Eszopiclone

Keep all appointments with your doctor.

Do not let anyone else take your medication. Eszopiclone is a controlled substance. Prescriptions may be refilled only a limited number of times; ask your pharmacist if you have any questions.

It is important for you to keep a written list of all of the prescription and nonprescription (over-the-counter) medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements. You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.

You should tell your doctor about all prescription, non-prescription, illegal, recreational, herbal, nutritional, or dietary drugs you're taking before taking Lunesta, especially:

• Antidepressants
• Antifungals such as itraconazole (Sporanox) and ketoconazole (Nizoral)
• Antihistamines
• Clarithromycin (Biaxin)
• Certain HIV protease inhibitors such as nelfinavir (Viracept) and ritonavir (Norvir)
• Drugs for anxiety, mental illness, or seizures
• Nefazodone (Serzone)
• Olanzapine (Zyprexa)
• Rifampin (Rifadin, Rimactane)
• Sedatives
• Other sleeping pills
• Tranquilizers
• Troleandomycin (TAO) (not available in the United States)

Lunesta and Grapefruit

You should talk to your doctor about drinking grapefruit juice while taking Lunesta, as it may cause high levels of the drug to build up in your bloodstream.

Lunesta and Alcohol

You shouldn't consume alcohol while taking Lunesta, as it can worsen side effects associated with the medication.

Lunesta and Other Interactions

Lunesta may make you drowsy during the day. You should not drive or perform any activity that requires alertness until you know how this medicine affects you.

Meals that are high in fat may reduce the effect of Lunesta. You should be aware of this possible interaction.

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 the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The premarketing development program for LUNESTA included eszopiclone exposures in patients and/or normal subjects from two different groups of studies: approximately 400 normal subjects in clinical pharmacology/pharmacokinetic studies, and approximately 1550 patients in placebo-controlled clinical effectiveness studies, corresponding to approximately 263 patient-exposure years. The conditions and duration of treatment with LUNESTA varied greatly and included (in overlapping categories) open-label and double-blind phases of studies, inpatients and outpatients, and short-term and longer-term exposure. Adverse reactions were assessed by collecting adverse events, results of physical examinations, vital signs, weights, laboratory analyses, and ECGs.

The stated frequencies of adverse reactions represent the proportion of individuals who experienced, at least once, adverse reaction of the type listed. A reaction was considered treatment-emergent if it occurred for the first time or worsened while the patient was receiving therapy following baseline evaluation.

Clinical Trials Experience

In placebo-controlled, parallel-group clinical trials in the elderly, 3.8% of 208 patients who received placebo, 2.3% of 215 patients who received 2 mg LUNESTA, and 1.4% of 72 patients who received 1 mg LUNESTA discontinued treatment due to an adverse reaction. In the 6-week parallel-group study in adults, no patients in the 3 mg arm discontinued because of an adverse reaction. In the long-term 6-month study in adult insomnia patients, 7.2% of 195 patients who received placebo and 12.8% of 593 patients who received 3 mg LUNESTA discontinued due to an adverse reaction. No reaction that resulted in discontinuation occurred at a rate of greater than 2%.

Table 1 shows the incidence of adverse reactions from a Phase 3 placebo-controlled study of LUNESTA at doses of 2 or 3 mg in non-elderly adults. Treatment duration in this trial was 44 days. The table includes only reactions that occurred in 2% or more of patients treated with LUNESTA 2 mg or 3 mg in which the incidence in patients treated with LUNESTA was greater than the incidence in placebotreated patients.

Table 1: Incidence (%) of Adverse Reactions in a 6-Week Placebo-Controlled Study in Non- Elderly Adults with LUNESTA1

Adverse reactions from Table 1 that suggest a dose-response relationship in adults include viral infection, dry mouth, dizziness, hallucinations, infection, rash, and unpleasant taste, with this relationship clearest for unpleasant taste.

