Ramelteon

Ramelteon is a melatonin receptor agonist with both high affinity for melatonin MT 1 and MT 2 receptors and relative selectivity over the MT 3 receptor. The activity of ramelteon at the MT 1 and MT 2 receptors is believed to contribute to its sleep- promoting properties, as these receptors, acted upon by endogenous melatonin, are thought to be involved in the maintenance of the circadian rhythm underlying the normal sleep-wake cycle.

• Ramelteon Tablets are indicated for the treatment of insomnia characterized by difficulty with sleep onset. The clinical trials performed in support of efficacy were up to six months in duration.ICD-10: G47.00

• Patients who develop angioedema after treatment with Ramelteon Tablets should not be rechallenged with the drug. Patients should not take Ramelteon Tablets in conjunction with fluvoxamine [see Drug Interactions (7) ].contraindicated

Adult dose: 8 mg taken within 30 minutes of going to bed. (2.1) Should not be taken with or immediately after a high-fat meal. (2.1) Total daily dose should not exceed 8 mg. (2.1) 2.1 Dosage in Adults The recommended dose of Ramelteon Tablets is 8 mg taken within 30 minutes of going to bed. It is recommended that Ramelteon Tablets not be taken with or immediately after a high-fat meal. The total Ramelteon Tablets dose should not exceed 8 mg per day. 2.2 Dosing in Patients with Hepatic Impairment Ramelteon Tablets is not recommended in patients with severe hepatic impairment. Ramelteon Tablets should be used with caution in patients with moderate hepatic impairment [see Warnings and Precautions (5.6) , Clinical Pharmacology (12.4)] . 2.3 Administration with Other Medications Ramelteon Tablets should not be used in combination with fluvoxamine. Ramelteon Tablets should be used with caution in patients taking other CYP1A2 inhibiting drugs [see Drug Interactions (7) , Clinical Pharmacology (12.5) ] .

Severe anaphylactic/anaphylactoid reactions: Angioedema and anaphylaxis have been reported. Do not rechallenge if such reactions occur. ( 5.1 ) Need to evaluate for comorbid diagnoses: Reevaluate if insomnia persists after 7 to 10 days of treatment. ( 5.2 ) Abnormal thinking, behavioral changes, complex behaviors: May include “sleep-driving” and hallucinations. Immediately evaluate any new onset behavioral changes. ( 5.3 ) Depression: Worsening of depression or suicidal thinking may occur. ( 5.3 ) CNS effects: Potential impairment of activities requiring complete mental alertness such as operating machinery or driving a motor vehicle, after ingesting the drug. ( 5.4 ) Reproductive effects: Include decreased testosterone and increased prolactin levels. Effect on reproductive axis in developing humans is unknown. ( 5.5 ) Patients with severe sleep apnea: Ramelteon Tablets is not recommended for use in this population. ( 5.6 ) 5.1 Severe Anaphylactic and Anaphylactoid Reactions Rare cases of angioedema involving the tongue, glottis or larynx have been reported in patients after taking the first or subsequent doses of Ramelteon Tablets. Some patients have had additional symptoms such as dyspnea, throat closing, or nausea and vomiting that suggest anaphylaxis. Some patients have required medical therapy in the emergency department. If angioedema involves the tongue, glottis or larynx, airway obstruction may occur and be fatal. Patients who develop angioedema after treatment with Ramelteon Tablets should not be rechallenged with the drug.

