Details of the Drug

General Information of Drug (ID: DM7IW9J)

Drug Name
Ramelteon
Synonyms
Rozerem; Ramelteon [USAN]; Rozerem (TN); TAK-375; Ramelteon (JAN/USAN/INN); Rozerem, TAK-375, Ramelteon; N-[2-[(8S)-2,6,7,8-tetrahydro-1H-cyclopenta[e][1]benzofuran-8-yl]ethyl]propanamide; N-{2-[(8s)-1,6,7,8-tetrahydro-2h-indeno[5,4-b]fur-8-yl]ethyl}propanamid; (-)-N-(2-(((8S)-1,6,7,8-Tetrahydro-2H-indeno(5,4-b)furan-8-yl)ethyl)propanamide; (S)-N-(2-(1,6,7,8-tetrahydro-2H-indeno-(5,4)furan-8-yl)ethyl)propionamide
Indication
Disease Entry ICD 11 Status REF
Insomnia 7A00-7A0Z Approved [1]
Circadian rhythm sleep disorder 7A60-7A65 Terminated [1]
Therapeutic Class
Hypnotics and Sedatives
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 259.339
Logarithm of the Partition Coefficient (xlogp) 2.7
Rotatable Bond Count (rotbonds) 4
Hydrogen Bond Donor Count (hbonddonor) 1
Hydrogen Bond Acceptor Count (hbondacc) 2
ADMET Property
Absorption
The absorption of drug is at least 84% []
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability [2]
Clearance
The drug present in the plasma can be removed from the body at the rate of 13.1 mL/min/kg [3]
Elimination
0.1% of drug is excreted from urine in the unchanged form [2]
Half-life
The concentration or amount of drug in body reduced by one-half in 1 - 2.6 hours [3]
Metabolism
The drug is metabolized via the hepatic []
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 0.4407 micromolar/kg/day [4]
Unbound Fraction
The unbound fraction of drug in plasma is 0.2% [3]
Vd
The volume of distribution (Vd) of drug is 73.6 L []
Chemical Identifiers
Formula
C16H21NO2
IUPAC Name
N-[2-[(8S)-2,6,7,8-tetrahydro-1H-cyclopenta[e][1]benzofuran-8-yl]ethyl]propanamide
Canonical SMILES
CCC(=O)NCC[C@@H]1CCC2=C1C3=C(C=C2)OCC3
InChI
InChI=1S/C16H21NO2/c1-2-15(18)17-9-7-12-4-3-11-5-6-14-13(16(11)12)8-10-19-14/h5-6,12H,2-4,7-10H2,1H3,(H,17,18)/t12-/m0/s1
InChIKey
YLXDSYKOBKBWJQ-LBPRGKRZSA-N
Cross-matching ID
PubChem CID
208902
ChEBI ID
CHEBI:109549
CAS Number
196597-26-9
DrugBank ID
DB00980
TTD ID
D0U0KW
INTEDE ID
DR1391
ACDINA ID
D00581
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Melatonin receptor type 1A (MTNR1A) TT0WAIE MTR1A_HUMAN Modulator [5]
Melatonin receptor type 1B (MTNR1B) TT32JK8 MTR1B_HUMAN Modulator [5]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [6]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Substrate [7]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Substrate [6]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Eyes absent homolog 1 (EYA1) OTHU807A EYA1_HUMAN Gene/Protein Processing [8]
Fibroblast growth factor 8 (FGF8) OTFU0IUW FGF8_HUMAN Gene/Protein Processing [8]
Homeobox protein Hox-B7 (HOXB7) OTC7WYU8 HXB7_HUMAN Gene/Protein Processing [8]
Homeobox protein MOX-1 (MEOX1) OTJEMT2D MEOX1_HUMAN Gene/Protein Processing [8]
Homeobox protein unc-4 homolog OTOW7WTS UNC4_HUMAN Gene/Protein Processing [8]
Mesoderm posterior protein 2 (MESP2) OT7H4LYA MESP2_HUMAN Gene/Protein Processing [8]
Oligodendrocyte transcription factor 3 (OLIG3) OTU8XLAF OLIG3_HUMAN Gene/Protein Processing [8]
Paired box protein Pax-6 (PAX6) OTOC9876 PAX6_HUMAN Gene/Protein Processing [8]
Protein Wnt-5a OT27ZYKJ WNT5A_HUMAN Gene/Protein Processing [8]
Retinal dehydrogenase 2 (ALDH1A2) OTJB560Z AL1A2_HUMAN Gene/Protein Processing [8]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Drug-Drug Interaction (DDI) Information of This Drug

Coadministration of a Drug Treating the Disease Different from Ramelteon (Comorbidity)
DDI Drug Name DDI Drug ID Severity Mechanism Comorbidity REF
Metreleptin DM1NOEK Moderate Increased metabolism of Ramelteon caused by Metreleptin mediated induction of CYP450 enzyme. Acute diabete complication [5A2Y] [9]
