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 |
|---|---|
|
Synonyms:
|
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.
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 | 131.06 | 16.93 | 45 | 5520 | 10471 | 63472986 |
| Initial insomnia | 124.33 | 16.93 | 38 | 5527 | 6119 | 63477338 |
| Nightmare | 118.09 | 16.93 | 49 | 5516 | 19145 | 63464312 |
| Middle insomnia | 104.69 | 16.93 | 40 | 5525 | 12603 | 63470854 |
| Somnolence | 74.87 | 16.93 | 85 | 5480 | 178600 | 63304857 |
| Product dispensing error | 69.12 | 16.93 | 28 | 5537 | 10277 | 63473180 |
| Poor quality sleep | 59.98 | 16.93 | 31 | 5534 | 19904 | 63463553 |
| Altered state of consciousness | 47.91 | 16.93 | 29 | 5536 | 25201 | 63458256 |
| Hepatic function abnormal | 46.77 | 16.93 | 33 | 5532 | 37109 | 63446348 |
| Ovarian cancer recurrent | 37.30 | 16.93 | 10 | 5555 | 1007 | 63482450 |
| Hallucination | 35.46 | 16.93 | 33 | 5532 | 54784 | 63428673 |
| Restlessness | 34.39 | 16.93 | 25 | 5540 | 29428 | 63454029 |
| Somnambulism | 33.56 | 16.93 | 14 | 5551 | 5529 | 63477928 |
| Feeling abnormal | 30.46 | 16.93 | 50 | 5515 | 148342 | 63335115 |
| Intentional overdose | 28.83 | 16.93 | 34 | 5531 | 74118 | 63409339 |
| Galactorrhoea | 26.86 | 16.93 | 11 | 5554 | 4144 | 63479313 |
| Blood pressure decreased | 25.58 | 16.93 | 30 | 5535 | 64992 | 63418465 |
| Hypersomnia | 24.97 | 16.93 | 17 | 5548 | 18038 | 63465419 |
| Hangover | 24.32 | 16.93 | 8 | 5557 | 1628 | 63481829 |
| Drug eruption | 24.01 | 16.93 | 20 | 5545 | 28674 | 63454783 |
| Anxiety | 21.39 | 16.93 | 54 | 5511 | 217487 | 63265970 |
| Impulsive behaviour | 20.59 | 16.93 | 7 | 5558 | 1576 | 63481881 |
| Platelet count decreased | 19.72 | 16.93 | 36 | 5529 | 116086 | 63367371 |
| Hallucination, visual | 19.44 | 16.93 | 15 | 5550 | 19283 | 63464174 |
| Delirium | 19.34 | 16.93 | 23 | 5542 | 50518 | 63432939 |
| Anaemia | 19.29 | 16.93 | 63 | 5502 | 293367 | 63190090 |
| Product administered to patient of inappropriate age | 18.93 | 16.93 | 8 | 5557 | 3260 | 63480197 |
| Interstitial lung disease | 18.65 | 16.93 | 25 | 5540 | 61883 | 63421574 |
| Arthralgia | 18.25 | 16.93 | 14 | 5551 | 569696 | 62913761 |
| Palpitations | 17.94 | 16.93 | 34 | 5531 | 112736 | 63370721 |
| Pneumonia aspiration | 17.14 | 16.93 | 18 | 5547 | 34522 | 63448935 |
| Renal impairment | 17.07 | 16.93 | 29 | 5536 | 88326 | 63395131 |
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 | 70.33 | 17.95 | 75 | 3988 | 111041 | 34841827 |
| Initial insomnia | 64.63 | 17.95 | 21 | 4042 | 3103 | 34949765 |
| Pneumonia aspiration | 55.71 | 17.95 | 43 | 4020 | 41860 | 34911008 |
| Hangover | 52.53 | 17.95 | 14 | 4049 | 1037 | 34951831 |
| Abnormal dreams | 49.73 | 17.95 | 22 | 4041 | 7556 | 34945312 |
| Middle insomnia | 48.71 | 17.95 | 21 | 4042 | 6781 | 34946087 |
| Nightmare | 47.08 | 17.95 | 26 | 4037 | 14365 | 34938503 |
| Interstitial lung disease | 41.09 | 17.95 | 44 | 4019 | 65238 | 34887630 |
| Hepatic function abnormal | 39.23 | 17.95 | 36 | 4027 | 44327 | 34908541 |
| Disseminated intravascular coagulation | 34.81 | 17.95 | 25 | 4038 | 21791 | 34931077 |
| Poor quality sleep | 32.86 | 17.95 | 17 | 4046 | 8239 | 34944629 |
| Delirium | 31.89 | 17.95 | 32 | 4031 | 43959 | 34908909 |
| Cerebral infarction | 27.67 | 17.95 | 24 | 4039 | 27431 | 34925437 |
| Upper respiratory tract inflammation | 25.35 | 17.95 | 9 | 4054 | 1735 | 34951133 |
| Restlessness | 21.20 | 17.95 | 20 | 4043 | 25462 | 34927406 |
| Altered state of consciousness | 21.04 | 17.95 | 19 | 4044 | 22874 | 34929994 |
| Renal impairment | 20.24 | 17.95 | 38 | 4025 | 94475 | 34858393 |