The following serious adverse reactions are discussed in greater detail in other sections: Severe anaphylactic and anaphylactoid reactions [see Warnings and Precautions (5.1) ] Abnormal thinking, behavior changes, and complex behaviors [see Warnings and Precautions (5.3) ] CNS effects [see Warnings and Precautions (5.4) ] Most common adverse reactions (≥3% and more common than with placebo) are: somnolence, dizziness, fatigue, nausea, and exacerbated insomnia. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Innogenix, LLC. at 1-844-466-6469 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Adverse Reactions Resulting in Discontinuation of Treatment The data described in this section reflect exposure to Ramelteon Tablets in 5373 subjects, including 722 exposed for six months or longer, and 448 subjects for one year. Six percent of the 5373 individual subjects exposed to Ramelteon Tablets in clinical studies discontinued treatment owing to an adverse event, compared with 2% of the 2279 subjects receiving placebo. The most frequent adverse events leading to discontinuation in subjects receiving Ramelteon Tablets were somnolence, dizziness, nausea, fatigue, headache, and insomnia; all of which occurred in 1% of the patients or less. Ramelteon Tablets Most Commonly Observed Adverse Events Table 1 displays the incidence of adverse events reported by the 2861 patients with chronic insomnia who participated in placebo-controlled trials of Ramelteon Tablets.

Pediatric use:Safety and effectiveness not established. (8.4) Geriatric use:No overall differences in safety and efficacy between elderly and younger adult subjects. (8.5) Hepatic impairment:Is not recommended in patients with severe impairment; use with caution in moderate impairment. (8.8) 8.1 Pregnancy Risk Summary Available data from post marketing reports with Ramelteon Tablets use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal studies, ramelteon produced evidence of developmental toxicity, including teratogenic effects, in rats at doses greater than 36 times the recommended human dose (RHD) of 8 mg/day based on body surface area (mg/m 2 ) (see Data). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 - 4% and 15 - 20%, respectively.

Metabolism

The pharmacokinetic profile of Ramelteon Tablets has been evaluated in healthy subjects as well as in subjects with hepatic or renal impairment. When administered orally to humans in doses ranging from 4 to 64 mg, ramelteon undergoes rapid, high first-pass metabolism, and exhibits linear pharmacokinetics.

General symptomatic and supportive measures should be used, along with immediate gastric lavage where appropriate. Intravenous fluids should be administered as needed. As in all cases of drug overdose, respiration, pulse, blood pressure, and other appropriate vital signs should be monitored, and general supportive measures employed. Hemodialysis does not effectively reduce exposure to Ramelteon Tablets. Therefore, the use of dialysis in the treatment of overdosage is not appropriate. Poison Control Center As with the management of all overdosage, the possibility of multiple drug ingestion should be considered. Contact a poison control center for current information on the management of overdosage.

• Jul 22, 2005NDANDA021782Takeda Pharms Usa
• Jul 26, 2013ANDAANDA091693Dr Reddys Labs Sa
• Aug 19, 2015ANDAANDA091610Actavis Labs Fl Inc
• Jul 22, 2019ANDAANDA211567Zydus Pharms
• Apr 10, 2020ANDAANDA212650I3 Pharms
• Aug 21, 2020ANDAANDA213186Granules
• Oct 26, 2020ANDAANDA213815Appco
• Aug 24, 2022ANDAANDA215435Andas 5 Holding

Reference statistics from the openFDA drug-shortage dataset. For a live view, consult the FDA database directly. Not clinical guidance.

• Rozerem, Tablet, 8 mg (NDC 64764-805-10)To be discontinued
  Sponsor: Takeda Pharmaceuticals USA Inc.
  Updated Mar 19, 2026
• Rozerem, Tablet, 8 mg (NDC 64764-805-30)To be discontinued
  Sponsor: Takeda Pharmaceuticals USA Inc.
  Updated Mar 19, 2026

1. 1Drug Ineffective91413%
2. 2Initial Insomnia4476.1%
3. 3Somnolence4155.7%
4. 4Insomnia3955.4%
5. 5Middle Insomnia3905.4%
6. 6Nausea3324.6%
7. 7Fatigue2873.9%
8. 8Dizziness2713.7%
9. 9Headache2573.5%
10. 10Off Label Use2383.3%
11. 11Poor Quality Sleep2183.0%
12. 12Diarrhoea2142.9%
13. 13Feeling Abnormal2072.8%
14. 14Fall2062.8%
15. 15Anxiety1912.6%

