Lunesta 2mg. Tablets.

DESCRIPTION

Short-acting non-benzodiazepine hypnotic.
Rapid onset and relatively short half-life reduces ‘hangover’ effects; does not cause early-AM awakening.
Used for treatment of insomnia.

COMMON BRAND NAMES

Lunesta

HOW SUPPLIED

Eszopiclone/Lunesta Oral Tab: 1mg, 2mg, 3mg

DOSAGE & INDICATIONS

MAXIMUM DOSAGE

3 mg/day PO.

2 mg/day PO.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

DOSING CONSIDERATIONS

Adult patients with severe hepatic impairment should receive the initial recommended starting dose of 1 mg PO immediately before bedtime, and should not receive more than 2 mg/day maximum dose because systemic exposure is doubled in this patient population. No dose adjustments are necessary in patients with mild or moderate hepatic impairment.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

ADMINISTRATION

NOTE: Eszopiclone may be used for the long-term treatment of insomnia. However, the failure of insomnia to remit after 7—10 days of treatment may indicate the presence of a primary psychiatry and/or medical illness that should be evaluated. Lower doses of eszopiclone should be considered during concurrent administration with other CNS depressant drugs.

A Med Guide that provides information about proper use and risks of sedative-hypnotics should be dispensed with each new prescription.

STORAGE

Lunesta:
– Store at 77 degrees F; excursions permitted to 59-86 degrees F

CONTRAINDICATIONS / PRECAUTIONS

This medication is contraindicated in those with eszopiclone hypersensitivity or hypersensitivity to any ingredient in the product. Reactions including anaphylaxis or angioedema may occur with sedative-hypnotics, and may become evident as early as the initial dose. Patients should be instructed on the appropriate action in the event of an allergic reaction. Treatment with eszopiclone should not be re-initiated in patients who experience angioedema after administration of the drug.

Because sleep disturbances may be the presenting manifestation of a physical and/or psychiatric disorder, symptomatic treatment of insomnia should be initiated only after a careful evaluation of the patient. The failure of insomnia to remit after 7 to 10 days of treatment may indicate the presence of a primary psychiatric and/or medical illness that should be evaluated. Worsening of insomnia or the emergence of new thinking or behavior abnormalities may be the consequence of an unrecognized psychiatric or physical disorder. Eszopiclone should be used with caution in patients exhibiting signs and symptoms of depression. Worsening of pre-existing depression, including suicidal ideation and completed suicides, has occurred in association with the use of sedative/hypnotics. The exact incidences among various sedative products are unknown; however patients should be informed of the risks prior to receiving any medication from this class, including eszopiclone. If use is warranted in this patient group, the least amount of eszopiclone feasible should be prescribed at any one time.

Eszopiclone has a rapid onset of action and causes CNS depression. It should only be administered prior to retiring. Patients should be instructed to avoid driving or operating machinery or performing other tasks requiring mental alertness after taking eszopiclone. A variety of abnormal thinking and behavioral changes have been reported to occur in association with the use of sedative/hypnotics. Some of these changes may be characterized by decreased inhibition (e.g., aggressiveness and extroversion that seem out of character), similar to effects produced by alcohol and other CNS depressants. Other reported behavioral changes have included bizarre behavior, agitation, hallucinations, and depersonalization. Amnesia and other neuropsychiatric symptoms may occur unpredictably. Complex sleep-related behaviors such as making phone calls, eating, having sexual intercourse, or sleep-driving while not fully awake and having no memory of the event, may occur. The exact incidences among various sedative products are unknown. Any emergence of changes in thinking or behavior should be evaluated. Although such behaviors may occur with the use of the drug alone at therapeutic doses, the use of higher doses, or the use of the drug with alcohol or the coadministration with other CNS depressants appears to increase the risks. Advise patients to avoid ethanol ingestion. Eszopiclone can cause next-day psychomotor and memory impairment, with patients often unaware that they are impaired. Results from one study indicate that peak impairment after a 3 mg dose occurs 7.5 hours later, with clinically relevant effects still present at 11.5 hours after the dose. Lower initial dosages of eszopiclone should be considered in patients taking other CNS depressant therapies concurrently.

Studies of healthy subjects receiving doses of eszopiclone 2.5 times higher than the recommended therapeutic doses did not reveal any respiratory-depressant effects. However, eszopiclone should be used with caution in patients with pre-existing respiratory depression, such as severe chronic obstructive pulmonary disease (COPD) or sleep apnea, to avoid the risk of depressing ventilatory function.

Eszopiclone should be used cautiously in patients with hepatic disease since the drug is extensively metabolized in the liver. Patients with severe hepatic impairment should not receive more than 2 mg/day because systemic exposure is doubled in this patient population, and data have shown that higher plasma concentrations of the drug may cause next-day psychomotor and memory impairment sufficient to affect driving or other activities requiring full mental alertness. No dose adjustments are necessary in patients with mild or moderate hepatic impairment.

