LUNESTA
Eszopiclone, marketed by Sunovion under the trade name Lunesta, is a non-benzodiazepine hypnotic, which has little effect on insomnia. Eszopiclone is the active dextrorist stereoisomer of zopiclone , and belongs to a class of drugs known as cyclopirrolones. Lunesta, along with other “Z-drugs”, including zolpidem (Ambien), zaleplon (Sonata), is one of the most commonly prescribed sedative hypnotics in the United States. Eszopiclone is not sold in the European Union after in 2009 the EMA made a negative decision regarding the new status of the active substance, deciding that Eszopiclone is too similar to zopiclone to be considered a new patented product.
Medical use of Lunesta
Lunesta has little efficacy in the treatment of insomnia, in which the main problem is difficulty in falling asleep. Kirsch et al. found that the conclusion that the drug is more effective compared with placebo, has questionable clinical significance. Although the effect of the drug and the response to placebo were rather small and their clinical significance is rather doubtful, together they cause a rather large clinical response. The drug is not recommended for permanent use in the elderly.
Elderly patients using Lunesta
Sedative hypnotic drugs, including Lunesta, are more commonly prescribed to older people than younger patients, despite the fact that the drug does not demonstrate impressive benefits. Care should be taken in choosing a suitable sleeping pill, and at the beginning of drug therapy, use the lowest possible dose of the substance to minimize side effects. An extensive review of the medical literature regarding the treatment of insomnia in the elderly has shown that there is ample evidence of the effectiveness of non-drug treatment of insomnia in adults of all ages, and that these mechanisms are not sufficiently used. Compared to benzodiazepines, non-benzodiazepine hypnotics and sedatives, including Lunesta, offer few clinical benefits of efficacy or tolerability in the elderly. It was found that new drugs with new mechanisms of action and improved safety profiles, such as melatonin agonists, may be promising for the treatment of chronic insomnia in the elderly. Prolonged use of sedative hypnotics for insomnia is not safe and is not recommended. Such drugs can have side effects such as cognitive impairment (anterograde amnesia), daytime sedation, impaired coordination of movements, and an increase in the risk of car accidents and falls. In addition, the efficacy and safety of long-term use of such drugs has not yet been proven. It was concluded that more research was needed to evaluate the long-term effects of treatment and the most appropriate treatment strategy for older people with chronic insomnia. that new drugs with new mechanisms of action and improved safety profiles, such as melatonin agonists, may be promising for the treatment of chronic insomnia in the elderly. Prolonged use of sedative hypnotics for insomnia is not safe and is not recommended. Such drugs can have side effects such as cognitive impairment (anterograde amnesia), daytime sedation, impaired coordination of movements, and an increase in the risk of car accidents and falls.
In addition, the efficacy and safety of long-term use of such drugs has not yet been proven. It was concluded that more research was needed to evaluate the long-term effects of treatment and the most appropriate treatment strategy for older people with chronic insomnia. that new drugs with new mechanisms of action and improved safety profiles, such as melatonin agonists, may be promising for the treatment of chronic insomnia in the elderly. Prolonged use of sedative hypnotics for insomnia is not safe and is not recommended. Such drugs can have side effects such as cognitive impairment (anterograde amnesia), daytime sedation, impaired coordination of movements, and an increase in the risk of car accidents and falls. In addition, the efficacy and safety of long-term use of such drugs has not yet been proven. It was concluded that more research was needed to evaluate the long-term effects of treatment and the most appropriate treatment strategy for older people with chronic insomnia. may be promising for the treatment of chronic insomnia in the elderly. Prolonged use of sedative hypnotics for insomnia is not safe and is not recommended. Such drugs can have side effects such as cognitive impairment (anterograde amnesia), daytime sedation, impaired coordination of movements, and an increase in the risk of car accidents and falls. In addition, the efficacy and safety of long-term use of such drugs has not yet been proven. It was concluded that more research was needed to evaluate the long-term effects of treatment and the most appropriate treatment strategy for older people with chronic insomnia. may be promising for the treatment of chronic insomnia in the elderly. Prolonged use of sedative hypnotics for insomnia is not safe and is not recommended. Such drugs can have side effects such as cognitive impairment (anterograde amnesia), daytime sedation, impaired coordination of movements, and an increase in the risk of car accidents and falls.
In addition, the efficacy and safety of long-term use of such drugs has not yet been proven. It was concluded that more research was needed to evaluate the long-term effects of treatment and the most appropriate treatment strategy for older people with chronic insomnia. Prolonged use of sedative hypnotics for insomnia is not safe and is not recommended. Such drugs can have side effects such as cognitive impairment (anterograde amnesia), daytime sedation, impaired coordination of movements, and an increase in the risk of car accidents and falls. In addition, the efficacy and safety of long-term use of such drugs has not yet been proven. It was concluded that more research was needed to evaluate the long-term effects of treatment and the most appropriate treatment strategy for older people with chronic insomnia. Prolonged use of sedative hypnotics for insomnia is not safe and is not recommended. Such drugs can have side effects such as cognitive impairment (anterograde amnesia), daytime sedation, impaired coordination of movements, and an increase in the risk of car accidents and falls. In addition, the efficacy and safety of long-term use of such drugs has not yet been proven. It was concluded that more research was needed to evaluate the long-term effects of treatment and the most appropriate treatment strategy for older people with chronic insomnia.
