Ramelteon (2 brand names, 1 dosage form, 1 route)
Available dosage forms: TABLET.
Routes of administration: ORAL.
Brand Names
- RAMELTEON
- ROZEREM
Indications and Usage
Ramelteon tablets are 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)].
Contraindications
Patients who develop angioedema after treatment with ramelteon tablets should not be rechallenged with the drug. Patients should not take ramelteon tablet in conjunction with fluvoxamine [see Drug Interactions (7)].
Adverse Reactions
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)]
Mechanism of Action
Ramelteon is a melatonin receptor agonist with both high affinity for melatonin MT 1and MT 2receptors and relative selectivity over the MT 3receptor. The activity of ramelteon at the MT 1and MT 2receptors 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. Ramelteon has no appreciable affinity for the GABA receptor complex or for receptors that bind neuropeptides, cytokines, serotonin, dopamine, noradrenaline, acetylcholine, and opiates. Ramelteon also does not interfere with the activity of a number of selected enzymes in a standard panel. The major metabolite of ramelteon, M-II, is pharmacologically active and has approximately one tenth and one fifth the binding affinity of the parent molecule for the human MT 1and MT 2receptors, respectively. However, M-II circulates at higher concentrations than the parent producing 20- to 100-fold greater mean systemic exposure when compared to ramelteon. Similar to ramelteon, M-II does not interfere with the activity of a number of endogenous enzymes. All other known metabolites of ramelteon are inactive.
Overdosage
General symptomatic and supportive measures should be used, along with immediate gastric lavage where appropriate. Intravenous fluids should be administered as needed. As in all cases of drug overdose, respiration, pulse, blood pressure, and other appropriate vital signs should be monitored, and general supportive measures employed. Hemodialysis does not effectively reduce exposure to ramelteon tablets. Therefore, the use of dialysis in the treatment of overdosage is not appropriate. Poison Control Center As with the management of all overdosage, the possibility of multiple drug ingestion should be considered. Contact a poison control center for current information on the management of overdosage.