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9.20.2017 | Logan Miers

A study of abuse potential of eszopiclone found that in persons with a known history of benzodiazepine abuse, eszopiclone at doses of 6 and 12 mg produced effects similar to those of diazepam 20 mg. The study found that at these doses which are two or more times greater than the maximum recommended doses, a dose-related increase in reports of amnesia, sedation, sleepiness, and hallucinations was observed for both eszopiclone (Lunesta) as well as for diazepam ( Valium ).

Eszopiclone is rapidly absorbed after oral administration, with serum levels peaking between. Eszopiclone acts on benzodiazepine binding site situated on GABA A neurons as an agonist. The elimination half-life of eszopiclone is approximay 6 hours and it is extensively metabolized by oxidation and demethylation. Cytochrome P450 (CYP) isozymes CYP3A4 and CYP2E1 are involved in the biotransformation of eszopiclone; thus, drugs that induce or inhibit these CYP isozymes may affect the metabolism of eszopiclone. 45 and 1.3 hours. Less than 10% of the orally administered dose is excreted in the urine as racemic zopiclone. In terms of benzodiazepine receptor binding and relevant potency, 3 mg of eszopiclone is equivalent to 10 mg of diazepam. Approximay 52% to 59% of a dose is weakly bound to plasma protein.

Kirsch et al. Although the drug effect and the placebo response were rather small and of questionable clinical importance, the two together produce a reasonably large clinical response. It is not recommended for chronic use in the elderly. found the benefit over placebo to be of questionable clinical significance. Eszopiclone is slightly effective in the treatment of insomnia where difficulty in falling asleep is the primary complaint.

Eszopiclone is the active dextrorotatory stereoisomer of zopiclone, and belongs to the class of drugs known as cyclopyrrolones. It is also classified as a therapeutic sedative hypnotic and pharmacological cyclopyrrolone. It is slightly effective for this use. Eszopiclone, marketed by Sunovion under the brand-name Lunesta, is a nonbenzodiazepine hypnotic agent used in the treatment of insomnia.

Texas poison control centers reported that during 2005–2006 there were 525 total eszopiclone overdoses recorded in the state of Texas, the majority of which were intentional suicide attempts.

There is an increased risk of increased central nervous system depression when it is used with eszopicolone including anti-psychotics, sedative/hypnotics, antihistamines, opioids, and antidepressants. Eszopicolone is more effective if it is not taken before a heavy meal. There is also increased risk of increased risk of central nervous system depression with other medications that inhibit the metabolic activities of the CYP3A4 enzyme system of the liver. Alcohol also has an additive effect when used concurrently with eszopicolone. Medications that inhibit this enzyme system include nelfinavir, ritonavir, ketoconazole, itraconazole and clarithromycin.

Care should be taken in choosing an appropriate hypnotic drug and if drug therapy is initiated it should be initiated at the lowest possible dose to minimise side effects. In addition, the effectiveness and safety of long-term use of these agents remain to be determined. Long-term use of sedative-hypnotics for insomnia lacks an evidence base and has traditionally been discouraged for reasons that include concerns about such potential adverse drug effects as cognitive impairment ( anterograde amnesia ), daytime sedation, motor incoordination, and increased risk of motor vehicle accidents and falls. It was concluded that more research is needed to evaluate the long-term effects of treatment and the most appropriate management strategy for elderly persons with chronic insomnia. An extensive review of the medical literature regarding the management of insomnia and the elderly found that there is considerable evidence of the effectiveness and durability of non-drug treatments for insomnia in adults of all ages and that these interventions are underutilized. Compared with the benzodiazepines, the nonbenzodiazepine sedative-hypnotics, including eszopiclone appeared to offer few, if any, significant clinical advantages in efficacy or tolerability in elderly persons. Sedative hypnotic drugs including eszopiclone are more commonly prescribed to the elderly than to younger patients despite benefits of medication being generally unimpressive. It was found that newer agents with novel mechanisms of action and improved safety profiles, such as the melatonin receptor agonists, hold promise for the management of chronic insomnia in elderly people.