Table 2 shows the incidence of adverse reactions from combined Phase 3 placebo-controlled studies of LUNESTA at doses of 1 or 2 mg in elderly adults (ages 65-86). Treatment duration in these trials was 14 days. The table includes only reactions that occurred in 2% or more of patients treated with LUNESTA 1 mg or 2 mg in which the incidence in patients treated with LUNESTA was greater than the incidence in placebo-treated patients.

Table 2: Incidence (%) of Adverse Reactions in Elderly Adults (Ages 65-86) in 2-Week Placebo- Controlled Trials with LUNESTA1

Adverse reactions from Table 2 that suggest a dose-response relationship in elderly adults include pain, dry mouth, and unpleasant taste, with this relationship again clearest for unpleasant taste.

These figures cannot be used to predict the incidence of adverse reactions in the course of usual medical practice because patient characteristics and other factors may differ from those that prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contributions of drug and non-drug factors to the adverse reaction incidence rate in the population studied.

Following is a list of modified COSTART terms that reflect adverse reactions as defined in the introduction to the Adverse Reactions section and reported by approximately 1550 subjects treated with LUNESTA at doses in the range of 1 to 3.5 mg/day during Phase 2 and 3 clinical trials throughout the United States and Canada. All reported reactions are included except those already listed in Tables 1 and 2 or elsewhere in labeling, minor reactions common in the general population, and reactions unlikely to be drug-related. Although the reactions reported occurred during treatment with LUNESTA, they were not necessarily caused by it.

Reactions are further categorized by body system and listed in order of decreasing frequency according to the following definitions: frequent adverse reactions are those that occurred on one or more occasions in at least 1/100 patients; infrequent adverse reactions are those that occurred in fewer than 1/100 patients but in at least 1/1,000 patients; rare adverse reactions are those that occurred in fewer than 1/1,000 patients. Gender-specific reactions are categorized based on their incidence for the appropriate gender.

Body as a Whole: Frequent: chest pain; Infrequent: allergic reaction, cellulitis, face edema, fever, halitosis, heat stroke, hernia, malaise, neck rigidity, photosensitivity.

Cardiovascular System: Frequent: migraine; Infrequent: hypertension; Rare: thrombophlebitis.

Digestive System: Infrequent: anorexia, cholelithiasis, increased appetite, melena, mouth ulceration, thirst, ulcerative stomatitis; Rare: colitis, dysphagia, gastritis, hepatitis, hepatomegaly, liver damage, stomach ulcer, stomatitis, tongue edema, rectal hemorrhage.

Hemic and Lymphatic System: Infrequent: anemia, lymphadenopathy.

Metabolic and Nutritional: Frequent: peripheral edema; Infrequent: hypercholesteremia, weight gain, weight loss; Rare: dehydration, gout, hyperlipemia, hypokalemia.

Musculoskeletal System: Infrequent: arthritis, bursitis, joint disorder (mainly swelling, stiffness, and pain), leg cramps, myasthenia, twitching; Rare: arthrosis, myopathy, ptosis.

Nervous System: Infrequent: agitation, apathy, ataxia, emotional lability, hostility, hypertonia, hypesthesia, incoordination, insomnia, memory impairment, neurosis, nystagmus, paresthesia, reflexes decreased, thinking abnormal (mainly difficulty concentrating), vertigo; Rare: abnormal gait, euphoria, hyperesthesia, hypokinesia, neuritis, neuropathy, stupor, tremor.

Respiratory System: Infrequent: asthma, bronchitis, dyspnea, epistaxis, hiccup, laryngitis.

Skin and Appendages: Infrequent: acne, alopecia, contact dermatitis, dry skin, eczema, skin discoloration, sweating, urticaria; Rare: erythema multiforme, furunculosis, herpes zoster, hirsutism, maculopapular rash, vesiculobullous rash.

Special Senses: Infrequent: conjunctivitis, dry eyes, ear pain, otitis externa, otitis media, tinnitus, vestibular disorder; Rare: hyperacusis, iritis, mydriasis, photophobia.

Urogenital System: Infrequent: amenorrhea, breast engorgement, breast enlargement, breast neoplasm, breast pain, cystitis, dysuria, female lactation, hematuria, kidney calculus, kidney pain, mastitis, menorrhagia, metrorrhagia, urinary frequency, urinary incontinence, uterine hemorrhage, vaginal hemorrhage, vaginitis; Rare: oliguria, pyelonephritis, urethritis.

