Somna

Somna, uykusuzluğun kısa süreli tedavisi için endikedir. Somna'nın kontrollü klinik çalışmalarda uyku başlangıç süresini 30 güne kadar azalttığı gösterilmiştir (bkz Klinik Araştırmalar altında KLİNİK FARMAKOLOJİ). Toplam uyku süresini arttırdığı veya uyanma sayısını azalttığı gösterilmemiştir.

Etkinliği desteklemek için yapılan klinik çalışmalar tek bir geceden 5 haftaya kadar değişmektedir. Uyku gecikmesinin nihai resmi değerlendirmeleri tedavinin sonunda gerçekleştirildi.

Somna dozu kişiselleştirilmelidir. Çoğu yaşlı yetişkin için önerilen Somna dozu 10 mg'dır. Bazı düşük kilolu bireyler için 5 mg yeterli bir doz olabilir. Somna kullanımı ile ilişkili bazı advers olayların riskinin doza bağlı olduğu görülmekle birlikte, 20 mg dozun yeterince tolere edildiği gösterilmiştir ve daha düşük bir dozun denenmesinden faydalanmayan ara sıra hasta için düşünülebilir. 20 mg'ın üzerindeki dozlar yeterince değerlendirilmemiştir ve önerilmez.

Somna yatmadan hemen önce veya hasta yatmadan ve uykuya dalmakta zorluk çektikten sonra alınmalıdır (bkz ÖNLEMLER). Somna'nın ağır, yüksek yağlı bir yemekle veya hemen sonrasında alınması daha yavaş emilim ile sonuçlanır ve Somna'nın uyku gecikmesi üzerindeki etkisini azaltması beklenir (bkz. Farmakokinetik altında KLİNİK FARMAKOLOJİ).

Özel Nüfuslar

Yaşlı hastalar ve zayıflamış hastalar hipnotiklerin etkilerine daha duyarlı gibi görünmektedir ve 5 mg Somna'ya yanıt vermektedir. Bu hastalar için önerilen doz 5 mg'dır. 10 mg'ın üzerindeki dozlar önerilmez.

Karaciğer yetmezliği: Hafif ila orta şiddette karaciğer yetmezliği olan hastalar Somna 5 mg ile tedavi edilmelidir, çünkü bu popülasyonda klerens azalır. Somna'nın şiddetli karaciğer yetmezliği olan hastalarda kullanılması önerilmez.

Böbrek yetmezliği: Hafif ila orta derecede böbrek yetmezliği olan hastalarda doz ayarlamasına gerek yoktur. Şiddetli böbrek yetmezliği olan hastalarda Somna yeterince çalışılmamıştır.

Simetidin alan hastalara 5 mg'lık bir başlangıç dozu verilmelidir, çünkü bu popülasyonda zaleplon klerensi azalır (bkz İLAÇ ETKİLEŞİMLERİ altında ÖNLEMLER).

Zaleplon veya formülasyondaki herhangi bir yardımcı maddeye karşı aşırı duyarlılık (ayrıca bakınız ÖNLEMLER).

UYARILAR

Uyku bozuklukları fiziksel ve / veya psikiyatrik bir bozukluğun ortaya çıkan tezahürü olabileceğinden, uykusuzluğun semptomatik tedavisi ancak hastanın dikkatli bir değerlendirmesinden sonra başlatılmalıdır. Uykusuzluğun 7 ila 10 günlük tedaviden sonra havale edilmemesi, değerlendirilmesi gereken birincil psikiyatrik ve / veya tıbbi hastalığın varlığını gösterebilir.

Uykusuzluğun kötüleşmesi veya yeni düşünme veya davranış anormalliklerinin ortaya çıkması, tanınmayan bir psikiyatrik veya fiziksel bozukluğun sonucu olabilir. Bu bulgular Somna dahil yatıştırıcı / hipnotik ilaçlarla tedavi sırasında ortaya çıkmıştır. Somna'nın bazı önemli olumsuz etkileri doza bağlı gibi göründüğünden, özellikle yaşlılarda mümkün olan en düşük etkili dozu kullanmak önemlidir (bkz DOZAJ VE YÖNETİM).

Sedatif / hipnotiklerin kullanımı ile ilişkili olarak çeşitli anormal düşünme ve davranış değişikliklerinin meydana geldiği bildirilmiştir. Bu değişikliklerin bazıları azalmış inhibisyon ile karakterize edilebilir (ör., alkol ve diğer CNS depresanlarının ürettiği etkilere benzer şekilde, karakter dışı görünen saldırganlık ve dışa dönüklük). Bildirilen diğer davranış değişiklikleri tuhaf davranış, ajitasyon, halüsinasyonlar ve duyarsızlaşmayı içermektedir.

