Esogno

Pharmacotherapeutic group: Nervous system; psycholeptics; hypnotics and sedatives; Benzodiazepine related drugs, ATC code: N05CF04 Mechanism of action Eszopiclone is a non-benzodiazepine hypnotic agent, which is a pyrrolopyrazine derivative of the cyclopyrrolone class with a chemical structure unrelated to pyrazolopyrimidines, imidazopyridines, benzodiazepines or barbiturates.‍​‍‍‍​‍‍‍‍‍‍‍‍​‍ The precise mechanism of action of eszopiclone is unknown but its effect is believed to result from modulation of gamma-aminobutyric acid (GABA)-A-receptor macromolecular complexes, containing alpha-1, alpha-2, alpha-3 and alpha-5 sub-units. It is believed to increase GABA evoked chloride conductance resulting in neuronal hyperpolarisation thereby inhibiting neuronal transmission and causing sleep. Transient insomnia In a single night model of transient insomnia in healthy adult volunteers, a 3 mg dose of eszopiclone was superior to placebo on measures of sleep onset and sleep maintenance using objective polysomnography. In addition, self-reported scores for sleep quality and sleep depth were significantly better for eszopiclone compared to placebo. Primary insomnia In placebo-controlled studies up to 6-months duration in subjects with chronic insomnia, eszopiclone demonstrated sustained improvement in sleep onset and nocturnal awakening measures, improved total sleep time, and sleep quality (restorative sleep) throughout the treatment duration as measured by objective polysomnography and subjective outcome measures. Next day function was improved by the administration of eszopiclone as assessed by a number of measures. No development of tolerance was observed in placebo-controlled studies in subjects with chronic insomnia treated with eszopiclone for up to 6 months duration and in subjects with insomnia or co-morbid conditions of depression, anxiety or pain treated with eszopiclone for up to 8 weeks. It should be noted that the 1 mg dose in adults demonstrated inconsistent efficacy in improving sleep onset or nocturnal awakening measures and did not improve total sleep time in any study. Thus, the usual effective dose is expected to be 2 or 3 mg for adults. Co-morbid insomnia In subjects with insomnia together with depression or anxiety, coadministration of eszopiclone with a selective serotonin reuptake inhibitor (SSRI) for 8 weeks demonstrated significant improvements in sleep measures as well as certain clinically relevant measures of antidepressant and anxiolytic response (e.g., Hamilton Depression and Anxiety Rating scales) compared to administration of SSRI monotherapy. In 4-week studies of insomnia due to rheumatoid arthritis or perimenopausal symptoms, eszopiclone demonstrated significant improvements in sleep measures (sleep onset and sleep maintenance) for the study duration. In these studies, improvements in the perception of pain in subjects with rheumatoid arthritis and improvements in mood and menopause-related symptoms in perimenopausal and menopausal women treated with eszopiclone were also noted. Elderly population Exposure to eszopiclone is increased in elderly patients 65 years or older (see section 5.2) and a total daily dose of eszopiclone should not exceed 2 mg in the elderly. In randomised, double-blind, placebo-controlled studies in elderly patients with chronic insomnia up to 12 weeks duration, 2 mg eszopiclone once daily before bedtime demonstrated significant improvements in sleep measures (sleep onset and sleep maintenance) for the study duration. Paediatric population The licensing authority has deferred the obligation to submit the results of studies with eszopiclone in all subsets of the paediatric population in the treatment of insomnia. See section 4.2 for information on paediatric use.