Post-Marketing Experience

In addition to the adverse reactions observed during clinical trials, dysosmia, an olfactory dysfunction that is characterized by distortion of the sense of smell, has been reported during post-marketing surveillance with LUNESTA. Because this event is reported spontaneously from a population of unknown size, it is not possible to estimate the frequency of this event.

Eszopiclone is a prescription medication used in adults for the treatment of a sleep problem called insomnia. Symptoms of insomnia include:

• trouble falling asleep
• waking up often during the night

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Medicines can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of eszopiclone there are no specific foods that you must exclude from your diet when receiving this medication.

Since eszopiclone is usually taken as needed, you may not be on a dosing schedule. Never take this medication if you do not have at least 8 hours to sleep before being active again. Do not take extra medicine to make up a missed dose.

Your pharmacist can provide more information about eszopiclone.

Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2013 Cerner Multum, Inc. Version: 1.06. Revision date: 12/15/2010.

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Since eszopiclone is taken only at bedtime, you will not be on a frequent dosing schedule. Never take this medicine if you do not have at least 7 to 8 hours to sleep before being active again. Do not take extra medicine to make up a missed dose.

Sedative and hypnotic; pyrrolopyrazine derivative; structurally unrelated to benzodiazepines.1 1 2 3 5 10 11

Administration

Oral Administration

Administer only immediately before retiring (when ready to sleep).1

Avoid administration with or immediately after a heavy, high-fat meal; may decrease rate of absorption and effect on sleep latency.1

Use only when able to get 7–8 hours of sleep before it is necessary to be active again.1

Dosage

Individualize dosage;1 use smallest effective dosage to minimize adverse effects.1

If used concomitantly with a potent CYP3A4 inhibitor, adjustment of eszopiclone dosage is recommended.1 (See Interactions.)

Adults

Initially, 1 mg.1 May increase to 2 or 3 mg if clinically indicated.1

Dosage range of 2–3 mg shown to decrease sleep latency and improve measures of sleep maintenance in adults <65 years of age.1 However, in some patients, 2- or 3-mg dose may produce higher morning blood concentrations of eszopiclone, resulting in an increased risk of next-day impairment of driving and other activities that require full alertness.1 (See CNS Depressant Effects and Next-day Impairment under Cautions.)

Prescribing Limits

Adults

Maximum 3 mg once daily immediately before bedtime.1

Special Populations

Hepatic Impairment

No dosage adjustment required in patients with mild to moderate hepatic impairment.1

In patients with severe hepatic impairment, do not exceed 2 mg once daily immediately before bedtime.1

Renal Impairment

No dosage adjustment required.1

Geriatric Patients

Initially, 1 mg immediately before bedtime.1 May increase to 2 mg if clinically indicated.1

Dosage range of 1–2 mg shown to decrease sleep latency and improve measures of sleep maintenance in geriatric patients.1

Do not exceed 2 mg once daily immediately before bedtime in adults ≥65 years of age.1

Debilitated Patients

Do not exceed 2 mg once daily immediately before bedtime.1 13

• Provide patient with a copy of manufacturer’s patient information.1 Importance of advising patients to read the manufacturer's medication guide and instructions for use carefully prior to initiating therapy and each time the prescription is refilled.1

• Importance of administering immediately before retiring.1

• Importance of taking only when able to get a full night’s sleep (i.e., 7–8 hours) before being active again.1

• Importance of taking only as prescribed (e.g., not with or immediately after a high-fat meal); do not increase dosage or duration of therapy unless otherwise instructed by a clinician.1

• Importance of not taking eszopiclone if alcohol has been consumed in the evening or before bedtime.1

• Risk of next-day impairment, even when used as prescribed; impairment may be present despite feeling fully awake.1 15 In patients receiving the 3-mg dose, importance of avoiding driving or engaging in other activities that require complete mental alertness the day after use.1 15

• Risk of severe anaphylactic and anaphylactoid reactions; importance of immediately seeking medical attention if hypersensitivity reactions occur.1

• Risk of abnormal thinking, behavioral changes, and complex behaviors (e.g., sleep-driving).1 Importance of contacting a clinician immediately if these changes occur.1

• Importance of immediately reporting any suicidal thoughts.1

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs and herbal products, as well as concomitant or past illnesses (e.g., depression, substance abuse).1

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

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

In the U.S.

