ramelteon 🐶 Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definition	Drug id	CAS RN
	2355	196597-26-9

Description:

Molecule	Description
Molfile Inchi Smiles Synonyms: ramelteon rozerem TAK-375	Ramelteon is a melatonin receptor agonist with both high affinity for melatonin MT1 and MT2 receptors and selectivity over the MT3 receptor. Ramelteon demonstrates full agonist activity in vitro in cells expressing human MT1 or MT2 receptors. The activity of ramelteon at the MT1 and MT2 receptors is believed to contribute to its sleep-promoting properties, as these receptors, acted upon by endogenous melatonin, are thought to be involved in the maintenance of the circadian rhythm underlying the normal sleep-wake cycle. Molecular weight: 259.35 Formula: C16H21NO2 CLOGP: 2.48 LIPINSKI: 0 HAC: 3 HDO: 1 TPSA: 38.33 ALOGS: -4.20 ROTB: 4 Status: OFP Legend: OFP - off patent OFM - off market ONP - on patent

Molecule

Description

Molfile Inchi Smiles

Synonyms:

ramelteon
rozerem
TAK-375

Ramelteon is a melatonin receptor agonist with both high affinity for melatonin MT1 and MT2 receptors and selectivity over the MT3 receptor. Ramelteon demonstrates full agonist activity in vitro in cells expressing human MT1 or MT2 receptors. The activity of ramelteon at the MT1 and MT2 receptors is believed to contribute to its sleep-promoting properties, as these receptors, acted upon by endogenous melatonin, are thought to be involved in the maintenance of the circadian rhythm underlying the normal sleep-wake cycle.

Molecular weight: 259.35
Formula: C16H21NO2
CLOGP: 2.48
LIPINSKI: 0
HAC: 3
HDO: 1
TPSA: 38.33
ALOGS: -4.20
ROTB: 4

Status: OFP

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

Drug dosage:

None

ADMET properties:

Property	Value	Reference
BDDCS (Biopharmaceutical Drug Disposition Classification System)	1	Benet LZ, Broccatelli F, Oprea TI
EoM (Fraction excreted unchanged in urine)	0.10 %	Benet LZ, Broccatelli F, Oprea TI
MRTD (Maximum Recommended Therapeutic Daily Dose)	0.44 µM/kg/day	Contrera JF, Matthews EJ, Kruhlak NL, Benz RD
BA (Bioavailability)	1.80 %	Kim MT, Sedykh A, Chakravarti SK, Saiakhov RD, Zhu H
Vd (Volume of distribution)	1.05 L/kg	Lombardo F, Berellini G, Obach RS
CL (Clearance)	13.10 mL/min/kg	Lombardo F, Berellini G, Obach RS
fu (Fraction unbound in plasma)	0.20 %	Lombardo F, Berellini G, Obach RS
t_half (Half-life)	1.90 hours	Lombardo F, Berellini G, Obach RS

Approvals:

Date	Agency	Company	Orphan
July 22, 2005	FDA	TAKEDA PHARMS USA

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
Abnormal dreams	129.89	17.28	45	5065	9332	50590682
Initial insomnia	121.70	17.28	37	5073	5078	50594936
Nightmare	116.37	17.28	48	5062	16038	50583976
Middle insomnia	108.63	17.28	40	5070	9881	50590133
Somnolence	69.90	17.28	82	5028	154903	50445111
Product dispensing error	69.29	17.28	28	5082	8863	50591151
Poor quality sleep	61.12	17.28	31	5079	16615	50583399
Altered state of consciousness	37.88	17.28	25	5085	21885	50578129
Ovarian cancer recurrent	37.31	17.28	10	5100	872	50599142
Hallucination	36.03	17.28	33	5077	46624	50553390
Hepatic function abnormal	35.23	17.28	28	5082	32653	50567361
Restlessness	30.24	17.28	23	5087	25150	50574864
Somnambulism	29.94	17.28	13	5097	4911	50595103
Intentional overdose	29.64	17.28	34	5076	62470	50537544
Galactorrhoea	26.53	17.28	11	5099	3712	50596302
Feeling abnormal	24.80	17.28	45	5065	125447	50474567
Hangover	24.50	17.28	8	5102	1381	50598633
Hypersomnia	22.95	17.28	16	5094	15298	50584716
Drug eruption	22.85	17.28	19	5091	23587	50576427
Blood pressure decreased	22.53	17.28	28	5082	55881	50544133
Anxiety	20.34	17.28	51	5059	177555	50422459
Impulsive behaviour	20.18	17.28	7	5103	1451	50598563
Hallucination, visual	19.58	17.28	15	5095	16567	50583447
Interstitial lung disease	18.86	17.28	25	5085	53151	50546863

