RxPRODUCT NEWS PROFILE: Lunesta (Eszopiclone)

Insomnia affects >50 million Americans,according to the NationalInstitutes of Health. Symptoms ofinsomnia include difficulty in fallingasleep, frequent awakening during thenight, early awakening, inability ordifficulty in falling back to sleep, orwaking up feeling unrefreshed.

A 2003 National Sleep FoundationSleep in America poll found that 37 millionolder Americans suffer from frequentsleep problems that could complicatethe treatment of other medicalconditions, such as arthritis, diabetes,or heart and lung disease. This pollalso showed that poor sleep goesunnoticed among older adults. Lunesta(eszopiclone), manufactured bySepracor, has received approval fromthe FDA for the treatment of transientand chronic insomnia.¹

Pharmacology/Pharmacokinetics

Eszopiclone is a cyclopyrrolone thatacts on the GABA receptor complex,but at a different site than benzodiazepines.Its onset of action is ~30minutes, with a duration of action of ~5 to 7 hours.

Clinical Trials

Sepracor submitted a total of 25clinical trials to the FDA for review,which included >2700 adult and elderlysubjects. One 6-month, phase 3,randomized, double-blind, placebo-controlledstudy was published in thejournal Sleep in November 2003.² Thisstudy included 788 chronic insomniapatients 21 to 69 years ofage. Patients were giveneither a placebo or 3 mgeszopiclone. Nightly use ofeszopiclone 3 mg resultedin statistically significantimprovement in sleep onset, maintenance,and quality, as well asimproved daytime alertness and functioningand an improved sense of well-being,versus placebo. Improvementswere seen in the first week of treatmentand were maintained throughout6 months of double-blind treatment,with no decline in efficacy (notolerance developed).

A 6-week, phase 3, randomized, double-blind, multicenter, placebo-controlledstudy involved adult patientsaged 21 to 64 years.³ Patients were treatedwith eszopiclone 2 or 3 mg or placeboand were assessed after the first doseand at 2, 4, and 6 weeks for efficacy andpotential for rebound insomnia. Patientstreated with either dose of eszopiclonedemonstrated a significantimprovement in latency to persistentsleep, sleep latency, sleep onset, sleepefficiency, total sleep time, and sleepquality and depth, versus placebo.Eszopiclone 3 mg significantly improvedobjective and subjective waketime after sleep onset, versus placebo.Efficacy did not decline over 6 weeks,and no rebound was observed on sleep-onsetor sleep-maintenance parametersupon eszopiclone discontinuation. Inaddition, no apparent adverse eventswere associated with withdrawal whenpatients ended eszopiclone treatment.

A phase 3, multicenter, randomized,double-blind, placebo-controlledstudy was conducted with 231 elderlypatients.⁴ Patients were given eithereszopiclone 2 mg or a placebo for 14nights. Eszopiclone 2 mg significantlyimproved sleep onset, wake time aftersleep onset, total sleep time, and sleepquality and depth, compared withplacebo. Patients also were evaluatedfor daytime napping, which is associatedwith a considerably increasedhealth risk. Eszopiclone 2 mg significantlyreduced the number and durationof daytime naps over the treatmentperiod. In addition, eszopiclone-treatedpatients reported significantlyimproved daytime alertness and senseof physical well-being. Eszopiclonewas well tolerated, with headache(15%) and daytime somnolence (4%)the most common side effects.Research is continuing on the efficacyof eszopiclone in patients with insomniaand other disease states, such asdepression, rheumatoid arthritis, andperimenopause.

Outlook

Eszopiclone's acceptable side-effectprofile and effectiveness are similar tothose of other available sleep aids andare supported by 6 months of clinicaltrials. As the only nonbenzodiazepinestudied for this long, eszopicloneshows promise for patients withchronic and transient insomnia,including elderly patients.

Dr. Holmberg is a pharmacist with PhoenixChildren's Hospital, Phoenix, Ariz. Dr.Schott is a pharmacist with Stop and Shop,Wallingford, Conn.

For a list of references, send astamped, self-addressed envelope to:References Department, Attn. A. Stahl,Pharmacy Times, 241 Forsgate Drive,Jamesburg, NJ 08831; or send an e-mailrequest to: astahl@ascendmedia.com.