Anormal Düşünme ve Davranışsal Değişiklikler

“Uyku sürüşü” gibi karmaşık davranışlar (ör., yatıştırıcı-hipnotik yutulduktan sonra tamamen uyanık olmasa da, olay için amnezi ile sürüş) bildirilmiştir. Bu olaylar yatıştırıcı-hipnotik-naif ve yatıştırıcı-hipnotik deneyimli kişilerde ortaya çıkabilir. Terapötik dozlarda sadece Somna ile uyku sürüşü gibi davranışlar ortaya çıkabilse de, Somna ile alkol ve diğer CNS depresanlarının kullanımı, Somna'nın önerilen maksimum dozu aşan dozlarda kullanılması gibi bu tür davranışların riskini artırdığı görülmektedir. Hasta ve toplum için risk nedeniyle, “uyku sürüşü” atağı bildiren hastalar için Somna'nın kesilmesi güçlü bir şekilde düşünülmelidir. Diğer karmaşık davranışlar (ör.yatıştırıcı-hipnotik aldıktan sonra tamamen uyanık olmayan hastalarda yemek hazırlama ve yemek yeme, telefon görüşmesi yapma veya seks yapma) bildirilmiştir. Uyku sürüşünde olduğu gibi, hastalar genellikle bu olayları hatırlamazlar. Amnezi ve diğer nöropsikiyatrik semptomlar öngörülemeyen bir şekilde ortaya çıkabilir. Öncelikle depresyondaki hastalarda, yatıştırıcı / hipnotiklerin kullanımı ile ilişkili olarak intihar düşünceleri ve eylemleri (tamamlanmış intiharlar dahil) dahil olmak üzere depresyonun kötüleştiği bildirilmiştir.

Yukarıda listelenen anormal davranışların belirli bir örneğinin ilaca bağlı, kendiliğinden veya altta yatan bir psikiyatrik veya fiziksel bozukluğun sonucu olup olmadığı nadiren belirlenebilir. Bununla birlikte, herhangi bir yeni davranışsal işaretin veya endişe belirtisinin ortaya çıkması dikkatli ve acil bir değerlendirme gerektirir.

Sedatif / hipnotik kullanımının hızlı dozunun azaltılmasını veya aniden kesilmesini takiben, diğer CNS-depresan ilaçlardan çekilme ile ilişkili olanlara benzer belirti ve semptomlar bildirilmiştir (bkz Uyuşturucu Kullanımı ve Bağımlılığı).

Somna, diğer hipnotikler gibi CNS-depresan etkilerine sahiptir. Hızlı hareket başlangıcı nedeniyle, Somna sadece yatmadan hemen önce veya hasta yatmadan ve uykuya dalmakta zorluk çektikten sonra yutulmalıdır. Somna alan hastalar, tam zihinsel uyanıklık veya motor koordinasyonu gerektiren tehlikeli mesleklere katılmaya karşı uyarılmalıdır (ör., makine kullanmak veya motorlu araç kullanmak) ilacı aldıktan sonra, Somna'nın yutulmasından sonraki gün meydana gelebilecek bu tür faaliyetlerin performansındaki potansiyel bozulma dahil. Somna ve diğer hipnotikler, diğer psikotropik ilaçlar, antikonvülsanlar, antihistaminikler, narkotik analjezikler, anestezikler, etanol ve CNS depresyonu üreten diğer ilaçlarla birlikte uygulandığında ilave CNS-depresan etkileri üretebilir. Somna alkolle alınmamalıdır. Potansiyel olarak ilave etkiler nedeniyle Somna diğer CNS-depresan ajanlarla birlikte uygulandığında doz ayarlaması gerekebilir.

Şiddetli Anafilaktik ve Anafilaktoid Reaksiyonlar

Nadir Somna dahil olmak üzere ilk veya sonraki yatıştırıcı hipnotik dozlarını aldıktan sonra hastalarda dil, glotis veya gırtlak içeren anjiyoödem vakaları bildirilmiştir. Bazı hastalarda dispne, boğaz kapanması veya anafilaksi gösteren bulantı ve kusma gibi ek semptomlar görülmüştür. Bazı hastalar acil serviste tıbbi tedaviye ihtiyaç duymuştur. Anjiyoödem dil, glotis veya gırtlak içeriyorsa, hava yolu tıkanıklığı meydana gelebilir ve ölümcül olabilir. Somna ile tedaviden sonra anjiyoödem gelişen hastalar ilaçla yeniden mücadele edilmemelidir.

ÖNLEMLER

Genel

İlaç Yönetiminin Zamanlaması

Somna yatmadan hemen önce veya hasta yatmadan ve uykuya dalmakta zorluk çektikten sonra alınmalıdır. Tüm yatıştırıcı / hipnotiklerde olduğu gibi, Somna'yı hala yukarı ve yaklaşık olarak almak kısa süreli hafıza bozukluğu, halüsinasyonlar, koordinasyon bozukluğu, baş dönmesi ve baş dönmesi ile sonuçlanabilir.

Yaşlı ve / veya Zayıflamış Hastalarda Kullanın

Tekrarlanan maruziyetten veya yatıştırıcı / hipnotik ilaçlara olağandışı duyarlılıktan sonra motor ve / veya bilişsel performans, yaşlı ve / veya zayıflamış hastaların tedavisinde bir endişe kaynağıdır. Yaşlı hastaların yan etki olasılığını azaltması için 5 mg'lık bir doz önerilir (bkz DOZAJ VE YÖNETİM). Yaşlı ve / veya zayıflamış hastalar yakından izlenmelidir.

Eşzamanlı Hastalığı Olan Hastalarda Kullanın

Eşzamanlı sistemik hastalığı olan hastalarda Somna ile klinik deneyim sınırlıdır. Somna, metabolizmayı veya hemodinamik yanıtları etkileyebilecek hastalık veya rahatsızlıkları olan hastalarda dikkatle kullanılmalıdır.