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 | 102.84 | 16.16 | 35 | 7976 | 6903 | 79729474 |
| Hepatic function abnormal | 82.10 | 16.16 | 64 | 7947 | 73043 | 79663334 |
| Middle insomnia | 80.58 | 16.16 | 37 | 7974 | 16032 | 79720345 |
| Somnolence | 80.38 | 16.16 | 109 | 7902 | 238872 | 79497505 |
| Pneumonia aspiration | 73.84 | 16.16 | 58 | 7953 | 66909 | 79669468 |
| Poor quality sleep | 62.90 | 16.16 | 35 | 7976 | 22687 | 79713690 |
| Altered state of consciousness | 61.79 | 16.16 | 44 | 7967 | 43778 | 79692599 |
| Abnormal dreams | 59.49 | 16.16 | 27 | 7984 | 11385 | 79724992 |
| Hangover | 53.40 | 16.16 | 16 | 7995 | 2096 | 79734281 |
| Interstitial lung disease | 53.25 | 16.16 | 61 | 7950 | 112539 | 79623838 |
| Delirium | 47.20 | 16.16 | 50 | 7961 | 84577 | 79651800 |
| Restlessness | 46.40 | 16.16 | 38 | 7973 | 46454 | 79689923 |
| Nightmare | 46.04 | 16.16 | 30 | 7981 | 25831 | 79710546 |
| Disseminated intravascular coagulation | 39.39 | 16.16 | 31 | 7980 | 35811 | 79700566 |
| Femoral neck fracture | 34.99 | 16.16 | 18 | 7993 | 9966 | 79726411 |
| Cerebral infarction | 32.86 | 16.16 | 31 | 7980 | 45645 | 79690732 |
| Drug eruption | 31.95 | 16.16 | 30 | 7981 | 43905 | 79692472 |
| Renal impairment | 30.63 | 16.16 | 56 | 7955 | 157727 | 79578650 |
| Product administered to patient of inappropriate age | 28.50 | 16.16 | 13 | 7998 | 5540 | 79730837 |
| Hypersomnia | 27.61 | 16.16 | 21 | 7990 | 23065 | 79713312 |
| Marasmus | 26.91 | 16.16 | 8 | 8003 | 1020 | 79735357 |
| Upper respiratory tract inflammation | 25.72 | 16.16 | 11 | 8000 | 4024 | 79732353 |
| Arthralgia | 25.25 | 16.16 | 13 | 7998 | 571790 | 79164587 |
| Intentional overdose | 24.99 | 16.16 | 41 | 7970 | 105919 | 79630458 |
| Platelet count decreased | 23.62 | 16.16 | 57 | 7954 | 194607 | 79541770 |
| Anaemia | 23.02 | 16.16 | 97 | 7914 | 444918 | 79291459 |
| Blood pressure decreased | 22.80 | 16.16 | 38 | 7973 | 99428 | 79636949 |
| Gastroenteritis eosinophilic | 20.51 | 16.16 | 5 | 8006 | 300 | 79736077 |
| Hallucination | 19.98 | 16.16 | 33 | 7978 | 85712 | 79650665 |
| Spinal compression fracture | 19.34 | 16.16 | 15 | 7996 | 16943 | 79719434 |
| Stoma site hypergranulation | 18.63 | 16.16 | 5 | 8006 | 440 | 79735937 |
| Cardiac failure acute | 17.89 | 16.16 | 15 | 7996 | 18914 | 79717463 |
| Zinc deficiency | 17.71 | 16.16 | 4 | 8007 | 172 | 79736205 |
| Ileus | 17.35 | 16.16 | 17 | 7994 | 26194 | 79710183 |
| Decreased appetite | 17.18 | 16.16 | 74 | 7937 | 342344 | 79394033 |
| Respiratory failure | 16.85 | 16.16 | 48 | 7963 | 180863 | 79555514 |
| Feeling abnormal | 16.57 | 16.16 | 44 | 7967 | 159155 | 79577222 |
| Somnambulism | 16.34 | 16.16 | 9 | 8002 | 5712 | 79730665 |
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 | AGONIST | Ki | 10.90 | WOMBAT-PK | CHEMBL | |||
| Melatonin receptor type 1B | GPCR | 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 |
| 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 | 42571-375 | 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 | 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 | 50436-3980 | TABLET, FILM COATED | 8 mg | ORAL | ANDA | 28 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 | 55700-874 | TABLET, FILM COATED | 8 mg | ORAL | ANDA | 28 sections |
| RAMELTEON | Human Prescription Drug Label | 1 | 59651-505 | TABLET, FILM COATED | 8 mg | ORAL | ANDA | 26 sections |
| Ramelteon | HUMAN PRESCRIPTION DRUG LABEL | 1 | 60687-692 | TABLET | 8 mg | ORAL | ANDA | 26 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 |
| 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 | 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 | 70010-028 | TABLET | 8 mg | ORAL | ANDA | 26 sections |