Ramelteon

What it is and how it works

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.

Mechanism class: Melatonin Receptor Agonists

Indications

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) . Ramelteon tablets are indicated for the treatment of insomnia characterized by difficulty with sleep onset.

Dosage and administration (summary)

Adult dose: 8 mg taken within 30 minutes of going to bed. Should not be taken with or immediately after a high-fat meal. Total daily dose should not exceed 8 mg. 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. Dosing in Patients with Hepatic Impairment Ramelteon tablets are not recommended in patients with severe hepatic impairment. Ramelteon tablets should be used with caution in patients with moderate hepatic impairment .

Contraindications

Patients who develop angioedema after treatment with ramelteon should not be rechallenged with the drug. Patients should not take ramelteon in conjunction with fluvoxamine . History of angioedema while taking ramelteon. Fluvoxamine (strong CYP1A2 inhibitor): Increases AUC for ramelteon and should not be used in combination.

Warnings and precautions

Severe anaphylactic/anaphylactoid reactions: Angioedema and anaphylaxis have been reported. Do not rechallenge if such reactions occur. Need to evaluate for comorbid 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.

Pregnancy

Pregnancy Risk Summary Available data from postmarketing reports with ramelteon use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

Storage and supply

Ramelteon tablets, 8 mg are available as light yellow to beige-coloured, round, biconvex bevel edged, film-coated tablets, debossed with "1344"on one side and plain on other side and are supplied as follows: NDC 76420-628-30 in bottles of 30 tablets (repackaged from NDC 70710-1344-X) NDC 76420-628-60 in bottles of 60 tablets (repackaged from NDC 70…

Source: Ramelteon (Ramelteon) — US FDA prescribing information, 2023-11-27, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.