Available pharmacovigilance data with eszopiclone use during pregnancy are insufficient to identify a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.[30571] The low molecular weight of eszopiclone and low protein binding suggest eszopiclone will cross the human placenta. Zopiclone (the racemic agent, not available in the U.S.) is known to cross the placenta. In an observational study (n = 40), an active treatment and control group were compared to determine pregnancy outcomes with first trimester exposure to zopiclone. The outcomes included: spontaneous abortion (7 in the active treatment group vs. 3 in the control group), elective abortion (1 vs. 0, respectively), and congenital dislocation of the hip (1 vs. 1, respectively). No major defects were observed in either group. The available data for zopiclone suggest that use of zopiclone or eszopiclone during human pregnancy is probably low risk; however, use during pregnancy is not generally recommended.[31872] [31873] Animal studies have shown no evidence of teratogenicity or structural defects with eszopiclone use. However, oral administration of eszopiclone to pregnant rats throughout pregnancy and lactation resulted in reduced fetal weight and increased incidences of skeletal variations and/or delayed ossification at all doses tested; the no-observed-effect dose for adverse effects was 200 times the maximum recommended human dose (MRHD) of 3 mg/day on a body surface area basis. When eszopiclone was given to rats throughout pregnancy and lactation at doses ranging from 200 to 600 times the MRHD, increased post-implantation loss, decreased postnatal pup weights, survival, and increased pup startle response were seen at all doses.[30571] Eszopiclone has no established use during labor or obstetric delivery. Administration of sedative/hypnotics including eszopiclone, during the late phase of pregnancy or during labor or obstetric delivery hasve been associated with effects on the neonate, such as hypothermia, hypotonia, feeding difficulties, and respiratory depression. Cases of severe neonatal respiratory depression have been reported. Moreover, neonates born to mothers who take sedative/hypnotics agents chronically during the latter stages of pregnancy may develop physical dependence and may be at risk of developing neonatal withdrawal symptoms in the postnatal period. Appropriate monitoring of the newborn during the postnatal period is recommended.[30571]

There are no data on the presence of eszopiclone in human milk, the effects on the breast-fed infant, or the effects on milk production.[30571] The low molecular weight and low protein binding of the drug suggest that excretion into the breast milk is likely, and the relatively long half-life (mean half-life, 6 hours) should be considered. Sedation and CNS toxicity may be of concern in the nursing infant. Racemic zopiclone (available outside the U.S.) is excreted into human milk. The milk: plasma AUC ratio for zopiclone has been reported as 0.6/0.8 after a 7.5 mg PO dose. Although the concentration excreted in breast milk is low, the European zopiclone label recommends avoidance of breast-feeding during use.[63746] Consider the developmental and health benefits of breast-feeding along with the mother’s clinical need for eszopiclone and any potential adverse effects on the breast-fed infant from the drug or the underlying maternal condition.[30571]

The safety and efficacy of eszopiclone have not been established in neonates, infants, children, and adolescents less than 18 years of age.

Geriatric and/or debilitated patients may be more sensitive to the effects of eszopiclone. The impairment of cognitive and motor function may be more marked in this patient group which could result in falls or mental status changes. A lower maximum dosage is recommended in this patient group, and dosing should occur with close monitoring. According to the Beers Criteria, eszopiclone is considered a potentially inappropriate medication (PIM) in geriatric patients and use should be avoided; benzodiazepine-receptor agonists such as eszopiclone may produce similar adverse effects as benzodiazepines in older adults, such as falls, fractures, and delirium. There are increased emergency department visits, hospitalizations, and motor vehicle crashes, as well as minimal improvement in sleep latency and duration in older adults. The Beers expert panel also recommends avoiding sedative hypnotics such as eszopiclone in geriatric patients with dementia or cognitive impairment due to the potential for drug-induced adverse CNS effects, and those with delirium or at high risk of delirium since new-onset or worsening delirium may occur. In addition, the Beers expert panel recommends avoiding eszopiclone in elderly patients with a history of falls or fractures, unless safer alternatives are not available, since eszopiclone can produce ataxia, impaired psychomotor function, syncope, and additional falls; if eszopiclone must be used, consider reducing use of other CNS-active medications that increase the risk of falls and fractures and implement other strategies to reduce fall risk. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). According to the OBRA guidelines, factors potentially causing insomnia should be evaluated before initiating a sedative (e.g., sleep environment, inadequate physical activity, provision of care disruptions, caffeine or medications, pain and discomfort, or other underlying conditions that cause insomnia). Most cases of insomnia are associated with other underlying conditions. It is expected that non-pharmacologic interventions and maximized treatment of underlying conditions (if applicable) are implemented to address the causative factor(s). Initiation of sleep induction or maintenance medication should be preceded or accompanied by other interventions to attempt sleep improvement. All sleep medications should be used in accordance with approved product labeling. The use of sedating medications for individuals with diagnosed sleep apnea requires careful assessment, documented clinical rationale, and close monitoring. Exceptions to the OBRA provisions include: single dose sedative use for a dental or medical procedure or short-term sedative use during initiation of treatment for depression, pain, or other comorbid condition until symptoms improve or the underlying causative factor can be identified and/or effectively treated. OBRA provides dosing guidance for most sedatives, including eszopiclone. When a drug is being used to induce sleep or treat a sleep disorder, the facility should attempt periodic tapering of the medication or provide documentation of medical necessity in accordance with OBRA guidelines.

Eszopiclone may be used for the long-term treatment of insomnia. However, problems associated with abrupt discontinuation of hypnotic drugs are more likely to occur following chronic therapy. In a clinical study, patients received eszopiclone nightly for 6 weeks. On the first and second days of withdrawal from study drug, patients received single-blind placebo. During this withdrawal period, patients in the 3 mg group spontaneously reported symptoms such as anxiety (1%), abnormal dreams (1.9%), hyperesthesia (1%), and neurosis (1%). Withdrawal of some hypnotics also precipitates a rebound insomnia. If therapy is continued for more than 2 weeks, the possibility of a withdrawal syndrome should be considered and abrupt discontinuation of therapy avoided. The possibility of physical and psychological dependence to eszopiclone requires close monitoring. Eszopiclone should be used cautiously in patients with a history of alcoholism or substance abuse.