FDA ( Food and Drug Administration ) has approved the New Drug Application ( NDA ) for Rozerem ( Ramelteon ) 8-mg tablets for the treatment of insomnia characterized by difficulty with sleep onset.

Rozerem is the first and only prescription sleep medication that has shown no evidence of abuse and dependence and, as a result, has not been designated as a controlled substance by the U.S. Drug Enforcement Administration ( DEA ).
With the exception of Rozerem, all other prescription medications indicated for insomnia are classified as Schedule IV controlled substances by the DEA.
Additionally, Rozerem is the first prescription insomnia medication with a new therapeutic mechanism of action in 35 years.

" People with insomnia are not only affected by their sleeplessness at night; insomnia's impact is also in how they feel and function the next day," said Thomas Roth, director of the Sleep Disorders and Research Center, Detroit. " Current therapies often used for insomnia work by broadly inhibiting the activity of neurons in the brain. Ramelteon treats insomnia by specifically affecting the activity of neurons in an area of the brain involved in the sleep-wake process, and has been shown to carry no risks of abuse, withdrawal, or dependency, and negligible risk for next-day 'hangover' effects."

Ramelteon has a unique therapeutic mechanism of action that selectively targets two receptors located in the brain's suprachiasmatic nucleus ( SCN ). The SCN is known as the body's "master clock" because it regulates 24-hour, or circadian, rhythms including the sleep-wake cycle.

The Rozerem NDA, submitted in September 2004 by Takeda, was based on data collected from an extensive clinical research program, including recently completed clinical studies with more than 4,200 patients ages 18 to 93.
In one study, 472 patients received single daily doses of Rozerem for up to one year. Also, based on recently presented clinical trials, Rozerem has been shown to be safe for older adults, as well as those who have mild-to-moderate chronic obstructive pulmonary disease ( COPD ) and mild-to-moderate sleep apnea.

Rozerem should not be used in patients with hypersensitivity to Ramelteon or any components of the formulation.
Rozerem can be prescribed for long-term use.
However, failure of insomnia to remit after a reasonable period of time, worsening of insomnia, or the emergence of new cognitive or behavioral abnormalities after taking Rozerem should be evaluated, as such symptoms may be the result of an unrecognized underlying medical disorder. In primarily depressed patients, worsening of depression, including suicidal ideation, has been reported in association with the use of hypnotics.

Rozerem should not be used by patients with severe hepatic impairment, or in patients in combination with Fluvoxamine.

Rozerem has not been studied in subjects with severe sleep apnea or severe COPD and is not recommended for use in those populations. Patients should be advised to exercise caution if they consume alcohol in combination with Rozerem.

Rozerem has been associated with decreased testosterone levels and increased prolactin levels. As a result, healthcare professionals should be mindful of any unexplained symptoms possibly associated with such changes in these hormone levels. Rozerem has not been studied in children or adolescents, and the effects in these populations are unknown.

Rozerem should be taken within 30 minutes before going to bed and activities should be confined to those necessary to prepare for bed. Rozerem should not be taken with or immediately after a high-fat meal. Engaging in hazardous activities that require concentration ( such as operating a motor vehicle or heavy machinery ) after taking Rozerem should be avoided.

The most common adverse events seen with Rozerem that had greater than 2% incidence difference from placebo were somnolence, dizziness, and fatigue.

Source: Takeda, 2005


XagenaMedicine2005