• Lunesta

Available Dosage Forms:

• Tablet

Therapeutic Class: Nonbarbiturate Hypnotic

• If your symptoms or health problems do not get better or if they become worse, call your doctor.
• Do not share your drugs with others and do not take anyone else's drugs.
• Keep a list of all your drugs (prescription, natural products, vitamins, OTC) with you. Give this list to your doctor.
• Talk with the doctor before starting any new drug, including prescription or OTC, natural products, or vitamins.
• This medicine comes with an extra patient fact sheet called a Medication Guide. Read it with care. Read it again each time eszopiclone is refilled. If you have any questions about this medicine, please talk with the doctor, pharmacist, or other health care provider.
• If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

This information should not be used to decide whether or not to take eszopiclone or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to eszopiclone. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Review Date: October 4, 2017

Use the lowest effective dose for the patient.

Dosage in Adults

The recommended starting dose is 1 mg. Dosing can be raised to 2 mg or 3 mg if clinically indicated. In some patients, the higher morning blood levels of Eszopiclone tablets following use of the 2 mg or 3 mg dose increase the risk of next day impairment of driving and other activities that require full alertness [see Warnings and Precautions (5.1)]. The total dose of Eszopiclone tablets should not exceed 3 mg, once daily immediately before bedtime [see Warnings and Precautions (5.6)].

Geriatric or Debilitated Patients

The total dose of Eszopiclone tablets should not exceed 2 mg in elderly or debilitated patients.

Patients with Severe Hepatic Impairment, or Taking Potent CYP3A4 Inhibitors

In patients with severe hepatic impairment, or in patients coadministered Eszopiclone tablets with potent CYP3A4 inhibitors, the total dose of Eszopiclone tablets should not exceed 2 mg [see Warning and Precautions (5.7)].

Use with CNS Depressants

Dosage adjustments may be necessary when Eszopiclone tablets is combined with other CNS depressant drugs because of the potentially additive effects [see Warnings and Precautions (5.1)].

Administration with Food

Taking Eszopiclone tablets with or immediately after a heavy, high-fat meal results in slower absorption and would be expected to reduce the effect of Eszopiclone tablets on sleep latency [see Clinical Pharmacology (12.3)].

Pregnancy

Pregnancy Category C
There are no adequate and well-controlled studies in pregnant women. Eszopiclone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Oral administration of Eszopiclone to pregnant rats (62.5, 125, or 250 mg/kg/day) and rabbits (4, 8, or 16 mg/kg/day) throughout organogenesis showed no evidence of teratogenicity up to the highest doses tested. In rats, reduced fetal weight and increased incidences of skeletal variations and/or delayed ossification were observed at the mid and high doses. The no-observed-effect dose for adverse effects on embryofetal development is 200 times the maximum recommended human dose (MRHD) of 3 mg/day on a mg/m2 basis. No effects on embryofetal development were observed in rabbits; the highest dose tested is approximately 100 times the MRHD on a mg/m2 basis.

Oral administration of Eszopiclone (60, 120, or 180 mg/kg/day) to pregnant rats throughout the pregnancy and lactation resulted in increased post-implantation loss, decreased postnatal pup weights and survival, and increased pup startle response at all doses. The lowest dose tested is approximately 200 times the MRHD on a mg/m2 basis. Eszopiclone had no effects on other developmental measures or reproductive function in the offspring.

Nursing Mothers

It is not known whether this drug is excreted in human milk.

Pediatric Use

Safety and effectiveness have not been established in pediatric patients.

The labeling for Sunovion Pharmaceutical Inc.’s Eszopiclone tablets includes additional information from a clinical study in which efficacy was not demonstrated in pediatric patients. However, due to Sunovion Pharmaceuticals, Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric information.

