Posted by ed_uk on July 24, 2005, at 6:38:48
In reply to Re: FDA okays sleep drug Rozerem(TM) (ramelteon) » linkadge, posted by ed_uk on July 24, 2005, at 4:58:30
So, Rozerem will be available in the US in about a month?? I hope it won't be delayed as much as Lunesta was!
From the Rozerem website..........
>The body's own melatonin binds to MT1 and MT2 receptors in the SCN, suppressing the circadian alerting signal. This is believed to facilitate sleep.
>ROZEREM (ramelteon) is a melatonin receptor agonist with both high affinity for melatonin MT1 and MT2 receptors and selectivity over the MT3 receptor.
The activity of ramelteon at the MT1 and MT2 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.
My question........
How does the hypnotic efficacy of ramelteon differ from that of melatonin?
What does the MT3 receptor do?
>M-II (the major active metabolite of ramelteon) has weak affinity for the serotonin 5-HT2B receptor..........
What is the significance of this??
>DOSAGE AND ADMINISTRATION
>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.
>HOW SUPPLIED?
>ROZEREM is available as round, pale orange-yellow, film-coated, 8 mg tablets.
>Controlled Trials Supporting Efficacy
Although ramelteon can help people fall asleep, it doesn't appear to increase total sleep time. Mild residual effects were observed the following day.
>Rebound Insomnia/Withdrawal
No w/d symptoms were detected. Let's see whether ramelteon lives up to its promise.
>Abnormalities were, however, noted within the reproductive axis. Overall, the mean serum prolactin level change from baseline was 4.9 µg/L (34 % increase) for women in the ROZEREM group compared with -0.6 µg/L (4% decrease) for women in the placebo group (p=0.003). No differences between active- and placebo-treated groups occurred among men. Thirty-two percent of all patients who were treated with ramelteon in this study (women and men) had prolactin levels that increased from normal baseline levels compared to nineteen percent of patients who were treated with placebo.
Oh dear.
>In a 12-month, open-label study in adult and elderly patients, there were two patients who were noted to have abnormal morning cortisol levels, and subsequent abnormal ACTH stimulation tests.
A 29-year-old female patient was also diagnosed with a prolactinoma.
Hmmm.......
>ROZEREM is indicated for the treatment of insomnia characterized by difficulty with sleep onset.
Makes sense.
>The failure of insomnia to remit after a reasonable period 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.Is this a euphemistic way of saying that ramelteon can cause psychiatric adverse effects LOL?! A bit like 'Halcion may uncover depressive tendencies'.
>As with other hypnotics, exacerbation of insomnia and emergence of cognitive and behavioral abnormalities were seen with ROZEREM during the clinical development program.
:-(
>Patients should be advised to take ROZEREM within 30 minutes prior to going to bed.....
Useful to know :-)
>Patients should be advised that they should not take ROZEREM with or immediately after a high fat meal.
Delays the onset of action.
>Patients should consult their health care provider if they experience one of the following: cessation of menses or galactorrhea in females, decreased libido, or problems with fertility.
Signs of hyperprolactinemia.
>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.
Ramelteon can apparantly lower testosterone levels, as well as increasing prolactin.
>ROZEREM has a highly variable inter-subject pharmacokinetic profile (approximately 100% coefficient of variation in Cmax and AUC).
That's not what we like to hear! Presumably, more 'individualisation' of dosing will be required to optimise the effect. Doctors don't like this! Anyway, Rozerem only comes as an 8mg tablet.
>CYP1A2 is the major isozyme involved in the hepatic metabolism of ramelteon....
>Fluvoxamine (strong CYP1A2 inhibitor): When fluvoxamine 100 mg twice daily was administered for 3 days prior to single-dose co-administration of ROZEREM 16 mg and fluvoxamine, the AUC0-inf for ramelteon increased approximately 190-fold, and the Cmax increased approximately 70-fold, compared to ROZEREM administered alone.
Whoa! Take care if you're on Luvox.
>Adverse Reactions Resulting in Discontinuation of Treatment Five percent of the 3594 individual subjects exposed to ROZEREM in clinical studies discontinued treatment owing to an adverse event, compared with 2% of the 1370 subjects receiving placebo. The most frequent adverse events leading to discontinuation in subjects receiving ROZEREM were somnolence (0.8%), dizziness (0.5%), nausea (0.3%), fatigue (0.3%), headache (0.3%), and insomnia (0.3%).
Worsening of insomnia in 3% on ramelteon versus 2% on placebo. Depression in 2% on ramelteon versus 1% on placebo.
>DRUG ABUSE AND DEPENDENCE
>ROZEREM is not a controlled substance.
This will surely increase its popularity - especially since it can be used on a long-term basis.
~Ed
poster:ed_uk
thread:532130
URL: http://www.dr-bob.org/babble/20050723/msgs/532594.html