Ön çalışmalar normal deneklerde hipnotik Somna dozlarında solunum depresan etkileri ortaya koymasa da, solunum fonksiyonları zayıf olan hastalara Somna (zaleplon) reçete edilirse dikkatli olunmalıdır, çünkü yatıştırıcı / hipnotikler solunum tahrikini baskılama kapasitesine sahiptir. Hafif ila orta şiddette kronik obstrüktif akciğer hastalığı veya orta derecede obstrüktif uyku apnesi olan hastalarda 10 mg akut Somna uygulamasının kontrollü çalışmaları, sırasıyla kan gazlarında veya apne / hipopne indeksinde değişiklik olduğuna dair bir kanıt göstermemiştir. Bununla birlikte, önceden var olan hastalık nedeniyle solunumu zayıf olan hastalar dikkatle izlenmelidir.

Hafif ila orta şiddette karaciğer yetmezliği olan hastalarda Somna dozu 5 mg'a düşürülmelidir (bkz DOZAJ VE YÖNETİM). Şiddetli karaciğer yetmezliği olan hastalarda kullanılması önerilmez.

Hafif ila orta derecede böbrek yetmezliği olan hastalarda doz ayarlamasına gerek yoktur. Şiddetli böbrek yetmezliği olan hastalarda Somna yeterince çalışılmamıştır.

Depresyonlu Hastalarda Kullanım

Diğer yatıştırıcı / hipnotik ilaçlarda olduğu gibi, Somna depresyon belirtileri veya semptomları gösteren hastalara dikkatle uygulanmalıdır. Bu hastalarda intihar eğilimleri olabilir ve koruyucu önlemler gerekebilir. Kasıtlı doz aşımı bu hasta grubunda daha yaygındır (bkz AŞIRI DOZ); bu nedenle, mümkün olan en az ilaç miktarı hasta için herhangi bir zamanda reçete edilmelidir.

Bu ürün FD & C Sarı No içerir. Bazı duyarlı kişilerde alerjik tip reaksiyonlara (bronşiyal astım dahil) neden olabilecek 5 (tartrazin). Rağmen FD & C Sarı No genel insidansı. Genel popülasyonda 5 (tartrazin) duyarlılığı düşüktür, aspirin aşırı duyarlılığı olan hastalarda sıklıkla görülür.

Hastalar İçin Bilgi

Bir hasta İlaç Kılavuzu Somna için de mevcuttur. Reçete yazan veya sağlık uzmanı hastalara, ailelerine ve bakıcılarına İlaç Kılavuzunu okumaları talimatını vermeli ve içeriğini anlamalarına yardımcı olmalıdır. Hastalara, içeriklerini tartışma fırsatı verilmelidir İlaç Kılavuzu ve sahip olabilecekleri sorulara cevap almak.

ÖZEL “Uyku Sürüşü” ve Diğer Karmaşık Davranışlarla ilgilidir

Sakinleştirici bir hipnotik ilaç aldıktan ve tamamen uyanık olmasa da arabalarını sürdükten sonra çoğu zaman olayın anısı olmadan yataktan çıkan insanların raporları var. Bir hasta böyle bir olay yaşarsa, derhal doktoruna bildirilmelidir, çünkü “uyku sürüşü” tehlikeli olabilir. Somna alkol veya diğer merkezi sinir sistemi depresanları ile alındığında bu davranışın ortaya çıkması daha olasıdır (bkz UYARILAR). Diğer karmaşık davranışlar (ör.uyku ilacı aldıktan sonra tamamen uyanık olmayan hastalarda yemek hazırlama ve yemek yeme, telefon görüşmesi yapma veya seks yapma) bildirilmiştir. Uyku sürüşünde olduğu gibi, hastalar genellikle bu olayları hatırlamazlar.

Laboratuvar Testleri

Özel laboratuvar testi önerilmez.

Kanserojenez, Mutajenez ve Doğurganlığın Bozukluğu

Karsinogenez

Farelerde ve sıçanlarda zaleplonun yaşam boyu karsinojenisite çalışmaları yapılmıştır. Fareler iki yıl boyunca diyette 25 mg / kg / gün, 50 mg / kg / gün, 100 mg / kg / gün ve 200 mg / kg / gün dozları aldı. Bu dozlar, mg / m² bazında 20 mg'lık önerilen maksimum insan dozunun (MRHD) 6 ila 49 katına eşittir. Yüksek doz grubunda dişi farelerde hepatosellüler adenom insidansında önemli bir artış olmuştur. Sıçanlar, iki yıl boyunca diyette 1 mg / kg / gün, 10 mg / kg / gün ve 20 mg / kg / gün dozları aldı. Bu dozlar, mg / m² bazında 20 mg'lık önerilen maksimum insan dozunun (MRHD) 0.5 ila 10 katına eşittir. Zaleplon sıçanlarda kanserojen değildi.

Mutajenez

Zaleplon, metabolik aktivasyonun varlığında ve yokluğunda klastojenikti ve içindeki kromozomal anormallikler açısından test edildiğinde yapısal ve sayısal sapmalara (poliploidi ve endoruplikasyon) neden oldu in vitro Çin hamster yumurtalık hücre tahlili. İçinde in vitro insan lenfosit deneyi, zaleplon, sadece test edilen en yüksek konsantrasyonlarda metabolik aktivasyon varlığında sayısal, ancak yapısal olmayan sapmalara neden oldu. Diğerinde in vitro deneyler, zaleplon Ames bakteriyel gen mutasyon testinde veya Çin hamster yumurtalık HGPRT gen mutasyon testinde mutajenik değildi. Zaleplon ikisinde klastojenik değildi in vivo deneyler, fare kemik iliği mikronükleus deneyi ve sıçan kemik iliği kromozomal sapma deneyi ve sıçan hepatosit planlanmamış DNA sentez testinde DNA hasarına neden olmadı.

