Ramelteoni s indicated for the treatment of insomnia characterized by difficulty with sleep onset

Miscellaneous sedatives & hypnotics

Ramelteon is a melatonin receptor agonist with both high affinity for melatonin MT1 and MT2receptors, and lower selectivity for the MT3 receptor. Melatonin production is concurrent with nocturnal sleep, meaning that an increase in melatonin levels is related to the onset of self-reported sleepiness and an increase in sleep propensity. MT1 receptors are believed to be responsible for regulation of sleepiness and facilitation of sleep onset, and MT2 receptors are believed to mediate phase-shifting effects of melatonin on the circadian rhythm. While MT1 and MT2 receptors are associated with the sleep-wake cycle, MT3 has a completely different profile, and therefore is not likely to be involved in the sleep-wake cycle. Remelteon has no appreciable affinity for the gamma-aminobutyric acid (GABA) receptor complex or receptors that bind neuropeptides, cytokines, serotonin, dopamine, norepinephrine, acetylcholine, or opiates.

Adult dose: 8 mg taken within 30 minutes of going to bed. Should not be taken with or immediately after a high-fat meal. The total daily dose should not exceed 8 mg.

Rifampin (strong CYP enzyme inducer): Decreases exposure to and effects of ramelteon.

Ketoconazole (strong CYP3A4 inhibitor): Increases AUC for ramelteon; administer with caution.

Fluconazole (strong CYP2C9 inhibitor): Increases systemic exposure of ramelteon; administer with caution. Donepezil increases systemic exposure of ramelteon; patients should be closely monitored when ramelteon is co administered with donepezil. Doxepin increases systemic exposure of ramelteon; patients should be closely monitored when ramelteon is co administered with doxepin.

Alcohol: Causes additive psychomotor impairment; should not be used in combination

Most common adverse reactions (≥3% and more common than with placebo) are: somnolence, dizziness, fatigue, nausea, and exacerbated insomnia

Pregnancy: Based on animal data may cause fetal harm. Do not use unless the potential benefit justifies the potential risk.

Nursing mothers: Use with caution.

Severe anaphylactic/anaphylactoid reactions: Angioedema and anaphylaxis have been reported. Do not rechallenge if such reactions occur.

Need to evaluate for co-morbid diagnoses: Reevaluate if insomnia persists after 7 to 10 days of treatment.

Abnormal thinking, behavioral changes, complex behaviors: May include "sleep-driving" and hallucinations. Immediately evaluate any new onset behavioral changes.

Depression: Worsening of depression or suicidal thinking may occur.

CNS effects: Potential impairment of activities requiring complete mental alertness such as operating machinery or driving a motor vehicle, after ingesting the drug. 

Reproductive effects: Include decreased testosterone and increased prolactin levels. Effect on the reproductive axis in developing humans is unknown

Patients with severe sleep apnea: Rozerem is not recommended for use in this population.

Pediatric use: Safety and effectiveness not established.

Geriatric use: No overall differences in safety and efficacy between elderly and younger adult subjects.

Hepatic impairment: Is not recommended in patients with severe impairment; use with caution in moderate impairment.

Store at 25°C; excursions permitted to 15° to 30°C. Keep container tightly closed and protected from moisture and humidity.