Important Safety Information for ROZEREM (ramelteon)

  • 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.
  • 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 and is not recommended for use in this population.
  • Safety and effectiveness of ROZEREM in pediatric patients have not been established.
  • 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.

Indication

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

Please see Full Prescribing Information and Medication Guide for ROZEREM.

  1. The American Geriatrics Society 2015 Beers Criteria Update Expert Panel. American Geriatrics Society 2015 updated Beers Criteria for potentially inappropriate medication use in older adults. J Am Geriatr Soc. 2015;63:2227-2246.
  2. Rozerem package insert, Takeda Pharmaceuticals America, Inc.
  3. 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 insomia. Sleep. 2009;32:351-360.
  4. Data on file, Takeda Pharmaceuticals U.S.A., Inc.
  5. 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.
  6. Rudolph U, Crestani F, Benke D, et al. Benzodiazepine actions mediated by specific g-aminobutyric acidA receptor subtypes. Nature. 1999;401:796-800.
  7. Dubocovich ML, Rivera-Bermúdez MA, Gerdin MJ, Masana MI. Molecular pharmacology, regulation and function of mammalian melatonin receptors. Front Biosci. 2003; 8:d1093-d1108.
  8. Ekmekcioglu C. Melatonin receptors in humans: biological role and clinical relevance. Biomed Pharmacother. 2006;60:97-108.
  9. Hummel M, Unterwald EM. D1 dopamine receptor: a putative neurochemical and behavioral link to cocaine action. J Cell Physiol. 2002;191:17-27.
  10. Malcolm RJ. GABA systems, benzodiazepines, and substance dependence. J Clin Psychiatry. 2003;64(suppl 3):36-40.
  11. Nestler EJ. Historical review: molecular and cellular mechanisms of opiate and cocaine addiction. Trends Pharmacol Sci. 2004;25:210-218.
  12. US Dept of Justice. Controlled Substances. Drug Enforcement Administration website. Available at: http://www.deadiversion.usdoj.gov/schedules/orangebook/orangebook.pdf. Accessed on April 18, 2017.

Important Safety Information for ROZEREM (ramelteon)

  • 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.
  • 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 and is not recommended for use in this population.
  • Safety and effectiveness of ROZEREM in pediatric patients have not been established.
  • 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.

Indication

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

Please see Full Prescribing Information and Medication Guide for ROZEREM.