Ramelteon

Name: Ramelteon

What should I know about storage and disposal of this medication?

Keep this medication in the container it came in, tightly closed, and out of reach of children. Store it at room temperature and away from excess heat and moisture (not in the bathroom).

Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program. Talk to your pharmacist or contact your local garbage/recycling department to learn about take-back programs in your community. See the FDA's Safe Disposal of Medicines website (http://goo.gl/c4Rm4p) for more information if you do not have access to a take-back program.

It is important to keep all medication out of sight and reach of children as many containers (such as weekly pill minders and those for eye drops, creams, patches, and inhalers) are not child-resistant and young children can open them easily. To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location – one that is up and away and out of their sight and reach. http://www.upandaway.org

Brand names

  • Rozerem®

Adverse Effects

1-10%

Dizziness

Somnolence (similar to placebo)

Fatigue

Headache

Dysgeusia

Nausea

Frequency Not Defined

Depression

Worsening of insomnia

Hallucinations

Mania

Angioedema (rare )

Pharmacology

Mechanism of Action

Melatonin receptor agonist with high affinity for MT1 & MT2 receptors

Absorption

Absorption: 84%

Bioavailability: 1.8%

Distribution

Protein bound: 82%

Metabolism

Extensive first-pass metabolism; mostly by hepatic CYP1A2

Excretion

Urine: 84%

Feces: 4%

Ramelteon Overview

Ramelteon is a prescription medication used to treat insomnia. Ramelteon belongs to a group of drugs called melatonin receptor agonists, which act like melatonin to promote sleep.

This medication comes in tablet form. It is usually taken once a day, within 30 minutes of going to bed, with a full glass of water. Do not break the tablets. Swallow tablets whole.

Do not take ramelteon with or right after a meal. This may delay how fast ramelteon will work or reduce how ramelteon works.

Common side effects of ramelteon are drowsiness, tiredness, and dizziness.

Ramelteon Drug Class

Ramelteon is part of the drug class:

  • Melatonin receptor agonists

Inform MD

Before starting ramelteon, tell your doctor about all of your health conditions, including if you:

  • have a history of depression
  • have a history of mental illness, or suicidal thoughts
  • have liver disease
  • have a lung disease or breathing problems

Tell your doctor if you are pregnant, planning to become pregnant, or breastfeeding.

Tell your doctor about all of the medicines you take including prescription and non-prescription medicines, vitamins and herbal supplements.

Ramelteon Usage

  • Take ramelteon exactly as prescribed. Do not take more ramelteon than prescribed for you.
  • Do not break the tablets. They should be swallowed whole.
  • Take ramelteon within 30 minutes of going to bed. After taking ramelteon only do activities to get ready for bed.
  • Do not take ramelteon with or right after a meal. This may delay how fast ramelteon will work or reduce how ramelteon works.
  • Do not take ramelteon unless you are able to get a full night's sleep before you must be active again.
  • Call your doctor if your insomnia worsens or is not better within 7-10 days. This may mean that there is another condition causing your sleep problems.
  • If you take too much ramelteon or overdose, call your doctor or poison control center right away, or get emergency treatment.

What is ramelteon?

Ramelteon is a sedative, also called a hypnotic. It works by affecting certain substances in your body that help regulate your "sleep-wake cycle."

Ramelteon is used to treat insomnia that is associated with having trouble falling asleep.

Unlike some other sleep medications, ramelteon is not known to be habit-forming.

Ramelteon may also be used for purposes not listed in this medication guide.

Ramelteon Dosage and Administration

Administration

Oral Administration

Administer orally within 30 minutes of bedtime.1 2

Avoid administration with or immediately after a high-fat meal because of potentially decreased rate of absorption.1 2 (See Food under Pharmacokinetics.)

Dosage

Adults

Insomnia Oral

8 mg.1 2

Special Populations

Hepatic Impairment

Increased exposure to drug and active metabolite.1 (See Special Populations under Pharmacokinetics.) No specific dosage recommendations at this time.1 However, use with caution in patients with moderate hepatic impairment; avoid use in patients with severe hepatic impairment.1

Renal Impairment

No dosage adjustment necessary in patients with mild, moderate, or severe renal impairment or in those requiring chronic hemodialysis.1

Cautions for Ramelteon

Contraindications

  • Hypersensitivity to ramelteon or any ingredient in the formulation.1

Warnings/Precautions

Warnings

Adequate Patient Evaluation

Sleep disturbances may be a manifestation of a physical and/or psychiatric disorder; carefully evaluate patient before providing symptomatic treatment.1