Doğurganlığın Bozukluğu

Sıçanlarda yapılan doğurganlık ve üreme performansı çalışmasında mortalite ve azalan doğurganlık, çiftleşme öncesinde ve sırasında erkeklere ve kadınlara 100 mg / kg / gün oral zaleplon dozu uygulanması ile ilişkilendirilmiştir. Bu doz, mg / m² bazında 20 mg'lık önerilen maksimum insan dozunun (MRHD) 49 katına eşdeğerdir. Takip çalışmaları, doğurganlığın bozulmasının kadın üzerindeki bir etkiye bağlı olduğunu göstermiştir.

Gebelik

Gebelik Kategorisi C

Sıçan ve tavşanlarda yapılan embriyofetal gelişim çalışmalarında, organogenez boyunca hamile hayvanlara sırasıyla 100 mg / kg / gün ve 50 mg / kg / gün oral uygulama teratojenisite kanıtı üretmemiştir. Bu dozlar, mg / m² bazında önerilen maksimum insan dozunun (MRHD) 49 (sıçan) ve 48 (tavşan) katına eşittir. Sıçanlarda, 100 mg / kg / gün alan barajların yavrularında doğum öncesi ve sonrası büyüme azalmıştır. Bu doz, klinik belirtilerle kanıtlandığı ve gebelik sırasında anne vücut ağırlığı artışının azaldığı gibi maternal olarak toksikti. Sıçan yavrularının büyümesinin azaltılması için etkisiz doz 10 mg / kg (mg / m² bazında 20 mg MRHD'nin 5 katına eşdeğer bir doz) idi. İncelenen dozlarda tavşanlarda embriyofetal gelişim üzerinde herhangi bir olumsuz etki gözlenmemiştir.

Sıçanlarda doğum öncesi ve sonrası gelişim çalışmasında, gebeliğin son bölümünde 7 mg / kg / gün veya daha yüksek dozlarla tedavi edilen kadınların yavrularında artan ölü doğum ve doğum sonrası mortalite ve azalan büyüme ve fiziksel gelişim gözlenmiştir. emzirme boyunca. Bu dozda maternal toksisite kanıtı yoktu. Yavruların gelişimi için etkisiz doz 1 mg / kg / gün idi (mg / m² bazında 20 mg MRHD'nin 0.5 katına eşdeğer bir doz). Çapraz destekleyici bir çalışmada yavruların yaşayabilirliği ve büyümesi üzerindeki olumsuz etkiler incelendiğinde, hem utero hem de ilaca laktasyonel maruziyetten kaynaklandığı görülmüştür.

Gebe kadınlarda zaleplon çalışması yoktur; bu nedenle Somna® (zaleplon) hamilelik sırasında kadınlarda kullanılması önerilmez.

Emek ve Teslimat

Somna'nın emek ve doğumda yerleşik bir kullanımı yoktur.

Hemşirelik Anneler

Emziren annelerde yapılan bir araştırma, zaleplonun klerensi ve yarılanma ömrünün genç normal deneklere benzer olduğunu göstermiştir. Somna uygulamasından yaklaşık 1 saat sonra bir beslenme sırasında en yüksek atılan miktar ile anne sütüne az miktarda zaleplon atılır. Anne sütünden alınan ilacın az miktarı bebeklerde potansiyel olarak önemli konsantrasyonlara neden olabileceğinden ve zaleplonun emziren bir bebek üzerindeki etkileri bilinmediğinden, emziren annelerin Somna almaması önerilir.

Pediatrik Kullanım

Pediyatrik hastalarda Somna'nın güvenliği ve etkinliği belirlenmemiştir.

Geriatrik Kullanım

Somna alan çift kör, plasebo kontrollü, paralel grup klinik çalışmalarında toplam 628 hasta en az 65 yaşındaydı; bunlardan 311'i 5 mg ve 317'si 10 mg aldı. Hem uyku laboratuvarı hem de ayakta tedavi çalışmalarında, uykusuzluklu yaşlı hastalar, uyku gecikmesi azaltılmış 5 mg'lık bir doza cevap verdiler ve bu nedenle bu popülasyonda önerilen doz 5 mg'dır. Somna'lı yaşlı hastaların kısa süreli tedavisi (14 gece çalışması) sırasında, plasebodan 5 mg veya 10 mg Somna ile önemli ölçüde daha yüksek bir oranda en az% 1 sıklıkta hiçbir advers olay meydana gelmedi.

The premarketing development program for Somna included zaleplon exposures in patients and/or normal subjects from 2 different groups of studies: approximately 900 normal subjects in clinical pharmacology/pharmacokinetic studies; and approximately 2,900 exposures from patients in placebo-controlled clinical effectiveness studies, corresponding to approximately 450 patient exposure years. The conditions and duration of treatment with Somna varied greatly and included (in overlapping categories) open-label and double-blind phases of studies, inpatients and outpatients, and short-term or longer-term exposure. Adverse reactions were assessed by collecting adverse events, results of physical examinations, vital signs, weights, laboratory analyses, and ECGs.

