ALZHEIMERS DISEASE

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Bioact source	MoA source
Orexin receptor type 1	GPCR	O43613	OX1R_HUMAN	ANTAGONIST	Ki	9.26	SCIENTIFIC LITERATURE	SCIENTIFIC LITERATURE
Orexin receptor type 2	GPCR	O43614	OX2R_HUMAN	ANTAGONIST	Ki	9.46	SCIENTIFIC LITERATURE	SCIENTIFIC LITERATURE
Orexin receptor type 2	GPCR		OX2R_MOUSE		Ki	8.06	CHEMBL
Orexin receptor type 1	GPCR		OX1R_MOUSE		Ki	8.77	CHEMBL

External reference:

ID	Source
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
C551624	MESH_SUPPLEMENTAL_RECORD_UI
2890	IUPHAR_LIGAND_ID
9435	INN_ID
1547099	RXNORM
227824	MMSL
30487	MMSL
d08281	MMSL
015650	NDDF
708714001	SNOMEDCT_US
715609002	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
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