Overview
11 DESCRIPTION Ramelteon is an orally active hypnotic chemically designated as (S-N-[2-(1,6,7,8-tetrahydro -2H-indeno-[5,4-b]furan-8-yl)ethyl] propionamide and containing one chiral center. The compound is produced as the (S)-enantiomer, with an empirical formula of C 16 H 21 NO 2 , molecular weight of 259.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Ramelteon is a melatonin receptor agonist with both high affinity for melatonin MT 1 and MT 2 receptors and relative selectivity over the MT 3 receptor. The activity of ramelteon at the MT 1 and MT 2 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. 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.
Indications
- 1 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) ] .
Common Doses
- 8 mg
Dosage
2 DOSAGE AND ADMINISTRATION Adult dose: 8 mg taken within 30 minutes of going to bed. (2.1) Should not be taken with or immediately after a high-fat meal. (2.1) Total daily dose should not exceed 8 mg. (2.1) 2.1 Dosage in Adults The recommended dose of Ramelteon Tablets is 8 mg taken within 30 minutes of going to bed. It is recommended that Ramelteon Tablets not be taken with or immediately after a high-fat meal. The total Ramelteon Tablets dose should not exceed 8 mg per day. 2.
Contraindications
- 4 CONTRAINDICATIONS Patients who develop angioedema after treatment with Ramelteon Tablets should not be rechallenged with the drug. Patients should not take Ramelteon Tablets in conjunction with fluvoxamine [see Drug Interactions (7) ]. History of angioedema while taking Ramelteon Tablets. (4) Fluvoxamine (strong CYP1A2 inhibitor): Increases AUC for ramelteon and should not be used in combination. (7.1)
Side Effects
- 6 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) ] Most common adverse reactions (≥3% and more common than with placebo) are: somnolence, dizziness, fatigue, nausea, and exacerbated insomnia. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Innogenix, LLC.
Interactions
- 7 DRUG INTERACTIONS Rifampin (strong CYP enzyme inducer): Decreases exposure to and effects of ramelteon. (7.1) Ketoconazole (strong CYP3A4 inhibitor): Increases AUC for ramelteon; administer with caution. (7.1) Fluconazole (strong CYP2C9 inhibitor): Increases systemic exposure of ramelteon; administer with caution. (7.1) Donepezil: Increases systemic exposure of ramelteon; patients should be closely monitored when ramelteon is co-administered with donepezil. (7.