Ivosidenib DM8S6T7 Moderate Increased metabolism of Ramelteon caused by Ivosidenib mediated induction of CYP450 enzyme. Acute myeloid leukaemia [2A60] [9]
Arn-509 DMT81LZ Moderate Increased metabolism of Ramelteon caused by Arn-509 mediated induction of CYP450 enzyme. Acute myeloid leukaemia [2A60] [9]
Oliceridine DM6MDCF Major Additive CNS depression effects by the combination of Ramelteon and Oliceridine. Acute pain [MG31] [10]
Posaconazole DMUL5EW Moderate Decreased metabolism of Ramelteon caused by Posaconazole mediated inhibition of CYP450 enzyme. Aspergillosis [1F20] [9]
Obeticholic acid DM3Q1SM Moderate Decreased metabolism of Ramelteon caused by Obeticholic acid mediated inhibition of CYP450 enzyme. Autoimmune liver disease [DB96] [9]
Clarithromycin DM4M1SG Moderate Decreased metabolism of Ramelteon caused by Clarithromycin mediated inhibition of CYP450 enzyme. Bacterial infection [1A00-1C4Z] [9]
Norfloxacin DMIZ6W2 Moderate Decreased metabolism of Ramelteon caused by Norfloxacin mediated inhibition of CYP450 enzyme. Bacterial infection [1A00-1C4Z] [9]
Troleandomycin DMUZNIG Moderate Decreased metabolism of Ramelteon caused by Troleandomycin mediated inhibition of CYP450 enzyme. Bacterial infection [1A00-1C4Z] [9]
Pexidartinib DMS2J0Z Moderate Increased metabolism of Ramelteon caused by Pexidartinib mediated induction of CYP450 enzyme. Bone/articular cartilage neoplasm [2F7B] [9]
Tucatinib DMBESUA Moderate Decreased metabolism of Ramelteon caused by Tucatinib mediated inhibition of CYP450 enzyme. Breast cancer [2C60-2C6Y] [9]
Alpelisib DMEXMYK Moderate Increased metabolism of Ramelteon caused by Alpelisib mediated induction of CYP450 enzyme. Breast cancer [2C60-2C6Y] [11]
Niclosamide DMJAGXQ Moderate Decreased metabolism of Ramelteon caused by Niclosamide mediated inhibition of CYP450 enzyme. Cestodes infection [1F70-1F76] [9]
Dihydrocodeine DMB0FWL Major Additive CNS depression effects by the combination of Ramelteon and Dihydrocodeine. Chronic pain [MG30] [12]
Osilodrostat DMIJC9X Moderate Decreased metabolism of Ramelteon caused by Osilodrostat mediated inhibition of CYP450 enzyme. Cushing syndrome [5A70] [9]
Lumacaftor DMCLWDJ Moderate Increased metabolism of Ramelteon caused by Lumacaftor mediated induction of CYP450 enzyme. Cystic fibrosis [CA25] [13]
MK-8228 DMOB58Q Moderate Decreased metabolism of Ramelteon caused by MK-8228 mediated inhibition of CYP450 enzyme. Cytomegaloviral disease [1D82] [14]
Nefazodone DM4ZS8M Moderate Decreased metabolism of Ramelteon caused by Nefazodone mediated inhibition of CYP450 enzyme. Depression [6A70-6A7Z] [9]
Esketamine DMVU687 Moderate Additive CNS depression effects by the combination of Ramelteon and Esketamine. Depression [6A70-6A7Z] [15]
Cenobamate DM8KLU9 Moderate Increased metabolism of Ramelteon caused by Cenobamate mediated induction of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [9]
Fosphenytoin DMOX3LB Moderate Increased metabolism of Ramelteon caused by Fosphenytoin mediated induction of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [9]
Phenobarbital DMXZOCG Moderate Increased metabolism of Ramelteon caused by Phenobarbital mediated induction of CYP450 enzyme. Epilepsy/seizure [8A61-8A6Z] [9]
Tazemetostat DMWP1BH Moderate Increased metabolism of Ramelteon caused by Tazemetostat mediated induction of CYP450 enzyme. Follicular lymphoma [2A80] [9]
Itraconazole DMCR1MV Moderate Decreased metabolism of Ramelteon caused by Itraconazole mediated inhibition of CYP450 enzyme. Fungal infection [1F29-1F2F] [9]