Adverse events during exposure were obtained primarily by general inquiry and recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of events into a smaller number of standardized event categories. In the tables and tabulations that follow, COSTART terminology has been used to classify reported adverse events.

The stated frequencies of adverse events represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse event of the type listed. An event was considered treatment-emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation.

Adverse Findings Observed In Short-Term, Placebo-Controlled Trials

Adverse Events Associated With Discontinuation Of Treatment

In premarketing placebo-controlled, parallel-group phase 2 and phase 3 clinical trials, 3.1% of 744 patients who received placebo and 3.7% of 2,149 patients who received Somna discontinued treatment because of an adverse clinical event. This difference was not statistically significant. No event that resulted in discontinuation occurred at a rate of ≥ 1%.

Adverse Events Occurring At An Incidence Of 1% Or More Among Somna 20 mg-Treated Patients

Table 1 enumerates the incidence of treatment-emergent adverse events for a pool of three 28night and one 35-night placebo-controlled studies of Somna at doses of 5 mg or 10 mg and 20 mg. The table includes only those events that occurred in 1% or more of patients treated with Somna 20 mg and that had a higher incidence in patients treated with Somna 20 mg than in placebo-treated patients.

The prescriber should be aware that these figures cannot be used to predict the incidence of adverse events in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and non-drug factors to the adverse event incidence rate in the population studied.

Table 1 : Incidence (%) of Treatment-Emergent Adverse Events in Long-Term (28 and 35 Nights) Placebo-Controlled Clinical Trials of Somna^a

Other Adverse Events Observed During The Premarketing Evaluation Of Somna

Listed below are COSTART terms that reflect treatment-emergent adverse events as defined in the introduction to the ADVERSE REACTIONS section. These events were reported by patients treated with Somna (zaleplon) at doses in a range of 5 mg/day to 20 mg/day during premarketing phase 2 and phase 3 clinical trials throughout the United States, Canada, and Europe, including approximately 2,900 patients. All reported events are included except those already listed in Table 1 or elsewhere in labeling, those events for which a drug cause was remote, and those event terms that were so general as to be uninformative. It is important to emphasize that although the events reported occurred during treatment with Somna, they were not necessarily caused by it.

Events are further categorized by body system and listed in order of decreasing frequency according to the following definitions: frequent adverse events are those occurring on one or more occasions in at least 1/100 patients; infrequent adverse events are those occurring in less than 1/100 patients but at least 1/1,000 patients; rare events are those occurring in fewer than 1/1,000 patients.

Body as a whole -Frequent: back pain, chest pain, fever; Infrequent: chest pain substernal, chills, face edema, generalized edema, hangover effect, neck rigidity.

Cardiovascular system -Frequent: migraine; Infrequent: angina pectoris, bundle branch block, hypertension, hypotension, palpitation, syncope, tachycardia, vasodilatation, ventricular extrasystoles; Rare: bigeminy, cerebral ischemia, cyanosis, pericardial effusion, postural hypotension, pulmonary embolus, sinus bradycardia, thrombophlebitis, ventricular tachycardia.

Digestive system -Frequent: constipation, dry mouth, dyspepsia; Infrequent: eructation, esophagitis, flatulence, gastritis, gastroenteritis, gingivitis, glossitis, increased appetite, melena, mouth ulceration, rectal hemorrhage, stomatitis; Rare: aphthous stomatitis, biliary pain, bruxism, cardiospasm, cheilitis, cholelithiasis, duodenal ulcer, dysphagia, enteritis, gum hemorrhage, increased salivation, intestinal obstruction, abnormal liver function tests, peptic ulcer, tongue discoloration, tongue edema, ulcerative stomatitis.

Endocrine system -Rare: diabetes mellitus, goiter, hypothyroidism.

Hemic and lymphatic system -Infrequent: anemia, ecchymosis, lymphadenopathy; Rare: eosinophilia, leukocytosis, lymphocytosis, purpura.

Metabolic and nutritional -Infrequent: edema, gout, hypercholesteremia, thirst, weight gain; Rare: bilirubinemia, hyperglycemia, hyperuricemia, hypoglycemia, hypoglycemic reaction, ketosis, lactose intolerance, AST (SGOT) increased, ALT (SGPT) increased, weight loss.

Musculoskeletal system -Frequent: arthralgia, arthritis, myalgia; Infrequent: arthrosis, bursitis, joint disorder (mainly swelling, stiffness, and pain), myasthenia, tenosynovitis; Rare: myositis, osteoporosis.

Nervous system -Frequent: anxiety, depression, nervousness, thinking abnormal (mainly difficulty concentrating); Infrequent: abnormal gait, agitation, apathy, ataxia, circumoral paresthesia, emotional lability, euphoria, hyperesthesia, hyperkinesia, hypotonia, incoordination, insomnia, libido decreased, neuralgia, nystagmus; Rare: CNS stimulation, delusions, dysarthria, dystonia, facial paralysis, hostility, hypokinesia, myoclonus, neuropathy, psychomotor retardation, ptosis, reflexes decreased, reflexes increased, sleep talking, sleep walking, slurred speech, stupor, trismus.