In studies in which Eszopiclone (2 to 300 mg/kg/day) was orally administered to young rats from weaning through sexual maturity, neurobehavioral impairment (altered auditory startle response) and reproductive toxicity (adverse effects on male reproductive organ weights and histopathology) were observed at doses ≥ 5 mg/kg/day. Delayed sexual maturation was noted in males and females at ≥ 10 mg/kg/day. The no-effect dose (2 mg/kg) was associated with plasma exposures (AUC) for Eszopiclone and metabolite (S)-desmethylzopiclone [(S)-DMZ] approximately 2 times plasma exposures in humans at the maximum recommended dose (MRHD) in adults (3 mg/day).

When Eszopiclone (doses from 1 to 50 mg/kg/day) was orally administered to young dogs from weaning through sexual maturity, neurotoxicity (convulsions) was observed at doses ≥ 5 mg/kg/day. Hepatotoxicity (elevated liver enzymes and hepatocellular vacuolation and degeneration) and reproductive toxicity (adverse effects on male reproductive organ weights and histopathology) were noted at dose ≥ 10 mg/kg/day. The no-effect dose (1 mg/kg) was associated with plasma exposures (AUC) to Eszopiclone and (S)-DMZ approximately 3 and 2 times, respectively, plasma exposures in humans at the MRHD in adults.

Geriatric Use

A total of 287 subjects in double-blind, parallel-group, placebo-controlled clinical trials who received Eszopiclone were 65 to 86 years of age. The overall pattern of adverse events for elderly subjects (median age = 71 years) in 2-week studies with nighttime dosing of 2 mg Eszopiclone was not different from that seen in younger adults [see Adverse Reactions (6)]. Eszopiclone 2 mg exhibited significant reduction in sleep latency and improvement in sleep maintenance in the elderly population. Compared with non-elderly adults, subjects 65 years and older had longer elimination and higher total exposure to Eszopiclone. Therefore, dose reduction is recommended in the elderly patients [see Dosage and Administration (2.2), Clinical Pharmacology (12.3)].

Hepatic Impairment

No dose adjustment is necessary for patients with mild-to-moderate hepatic impairment. Exposure was increased in severely impaired patients compared with the healthy volunteers. The dose of Eszopiclone should not exceed 2 mg in patients with severe hepatic impairment. Eszopiclone should be used with caution in patients with hepatic impairment [see Dosage and Administration (2.3), Clinical Pharmacology (12.3)].

In clinical trials with Eszopiclone, one case of overdose with up to 36 mg of Eszopiclone was reported in which the subject fully recovered. Since commercial marketing began, spontaneous cases of Eszopiclone overdoses up to 270 mg (90 times the maximum recommended dose of Eszopiclone) have been reported, in which patients have recovered. Fatalities related to Eszopiclone overdoses were reported only in combination with other CNS drugs or alcohol.

Signs and Symptoms

Signs and symptoms of overdose effects of CNS depressants can be expected to present as exaggerations of the pharmacological effects noted in preclinical testing. Impairment of consciousness ranging from somnolence to coma has been described. Rare individual instances of fatal outcomes following overdose with racemic zopiclone have been reported in European postmarketing reports, most often associated with overdose with other CNS-depressant agents.

Recommended Treatment

General symptomatic and supportive measures should be used along with immediate gastric lavage where appropriate. Intravenous fluids should be administered as needed. Flumazenil may be useful. As in all cases of drug overdose, respiration, pulse, blood pressure, and other appropriate signs should be monitored and general supportive measures employed. Hypotension and CNS depression should be monitored and treated by appropriate medical intervention. The value of dialysis in the treatment of overdosage has not been determined.

