ramelteon ROZEREM

Class: Selective Melatonin Receptor Agonist
FDA Indications: Sleep Onset Insomnia
Off-Label Use: Delirium, 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
Prescribing
Forms: 8mg tablet
Dose 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.

NAMI drug fact sheet

Precautions
Contraindications: None, other than patients with known hypersensitivity to ramelteon
Serious Side Effects: ↑ serum prolactin in women by ~34%; can also ↓ testosterone
Side Effects: headache, sedation/somnolence, dizziness
Pharmacodynamics
1° MOA: MT1/MT2 melatonin receptor agonist (MT1 selective)
Target: MT1, MT2
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
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

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Last updated August 27 2018 18:45:06. Disclaimer: This website does not provide medical advice, nor is it a substitute for clinical judgment.