The efficacy and safety of long-term use of such drugs has not yet been proven. It was concluded that more research was needed to evaluate the long-term effects of treatment and the most appropriate treatment strategy for older people with chronic insomnia. the efficacy and safety of long-term use of such drugs has not yet been proven. It was concluded that more research was needed to evaluate the long-term effects of treatment and the most appropriate treatment strategy for older people with chronic insomnia.
Lunesta Side effects
Lunesta exhibits fewer anticholinergic side effects than racemic zopiclone. The following side effects may occur with Eszopiclone (Lunesta): Common side effects:
- unpleasant bitter or metallic taste in the mouth;
- headache;
- chest pain;
- symptoms of influenza;
- pain;
- dry mouth;
- daytime sleepiness;
- lightheadedness;
- dizziness;
- upset stomach;
- decreased libido;
- painful menstruation;
- heartburn;
Less common side effects may include:
- rash;
- itching;
- incoordination;
- swelling of the arms, legs, ankles, or lower legs;
- painful or frequent urination;
- back pain;
Neuropsychiatric side effects include:
- aggressive behavior;
- mental confusion;
- nervousness;
- auditory and visual hallucinations;
- worsening depression;
- suicidal thoughts;
- depersonalization; amnesia;
If a person does not fall asleep immediately after applying Lunesta or if he wakes up shortly after taking the drug, he may experience dizziness, faintness, hallucinations (see things or hear voices that do not exist), as well as problems with coordination and memory.
Addiction
In the United States, Lunesta is on the list of IV controlled substances. The use of benzodiazepines and benzodiazepine-like drugs, such as eszopiclone, can lead to the development of physical and psychological dependence. The risk of abuse and dependence increases with increasing dose and duration of use and the use of other psychoactive substances. Patients with a history of alcohol or drug abuse or a history of mental disorders are also at increased risk. After repeated use of benzodiazepines and benzodiazepine drugs for several weeks, tolerance may develop. The effects of Lunesta was studied when taken for up to 6 months in a group of patients who showed no signs of tolerance or dependence during the study,
Abuse
A study of the abuse potential of Lunesta showed that in individuals with a known history of benzodiazepine abuse, Lunesta in doses of 6 and 12 mg produces effects similar to 20 mg of diazepam . The study showed that when taking doses two or more times higher than the maximum recommended dose, there was a dose-dependent increase in reports of amnesia and hallucinations for both Eszopiclone (Lunesta) and Diazepam (Valium).
Overdose
An overdose of Lunesta can be dangerous. Signs of Lunesta overdose include a dulling of the mental state, an increase in the threshold of coronary spasm sensitivity, troponemia, a slowing of ventricular fibrillation, and prolonged coma (up to 48 hours). Texas Toxicology Centers report that in all over 2005–2006, a total of 525 cases of Eszopiclone overdose were reported in the state of Texas, most of which are associated with intentional suicide attempts. If an hour does not pass after consuming Eszopiclone, overdose can be avoided by using activated charcoal or using a gastric probe.
Pharmacology
Eszopiclone acts as an agonist on the benzodiazepine binding sites located on GABA-A neurons. Eszopiclone is rapidly absorbed after oral administration, serum levels peak after 1-1.3 hours after ingestion. The half-life of eszopiclone is approximately 6 hours. The substance is extensively metabolized by oxidation and demethylation. Approximately 52% to 59% of the dose is poorly bound to plasma proteins. CYP3A4 and CYP2E1 isoenzymes of cytochrome P450 (CYP) are involved in Esotropiclone biotransformation; thus, drugs that induce or inhibit these CYP isoenzymes can affect Lunesta metabolism. Less than 10% of the dose taken orally is excreted in the urine as racemic zopiclone.. In terms of benzodiazepine receptor binding and actual potency, 3 mg of Lunesta is equivalent to 10 mg of diazepam .
Dispute
An article published in the New England Journal of Medicine in 2009 states that the largest of the three Lunesta trials found that Lunesta was “superior to placebo”, reducing the initial sleep time by an average of 15 minutes. “Doctors interested in the effectiveness of the drug will not be able to find information about its effectiveness on the label: it is only said that Lunesta is superior to placebo. FDA medical research provides efficacy data. In the largest and largest phase 3 trials, it was reported that patients from the Lunesta group fell asleep an average of 15 minutes faster and sleep lasted an average of 37 minutes longer than in the placebo group. On average, however, patients taking Lunesta did not report any clinically significant improvement the next day regarding activity or functioning. ”
Availability in Europe
On September 11, 2007, Sepracor signed a marketing agreement with the British pharmaceutical company GlaxoSmithKline for the rights to sell Lunesta (called Lunivia, not Lunesta) in Europe. It was expected that if the transaction was successful, Sepracor would receive about $ 155 million. In 2008, Sepracor submitted an application to EMA (equivalent to the US FDA in the European Union) to authorize rights to market the drug in the EU, and initially received a positive response. Sepracor, however, withdrew its application in 2009, after the EMA announced that it would not give Eszopiclone the status of “new active substance”, because it is too pharmacologically and therapeutically similar to zopiclone. Since the expired patent for Zopiclone, this solution would allow competing companies to also legitimately produce cheaper Lunesta generics for the European market. As of November 2012, Sepracor has not re-applied for the drug, and Lunesta / Lunivia is still not available for purchase in Europe. The deal with GSK also fell through, and GSK instead launched a $ 3.3 billion deal to sell Altelxant from Actelion, which entered the third phase of clinical trials before its development was halted due to side effects.