Insomnia, a common sleep disorder, affects more than 70 million Americans. According to the National Sleep Foundation's
2005 Sleep in America poll, about 75% of adults have experienced a symptom of a sleep problem a few nights a week or more
in the past year.
TIPS TO REMEMBER
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For those suffering from insomnia, the recent approval of ramelteon (Rozerem, Takeda Pharmaceuticals) by the Food & Drug Administration
should be a welcome relief. "Ramelteon is indicated for the treatment of insomnia characterized by difficulty with sleep onset,"
said Jeffrey Nahmias, M.D., director of the Sleep Fellowship Program at Newark Beth Israel Medical Center, Newark, N.J. "Unlike
other prescription sleep medications, ramelteon works by selectively affecting melatonin MT1 and MT2 receptors, which are
believed to be involved in the circadian rhythm underlying the normal sleep-wake cycle," he said. This contrasts with other
prescribed sleep agents that work by binding to gamma-aminobutyric acid (GABA) receptors, which reduce central nervous system
activity. "Ramelteon has been shown to carry no risks of abuse, withdrawal, or dependency, and negligible risk for next-day hangover
effects," said Thomas Roth, Ph.D., director of the Sleep Disorders & Research Center at Henry Ford Health System in Detroit.
"It is the first prescription sleep medication that has not been designated as a controlled substance," said Nahmias. Takeda
officials said the FDA approval may allow physicians to prescribe ramelteon for long-term use in adults.
The approval of ramelteon was based on data collected from clinical trials with more than 4,000 patients, 18 to 93 years of
age. Study patients receiving ramelteon experienced reduced average latency to sleep compared with placebo. In one of these
studies, more than 400 patients received single daily doses of ramelteon for up to one year. According to Nahmias, melatonin has been quite useful in patients with circadian rhythm disorders, jet lag, and delayed sleep
phase syndrome. "I would like to see studies performed with ramelteon in these patients to further evaluate its efficacy,"
he said.
Ramelteon is hepatically metabolized, primarily by the CYP1A2 isoenzyme. The manufacturer advises that ramelteon not be used
in combination with fluvoxamine, a strong CYP1A2 inhibitor. The coadministration of the two agents has been shown to significantly
increase ramelteon concentrations. Additionally, ramelteon should be administered with caution in patients taking rifampin,
ketoconazole, and fluconazole.
The most common adverse events associated with ramelteon in clinical trials were somnolence, dizziness, nausea, and fatigue.
Ramelteon has been associated with decreased testosterone levels and increased prolactin levels. Therefore, the package labeling
recommends that for patients presenting with any unexplained symptoms possibly associated with these hormone level changes,
assessment of prolactin and testosterone levels should be considered appropriate.
The manufacturer cautions that the effect of ramelteon in patients with severe sleep apnea or severe chronic obstructive pulmonary
disease (COPD) has not been studied and the drug is not recommended for use in these patients.
The recommended dose of ramelteon is 8 mg, to be taken within 30 minutes of bedtime. Takeda suggests that ramelteon not be
used in patients with severe hepatic impairment. However, no dosage adjustments are necessary in patients with severe renal
impairment or those who require chronic hemodialysis. Ramelteon is classified as pregnancy category C. It should be used during
pregnancy only if the potential benefit to the mother outweighs any risk to the fetus.
Ramelteon should be available for patients in late September.
Monica Shah is a writer and a hospital pharmacist in New Jersey.
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