Eszopiclone

Pronunciation

Pronunciation: ES-zoe-PIK-lone
Class: Sedative and hypnotic, nonbarbiturate

Trade Names

Lunesta
- Tablets 1 mg
- Tablets 2 mg
- Tablets 3 mg

Pharmacology

Precise mechanism is unknown; however, binding with GABA-receptor complexes located close to or allosterically coupled to benzodiazepine receptors is suspected.

Slideshow: Need To Catch Some Shut-Eye? Tips on Getting the Sleep You Need

Pharmacokinetics

Absorption

Rapidly absorbed after oral administration, reaching C max within about 1 h.

Distribution

Weakly bound to plasma protein (52% to 59%).

Metabolism

Extensively metabolized by oxidation and demethylation. One metabolite, (S)-N-desmethyl zopiclone, binds to GABA receptors with substantially lower potency than the parent drug. The CYP2E1 and CYP3A4 isozymes are involved with eszopiclone metabolism.

Elimination

Mean elimination half-life is 6 h. Up to 75% is excreted in the urine, mainly as metabolites, and less than 10% is excreted in the urine as the parent drug.

Special Populations

Renal Function Impairment

Because less than 10% of the orally administered dose is excreted in the urine, no dose adjustment is needed in patients with renal function impairment.

Hepatic Function Impairment

Use with caution in patients with hepatic function impairment. No dosage adjustment is needed in patients with mild to moderate hepatic function impairment. The dose should not exceed 2 mg in patients with severe hepatic function impairment.

Elderly

Subjects 65 yr of age and older had a 41% increase in total exposure (AUC) to and a slightly prolonged elimination of eszopiclone (half-life about 9 h).

Indications and Usage

Treatment of insomnia.

Contraindications

Standard considerations.

Dosage and Administration

Adults

PO Recommended starting dose is 2 mg immediately before bedtime. Dosing can be initiated at or raised to 3 mg if clinically indicated.

Elderly

PO For elderly patients whose primary complaint is difficulty falling asleep, the recommended starting dose is 1 mg immediately before bedtime. For elderly patients whose primary complaint is difficulty staying asleep, the recommended starting dose is 2 mg immediately before bedtime.

Coadministration with CYP3A4 Inhibitor
Adults

PO Recommended starting dose is 1 mg. If needed, increase dose to 2 mg.

Severe Hepatic Function Impairment
Adults

PO Recommended starting dose is 1 mg (max, 2 mg).

General Advice

Administer on an empty stomach. Administer with a snack if GI upset occurs. Administration after a high-fat meal may reduce effects on sleep. Administer immediately before bedtime.

Storage/Stability

Store tablets at 59° to 86°F.

Drug Interactions

Drugs that induce CYP3A4 (eg, rifampin)

Eszopiclone plasma concentrations may be reduced, decreasing the pharmacologic effects.

Drugs that inhibit CYP3A4 (eg, clarithromycin, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir)

Eszopiclone plasma concentrations may be elevated, increasing the pharmacologic effects and adverse reactions.

Ethanol

Additive effects on psychomotor performance.

Olanzapine

Pharmacodynamic interaction may result in a decrease in digit symbol substitutional test scores.

Laboratory Test Interactions

None well documented.

Adverse Reactions

CNS

Headache (21%); somnolence (10%); dizziness (7%); nervousness (5%); depression (4%); abnormal dreams, anxiety, confusion, decreased libido, hallucinations, neuralgia (3%); migraine (at least 1%).

Dermatologic

Pruritus, rash (4%).

GI

Unpleasant taste (34%); dry mouth (7%); dyspepsia (6%); nausea (5%); diarrhea (4%); vomiting (3%).

Genitourinary

Dysmenorrhea, gynecomastia, UTI (3%).

Respiratory

Respiratory infection (10%).

Miscellaneous

Pain (5%); accidental injury, viral infection (3%); chest pain, peripheral edema (at least 1%).

Precautions

Monitor

Baseline symptoms

Identify baseline symptoms (difficulty falling asleep, nocturnal awakening, and/or early morning awakening) and monitor patient's response to therapy.


Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

In elderly patients, decrease dose to 1 mg (max, 2 mg).

Special Risk Patients

Use with caution in patients with concomitant illness, compromised respiratory function, signs and symptoms of depression, diseases, or conditions that could affect metabolism or hemodynamic responses.

Anaphylactic/Anaphylactoid reactions

Angioedema involving the tongue, glottis, or larynx have been reported.

Complex behavior

Behavioral actions, including preparing and eating food, making phone calls, having sex, and sleep-driving, have been performed by patients who are not fully awake. Patients often have no memory of the event.

Duration of therapy

Eszopiclone is indicated for short-term (eg, 7 to 10 days) treatment of insomnia. If medication is used for more than 2 to 3 wk, periodically reevaluate patient determine whether there is a continuing need for the medication.

Psychiatric or physical disorders

Worsening of insomnia or emergence of new thinking or behavior abnormalities may be the consequence of unrecognized psychiatric or physical disorders and requires immediate evaluation.

Suicide

Supervise depressed patients at risk during therapy. Prescribe the smallest quantity consistent with good patient management in order to reduce the risk of overdose.

Withdrawal

If treatment is to be discontinued or the dose reduced after long-term treatment, gradually taper the dose. Monitor patient for withdrawal symptoms (eg, increased anxiety, muscle or abdominal cramps, sweating, tremor). If withdrawal symptoms develop, reinstitute previous dosing schedule and attempt a less rapid tapering regimen after patient has stabilized.

Overdosage

Symptoms

Exaggeration of pharmacologic effects, impairment of consciousness ranging from somnolence to coma, and death.

Patient Information

  • Advise patient to read the patient information leaflet before starting therapy and with each refill.
  • Review lifestyle changes that may improve sleep (eg, quiet and dark environment, avoidance of caffeine and nicotine, warm water bath, relaxation techniques).
  • Advise patient that medication is usually started at a low dose and then gradually increased until max benefit is obtained.
  • Advise patient to take prescribed dose immediately before going to bed to reduce the risk of falling.
  • Advise patient to take prescribed dose with a full glass of water.
  • Advise patient to take on an empty stomach, but to take with food if stomach upset occurs. Caution patient not to take after a high-fat meal because medication may not work as well.
  • Caution patient not to take eszopiclone unless they will be able to get 8 h or more of sleep before being active again. Advise patient that taking eszopiclone with less than 8 h sleep may result in daytime amnesia or memory loss.
  • Review safety precautions with regard to falls, especially for elderly and debilitated patients.
  • Caution patient that medication may be habit forming and to take as prescribed, and not to stop taking or change the dose unless advised by health care provider.
  • Advise patient that sleep may be disturbed for 1 or 2 nights following discontinuation of eszopiclone therapy.
  • Advise patient that if medication needs to be discontinued after long-term use, it will be slowly withdrawn unless safety concerns (eg, rash) require a more rapid withdrawal.
  • Instruct patient to avoid alcoholic beverages and other depressants while taking this medication.
  • Instruct patient to contact health care provider if symptoms do not appear to be getting better, worsen, or if bothersome adverse reactions (eg, changes in thinking or behavior, daytime drowsiness, dizziness, incoordination, memory problems) occur. Caution patient not to increase the dose on their own if symptoms do not appear to be improving.
  • Advise patient to take sips of water, suck on ice chips or sugarless hard candy, or chew sugarless gum if dry mouth occurs.
  • Advise patient that drug may cause drowsiness or impair judgment, thinking, or reflexes, and to use caution while driving or performing other tasks requiring mental alertness until tolerance is determined.

Copyright © 2009 Wolters Kluwer Health.

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