ROZEREM- ramelteon tablet, film coated
Takeda Pharmaceuticals America, Inc.
ROZEREM is 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. The final formal assessments of sleep latency were performed after two days of treatment during the crossover study (elderly only), at five weeks in the six week studies (adults and elderly), and at the end of the six month study (adults and elderly) [see Clinical Studies (14)].
The recommended dose of ROZEREM is 8 mg taken within 30 minutes of going to bed. It is recommended that ROZEREM not be taken with or immediately after a high-fat meal.
The total ROZEREM dose should not exceed 8 mg per day.
ROZEREM is not recommended in patients with severe hepatic impairment. ROZEREM should be used with caution in patients with moderate hepatic impairment [see Warnings and Precautions (5.6), Clinical Pharmacology (12.4)].
ROZEREM should not be used in combination with fluvoxamine. ROZEREM should be used with caution in patients taking other CYP1A2 inhibiting drugs [see Drug Interactions (7), Clinical Pharmacology (12.5)].
ROZEREM is available in an 8 mg strength tablet for oral administration.
ROZEREM 8 mg tablets are round, pale orange-yellow, film-coated, with “TAK” and “RAM-8” printed on one side.
Patients who develop angioedema after treatment with ROZEREM should not be rechallenged with the drug.
Patients should not take ROZEREM in conjunction with fluvoxamine [see Drug Interactions (7)].
Rare cases of angioedema involving the tongue, glottis or larynx have been reported in patients after taking the first or subsequent doses of ROZEREM. 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 ROZEREM should not be rechallenged with the drug.
Since sleep disturbances may be the presenting manifestation of a physical and/or psychiatric disorder, symptomatic treatment of insomnia should be initiated only after a careful evaluation of the patient. The failure of insomnia to remit after 7 to 10 days of treatment may indicate the presence of a primary psychiatric and/or medical illness that should be evaluated. Worsening of insomnia, or the emergence of new cognitive or behavioral abnormalities, may be the result of an unrecognized underlying psychiatric or physical disorder and requires further evaluation of the patient. Exacerbation of insomnia and emergence of cognitive and behavioral abnormalities were seen with ROZEREM during the clinical development program.
A variety of cognitive and behavior changes have been reported to occur in association with the use of hypnotics. In primarily depressed patients, worsening of depression (including suicidal ideation and completed suicides) has been reported in association with the use of hypnotics.
Hallucinations, as well as behavioral changes such as bizarre behavior, agitation and mania have been reported with ROZEREM use. Amnesia, anxiety and other neuro-psychiatric symptoms may also occur unpredictably.
Complex behaviors such as “sleep-driving” (i.e., driving while not fully awake after ingestion of a hypnotic) and other complex behaviors (e.g., preparing and eating food, making phone calls, or having sex), with amnesia for the event, have been reported in association with hypnotic use. The use of alcohol and other CNS depressants may increase the risk of such behaviors. These events can occur in hypnotic-naive as well as in hypnotic-experienced persons. Complex behaviors have been reported with the use of ROZEREM. 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.
After taking ROZEREM, patients should confine their activities to those necessary to prepare 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 an effect on reproductive hormones in adults, e.g., decreased testosterone levels and increased prolactin levels. It is not known what effect chronic or even chronic intermittent use of ROZEREM may have on the reproductive axis in developing humans [see Clinical Trials (14.3)].
ROZEREM has not been studied in subjects with severe sleep apnea and is not recommended for use in this population [see Use in Specific Populations (8.7)].
ROZEREM should not be used by patients with severe hepatic impairment [see Clinical Pharmacology (12.4)].
No standard monitoring is required.
For patients presenting with unexplained amenorrhea, galactorrhea, decreased libido, or problems with fertility, assessment of prolactin levels and testosterone levels should be considered as appropriate.
Interference with Laboratory Tests
ROZEREM is not known to interfere with commonly used clinical laboratory tests. In addition, in vitro data indicate that ramelteon does not cause false-positive results for benzodiazepines, opiates, barbiturates, cocaine, cannabinoids, or amphetamines in two standard urine drug screening methods in vitro.
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)]
Adverse Reactions Resulting in Discontinuation of Treatment
The data described in this section reflect exposure to ROZEREM 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 ROZEREM 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 ROZEREM were somnolence, dizziness, nausea, fatigue, headache, and insomnia; all of which occurred in 1% of the patients or less.
ROZEREM 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 ROZEREM.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of other drugs, and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.
|MedDRA Preferred Term||Placebo |
|Ramelteon 8 mg |
All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.