Drug information of eszopiclone

eszopiclone

Drug group:

Eszopiclone is a nonbenzodiazepine hypnotic drug used to treat insomnia. It is the active stereoisomer of zopiclone, belonging to the class of drugs known as cyclopyrrolones. Cyclopyrrolone drugs demonstrate high efficacy and low toxicity, offering a safer alternative to other drugs used for insomnia

One major benefit of eszopiclone is that it is approved by the FDA for the long-term treatment of insomnia. This sets it apart from many other hypnotic sedatives, which are generally approved only for the relief of short-term (6-8 weeks) insomnia

:Dosage Forms & Strengths
Tablet: 1mg, 2mg and 3mg

Mechanism of effect

The exact mechanism of action of eszopiclone is unknown at this time but is thought to occur via binding with the GABA receptor complexes at binding sites located near benzodiazepine receptors, possibly explaining its hypnotic and sedative effects. It has particular affinity for GABA-A (or GABAA) receptor subunits 1, 3 and 5. Eszopiclone increases GABA-A channel currents significantly. GABA-A channels are major inhibitory channels that cause CNS depression when their receptors are activated

Pharmacodynamic

Eszopiclone rapidly induces sleep and decreases sleep latency. It also aids in the maintenance of sleep, preventing frequent awakenings. This drug has shown anticonvulsant and muscle relaxant properties in animals but is used in humans for its sedating effects

Eszopiclone is a central nervous system depressant with various effects. These include changes in alertness and motor coordination and the risk of next morning impairment, increasing with the amount of eszopiclone administered. Exercise caution and advise against driving a motor vehicle or activities that require full mental alertness the next morning. Complex sleep behaviors may result from eszopiclone use. Eszopiclone should be discontinued in these cases. Avoid the use of alcohol and other CNS depressants when eszopiclone is administered. Advise patients to skip the eszopiclone dose if alcohol has been consumed before bed or during the evening. Use the smallest dose of eszopiclone as possible, especially in elderly patients, who may experience exaggerated drug effects. Though the potential for dependence and abuse with eszopiclone is lower than for other hypnotic drugs, this drug has been abused and is known to cause dependence

Pharmacokinetics

Absorption: Rapid » attenuated by high-fat meal

Protein Bound: 52-59%

Peak Plasma Time: 1 hr

Half-life, elimination: 6 hr » <65 years old and 9 hr » ≥65 years

Metabolism: Primarily by CYP3A4 & CYP2E1 via oxidation & demethylation

Metabolites: (S)-zopiclone-N-oxide & (S)-N-desmethylzopiclone

Excretion: Urine » 85%

Dosage

Starting dose: 1 mg PO HS for nonelderly adults

Dose may be increased to 2-3 mg HS if clinically indicated

Higher doses are known to cause next morning drowsiness/impairment

Alerts

WARNING: Complex sleep behaviors including sleep-walking, sleep-driving, and engaging in other activities while not fully awake may occur with therapy; some of these events may result in serious injuries, including death; they may occur with drug alone at recommended dosages, with or without the concomitant use of alcohol or other CNS depressants but concomitant administration with other CNS depressants, may increase risk of sleep-related episodes. Discontinue therapy immediately if patient experiences a complex sleep behavior

Take immediately before going to bed - taking earlier may cause memory loss, hallucinations, dizziness, lightheadedness

Can impair daytime function in some patients at the higher doses (2 mg or 3 mg), even when used as prescribed; monitor for next-day psychomotor impairment

Take only when able to have a full night of sleep (7-8 hr); coadministration with other sedative-hypnotics at bedtime or taking eszopiclone the middle of the night is not recommended because of risk for next-day psychomotor impairment

May cause CNS depression and impair physical and mental abilities

May worsen clinical depression

Use minimum dose that will effectively treat patient

May cause abnormal thinking & bizarre behavior

Caution in history of drug or substance abuse, respiratory diseases, hepatic impairment

Amnesia may occur

Failure of sleep disturbance to resolve after 7-10 days may indicate psychiatric and/or medical illness

Abrupt discontinuation or rapid dose decreases may lead to withdrawal symptoms

Therapy can cause drowsiness and a decreased level of consciousness; patients, particularly the elderly, are at higher risk of falls

Points of recommendation

Take immediately before bedtime, with at least 7-8 hr remaining before the planned before awakening. Taking with or immediately after a heavy, high-fat meal results in slower absorption and would be expected to reduce efficacy

:Adverse Effects
Headache, Unpleasant taste, Abnormal dreams (elderly), Accidental injury (elderly), Diarrhea, Dizziness, Dry mouth, Dyspepsia, Nervousness, Neuralgia, Pain, Pruritus, Rash (in non-elderly), Somnolence, UTI, Agitation, Alopecia, Angioedema, Asthma, Anorexia, Cystitis, Dysphagia, Fever, Epistaxis, Hypertension, Hostility, Hypercholesterolemia, Hypokalemia, Dysosmia and Complex sleep behaviors



:Drug Interactions
Contraindicated: calcium/magnesium/potassium/sodium oxybates
Serious, Use Alternative: abametapir, amobarbital, apalutamide, benzhydrocodone/acetaminophen, chloramphenicol, cobicistat, conivaptan, fentanyl, hydrocodone, idelalisib, itraconazole, ivosidenib, ketoconazole, lemborexant, metoclopramide intranasal, mifepristone, nefazodone, oxycodone, posaconazole, selinexor, sufentanil SL, tucatinib, valerian, voxelotor

Pregnancy level

Available pharmacovigilance data with use in pregnant women are insufficient to identify drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes

:Animal Data
In animal reproduction studies conducted in pregnant rats and rabbits throughout organogenesis, there was no evidence of teratogenicity; administration to rats throughout pregnancy and lactation resulted in offspring toxicities at all doses tested; lowest dose was approximately 200 times maximum recommended human dose (MRHD) of 3 mg/day based on mg/ m² body surface area

Breast feeding warning

There are no data on prescence in either human or animal milk, effects on breastfed infant, or on milk production; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for therapy and any potential adverse effects on breastfed infant from therapy or underlying maternal condition

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