Miconazole DMPMYE8 Moderate Decreased metabolism of Ramelteon caused by Miconazole mediated inhibition of CYP450 enzyme. Fungal infection [1F29-1F2F] [9]
Ketoconazole DMPZI3Q Moderate Decreased metabolism of Ramelteon caused by Ketoconazole mediated inhibition of CYP450 enzyme. Fungal infection [1F29-1F2F] [9]
Sulfinpyrazone DMEV954 Moderate Increased metabolism of Ramelteon caused by Sulfinpyrazone mediated induction of CYP450 enzyme. Gout [FA25] [9]
Boceprevir DMBSHMF Moderate Decreased metabolism of Ramelteon caused by Boceprevir mediated inhibition of CYP450 enzyme. Hepatitis virus infection [1E50-1E51] [9]
Telaprevir DMMRV29 Moderate Decreased metabolism of Ramelteon caused by Telaprevir mediated inhibition of CYP450 enzyme. Hepatitis virus infection [1E50-1E51] [9]
Rifampin DMA8J1G Moderate Increased metabolism of Ramelteon caused by Rifampin mediated induction of CYP450 enzyme. HIV-infected patients with tuberculosis [1B10-1B14] [16]
Rifapentine DMCHV4I Moderate Increased metabolism of Ramelteon caused by Rifapentine mediated induction of CYP450 enzyme. HIV-infected patients with tuberculosis [1B10-1B14] [9]
Fosamprenavir DM4W9B3 Moderate Decreased metabolism of Ramelteon caused by Fosamprenavir mediated inhibition of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [9]
Cobicistat DM6L4H2 Moderate Decreased metabolism of Ramelteon caused by Cobicistat mediated inhibition of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [9]
Saquinavir DMG814N Moderate Decreased metabolism of Ramelteon caused by Saquinavir mediated inhibition of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [9]
Etravirine DMGV8QU Moderate Increased metabolism of Ramelteon caused by Etravirine mediated induction of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [9]
Darunavir DMN3GCH Moderate Decreased metabolism of Ramelteon caused by Darunavir mediated inhibition of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [17]
Atazanavir DMSYRBX Moderate Decreased metabolism of Ramelteon caused by Atazanavir mediated inhibition of CYP450 enzyme. Human immunodeficiency virus disease [1C60-1C62] [9]
Gemfibrozil DMD8Q3J Moderate Decreased metabolism of Ramelteon caused by Gemfibrozil mediated inhibition of CYP450 enzyme. Hyper-lipoproteinaemia [5C80] [9]
Fenofibrate DMFKXDY Moderate Decreased metabolism of Ramelteon caused by Fenofibrate mediated inhibition of CYP450 enzyme. Hyper-lipoproteinaemia [5C80] [15]
Teriflunomide DMQ2FKJ Moderate Increased metabolism of Ramelteon caused by Teriflunomide mediated induction of CYP450 enzyme. Hyper-lipoproteinaemia [5C80] [9]
Givosiran DM5PFIJ Moderate Decreased metabolism of Ramelteon caused by Givosiran mediated inhibition of CYP450 enzyme. Inborn porphyrin/heme metabolism error [5C58] [9]
Ceritinib DMB920Z Moderate Decreased metabolism of Ramelteon caused by Ceritinib mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [9]
PF-06463922 DMKM7EW Moderate Increased metabolism of Ramelteon caused by PF-06463922 mediated induction of CYP450 enzyme. Lung cancer [2C25] [9]
Osimertinib DMRJLAT Moderate Increased metabolism of Ramelteon caused by Osimertinib mediated induction of CYP450 enzyme. Lung cancer [2C25] [9]
Capmatinib DMYCXKL Moderate Decreased metabolism of Ramelteon caused by Capmatinib mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [9]
Selpercatinib DMZR15V Moderate Decreased metabolism of Ramelteon caused by Selpercatinib mediated inhibition of CYP450 enzyme. Lung cancer [2C25] [18]
Primaquine DMWQ16I Moderate Decreased metabolism of Ramelteon caused by Primaquine mediated inhibition of CYP450 enzyme. Malaria [1F40-1F45] [9]
Idelalisib DM602WT Moderate Decreased metabolism of Ramelteon caused by Idelalisib mediated inhibition of CYP450 enzyme. Mature B-cell leukaemia [2A82] [9]
