Ramelteon

Ramelteon is used for insomnia, particularly delayed sleep onset. Ramelteon has not been shown to produce dependence and has shown no potential for abuse, and the withdrawal and rebound insomnia that is typical with other GABA modulators is not present in Ramelteon. It is currently the only non-scheduled prescription drug for the treatment of insomnia available in the United States. Some clinicians also use Ramelteon for the treatment of Delayed sleep phase disorder

Ramelteon belongs to the group of medicines called central nervous system (CNS) depressants (medicines that slow down the nervous system). Ramelteon is used to treat insomnia (trouble in sleeping). Ramelteon helps you get to sleep faster and sleep through the night. In general, when sleep medicines are used every night for a long time, they may lose their effectiveness. In most cases, sleep medicines should be used only for short periods of time, such as 1 or 2 days, and generally for no longer than 1 or 2 weeks.

Ramelteon is available only with your doctor's prescription.

Dosage in Adults

The recommended dose of Ramelteon (Ramelteon) is 8 mg taken within 30 minutes of going to bed. It is recommended that Ramelteon (Ramelteon) not be taken with or immediately after a high-fat meal.

The total Ramelteon (Ramelteon) dose should not exceed 8 mg per day.

Dosing in Patients with Hepatic Impairment

Ramelteon (Ramelteon) is not recommended in patients with severe hepatic impairment. Ramelteon (Ramelteon) should be used with caution in patients with moderate hepatic impairment.

Administration with Other Medications

Ramelteon (Ramelteon) should not be used in combination with fluvoxamine. Ramelteon (Ramelteon) should be used with caution in patients taking other CYP1A2 inhibiting drugs.

How supplied

Dosage Forms And Strengths

Ramelteon (Ramelteon) is available in an 8 mg strength tablet for oral administration.

Ramelteon (Ramelteon) 8 mg tablets are round, pale orange-yellow, film-coated, with “TAK” and “RAM-8” printed on one side.

Storage And Handling

Ramelteon (Ramelteon) is available as round, pale orange-yellow, film-coated, 8 mg tablets, with “TAK” and “RAM-8” printed on one side, in the following quantities:

NDC 64764-805-30 Bottles of 30

NDC 64764-805-10 Bottles of 100

NDC 64764-805-50 Bottles of 500

Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F). Keep container tightly closed and protected from moisture and humidity.

Distributed by: Takeda Pharmaceuticals America, Inc. Deerfield, IL 60015. Revised: 11/10

See also:
What is the most important information I should know about Ramelteon?

You should not use this medication if you are allergic to Ramelteon, or if you have severe liver disease.

You should not take Ramelteon if you are also taking the antidepressant fluvoxamine (Luvox).

Before taking Ramelteon, tell your doctor if you have liver disease, sleep apnea, a breathing disorder such as chronic obstructive pulmonary disease, or a history of depression, mental illness, or suicidal thoughts.

Take Ramelteon 30 minutes before your normal bedtime. After you take Ramelteon, avoid doing anything other than getting ready for bed.

Avoid taking Ramelteon together with or just after eating a high-fat meal. This will make it harder for your body to absorb the medication.

Some people using this medicine have engaged in activity such as driving, eating, or making phone calls and later having no memory of the activity. If this happens to you, stop taking Ramelteon and talk with your doctor about another treatment for your sleep disorder.

Use Ramelteon as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Ramelteon comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Ramelteon refilled.
• Do not take Ramelteon with or immediately after a high-fat meal.
• Take Ramelteon by mouth within 30 minutes prior to going to bed.
• Swallow Ramelteon whole. Do not break, crush, or chew before swallowing.
• Use Ramelteon only when you are able to get a full night's sleep (7 to 8 hours).
• After you take Ramelteon, limit your activities to those necessary to prepare for bed.
• If you miss a dose of Ramelteon, skip the missed dose. Do not take the dose in the morning or take 2 doses at once.

Ask your health care provider any questions you may have about how to use Ramelteon.

This medication is used to treat sleeplessness (insomnia). It helps you fall asleep faster so you can get a full night's rest. Sleep is important for your ability to function, think clearly, and remain alert. Lack of sleep can cause problems such as depression, heart disease and accidents. Getting enough sleep allows your mind and body to repair itself and increases your energy throughout the day.

Ramelteon works like a natural substance called melatonin that is produced by your body. It helps regulate your sleep-wake cycle (circadian rhythm).

How to use Ramelteon

Read the Medication Guide provided by your pharmacist before you start taking Ramelteon and each time you get a refill. If you have any questions, ask your doctor or pharmacist.

Take this medication by mouth with or without food, 30 minutes before bedtime, or as directed by your doctor. Do not take Ramelteon with or immediately after a high-fat meal because fat can affect how well this drug works.

The manufacturer directs not to break the tablet before taking it. However, many similar drugs (immediate-release tablets) can be broken. Follow your doctor's directions on how to take this medication.

Do not take a dose of this medication unless you have time for a full night's sleep that lasts at least 7 to 8 hours.

Your dosage is based on your medical condition and response to therapy. Do not increase your dose or take it more frequently than prescribed.

Inform your doctor if you have any changes in mood (e.g., feelings of depression), if you continue to have trouble falling asleep, or if your insomnia worsens.