Respiratory system -Frequent: bronchitis; Infrequent: asthma, dyspnea, laryngitis, pneumonia, snoring, voice alteration; Rare: apnea, hiccup, hyperventilation, pleural effusion, sputum increased.

Skin and appendages -Frequent: pruritus, rash; Infrequent: acne, alopecia, contact dermatitis, dry skin, eczema, maculopapular rash, skin hypertrophy, sweating, urticaria, vesiculobullous rash; Rare: melanosis, psoriasis, pustular rash, skin discoloration.

Special senses -Frequent: conjunctivitis, taste perversion; Infrequent: diplopia, dry eyes, photophobia, tinnitus, watery eyes; Rare: abnormality of accommodation, blepharitis, cataract specified, corneal erosion, deafness, eye hemorrhage, glaucoma, labyrinthitis, retinal detachment, taste loss, visual field defect.

Urogenital system -Infrequent: bladder pain, breast pain, cystitis, decreased urine stream, dysuria, hematuria, impotence, kidney calculus, kidney pain, menorrhagia, metrorrhagia, urinary frequency, urinary incontinence, urinary urgency, vaginitis; Rare: albuminuria, delayed menstrual period, leukorrhea, menopause, urethritis, urinary retention, vaginal hemorrhage.

Postmarketing Reports

Anaphylactic/anaphylactoid reactions, including severe reactions, and nightmares.

Drug Abuse And Dependence

Controlled Substance Class

Somna is classified as a Schedule IV controlled substance by federal regulation.

Abuse, Dependence, And Tolerance

Abuse and addiction are separate and distinct from physical dependence and tolerance. Abuse is characterized by misuse of the drug for non-medical purposes, often in combination with other psychoactive substances. Physical dependence is a state of adaption that is manifested by a specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug and/or administration of an antagonist. Tolerance is a state of adaptation in which exposure to a drug induces changes that result in a diminution of one or more of the drug's effects over time. Tolerance may occur to both the desired and undesired effects of drugs and may develop at different rates for different effects.

Addiction is a primary, chronic, neurobiological disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. It is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving. Drug addiction is a treatable disease, utilizing a multidisciplinary approach, but relapse is common.

Abuse

Two studies assessed the abuse liability of Somna at doses of 25 mg, 50 mg, and 75 mg in subjects with known histories of sedative drug abuse. The results of these studies indicate that Somna has an abuse potential similar to benzodiazepine and benzodiazepine-like hypnotics.

Dependence

The potential for developing physical dependence on Somna and a subsequent withdrawal syndrome was assessed in controlled studies of 14-, 28-, and 35-night durations and in open-label studies of 6- and 12-month durations by examining for the emergence of rebound insomnia following drug discontinuation. Some patients (mostly those treated with 20 mg) experienced a mild rebound insomnia on the first night following withdrawal that appeared to be resolved by the second night. The use of the Benzodiazepine Withdrawal Symptom Questionnaire and examination of any other withdrawal-emergent events did not detect any other evidence for a withdrawal syndrome following abrupt discontinuation of Somna therapy in pre-marketing studies.

However, available data cannot provide a reliable estimate of the incidence of dependence during treatment at recommended doses of Somna. Other sedative/hypnotics have been associated with various signs and symptoms following abrupt discontinuation, ranging from mild dysphoria and insomnia to a withdrawal syndrome that may include abdominal and muscle cramps, vomiting, sweating, tremors, and convulsions. Seizures have been observed in two patients, one of which had a prior seizure, in clinical trials with Somna. Seizures and death have been seen following the withdrawal of zaleplon from animals at doses many times higher than those proposed for human use. Because individuals with a history of addiction to, or abuse of, drugs or alcohol are at risk of habituation and dependence, they should be under careful surveillance when receiving Somna or any other hypnotic.

Tolerance

Possible tolerance to the hypnotic effects of Somna 10 mg and 20 mg was assessed by evaluating time to sleep onset for Somna compared with placebo in two 28-night placebo-controlled studies and latency to persistent sleep in one 35-night placebo-controlled study where tolerance was evaluated on nights 29 and 30. No development of tolerance to Somna was observed for time to sleep onset over 4 weeks.

Signs And Symptoms

Signs and symptoms of overdose effects of CNS depressants can be expected to present as exaggerations of the pharmacological effects noted in preclinical testing. Overdose is usually manifested by degrees of central nervous system depression ranging from drowsiness to coma. In mild cases, symptoms include drowsiness, mental confusion, and lethargy; in more serious cases, symptoms may include ataxia, hypotonia, hypotension, respiratory depression, rarely coma, and very rarely death.

Loss of consciousness, in addition to signs and symptoms consistent with CNS depressants as described above, have been reported following zaleplon overdose. Individuals have fully recovered from zaleplon overdoses of greater than 200 mg (10 times the maximum recommended dose of zaleplon). Rare instances of fatal outcomes following overdose with zaleplon, most often associated with overdose of additional CNS depressants, have been reported.

Recommended Treatment

General symptomatic and supportive measures should be used along with immediate gastric lavage where appropriate. Intravenous fluids should be administered as needed. Animal studies suggest that flumazenil is an antagonist to zaleplon. However, there is no pre-marketing clinical experience with the use of flumazenil as an antidote to a Somna overdose. As in all cases of drug overdose, respiration, pulse, blood pressure, and other appropriate signs should be monitored and general supportive measures employed. Hypotension and CNS depression should be monitored and treated by appropriate medical intervention.