Failure of insomnia to remit after a reasonable treatment period, exacerbation of insomnia, and/or emergence of new cognitive or behavioral abnormalities may indicate the presence of an underlying psychiatric or physical disorder requiring further patient evaluation.1

Complex Sleep-related Behaviors

Potential risk of complex sleep-related behaviors such as sleep-driving (i.e., driving while not fully awake after ingesting a sedative-hypnotic drug, with no memory of the event), making phone calls, or preparing and eating food while asleep.6

Sensitivity Reactions

Potential risk of anaphylaxis and angioedema; may occur as early as with the first dose of drug.6

Major Toxicities

Psychiatric Effects

Cognitive and behavioral changes reported.1 In primarily depressed patients, exacerbation of depression and suicidal ideation reported following use of hypnotics.1

Immediately evaluate any new psychiatric abnormalities.1

Endocrine Effects

Increased prolactin concentrations reported in patients with chronic insomnia receiving ramelteon 16 mg daily for 6 months.1

Abnormal morning cortisol concentrations (resulting in abnormal corticotropin [ACTH] stimulation test results) reported in 2 patients and prolactinoma reported in 1 patient receiving long-term (up to 12 months) therapy; causal relationship to drug not established.1

If unexplained amenorrhea, galactorrhea, decreased libido, or fertility problems occur, consider evaluating prolactin or testosterone concentrations.1

Abuse Potential and Dependence

No evidence of abuse potential detected following administration of doses up to 20 times the recommended hypnotic dose in patients with a history of drug abuse or dependence.1 2

No evidence of physical dependence.1

Withdrawal

No evidence of a withdrawal syndrome, including rebound insomnia, following discontinuance of long-term therapy (4, 8, or 16 mg daily for up to 35 days).1 2

Residual Effects

Next-day residual effects (reduced immediate/delayed memory recall and increased sluggishness, fatigue, and irritation) detected at weeks 1 and 3 but not week 5 of therapy in adult patients receiving ramelteon 8 mg daily.1 2 Residual effects not detected in a similar study in geriatric patients receiving ramelteon 4 or 8 mg daily.1 2

General Precautions

Long-term Safety

No clinically meaningful changes in laboratory parameters, endocrine tests, vital signs, ECG recordings, or intensity of menstrual bleeding detected in patients with chronic insomnia following up to 1 year of therapy.2 Rebound insomnia not observed following 1 year of therapy.2

Concomitant Diseases

No respiratory depressant effect in patients with mild to moderate COPD.1 Effects in patients with severe COPD (e.g., those with elevated pCO2, those requiring nocturnal oxygen therapy) not studied; use in these patients not recommended.1

No differences in measures of apnea indices observed in patients with mild to moderate obstructive sleep apnea.1 Effects in patients with severe obstructive sleep apnea not studied; use in these patients not recommended.1

Specific Populations

Pregnancy

Category C.1

Lactation

Distributed into milk in rats; not known whether distributed into human milk.1 Use not recommended.1

Pediatric Use

Safety and efficacy not established in pediatric patients.1

Geriatric Use

Increased exposure to drug and active metabolite.1 (See Special Populations under Pharmacokinetics.) However, no overall differences in safety or efficacy relative to younger adults.1

Hepatic Impairment

Use with caution in patients with moderate hepatic impairment; avoid use in patients with severe hepatic impairment.1 (See Special Populations under Pharmacokinetics.)

Common Adverse Effects

Headache, somnolence, dizziness, fatigue, nausea, exacerbation of insomnia, upper respiratory tract infection, diarrhea, myalgia, depression, dysgeusia, arthralgia.1

Advice to Patients

  • Necessity of administering within 30 minutes of bedtime and limiting activities to only those necessary to prepare for bed.1 Avoid administration with or immediately after a high-fat meal.1

  • Necessity of avoiding driving, operating machinery, or performing hazardous tasks following administration.1 Importance of avoiding alcohol during therapy.1

  • Importance of consulting a clinician if worsening insomnia or emergence of new behavioral manifestations occurs.1

  • Importance of consulting a clinician if cessation of menses or galactorrhea (in women), decreased libido, or problems with fertility occur.1

  • Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses.1

  • Importance of informing patients of other important precautionary information.1 (See Cautions.)

Commonly used brand name(s)

In the U.S.

  • Rozerem

Available Dosage Forms:

  • Tablet

Therapeutic Class: Nonbarbiturate Hypnotic

Pharmacologic Class: Melatonin Receptor Agonist

What do I need to tell my doctor BEFORE I take Ramelteon?

