ramelteon ROZEREM
Class: Selective Melatonin Receptor AgonistFDA Indications: Sleep Onset Insomnia
Off-Label Use: Circadian Rhythm Sleep Disorders, Bipolar Disorder, Sleep Disturbances In Dementia, Lewy Body Dementia, Visual Hallucinations In Dementia With Lewy Bodies, Refractory Behavioral And Psychological Symptoms Of Dementia In Alzheimer Disease, Delirium Prevention
Prescribing
Forms: 8mg tabletDose Range: 8 mg/day
Starting: 8 mg QHS for most patients. Be aware that t½ is ↑'d by 45 min when given with food.
Stopping: No discontinuation symptoms ∴ should be able to discontinue w/o tapering.
Precautions
Contraindications: None, other than patients with known hypersensitivity to ramelteonSerious Side Effects: ↑ serum prolactin in women by ~34%; can also ↓ testosterone
Side Effects: headache, sedation/somnolence, dizziness
Pharmacokinetics
t½: 2 (1-2.6)° TMAX: 0.5-1.5°Substrate of: 1A2; 2C9, 3A4
Inhibits: ∅ ; Induces: ∅
Active Metabolites: M-II — has a 2-5° t½ but only ~10% as potent as ramelteon; M-I, M-III & M-IV are also active
DDIs
- - caution with other CNS-depressants
- - 1A2 inhibitors can ↑ levels, likewise 1A2 inducers can ↓ levels
Misc
- - not a CNS depressant; promotes sleep by regulating the sleep/wake cycle rather than via CNS-depression
- - lacks strong sleep-onset induction that the benzos and nonbenzos confer
- - melatoninergic agonists do not cause next-day hangover and withdrawal effects
- - no tolerance or abuse potential
- - exhibits linear pharmacokinetics
- - compared to melatonin it is: 3x more potent at MT1 and 16x more potent at MT2, has ↑ lipophilic properties (∴ ↑'d tissue absorption), has an active metabolites (˜10% MT1/MT2 affinity as parent drug), and has a much longer t½ (2-5° vs ~30 minutes)
- - affinity of ramelteon for MT1 is 8-fold higher than its affinity for MT2
- - did not get the sleep maintenance indication because it couldn't demonstrate ↓ WASO
- - avoid in children & adolescents – reproductive development can be affected because of its impact on the endocrine system
Special Populations
Category C—No reports describing the use of ramelteon in human pregnancy have been located. Although the animal data are reassuring, the absence of human pregnancy experience prevents a better assessment of the embryo-fetal risk.
No reports describing the use of ramelteon during human lactation have been located. The molecular weight (about 259), serum protein binding (about 82%), and the elimination half-life suggest that the drug will be excreted into breast milk. The effect of this exposure on a nursing infant is unknown.
No dosage adjustment necessary
No dosage adjustment necessary
With 4 active metabolites, even mild impairment can ↑ levels 4-fold
References
Foye's Principles Of Medicinal Chemistry 7th EdCarlat Psychiatry Report Ramelteon Fact Sheet
Pharmacotherapy Of Insomnia With Ramelteon: Safety, Efficacy And Clinical Applications
Rozerem Package Insert
Association Of Delirium Response And Safety Of Pharmacological Interventions For The Management And Prevention Of Delirium
Thank you for using psychopharmacopeia.com!