Poison Control Center

As with the management of all overdosage, the possibility of multiple drug ingestion should be considered. The physician may wish to consider contacting a poison control center for up-to-date information on the management of hypnotic drug product overdosage.

Special Populations

Elderly patients and debilitated patients appear to be more sensitive to the effects of hypnotics, and respond to 5 mg of Somna. The recommended dose for these patients is therefore 5 mg. Doses over 10 mg are not recommended.

Hepatic insufficiency: Patients with mild to moderate hepatic impairment should be treated with Somna 5 mg because clearance is reduced in this population. Somna is not recommended for use in patients with severe hepatic impairment.

Renal insufficiency: No dose adjustment is necessary in patients with mild to moderate renal impairment. Somna has not been adequately studied in patients with severe renal impairment.

An initial dose of 5 mg should be given to patients concomitantly taking cimetidine because zaleplon clearance is reduced in this population (see DRUG INTERACTIONS under PRECAUTIONS).

HOW SUPPLIED

Somna (zaleplon) capsules are supplied as follows:

5 mg: opaque green cap and opaque pale green body with “5 mg” on the cap and “Somna” on the body.

NDC 60793-145-01 Bottles of 100

10 mg: opaque green cap and opaque light green body with “10 mg” on the cap and “Somna” on the body.

NDC 60793-146-01 Bottles of 100

Storage Conditions

Store at controlled room temperature, 20°C to 25°C (68°F to 77°F).

Dispense in a light-resistant container as defined in the USP.

Prescribing Information as of December 2007.

Distributed by: King Pharmaceuticals, Inc., Bristol, TN 37620 Manufactured by: Corepharma LLC, 215 Wood Avenue Middlesex, NJ 08846. Revised: April 2013

SIDE EFFECTS

The premarketing development program for Somna included zaleplon exposures in patients and/or normal subjects from 2 different groups of studies: approximately 900 normal subjects in clinical pharmacology/pharmacokinetic studies; and approximately 2,900 exposures from patients in placebo-controlled clinical effectiveness studies, corresponding to approximately 450 patient exposure years. The conditions and duration of treatment with Somna varied greatly and included (in overlapping categories) open-label and double-blind phases of studies, inpatients and outpatients, and short-term or longer-term exposure. Adverse reactions were assessed by collecting adverse events, results of physical examinations, vital signs, weights, laboratory analyses, and ECGs.

Adverse events during exposure were obtained primarily by general inquiry and recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of events into a smaller number of standardized event categories. In the tables and tabulations that follow, COSTART terminology has been used to classify reported adverse events.

The stated frequencies of adverse events represent the proportion of individuals who experienced, at least once, a treatment-emergent adverse event of the type listed. An event was considered treatment-emergent if it occurred for the first time or worsened while receiving therapy following baseline evaluation.

Adverse Findings Observed In Short-Term, Placebo-Controlled Trials

Adverse Events Associated With Discontinuation Of Treatment

In premarketing placebo-controlled, parallel-group phase 2 and phase 3 clinical trials, 3.1% of 744 patients who received placebo and 3.7% of 2,149 patients who received Somna discontinued treatment because of an adverse clinical event. This difference was not statistically significant. No event that resulted in discontinuation occurred at a rate of ≥ 1%.

Adverse Events Occurring At An Incidence Of 1% Or More Among Somna 20 mg-Treated Patients

Table 1 enumerates the incidence of treatment-emergent adverse events for a pool of three 28night and one 35-night placebo-controlled studies of Somna at doses of 5 mg or 10 mg and 20 mg. The table includes only those events that occurred in 1% or more of patients treated with Somna 20 mg and that had a higher incidence in patients treated with Somna 20 mg than in placebo-treated patients.

The prescriber should be aware that these figures cannot be used to predict the incidence of adverse events in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other clinical investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and non-drug factors to the adverse event incidence rate in the population studied.

Table 1 : Incidence (%) of Treatment-Emergent Adverse Events in Long-Term (28 and 35 Nights) Placebo-Controlled Clinical Trials of Somna^a

Other Adverse Events Observed During The Premarketing Evaluation Of Somna

Listed below are COSTART terms that reflect treatment-emergent adverse events as defined in the introduction to the ADVERSE REACTIONS section. These events were reported by patients treated with Somna (zaleplon) at doses in a range of 5 mg/day to 20 mg/day during premarketing phase 2 and phase 3 clinical trials throughout the United States, Canada, and Europe, including approximately 2,900 patients. All reported events are included except those already listed in Table 1 or elsewhere in labeling, those events for which a drug cause was remote, and those event terms that were so general as to be uninformative. It is important to emphasize that although the events reported occurred during treatment with Somna, they were not necessarily caused by it.

Events are further categorized by body system and listed in order of decreasing frequency according to the following definitions: frequent adverse events are those occurring on one or more occasions in at least 1/100 patients; infrequent adverse events are those occurring in less than 1/100 patients but at least 1/1,000 patients; rare events are those occurring in fewer than 1/1,000 patients.

Body as a whole -Frequent: back pain, chest pain, fever; Infrequent: chest pain substernal, chills, face edema, generalized edema, hangover effect, neck rigidity.