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
Somnolence	66.91	17.69	70	3643	93885	29476929
Initial insomnia	65.48	17.69	21	3692	2754	29568060
Hangover	52.47	17.69	14	3699	963	29569851
Nightmare	50.87	17.69	26	3687	11391	29559423
Middle insomnia	50.70	17.69	21	3692	5687	29565127
Abnormal dreams	50.03	17.69	22	3691	6898	29563916
Pneumonia aspiration	46.90	17.69	38	3675	36699	29534115
Interstitial lung disease	37.46	17.69	41	3672	57677	29513137
Hepatic function abnormal	34.78	17.69	33	3680	39226	29531588
Poor quality sleep	33.75	17.69	17	3696	7216	29563598
Disseminated intravascular coagulation	30.53	17.69	23	3690	19957	29550857
Delirium	29.11	17.69	30	3683	39367	29531447
Cerebral infarction	28.29	17.69	24	3689	24651	29546163
Upper respiratory tract inflammation	25.32	17.69	9	3704	1611	29569203
Restlessness	20.33	17.69	19	3694	22126	29548688
Enterocolitis	18.19	17.69	11	3702	6655	29564159

FDA Adverse Event Reporting System (Geriatric)

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
Initial insomnia	104.99	15.77	35	7242	5769	64485686
Middle insomnia	84.32	15.77	37	7240	12840	64478615
Somnolence	73.44	15.77	102	7175	203543	64287912
Hepatic function abnormal	65.86	15.77	56	7221	64257	64427198
Poor quality sleep	65.05	15.77	35	7242	18916	64472539
Pneumonia aspiration	63.55	15.77	53	7224	59218	64432237
Abnormal dreams	59	15.77	27	7250	10329	64481126
Hangover	53.23	15.77	16	7261	1885	64489570
Interstitial lung disease	51.14	15.77	59	7218	97673	64393782
Altered state of consciousness	49.37	15.77	38	7239	37864	64453591
Nightmare	48.59	15.77	30	7247	20963	64470492
Delirium	41.73	15.77	45	7232	69149	64422306
Restlessness	41.44	15.77	35	7242	39750	64451705
Disseminated intravascular coagulation	34.80	15.77	29	7248	32319	64459136
Cerebral infarction	32.62	15.77	31	7246	41013	64450442
Drug eruption	30.07	15.77	28	7249	36108	64455347
Femoral neck fracture	29.62	15.77	16	7261	8708	64482747
Intentional overdose	26.46	15.77	41	7236	89903	64401552
Hypersomnia	26.17	15.77	20	7257	19697	64471758
Upper respiratory tract inflammation	25.18	15.77	11	7266	3771	64487684
Marasmus	22.99	15.77	7	7270	861	64490594
Renal impairment	21.26	15.77	47	7230	134970	64356485
Arthralgia	20.90	15.77	12	7265	442248	64049207
Product administered to patient of inappropriate age	20.11	15.77	10	7267	4591	64486864
Hallucination	19.78	15.77	32	7245	72756	64418699
Platelet count decreased	19.57	15.77	52	7225	167659	64323796
Blood pressure decreased	18.32	15.77	34	7243	86165	64405290
Hallucination, visual	16.58	15.77	18	7259	27816	64463639
Respiratory failure	15.87	15.77	47	7230	161136	64330319

FDA Adverse Event Reporting System (Pediatric)

None

Pharmacologic Action:

Source	Code	Description
ATC	N05CH02	NERVOUS SYSTEM PSYCHOLEPTICS HYPNOTICS AND SEDATIVES Melatonin receptor agonists
FDA MoA	N0000000250	Melatonin Receptor Agonists
FDA EPC	N0000175743	Melatonin Receptor Agonist

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

Disease	Relation	SNOMED_ID	DOID
Initial insomnia	indication	59050008
Suicidal thoughts	contraindication	6471006
Alcoholism	contraindication	7200002
Depressive disorder	contraindication	35489007
Hepatic failure	contraindication	59927004
Sleep apnea	contraindication	73430006	DOID:0050847
Disease of liver	contraindication	235856003	DOID:409
Hyperprolactinemia	contraindication	237662005	DOID:12700
Sleep automatism	contraindication	247962006

🐶 Veterinary Drug Use

None

🐶 Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation level	Dissociation constant	Type (acidic/basic)
pKa1	13.14	acidic

Orange Book patent data (new drug applications)

None

Orange Book exclusivity data (new drug applications)

None

Bioactivity Summary:

Target	Class	Pharos	UniProt	Action	Type	Activity value (-log[M])	Mechanism action	Bioact source	MoA source
Melatonin receptor type 1A	GPCR	P48039	MTR1A_HUMAN	AGONIST	Ki	10.90		WOMBAT-PK	CHEMBL
Melatonin receptor type 1B	GPCR	P49286	MTR1B_HUMAN	AGONIST	Ki	10.39		WOMBAT-PK	CHEMBL

External reference:

ID	Source
4024923	VUID
N0000171613	NUI
D02689	KEGG_DRUG
4024923	VANDF
C1565316	UMLSCUI
CHEBI:109549	CHEBI
JEV	PDB_CHEM_ID
CHEMBL1218	ChEMBL_ID
DB00980	DRUGBANK_ID
C495910	MESH_SUPPLEMENTAL_RECORD_UI
208902	PUBCHEM_CID
1356	IUPHAR_LIGAND_ID
8447	INN_ID
901AS54I69	UNII
596205	RXNORM
20324	MMSL
320752	MMSL
70325	MMSL
d05578	MMSL
010947	NDDF
419588002	SNOMEDCT_US
419878007	SNOMEDCT_US

Pharmaceutical products:

Product	Category	Ingredients	NDC	Form	Quantity	Route	Marketing	Label
Ramelteon	HUMAN PRESCRIPTION DRUG LABEL	1	0591-2191	TABLET	8 mg	ORAL	ANDA	27 sections
Ramelteon	HUMAN PRESCRIPTION DRUG LABEL	1	0591-2191	TABLET	8 mg	ORAL	ANDA	27 sections
Ramelteon	HUMAN PRESCRIPTION DRUG LABEL	1	0832-1250	TABLET, FILM COATED	8 mg	ORAL	ANDA	30 sections
Rozerem	HUMAN PRESCRIPTION DRUG LABEL	1	21695-183	TABLET, FILM COATED	8 mg	ORAL	NDA	30 sections
Ramelteon	HUMAN PRESCRIPTION DRUG LABEL	1	42291-776	TABLET	8 mg	ORAL	ANDA	26 sections
Ramelteon	HUMAN PRESCRIPTION DRUG LABEL	1	43598-741	TABLET	8 mg	ORAL	ANDA	25 sections
Ramelteon	HUMAN PRESCRIPTION DRUG LABEL	1	43598-741	TABLET	8 mg	ORAL	ANDA	25 sections
Ramelteon	HUMAN PRESCRIPTION DRUG LABEL	1	50268-708	TABLET	8 mg	ORAL	ANDA	26 sections
Ramelteon	HUMAN PRESCRIPTION DRUG LABEL	1	50268-708	TABLET	8 mg	ORAL	ANDA	26 sections
Ramelteon	HUMAN PRESCRIPTION DRUG LABEL	1	51407-375	TABLET	8 mg	ORAL	ANDA	26 sections
Ramelteon	HUMAN PRESCRIPTION DRUG LABEL	1	51407-375	TABLET	8 mg	ORAL	ANDA	26 sections
Ramelteon	HUMAN PRESCRIPTION DRUG LABEL	1	52817-235	TABLET, FILM COATED	8 mg	ORAL	ANDA	28 sections
Rozerem	HUMAN PRESCRIPTION DRUG LABEL	1	54868-5649	TABLET, FILM COATED	8 mg	ORAL	NDA	18 sections
Ramelteon	HUMAN PRESCRIPTION DRUG LABEL	1	55700-874	TABLET, FILM COATED	8 mg	ORAL	ANDA	28 sections
Ramelteon	HUMAN PRESCRIPTION DRUG LABEL	1	63629-8264	TABLET	8 mg	ORAL	ANDA	28 sections
Ramelteon	HUMAN PRESCRIPTION DRUG LABEL	1	63629-8264	TABLET	8 mg	ORAL	ANDA	28 sections
Ramelteon	HUMAN PRESCRIPTION DRUG LABEL	1	63629-8531	TABLET	8 mg	ORAL	ANDA	26 sections
Ramelteon	HUMAN PRESCRIPTION DRUG LABEL	1	63629-8531	TABLET	8 mg	ORAL	ANDA	26 sections
Rozerem	HUMAN PRESCRIPTION DRUG LABEL	1	64764-805	TABLET, FILM COATED	8 mg	ORAL	NDA	27 sections
Rozerem	HUMAN PRESCRIPTION DRUG LABEL	1	68151-4881	TABLET, FILM COATED	8 mg	ORAL	NDA	28 sections
Ramelteon	HUMAN PRESCRIPTION DRUG LABEL	1	70010-028	TABLET	8 mg	ORAL	ANDA	26 sections
Ramelteon	HUMAN PRESCRIPTION DRUG LABEL	1	70710-1344	TABLET	8 mg	ORAL	ANDA	27 sections
Ramelteon	HUMAN PRESCRIPTION DRUG LABEL	1	70771-1495	TABLET	8 mg	ORAL	ANDA	1 sections
Ramelteon	HUMAN PRESCRIPTION DRUG LABEL	1	71205-918	TABLET	8 mg	ORAL	ANDA	26 sections
Ramelteon	HUMAN PRESCRIPTION DRUG LABEL	1	71205-918	TABLET	8 mg	ORAL	ANDA	26 sections
Ramelteon	HUMAN PRESCRIPTION DRUG LABEL	1	71335-1853	TABLET	8 mg	ORAL	ANDA	27 sections
RAMELTEON	HUMAN PRESCRIPTION DRUG LABEL	1	72189-153	TABLET	8 mg	ORAL	ANDA	16 sections
Ramelteon	HUMAN PRESCRIPTION DRUG LABEL	1	72319-005	TABLET, FILM COATED	8 mg	ORAL	ANDA	28 sections