As with the management of all overdosage, the possibility of multiple drug ingestion should be considered. The physician may wish to consider contacting a poison control center for up-to-date information on the management of hypnotic drug product overdosage.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis
In a carcinogenicity study in rats, oral administration of Eszopiclone for 97 (males) or 104 (females) weeks resulted in no increases in tumors; plasma levels (AUC) of Eszopiclone at the highest dose tested (16 mg/kg/day) are approximately 80 (females) and 20 (males) times those in humans at the maximum recommended human dose (MRHD) of 3 mg/day. However, in a 2-year carcinogenicity study in rats, oral administration of racemic zopiclone (1, 10, or 100 mg/kg/day) resulted in increases in mammary gland adenocarcinomas (females) and thyroid gland follicular cell adenomas and carcinomas (males) at the highest dose tested. Plasma levels of Eszopiclone at this dose are approximately 150 (females) and 70 (males) times those in humans at the MRHD of Eszopiclone. The mechanism for the increase in mammary adenocarcinomas is unknown. The increase in thyroid tumors is thought to be due to increased levels of TSH secondary to increased metabolism of circulating thyroid hormones, a mechanism not considered relevant to humans.


In a 2-year carcinogenicity study in mice, oral administration of racemic zopiclone (1, 10, or 100 mg/kg/day) produced increases in pulmonary carcinomas and carcinomas plus adenomas (females) and skin fibromas and sarcomas (males) at the highest dose tested. The skin tumors were due to skin lesions induced by aggressive behavior, a mechanism not relevant to humans. A carcinogenicity study of Eszopiclone was conducted in mice at oral doses up to 100 mg/kg/day. Although this study did not reach a maximum tolerated dose, and was thus inadequate for overall assessment of carcinogenic potential, no increases in either pulmonary or skin tumors were seen at doses producing plasma levels of Eszopiclone approximately 90 times those in humans at the MRHD of Eszopiclone (and 12 times the exposure in the racemate study).

Eszopiclone did not increase tumors in a p53 transgenic mouse bioassay at oral doses up to 300 mg/kg/day.

Mutagenesis
Eszopiclone was clastogenic in in vitro (mouse lymphoma and chromosomal aberration) assays in mammalian cells. Eszopiclone was negative in the in vitro bacterial gene mutation (Ames) assay and in an in vivo micronucleus assay.

(S)-N-desmethyl zopiclone, a metabolite of Eszopiclone, was positive in in vitro chromosomal aberration assays in mammalian cells. (S)-N-desmethyl zopiclone was negative in the in vitro bacterial gene mutation (Ames) assay and in an in vivo chromosomal aberration and micronucleus assay.

Impairment of Fertility
Oral administration of Eszopiclone to rats prior to and during mating, and continuing in females to day 7 of gestation (doses up to 45 mg/kg/day to males and females or up to 180 mg/kg/day to females only) resulted in decreased fertility, with no pregnancy at the highest dose tested when both males and females were treated. In females, there was an increase in abnormal estrus cycles at the highest dose tested. In males, decreases in sperm number and motility and increases in morphologically abnormal sperm were observed at the mid and high doses. The no-effect dose for adverse effects on fertility (5 mg/kg/day) is 16 times the MRHD on a mg/m2 basis.

NDC 47335-587-83
Eszopiclone Tablets C-IV
2 mg
Rx only
30 Tablets
SUN PHARMA
PHARMACIST: Dispense the Medication Guide provided separately to each patient

(es zoe PIK lone)

• Lunesta

Insomnia: Treatment of insomnia

No dosage adjustment necessary.

Initial dose: 1 mg orally immediately before bedtime
Maintenance dose: 1 to 3 mg orally immediately before bedtime
Maximum dose: 3 mg orally immediately before bedtime

Comments: Patients should be reevaluated if insomnia persists after 7 to 10 days of eszopiclone therapy.

Initial dose: 1 mg orally immediately before bedtime
Maximum dose: 2 mg orally immediately before bedtime

Comments: Patients should be reevaluated if insomnia persists after 7 to 10 days of eszopiclone therapy.

No dosage adjustment recommended

Mild to moderate liver dysfunction: No adjustment recommended
Severe liver dysfunction: Maximum dose is 2 mg orally immediately before bedtime

Data not available

• Experts aren't exactly sure how eszopiclone works but believe it has an effect on GABA receptors within the brain. This causes the release of natural chemicals associated with sleep.