1. Insomnia pharmacotherapy: Ramelteon
Flavio Guzmán, MD

2. Outline MOA: MT1 and MT2 agonist Indications Pharmacokinetics
Side effects
Dosing

3. Mechanism of action

4. Mechanism of action - Ramelteon
Reproduced from:
Circadian sleep–wake rhythm disturbances in end-stage renal disease. Birgit C. P. Koch, J. Elsbeth Nagtegaal, Gerard A. Kerkhof & Piet M. ter Wee. Nature Reviews Nephrology 5, (July 2009)

5. Ramelteon MOA Decreases evening alerting signal Enhances sleep onset
Reinforces or shifts the timing of the circadian rhythm
Influences regulation of circadian rhythms
Miyamoto, M. (2009). Pharmacology of ramelteon, a selective MT1/MT2 receptor agonist: a novel therapeutic drug for sleep disorders. CNS neuroscience & therapeutics, 15(1),

6. Indications

7. Indication for ramelteon
Clinical trials
Decreases sleep onset latency
No improvement in sleep maintenance
Phase-shifting capacity
Jet lag
Shift sleep problems
FDA-approved
Treatment of insomnia characterized by difficulty with sleep onset
Richardson, G. S., Zee, P. C., et al(2008). Circadian phase-shifting effects of repeated ramelteon administration in healthy adults. Journal of clinical sleep medicine: JCSM  4(5), 456.

8. Pharmacokinetics Ramelteon Half-life Fluvoxamine 1-2.6 hours
Rozerem (Ramelteon) [Prescribing Information] Deerfield, IL : Takeda Pharmaceuticals America, Inc. 

9. Side effects Side effects Somnolence Dizziness Fatigue
Hormonal changes
Moderate prolactin elevations in women
Decreased testosterone levels
Clinical significance unclear
Marin, H; Escobar, J. Clinical Psychopharmacology : A Practical Approach. 1st edition. World Scientific Publishing Company, 2013
Neubauer, D. N. (2008). A review of ramelteon in the treatment of sleep disorders. Neuropsychiatric disease and treatment, 4(1), 69.

10. Side effects No potential for
Abuse
Dependence
Tolerance
Lack of significant next-morning residual sedation and cognitive impairment
PI warning for sleep-related behaviors
Marin, H; Escobar, J. Clinical Psychopharmacology : A Practical Approach. 1st edition. World Scientific Publishing Company, 2013
Neubauer, D. N. (2008). A review of ramelteon in the treatment of sleep disorders. Neuropsychiatric disease and treatment, 4(1), 69.

11. Dosing Tablet: 8 mg 8 mg 30 minutes before bedtime
Dosage forms
8 mg
Dosage range
30 minutes before bedtime
Start dose = target dose
Delays therapeutic effect by 45 mins
Avoid administering with high fat meals
Rozerem (Ramelteon) [Prescribing Information] Deerfield, IL : Takeda Pharmaceuticals America, Inc. 

12. End of presentation