See also:
What other drugs will affect Ramelteon?

Effects of Other Drugs on Ramelteon (Ramelteon)

Fluvoxamine (strong CYP1A2 inhibitor)

AUC0-inf for Ramelteon increased approximately 190-fold, and the Cmax increased approximately 70-fold upon coadministration of fluvoxamine and Ramelteon (Ramelteon), compared to Ramelteon (Ramelteon) administered alone. Ramelteon (Ramelteon) should not be used in combination with fluvoxamine. Other less strong CYP1A2 inhibitors have not been adequately studied. Ramelteon (Ramelteon) should be administered with caution to patients taking less strong CYP1A2 inhibitors.

Rifampin (strong CYP enzyme inducer)

Administration of multiple doses of rifampin resulted in a mean decrease of approximately 80% in total exposure to Ramelteon and metabolite M-II. Efficacy may be reduced when Ramelteon (Ramelteon) is used in combination with strong CYP enzyme inducers such as rifampin.

Ketoconazole (strong CYP3A4 inhibitor)

The AUC0-inf and Cmax of Ramelteon increased by approximately 84% and 36% upon coadministration of ketoconazole with Ramelteon (Ramelteon). Ramelteon (Ramelteon) should be administered with caution in subjects taking strong CYP3A4 inhibitors such as ketoconazole.

Fluconazole (strong CYP2C9 inhibitor)

The AUC0-inf and Cmax of Ramelteon was increased by approximately 150% when Ramelteon (Ramelteon) was coadministered with fluconazole. Ramelteon (Ramelteon) should be administered with caution in subjects taking strong CYP2C9 inhibitors such as fluconazole.

Donepezil

The AUC0-inf and Cmax of Ramelteon increased by approximately 100% and 87%, respectively upon coadministration of donepezil with Ramelteon (Ramelteon). Patients should be closely monitored when Ramelteon (Ramelteon) is coadministered with donepezil.

Doxepin

The AUC0-inf and Cmax of Ramelteon increased by approximately 66% and 69%, respectively, upon coadministration of doxepin donepezil with Ramelteon (Ramelteon). Patients should be closely monitored when Ramelteon (Ramelteon) is coadministered with doxepin.

Effect of Alcohol on Ramelteon (Ramelteon)

Alcohol by itself impairs performance and can cause sleepiness. Since the intended effect of Ramelteon (Ramelteon) is to promote sleep, patients should be cautioned not to consume alcohol when using Ramelteon. Use of the products in combination may have an additive effect.

Drug/Laboratory Test Interactions

Ramelteon (Ramelteon) is not known to interfere with commonly used clinical laboratory tests. In addition, in vitro data indicate that Ramelteon does not cause false-positive results for benzodiazepines, opiates, barbiturates, cocaine, cannabinoids, or amphetamines in two standard urine drug screening methods in vitro .

Drug Abuse And Dependence

Ramelteon (Ramelteon) is not a controlled substance.

Discontinuation of Ramelteon in animals or in humans after chronic administration did not produce withdrawal signs. Ramelteon does not appear to produce physical dependence.

Human Data

A laboratory abuse potential study was performed with Ramelteon.

Animal Data

Ramelteon did not produce any signals from animal behavioral studies indicating that the drug produces rewarding effects. Monkeys did not self-administer Ramelteon and the drug did not induce a conditioned place preference in rats. There was no generalization between Ramelteon and midazolam. Ramelteon did not affect rotorod performance, an indicator of disruption of motor function, and it did not potentiate the ability of diazepam to interfere with rotorod performance.

See also:
What are the possible side effects of Ramelteon?

The following serious adverse reactions are discussed in greater detail in other sections:

• Severe anaphylactic and anaphylactoid reactions
• Abnormal thinking, behavior changes, and complex behaviors
• CNS effects

Clinical Trials Experience

Adverse Reactions Resulting in Discontinuation of Treatment

The data described in this section reflect exposure to Ramelteon (Ramelteon) in 5373 subjects, including 722 exposed for 6 months or longer, and 448 subjects for one year.

Six percent of the 5373 individual subjects exposed to Ramelteon (Ramelteon) in clinical studies discontinued treatment owing to an adverse event, compared with 2% of the 2279 subjects receiving placebo. The most frequent adverse events leading to discontinuation in subjects receiving Ramelteon (Ramelteon) were somnolence, dizziness, nausea, fatigue, headache, and insomnia; all of which occurred in 1% of the patients or less.

Ramelteon (Ramelteon) Most Commonly Observed Adverse Events

Table 1 displays the incidence of adverse events reported by the 2861 patients with chronic insomnia who participated in placebo-controlled trials of Ramelteon (Ramelteon).

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in clinical trials of other drugs, and may not reflect the rates observed in practice. The adverse reaction information from clinical trials does, however, provide a basis for identifying the adverse events that appear to be related to drug use and for approximating rates.

Table 1: Incidence (% of subjects) of Treatment-Emergent Adverse Events

Ramelteon is the first in a new class of sleep agents that selectively binds to the melatonin receptors in the suprachiasmatic nucleus (SCN). It is used for insomnia, particularly delayed sleep onset. Ramelteon has not been shown to produce dependence and has shown no potential for abuse.