  • If you have an allergy to ramelteon or any other part of ramelteon.
  • If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
  • If you have liver disease.
  • If you have sleep apnea.
  • If you do not have time to get a full night's sleep.
  • If you are taking fluvoxamine.
  • If you are taking any other drugs that can make you sleepy. There are many drugs that can do this. Ask your doctor or pharmacist if you are not sure.

This is not a list of all drugs or health problems that interact with this medicine.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take ramelteon with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

What are some other side effects of Ramelteon?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

  • Feeling sleepy.
  • Dizziness.
  • Feeling tired or weak.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

Adverse Reactions

1% to 10%:

Central nervous system: Dizziness (4% to 5%), somnolence (3% to 5%), fatigue (3% to 4%), insomnia worsened (3%), depression (2%)

Endocrine & metabolic: Serum cortisol decreased (1%)

Gastrointestinal: Nausea (3%), taste perversion (2%)

Neuromuscular & skeletal: Myalgia (2%), arthralgia (2%)

Respiratory: Upper respiratory infection (3%)

Miscellaneous: Influenza (1%)

Postmarketing and/or case reports: Anaphylaxis, angioedema, complex sleep-related behavior (sleep-driving, cooking or eating food, making phone calls), prolactin levels increased, testosterone levels decreased

Warnings/Precautions

Concerns related to adverse effects:

• Abnormal thinking/behavioral changes: Hypnotics/sedatives have been associated with abnormal thinking and behavior changes including decreased inhibition, aggression, bizarre behavior, agitation, hallucinations, and depersonalization. These changes may occur unpredictably and may indicate previously unrecognized psychiatric disorders; evaluate appropriately.

• CNS depression: May cause CNS depression impairing physical and mental capabilities; patients must be cautioned about performing tasks, which require mental alertness (operating machinery or driving).

• Hyperprolactinemia: May increase prolactin levels.

• Hypersensitivity reactions: Hypersensitivity reactions, including angioedema, have been reported (rare). Do not rechallenge patient if such reactions occur.

• Sleep-related activities: An increased risk for hazardous sleep-related activities such as sleep-driving, cooking and eating food, having sex, and making phone calls while asleep have been noted; amnesia, anxiety, and other neuropsychiatric symptoms may also occur. The use of alcohol, other CNS depressants, and exceeding the recommended maximum dose may increase the risk of these activities. Discontinue treatment in patients who report any complex sleep behavior.

Disease-related concerns:

• Depression: Use with caution in patients with depression; worsening of depression, including suicidal ideation has been reported with the use of hypnotics.

• Hepatic impairment: Use with caution in patients with hepatic impairment; use not recommended with severe impairment.

• Respiratory disease: Use with caution in patients with respiratory compromise, COPD or sleep apnea. Use is not recommended in patients with severe sleep apnea (has not been studied).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Other warnings/precautions:

• Appropriate use: Symptomatic treatment of insomnia should be initiated only after careful evaluation of potential causes of sleep disturbance. Failure of sleep disturbance to resolve after 7 to 10 days may indicate psychiatric and/or medical illness.

• Rapid onset: Because of the rapid onset of action, administer immediately prior to bedtime.

For the Consumer

Applies to ramelteon: oral tablet

Along with its needed effects, ramelteon may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Some side effects of ramelteon may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common
  • Dizziness
  • sleepiness or unusual drowsiness
Less common
  • Body aches or pain
  • change in taste
  • chills
  • cough
  • difficulty in breathing
  • difficulty in moving
  • discouragement
  • ear congestion
  • fatigue
  • feeling sad or empty
  • fever
  • general feeling of discomfort or illness
  • irritability
  • joint pain
  • loss of appetite
  • loss of interest or pleasure
  • loss of taste
  • loss of voice
  • muscle aching or cramping
  • muscle pain or stiffness
  • nasal congestion
  • nausea
  • pain in joints
  • runny nose
  • shivering
  • sleeplessness
  • sneezing
  • sore throat
  • sweating
  • swollen joints
  • trouble concentrating
  • trouble sleeping
  • unable to sleep
  • unusual tiredness or weakness
  • vomiting

Liver Dose Adjustments

-Mild Hepatic Impairment (Child-Pugh A): Data not available.
-Moderate Hepatic Impairment (Child-Pugh B): Use with caution.
-Severe Hepatic Impairment (Child-Pugh C): Not recommended.

Dialysis

-Hemodialysis: No adjustment recommended.
-Peritoneal dialysis: Data not available.

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