Insomnia pharmacotherapy: Ramelteon Flavio Guzmán, MD

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

Mechanism of action

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, 407-416 (July 2009)

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), 32-51.

Indications

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.

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

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.

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.

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. 

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