The risk is also greater in patients with a history of alcohol abuse or other drug abuse or history of psychiatric disorders. Tolerance may develop after repeated use of benzodiazepines and benzodiazepine-like drugs for a few weeks. Use of benzodiazepines and similar benzodiazepine-like drugs such as eszopiclone may lead to physical and psychological dependence. In the United States Eszopiclone is a schedule IV controlled substance under the Controlled Substances Act. Eszopiclone was studied for up to 6 months in a group of patients which showed no signs of tolerance or dependence in a study funded and carried out by Sepracor. The risk of abuse and dependence increases with the dose and duration of usage and concomitant use of other psychoactive drugs.

If consumed within the last hour, eszopiclone overdose can be treated with the administration of activated charcoal or via gastric lavage.

According to the U.S. Prescribing Information, overdoses of eszopiclone up to 90 times the recommended dose have been reported in which the patient fully recovered. According to the May 2014 edition of the official U.S. Prescribing Information, fatalities have been reported only in cases in which eszopliclone was combined with other drugs or alcohol.

As of November 2012, Sepracor has not resubmitted its authorization application and Lunesta/Lunivia is not available in Europe. In 2008 Sepracor submitted an application to the EMA (the European Union's equivalent to the U.S. However, Sepracor withdrew its authorization application in 2009 after the EMA stated it would not be granting eszopiclone 'new active substance' status, as it was essentially pharmacologically and therapeutically too similar to zopiclone to be considered a new patentable product. Since zopiclone's patent has expired, this ruling would have allowed rival companies to also legally produce cheaper generic versions of eszopiclone for the European market. Sepracor was expected to receive approximay 155 million dollars if the deal went through. On September 11, 2007, Sepracor signed a marketing deal with British pharmaceutical company GlaxoSmithKline for the rights to sell Eszopiclone (under the name Lunivia rather than Lunesta) in Europe. The deal with GSK fell through, and GSK instead launched a $3.3 billion deal to market Acion's Almorexant sleeping tablet, which entered stage three medical trials before development was abandoned due to side effects. FDA ) for authorization to market the drug in the EU, and initially received a favourable response.

Recommendations around use of eszopiclone may be altered by other health conditions. Hypersensitivity to eszopiclone is contraindicated. Some side effects are more common than others. The presence of liver impairment, lactation and activities requiring mental alertness (driving) may be considered when determining frequency and dosage. These conditions or circumstances may occur in people that have lowered metabolism and other conditions.

In the longest, largest phase 3 trial, patients in the Lunesta group reported falling asleep an average of 15 minutes faster and sleeping an average of 37 minutes longer than those in the placebo group. "Clinicians who are interested in the drug’s efficacy cannot find efficacy information in the label: it states only that Lunesta is superior to placebo. However, on average, Lunesta patients still met criteria for insomnia and reported no clinically meaningful improvement in next-day alertness or functioning.". In a controversial 2009 article in the New England Journal of Medicine, "Lost in Transmission — FDA Drug Information That Never Reaches Clinicians", it was reported that the largest of three Lunesta trials found that compared to placebo Lunesta "was superior to placebo" while it only shortened initial time falling asleep by 15 minutes on average. The FDA’s medical review provides efficacy data, albeit not until page 306 of the 403-page document.

On May 15, 2014, the USFDA asked that the starting dose of Eszopiclone (Lunesta) be lowered from 2 milligrams to 1 milligram after it was observed in a study that even 8 hours after taking the drug at night, some patients were not able to cope with their next-day activities like driving and other activities that require full alertness. Eszopiclone along with other Z-drugs are the most commonly prescribed sedative hypnotics in the United States. Eszopiclone is not marketed in the European Union following a 2009 decision by the EMA denying it new active substance status, in which it ruled that eszopiclone was too similar to zopiclone to be considered a new patentable product. It works by interacting with the GABA receptors. Eszopiclone is now available in a generic form in the United States as of May 2014.