IPI-145 DMWA24P Moderate Decreased metabolism of Ramelteon caused by IPI-145 mediated inhibition of CYP450 enzyme. Mature B-cell leukaemia [2A82] [19]
Vemurafenib DM62UG5 Moderate Decreased metabolism of Ramelteon caused by Vemurafenib mediated inhibition of CYP450 enzyme. Melanoma [2C30] [9]
Dabrafenib DMX6OE3 Moderate Increased metabolism of Ramelteon caused by Dabrafenib mediated induction of CYP450 enzyme. Melanoma [2C30] [9]
Allopregnanolone DMNLHAC Moderate Additive CNS depression effects by the combination of Ramelteon and Allopregnanolone. Mental/behavioural/neurodevelopmental disorder [6E20-6E8Z] [20]
Lasmiditan DMXLVDT Moderate Additive CNS depression effects by the combination of Ramelteon and Lasmiditan. Migraine [8A80] [21]
Exjade DMHPRWG Moderate Decreased metabolism of Ramelteon caused by Exjade mediated inhibition of CYP450 enzyme. Mineral absorption/transport disorder [5C64] [9]
Flibanserin DM70DTN Moderate Additive CNS depression effects by the combination of Ramelteon and Flibanserin. Mood disorder [6A60-6E23] [22]
Thalidomide DM70BU5 Moderate Additive CNS depression effects by the combination of Ramelteon and Thalidomide. Multiple myeloma [2A83] [23]
Fedratinib DM4ZBK6 Moderate Decreased metabolism of Ramelteon caused by Fedratinib mediated inhibition of CYP450 enzyme. Myeloproliferative neoplasm [2A20] [24]
Levomethadyl Acetate DM06HG5 Major Additive CNS depression effects by the combination of Ramelteon and Levomethadyl Acetate. Opioid use disorder [6C43] [12]
Rucaparib DM9PVX8 Moderate Decreased metabolism of Ramelteon caused by Rucaparib mediated inhibition of CYP450 enzyme. Ovarian cancer [2C73] [9]
Oxymorphone DM65AGJ Major Additive CNS depression effects by the combination of Ramelteon and Oxymorphone. Pain [MG30-MG3Z] [10]
Dezocine DMJDB0Y Major Additive CNS depression effects by the combination of Ramelteon and Dezocine. Pain [MG30-MG3Z] [10]
Abametapir DM2RX0I Moderate Decreased metabolism of Ramelteon caused by Abametapir mediated inhibition of CYP450 enzyme. Pediculosis [1G00] [25]
Lefamulin DME6G97 Moderate Decreased metabolism of Ramelteon caused by Lefamulin mediated inhibition of CYP450 enzyme. Pneumonia [CA40] [26]
Lonafarnib DMGM2Z6 Moderate Decreased metabolism of Ramelteon caused by Lonafarnib mediated inhibition of CYP450 enzyme. Premature ageing appearance [LD2B] [9]
Enzalutamide DMGL19D Moderate Increased metabolism of Ramelteon caused by Enzalutamide mediated induction of CYP450 enzyme. Prostate cancer [2C82] [9]
Dexamethasone DMMWZET Moderate Increased metabolism of Ramelteon caused by Dexamethasone mediated induction of CYP450 enzyme. Rheumatoid arthritis [FA20] [9]
Telotristat ethyl DMDIYFZ Moderate Increased metabolism of Ramelteon caused by Telotristat ethyl mediated induction of CYP450 enzyme. Small intestine developmental anomaly [DA90] [16]
Larotrectinib DM26CQR Moderate Decreased metabolism of Ramelteon caused by Larotrectinib mediated inhibition of CYP450 enzyme. Solid tumour/cancer [2A00-2F9Z] [15]
Armodafinil DMGB035 Moderate Increased metabolism of Ramelteon caused by Armodafinil mediated induction of CYP450 enzyme. Solid tumour/cancer [2A00-2F9Z] [9]
Fostamatinib DM6AUHV Moderate Decreased metabolism of Ramelteon caused by Fostamatinib mediated inhibition of CYP450 enzyme. Thrombocytopenia [3B64] [27]
Elagolix DMB2C0E Moderate Increased metabolism of Ramelteon caused by Elagolix mediated induction of CYP450 enzyme. Uterine fibroid [2E86] [9]
Propafenone DMPIBJK Moderate Decreased metabolism of Ramelteon caused by Propafenone mediated inhibition of CYP450 enzyme. Ventricular tachyarrhythmia [BC71] [9]
