RAMELTEON tablet

Negara: Amerika Serikat

Bahasa: Inggris

Sumber: NLM (National Library of Medicine)

Bahan aktif:

RAMELTEON (UNII: 901AS54I69) (RAMELTEON - UNII:901AS54I69)

Tersedia dari:

Actavis Pharma, Inc.

Rute administrasi :

ORAL

Jenis Resep:

PRESCRIPTION DRUG

Indikasi Terapi:

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)] . 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)] . Risk Summary Available data from postmarketing reports with ramelteon tablets use in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In animal studies, ramelteon produced evidence of developmental toxicity, including teratogenic effects, in rats at doses greater than 36 times the recommended human dose (RHD) of 8 mg/day based on body surface area (mg/m2 ) (see Data ). The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Data Animal Data Oral administration of ramelteon (10, 40, 150 or 600 mg/kg/day) to pregnant rats during the period of organogenesis was associated with increased incidences of fetal structural abnormalities (malformations and variations) at doses greater than 40 mg/kg/day. The no-effect dose is approximately 50 times the RHD based on mg/m2 . Treatment of pregnant rabbits during the period of organogenesis produced no evidence of embryo-fetal toxicity at oral doses of up to 300 mg/kg/day (or up to 720 times the RHD based on mg/m2 ). When rats were orally administered ramelteon (30, 100, or 300 mg/kg/day) throughout gestation and lactation, growth retardation, developmental delay, and behavioral changes were observed in the offspring at doses greater than 30 mg/kg/day. The no-effect dose is 36 times the RHD based on mg/m2 . Increased incidences of malformation and death among offspring were seen at the highest dose. Risk Summary There are no data regarding the presence of ramelteon or its metabolites in human milk, the effects on the breastfed infant, or the effects on milk production. Ramelteon and/or its metabolites are present in rat milk. When a drug is present in animal milk, it is likely that the drug will be present in human milk. Because of the mechanism of action of ramelteon, there is a potential risk for somnolence in a breastfed infant (see Clinical Considerations) . The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ramelteon tablets and any potential adverse effects on the breastfed infant from ramelteon tablets or from the underlying maternal condition. Clinical Considerations Infants exposed to ramelteon tablets through breastmilk should be monitored for somnolence and feeding problems. A lactating woman may consider interrupting breastfeeding and pumping and discarding breast milk during treatment and for 25 hours (approximately 5 elimination half-lives) after ramelteon tablets administration in order to minimize drug exposure to a breastfed infant. Safety and effectiveness of ramelteon tablets in pediatric patients have not been established. Further study is needed prior to determining that this product may be used safely in prepubescent and pubescent patients. A total of 654 subjects in double-blind, placebo-controlled, efficacy trials who received ramelteon tablets were at least 65 years of age; of these, 199 were 75 years of age or older. No overall differences in safety or efficacy were observed between elderly and younger adult subjects. A double-blind, randomized, placebo-controlled study in elderly subjects with insomnia (n=33) evaluated the effect of a single dose of ramelteon tablets on balance, mobility, and memory functions after middle of the night awakening. There is no information on the effect of multiple dosing. Night time dosing of ramelteon tablets 8 mg did not impair middle of the night balance, mobility, or memory functions relative to placebo. The effects on night balance in the elderly cannot be definitively known from this study. The respiratory depressant effect of ramelteon tablets was evaluated in a crossover design study of subjects (n=26) with mild to moderate COPD after administering a single 16 mg dose or placebo, and in a separate study (n=25), the effects of ramelteon tablets on respiratory parameters were evaluated after administering an 8 mg dose or placebo in a crossover design to patients with moderate to severe COPD, defined as patients who had forced expiratory volume at one second (FEV1 )/forced vital capacity ratio of <70%, and a FEV1 <80% of predicted with <12% reversibility to albuterol. Treatment with a single dose of ramelteon tablets has no demonstrable respiratory depressant effects in subjects with mild to severe COPD, as measured by arterial O2 saturation (SaO2). There is no available information on the respiratory effects of multiple doses of ramelteon tablets in patients with COPD. The respiratory depressant effects in patients with COPD cannot be definitively known from this study. The effects of ramelteon tablets were evaluated after administering a 16 mg dose or placebo in a crossover design to subjects (n=26) with mild to moderate obstructive sleep apnea. Treatment with ramelteon tablets 16 mg for one night showed no difference compared with placebo on the Apnea/Hypopnea Index (the primary outcome variable), apnea index, hypopnea index, central apnea index, mixed apnea index, and obstructive apnea index. Treatment with a single dose of ramelteon tablets does not exacerbate mild to moderate obstructive sleep apnea. There is no available information on the respiratory effects of multiple doses of ramelteon tablets in patients with sleep apnea. The effects on exacerbation in patients with mild to moderate sleep apnea cannot be definitively known from this study. Ramelteon has not been studied in subjects with severe obstructive sleep apnea; use of ramelteon tablets is not recommended in such patients. Exposure to ramelteon tablets was increased by four-fold in subjects with mild hepatic impairment and by more than ten-fold in subjects with moderate hepatic impairment. Ramelteon tablets should be used with caution in patients with moderate hepatic impairment [see Clinical Pharmacology (12.4)] . Ramelteon tablets are not recommended in patients with severe hepatic impairment. No effects on Cmax and AUC0-t of parent drug or M-II were seen. No adjustment of ramelteon tablets dosage is required in patients with renal impairment [see Clinical Pharmacology (12.4)] . Ramelteon tablets are 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 tablets [see Clinical Studies (14.2)] . 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.

