Trade Names:Rozerem- Tablets 8 mg
Melatonin receptor agonist with high affinity for melatonin MT 1 and MT 2 receptors and selectivity over the MT 3 receptor. Activation of MT 1 and MT 2 receptors is believed to contribute to ramelteon's sleep-promoting properties.
Rapidly absorbed; T max 0.75 h after fasted oral administration. Total absorption 84%; absolute bioavailability is 1.8% because of extensive first-pass metabolism.
82% protein bound (albumin). Vd is 73.6 L.
Oxidized (primarily by CYP1A2; CYP2C subfamily and CYP3A4 to minor degree) to hydroxyl and carbonyl derivatives, with secondary metabolism to glucuronide conjugates. M-II metabolite is active.
The t ½ is 1 to 2.6 h. The t ½ of M-II metabolite is 2 to 5 h. 84% excreted in urine, 4% in feces. Less than 0.1% excreted as parent compound.
4-fold exposure in patients with mild hepatic function impairment. More than 10-fold exposure in patients with moderate hepatic function impairment.Elderly
AUC is 97% and C max is 86% higher than in younger adults. AUC and C max of M-II metabolite increased 30% and 13%, respectively.Food Effects
AUC increased 31%, C max reduced 22%, and T max delayed 45 min following administration with high-fat meal.
Treatment of insomnia characterized by sleep onset difficulty.
PO 8 mg within 30 min of going to bed.
Store at controlled room temperature (59° to 86°F). Protect from moisture and humidity.
May have additive pharmacologic effects. Avoid concurrent use.Strong CYP enzyme inducers (eg, rifampin)
Ramelteon plasma concentrations may be reduced, decreasing the pharmacologic effects.Strong CYP1A2 inhibitors (eg, fluvoxamine)
Ramelteon plasma concentrations may be elevated, increasing the pharmacologic and adverse effects. Avoid coadministration.Strong CYP2C9 inhibitors (eg, fluconazole)
Ramelteon plasma concentrations may be elevated, increasing the pharmacologic and adverse effects. Coadminister with caution.Strong CYP3A4 inhibitors (eg, ketoconazole)
Ramelteon plasma concentrations may be elevated, increasing the pharmacologic and adverse effects. Coadminister with caution.
None well documented.
Headache (7%); somnolence, dizziness (5%); fatigue (4%); exacerbated insomnia (3%); depression (2%).
Nausea (3%); diarrhea, dysgeusia (2%).
Decreased blood cortisol (1%).
Arthralgia, myalgia (2%).
Upper respiratory tract infection (3%); influenza (1%).
Consider assessment of prolactin and testosterone levels, as appropriate, for patients presenting with unexplained amenorrhea, galactorrhea, decreased libido, or infertility.
Category C .
Safety and efficacy not established.
Use with caution in patients with moderate hepatic function impairment; do not use in patients with severe hepatic function impairment.
Patients should avoid engaging in hazardous activities requiring concentration after taking ramelteon.
Ramelteon has been associated with an effect on reproductive hormones in adults (eg, decreased testosterone and increased prolactin levels). It is not known what effect chronic or chronic intermittent use may have on the reproductive axis in adolescents and children.
Not recommended for patients with severe COPD.
Use with caution; worsening of depression, including suicidal ideation, has been reported in depressed patients receiving hypnotics.
Sleep disturbances may be the presenting manifestation of a physical and/or psychiatric disorder. Initiate treatment only after careful evaluation. Failure of insomnia to remit after a reasonable period of treatment, worsening of insomnia, or emergence of new cognitive or behavioral abnormalities may indicate the presence of a primary psychiatric or medical illness that should be evaluated.
Not recommended for patients with severe sleep apnea.
No cases reported.
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