ramelteon ๐Ÿถ Veterinary Use | Indications/Contra | FAERs-F | FAERs-M | Orange Bk | BioActivity |

Stem definitionDrug idCAS RN
2355 196597-26-9

Description:

MoleculeDescription

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:

PropertyValueReference
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 ยตM/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:

DateAgencyCompanyOrphan
July 22, 2005 FDA TAKEDA PHARMS USA

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
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 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
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 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
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:

SourceCodeDescription
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|

DiseaseRelationSNOMED_IDDOID
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




๐Ÿถ Veterinary Drug Use

None

๐Ÿถ Veterinary products

None

Acid dissociation constants calculated using MoKa v3.0.0

Dissociation levelDissociation constantType (acidic/basic)
pKa1 13.14 acidic

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
Melatonin receptor type 1A GPCR AGONIST Ki 10.90 WOMBAT-PK CHEMBL
Melatonin receptor type 1B GPCR AGONIST Ki 10.39 WOMBAT-PK CHEMBL

External reference:

IDSource
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:

ProductCategoryIngredientsNDCFormQuantityRouteMarketingLabel
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