Ringkasan produk:

Ramelteon Tablets, 8 mg are available as orange colored, unscored, round, biconvex tablets, debossed with “WPI” on one side and plain on the other side, in the following quantities: NDC 0591-2191-30                               Bottles of 30 NDC 0591-2191-01                               Bottles of 100 Dispense in a tight, light-resistant container with child-resistant closure. Store at 20° to 25°C (68° to 77°F) [See USP Controlled Room Temperature]. Keep container tightly closed and protected from moisture and humidity.

Status otorisasi:

Abbreviated New Drug Application

Selebaran informasi

RAMELTEON- RAMELTEON TABLET
Actavis Pharma, Inc.
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MEDICATION GUIDE
Ramelteon (ra mel' tee on) Tablets
Read the Medication Guide that comes with ramelteon tablets before you
start taking it and each time you
get a refill. There may be new information. This Medication Guide does
not take the place of talking to
your doctor about your medical condition or treatment.
_____________________________________________________________________________________
_______________________________________
What is the most important information I should know about ramelteon
tablets?
Ramelteon tablets may cause severe allergic reactions. Symptoms
include swelling of the tongue or
throat, trouble breathing, and nausea and vomiting. Get emergency
medical help if you get these
symptoms after taking ramelteon tablets.
After taking ramelteon tablets, you may get up out of bed while not
being fully awake and do an activity
that you do not know you are doing. The next morning, you may not
remember that you did anything
during the night. You have a higher chance for doing these activities
if you drink alcohol or take other
medicines that make you sleepy with ramelteon tablets. Activities may
include:
•
driving a car ("sleep-driving")
•
making and eating food
•
talking on the phone
•
having sex
•
sleep-walking
Call your doctor right away if you find out that you have done any of
the above activities after taking
ramelteon tablets.
Important:
1. Take ramelteon tablets exactly as prescribed
•
Do not take more ramelteon tablets than prescribed.
•
Take ramelteon tablets within 30 minutes of going to bed, not sooner.
2. Do not take ramelteon tablets if you:
•
drink alcohol
•
take other medicines that can make you sleepy. Talk to your doctor
about all of your medicines.
Your doctor will tell you if you can take ramelteon tablets with your
other medicines
•
cannot get a full night’s sleep
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_____________________________________
WHAT AR

Karakteristik produk

RAMELTEON- RAMELTEON TABLET
ACTAVIS PHARMA, INC.
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
RAMELTEON
TABLETS SAFELY AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR
RAMELTEON TABLETS.
RAMELTEON TABLETS, FOR ORAL USE
INITIAL U.S. APPROVAL: 2005
INDICATIONS AND USAGE
Ramelteon tablets are indicated for the treatment of insomnia
characterized by difficulty with sleep onset.
(1)
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)
DOSAGE FORMS AND STRENGTHS
8 mg tablets. (3)
CONTRAINDICATIONS
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)
WARNINGS AND PRECAUTIONS
Severe anaphylactic/anaphylactoid reactions: Angioedema and
anaphylaxis have been reported. Do not
rechallenge if such reactions occur. (5.1)
Need to evaluate for comorbid diagnoses: Reevaluate if insomnia
persists after 7 to 10 days of
treatment. (5.2)
Abnormal thinking, behavioral changes, complex behaviors: May include
“sleep-driving” and
hallucinations. Immediately evaluate any new onset behavioral changes.
(5.3)
Depression: Worsening of depression or suicidal thinking may occur.
(5.3)
CNS effects: Potential impairment of activities requiring complete
mental alertness such as operating
machinery or driving a motor vehicle, after ingesting the drug. (5.4)
Reproductive effects: Include decreased testosterone and increased
prolactin levels. Effect on
reproductive axis in developing humans is unknown. (5.5)
Patients with severe sleep apnea: Ramelteon tablets are not
recommended for use in this population.
(5.6)
ADVERSE REACTIONS
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 REAC