Rozerem—References

Rozerem is indicated for the treatment of insomnia characterized by difficulty with sleep onset.

Zammit G, Erman M, Wang-Weigand S, Sainati S, Zhang J, Roth T. Evaluation of the efficacy and safety of ramelteon in subjects with chronic insomnia. J Clin Sleep Med. 2007;3:495-504.
Zammit G, Schwartz H, Roth T, Wang-Weigand S, Sainati S, Zhang J. The effects of ramelteon in a first-night model of transient insomnia. Sleep Med. 2009;10(1):55-59.
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;32:351-360.
Rozerem package insert, Takeda Pharmaceuticals America, Inc.
Johnson MW, Suess PE, Griffiths RR. Ramelteon: a novel hypnotic lacking abuse liability and sedative adverse effects. Arch Gen Psychiatry. 2006;63:1149-1157.
Data on file, Takeda Pharmaceuticals North America, Inc.
Dubocovich ML, Rivera-Bermúdez MA, Gerdin MJ, Masana MI. Molecular pharmacology, regulation and function of mammalian melatonin receptors. Front Biosci. 2003;8:d1093-d1108.
Kato K, Hirai K, Nishiyama K, et al. Neurochemical properties of ramelteon (TAK-375), a selective MT₁/MT₂ receptor agonist. Neuropharmacology. 2005;48:301-310.
Ekmekcioglu C. Melatonin receptors in humans: biological role and clinical relevance. Biomed Pharmacother. 2006;60:97-108.
Dubocovich ML, Benloucif S, Masana MI. Melatonin receptors in the mammalian suprachiasmatic nucleus. Behav Brain Res. 1996;73:141-147.
Liu C, Weaver DR, Jin X, et al. Molecular dissection of two distinct actions of melatonin on the suprachiasmatic circadian clock. Neuron. 1997;19:91-102.
Lavie P. Sleep-wake as a biological rhythm. Annu Rev Psychol. 2001;52:277-303.
DataStat. Sleep in America: 1999: results from the National Sleep Foundation’s 1999 Omnibus Sleep Poll. National Sleep Foundation; 1999.
DataStat. Sleep in America: 2000: results from the National Sleep Foundation’s 2000 Omnibus Sleep Poll. National Sleep Foundation; 2000.
US Dept of Justice. Schedule IV controlled substances. Drug Enforcement Administration website. Available at: http://www.deadiversion.usdoj.gov/schedules/orangebook/orangebook.pdf. Accessed March 19, 2010.
Roth T, Seiden D, Sainati S, Wang-Weigand, Zhang J, Zee P. Effects of ramelteon on patient-reported sleep latency in older adults with chronic insomnia. Sleep Med. 2006;7:312-318.
Hummel M, Unterwald EM. D1 dopamine receptor: a putative neurochemical and behavioral link to cocaine action. J Cell Physiol. 2002;191:17-27.
Malcolm RJ. GABA systems, benzodiazepines, and substance dependence. J Clin Psychiatry. 2003;64(suppl 3):36-40.
Nestler EJ. Historical review: molecular and cellular mechanisms of opiate and cocaine addiction. Trends Pharmacol Sci. 2004;25:210-218.
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.
Roth T, Seiden D, Wang-Weigand S, Zhang J. A 2-night, 3-period, crossover study of ramelteon's efficacy and safety in older adults with chronic insomnia. Curr Med Res Opin. 2007;23:1005-1014.
Zammit G, Wang-Weigand S, Rosenthal M, Peng X. Effect of ramelteon on middle-of-the-night balance in older adults with chronic insomnia. J Clin Sleep Med. 2009;5:34-40.
Kryger M, Wang-Weigand S, Zhang J, Roth T. Effect of ramelteon, a selective MT(1)/MT(2)-receptor agonist, on respiration during sleep in mild to moderate COPD. Sleep Breath. 2008;12:243-250.
Kryger M, Roth T, Wang-Weigand S, Zhang J. The effects of ramelteon on respiration during sleep in subjects with moderate to severe chronic obstructive pulmonary disease. Sleep Breath. 2009;13:79-84.

Important Safety Information

In rare cases, severe anaphylactic and anaphylactoid reactions have occurred following use of Rozerem. Angioedema involving the tongue, glottis, or larynx has been reported. Some patients have had additional symptoms such as dyspnea, throat closing, or nausea and vomiting that suggest anaphylaxis. Reactions may require emergency treatment and may be fatal. Patients who develop such reactions should not be rechallenged.
Rozerem should not be used in patients with severe hepatic impairment or in combination with Luvox^® (fluvoxamine).
Failure of insomnia to remit after 7-10 days, worsening of insomnia, or emergence of new cognitive or behavioral abnormalities should be medically evaluated, as this may be the result of an unrecognized underlying medical/psychiatric disorder.
In primarily depressed patients, worsening of depression, including suicidal ideation and completed suicides, can occur with hypnotics.
Hallucinations, as well as behavioral changes such as bizarre behavior, agitation, and mania, have been reported with Rozerem use. Amnesia, anxiety, and other neuropsychiatric symptoms may also occur unpredictably.
Complex behaviors such as "sleep-driving, making or eating food, talking on the phone, sleep-walking, or engaging in other activities while not fully awake," with amnesia for the event, may occur with use of hypnotics, including Rozerem. The use of alcohol with Rozerem may increase the risk of such behaviors. Discontinuation of Rozerem should be strongly considered for patients who report any complex sleep behavior.
Patients should avoid engaging in hazardous activities that require concentration (such as operating a motor vehicle or heavy machinery) after taking Rozerem.
Rozerem should be taken within 30 minutes before going to bed and activities confined to preparing for bed.
Patients should be advised not to consume alcohol in combination with Rozerem, as alcohol and Rozerem may have additive effects when used in conjunction.
Rozerem has been associated with decreased testosterone levels and increased prolactin levels. Patients may experience cessation of menses or galactorrhea in females, decreased libido, or fertility problems that are possibly associated with such hormone changes.
Rozerem has not been studied in patients with severe sleep apnea, or in children or adolescents. The effects in these populations are unknown.
Rozerem should not be taken with or immediately after a high-fat meal.
The most common adverse reactions (≥3% and more common than with placebo) are somnolence, dizziness, fatigue, nausea, and exacerbated insomnia.

LUVOX^® is a registered trademark of Solvay Pharmaceuticals, Inc.

Go to Full Prescribing Information, including Medication Guide.

ROZEREM is a trademark of Takeda Pharmaceutical Company Limited registered with the U. S. Patent and Trademark Office and used under license by Takeda Pharmaceuticals America, Inc.