Amiodarone DMUTEX3 Moderate Decreased metabolism of Ramelteon caused by Amiodarone mediated inhibition of CYP450 enzyme. Ventricular tachyarrhythmia [BC71] [9]
⏷ Show the Full List of 73 DDI Information of This Drug

Drug Inactive Ingredient(s) (DIG) and Formulation(s) of This Drug

DIG
DIG Name DIG ID PubChem CID Functional Classification
Ferric hydroxide oxide yellow E00539 23320441 Colorant
Ferrosoferric oxide E00231 14789 Colorant
Hypromellose E00634 Not Available Coating agent
Lactose monohydrate E00393 104938 Binding agent; Diluent; Dry powder inhaler carrier; Lyophilization aid
Magnesium stearate E00208 11177 lubricant
Titanium dioxide E00322 26042 Coating agent; Colorant; Opacifying agent
⏷ Show the Full List of 6 Pharmaceutical Excipients of This Drug
Pharmaceutical Formulation
Formulation Name Drug Dosage Dosage Form Route
Ramelteon 8 mg tablet 8 mg Oral Tablet Oral
Jump to Detail Pharmaceutical Formulation Page of This Drug

References

1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 1356).
2 BDDCS applied to over 900 drugs
3 Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds
4 Estimating the safe starting dose in phase I clinical trials and no observed effect level based on QSAR modeling of the human maximum recommended daily dose
5 MT1 and MT2 melatonin receptors: ligands, models, oligomers, and therapeutic potential. J Med Chem. 2014 Apr 24;57(8):3161-85.
6 Metabolism of ramelteon in human liver microsomes and correlation with the effect of fluvoxamine on ramelteon pharmacokinetics. Drug Metab Dispos. 2010 Aug;38(8):1381-91.
7 Pharmacotherapy of insomnia with ramelteon: safety, efficacy and clinical applications. J Cent Nerv Syst Dis. 2011 Apr 12;3:51-65.
8 Exposure-based assessment of chemical teratogenicity using morphogenetic aggregates of human embryonic stem cells. Reprod Toxicol. 2020 Jan;91:74-91. doi: 10.1016/j.reprotox.2019.10.004. Epub 2019 Nov 8.
9 Product Information. Rozerem (ramelteon). Takeda Pharmaceuticals America, Lincolnshire, IL.
10 US Food and Drug Administration "FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines requires its strongest warning.".
11 Product Information. Piqray (alpelisib). Novartis Pharmaceuticals, East Hanover, NJ.
12 US Food and Drug Administration "FDA warns about serious risks and death when combining opioid pain or cough medicines with benzodiazepines requires its strongest warning.".
13 Cerner Multum, Inc. "Canadian Product Information.".
14 Product Information. Prevymis (letermovir). Merck & Company Inc, Whitehouse Station, NJ.
15 Cerner Multum, Inc. "Australian Product Information.".
16 Product Information. Diabinese (chlorpropamide). Pfizer US Pharmaceuticals, New York, NY.
17 Product Information. Prezista (darunavir). Ortho Biotech Inc, Bridgewater, NJ.
18 Product Information. Retevmo (selpercatinib). Lilly, Eli and Company, Indianapolis, IN.
19 Product Information. Copiktra (duvelisib). Verastem, Inc., Needham, MA.
20 Product Information. Zulresso (brexanolone). Sage Therapeutics, Inc., Cambridge, MA.
21 Product Information. Reyvow (lasmiditan). Lilly, Eli and Company, Indianapolis, IN.
22 Product Information. Addyi (flibanserin). Sprout Pharmaceuticals, Raleigh, NC.
23 Product Information. Thalomid (thalidomide). Celgene Corporation, Warren, NJ.
24 Cerner Multum, Inc. "UK Summary of Product Characteristics.".
25 Product Information. Xeglyze (abametapir topical). Dr. Reddy's Laboratories Inc, Upper Saddle River, NJ.
26 Product Information. Xenleta (lefamulin). Nabriva Therapeutics US, Inc., King of Prussia, PA.
27 Product Information. Tavalisse (fostamatinib). Rigel Pharmaceuticals, South San Francisco, CA.