Ramelteon is a melatonin receptor agonist that is used for the treatment of insomnia. Ramelteon has not been implicated in causing serum enzyme elevations or clinically apparent liver injury.
Ramelteon (ra mel' tee on) is a synthetic melatonin receptor agonist with affinity for both the melatonin type 1 and type 2 receptors (MT1 and MT2). These receptors are believed to be involved in the maintenance of the circadian rhythm that regulates the normal sleep-wake cycle. Melatonin itself has been proposed as therapy of sleep disturbances including insomnia and jet lag, but systematic reviews and meta analyses of controlled trials of various melatonin formulations have failed to demonstrate consistent efficacy. In contrast, ramelteon was found to reduce the average latency to persistent sleep with little residual sleepiness the following day or rebound insomnia upon withdrawal. Ramelteon was approved for use in chronic insomnia in the United States in 2005. It is available in 8 mg tablets under the brand name Rozerem. The recommended dose is 8 mg taken orally 30 minutes before going to bed. Side effects are few but may include daytime somnolence, fatigue, dizziness and headache and rarely hypersensitivity reactions with angioedema of the tongue and larynx.
In several clinical trials, ramelteon was found to be well tolerated and not associated with serum enzyme elevations or evidence of liver injury. Despite, wide scale use, it has not been convincingly linked to instances of clinically apparent liver injury. Nevertheless, ramelteon is metabolized by the cytochrome P450 system (predominantly CYP 1A2) which can result in significant drug-drug interactions.
Other Drugs in the Subclass, Melatonin and its Analogues: Melatonin, Tasimelteon
REPRESENTATIVE TRADE NAMES
Ramelteon – Rozerem®
Sedatives and Hypnotics
Product labeling at DailyMed, National Library of Medicine, NIH
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References updated: 08 January 2014
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Ramelteon(Rozerem) for insomnia. Med Lett Drugs Ther 2005; 47(1221): 89-91. PubMed Citation (Concise review of the mechanism of action, efficacy and safety of ramelteon published shortly after its approval for use in insomnia in the US; adverse effects include somnolence, dizziness, nausea, fatigue, headache and insomnia, but no mention is made of ALT elevations or hepatotoxicity; mentions that melatonin itself is available in the US only as a "dietary supplement").
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Erman M, Seiden D, Zammit G, Sainati S, Zhang J. An efficacy, safety, and dose-response study of Ramelteon in patients with chronic primary insomnia. Sleep Med 2006; 7: 17-24. PubMed Citation (Controlled crossover trial of 4 doses of ramelteon vs placebo in 107 patients with chronic primary insomnia found no difference in rate of side effects compared to placebo, the most common being headache and somnolence; serum enzymes not tested).
Devi V, Shankar PK. Ramelteon: a melatonin receptor agonist for the treatment of insomnia. J Postgrad Med 2008; 54: 45-8. PubMed Citation (Review of the mechanism of action, efficacy and safety of ramelteon in treatment of insomnia; adverse events include headache, somnolence, dizziness, fatigue, insomnia and nausea; no mention made of ALT elevations or hepatotoxicity; superpharmacological, high doses of ramelteon cause liver cancer in mice).
Mayer G, Wang-Weigand S, Roth-Schechter B, Lehmann R, Staner C, Partinen M. Efficacy and safety of 6-month nightly ramelteon administration in adults with chronic primary insomnia. Sleep 2009; 32: 351-60. PubMed Citation (Controlled trial of 6 month course of ramelteon vs placebo in 451 adults with primary chronic insomnia; adverse effects were similar between the two groups; no mention of ALT levels).
Morris CJ, Aeschbach D, Scheer FA. Circadian system, sleep and endocrinology. Mol Cell Endocrinol 2012; 349: 91-104. PubMed Citation (Review of the biologic basis of circadian rhythm including the role of melatonin).
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