The 10 most recently updated of 80 ClinicalTrials.gov registrations naming Ramelteon as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Doxepin Alone or Combined With Ramelteon Versus Placebo for Improving Sleep Quality After Primary Total Knee Arthroplasty
  Not yet recruiting · Phase 4 · Interventional · 129 enrolled · University of Washington
  NCT07598734updated 2026-05-20
• Melatonin Agonist for Shift-time Workers.
  Completed · Phase 4 · Interventional · 61 enrolled · Tri-Service General Hospital
  NCT07382843updated 2026-02-03
• Comparative Pharmacokinetic Study of Ramelteon Modified-Release Tablets and Ramelteon Tablets in Healthy Subjects
  Completed · Phase 1 · Interventional · 12 enrolled · Overseas Pharmaceuticals, Ltd.
  NCT06890715updated 2025-03-24
• The Study of Combination Use of Melatonin Receptor Agonist for Dose Reduction or Interruptions of Benzodiazepine (BZD) and Non-BZD Hypnotics on Chronic Insomnia
  Completed · Phase 4 · Interventional · 17 enrolled · Translational Research Center for Medical Innovation, Kobe, Hyogo, Japan
  NCT03461042updated 2024-11-20
• Delirium Reduction With Ramelteon
  Recruiting · Phase 4 · Interventional · 506 enrolled · Centennial Medical Center
  NCT05069428updated 2024-08-22
• A Study of Ramelteon in Chinese Patients With Chronic Insomnia
  Not yet recruiting · Phase 3 · Interventional · 280 enrolled · Nanjing Chia-tai Tianqing Pharmaceutical
  NCT06512363updated 2024-07-22
• The Effect of Ramelteon on Delirium and Sleep in Patients Admitted to the ICU
  Completed · Phase 4 · Interventional · 112 enrolled · Rhode Island Hospital
  NCT03931070updated 2024-04-10
• Efficacy and Tolerability of Ramelteon in Patients With Rapid Eye Movement (REM) Behavior Disorder and Parkinsonism
  Terminated · Interventional · 3 enrolled · Northwestern University
  NCT00745030updated 2024-01-09
• Treatment of Insomnia in Elderly Sleep Apnea Patients With Ramelteon (TAK 375)
  Completed · Phase 3 · Interventional · 27 enrolled · University of Pennsylvania
  NCT01048242updated 2023-05-25
• Insomnia Prevalence and Treatment Impact on Systemic Hypertension
  Terminated · Phase 4 · Interventional · 5 enrolled · University of Sao Paulo
  NCT05414864updated 2022-12-29

Frequently asked questions

How does Ramelteon work?

Ramelteon is a melatonin receptor agonist with both high affinity for melatonin MT 1 and MT 2 receptors and relative selectivity over the MT 3 receptor. The activity of ramelteon at the MT 1 and MT 2 receptors is believed to contribute to its sleep- promoting properties, as these receptors, acted upon by endogenous melatonin, are thought to be involved in the maintenance of the circadian rhythm underlying the normal sleep-wake cycle.

What is Ramelteon used for?

According to FDA labeling, Ramelteon carries indications including: Ramelteon Tablets are indicated for the treatment of insomnia characterized by difficulty with sleep onset. The clinical trials performed in support of efficacy were up to six months in duration.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Ramelteon?

Ramelteon is classified as Melatonin receptor agonists, Melatonin Receptor Agonist, Melatonin Receptor Agonists, Increased Melatonin Activity.

What are the brand names for Ramelteon?

Ramelteon is marketed under brand names including Rozerem.

What are the contraindications for Ramelteon?

Ramelteon labeling lists contraindications including: Patients who develop angioedema after treatment with Ramelteon Tablets should not be rechallenged with the drug. Patients should not take Ramelteon Tablets in conjunction with fluvoxamine [see Drug Interactions (7) ].. Always consult the full prescribing information and a clinician.