Cardiovascular system -Frequent: migraine; Infrequent: angina pectoris, bundle branch block, hypertension, hypotension, palpitation, syncope, tachycardia, vasodilatation, ventricular extrasystoles; Rare: bigeminy, cerebral ischemia, cyanosis, pericardial effusion, postural hypotension, pulmonary embolus, sinus bradycardia, thrombophlebitis, ventricular tachycardia.

Digestive system -Frequent: constipation, dry mouth, dyspepsia; Infrequent: eructation, esophagitis, flatulence, gastritis, gastroenteritis, gingivitis, glossitis, increased appetite, melena, mouth ulceration, rectal hemorrhage, stomatitis; Rare: aphthous stomatitis, biliary pain, bruxism, cardiospasm, cheilitis, cholelithiasis, duodenal ulcer, dysphagia, enteritis, gum hemorrhage, increased salivation, intestinal obstruction, abnormal liver function tests, peptic ulcer, tongue discoloration, tongue edema, ulcerative stomatitis.

Endocrine system -Rare: diabetes mellitus, goiter, hypothyroidism.

Hemic and lymphatic system -Infrequent: anemia, ecchymosis, lymphadenopathy; Rare: eosinophilia, leukocytosis, lymphocytosis, purpura.

Metabolic and nutritional -Infrequent: edema, gout, hypercholesteremia, thirst, weight gain; Rare: bilirubinemia, hyperglycemia, hyperuricemia, hypoglycemia, hypoglycemic reaction, ketosis, lactose intolerance, AST (SGOT) increased, ALT (SGPT) increased, weight loss.

Musculoskeletal system -Frequent: arthralgia, arthritis, myalgia; Infrequent: arthrosis, bursitis, joint disorder (mainly swelling, stiffness, and pain), myasthenia, tenosynovitis; Rare: myositis, osteoporosis.

Nervous system -Frequent: anxiety, depression, nervousness, thinking abnormal (mainly difficulty concentrating); Infrequent: abnormal gait, agitation, apathy, ataxia, circumoral paresthesia, emotional lability, euphoria, hyperesthesia, hyperkinesia, hypotonia, incoordination, insomnia, libido decreased, neuralgia, nystagmus; Rare: CNS stimulation, delusions, dysarthria, dystonia, facial paralysis, hostility, hypokinesia, myoclonus, neuropathy, psychomotor retardation, ptosis, reflexes decreased, reflexes increased, sleep talking, sleep walking, slurred speech, stupor, trismus.

Respiratory system -Frequent: bronchitis; Infrequent: asthma, dyspnea, laryngitis, pneumonia, snoring, voice alteration; Rare: apnea, hiccup, hyperventilation, pleural effusion, sputum increased.

Skin and appendages -Frequent: pruritus, rash; Infrequent: acne, alopecia, contact dermatitis, dry skin, eczema, maculopapular rash, skin hypertrophy, sweating, urticaria, vesiculobullous rash; Rare: melanosis, psoriasis, pustular rash, skin discoloration.

Special senses -Frequent: conjunctivitis, taste perversion; Infrequent: diplopia, dry eyes, photophobia, tinnitus, watery eyes; Rare: abnormality of accommodation, blepharitis, cataract specified, corneal erosion, deafness, eye hemorrhage, glaucoma, labyrinthitis, retinal detachment, taste loss, visual field defect.

Urogenital system -Infrequent: bladder pain, breast pain, cystitis, decreased urine stream, dysuria, hematuria, impotence, kidney calculus, kidney pain, menorrhagia, metrorrhagia, urinary frequency, urinary incontinence, urinary urgency, vaginitis; Rare: albuminuria, delayed menstrual period, leukorrhea, menopause, urethritis, urinary retention, vaginal hemorrhage.

Postmarketing Reports

Anaphylactic/anaphylactoid reactions, including severe reactions, and nightmares.

Drug Abuse And Dependence

Controlled Substance Class

Somna is classified as a Schedule IV controlled substance by federal regulation.

Abuse, Dependence, And Tolerance

Abuse and addiction are separate and distinct from physical dependence and tolerance. Abuse is characterized by misuse of the drug for non-medical purposes, often in combination with other psychoactive substances. Physical dependence is a state of adaption that is manifested by a specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug and/or administration of an antagonist. Tolerance is a state of adaptation in which exposure to a drug induces changes that result in a diminution of one or more of the drug's effects over time. Tolerance may occur to both the desired and undesired effects of drugs and may develop at different rates for different effects.

Addiction is a primary, chronic, neurobiological disease with genetic, psychosocial, and environmental factors influencing its development and manifestations. It is characterized by behaviors that include one or more of the following: impaired control over drug use, compulsive use, continued use despite harm, and craving. Drug addiction is a treatable disease, utilizing a multidisciplinary approach, but relapse is common.

Abuse

Two studies assessed the abuse liability of Somna at doses of 25 mg, 50 mg, and 75 mg in subjects with known histories of sedative drug abuse. The results of these studies indicate that Somna has an abuse potential similar to benzodiazepine and benzodiazepine-like hypnotics.

Dependence

The potential for developing physical dependence on Somna and a subsequent withdrawal syndrome was assessed in controlled studies of 14-, 28-, and 35-night durations and in open-label studies of 6- and 12-month durations by examining for the emergence of rebound insomnia following drug discontinuation. Some patients (mostly those treated with 20 mg) experienced a mild rebound insomnia on the first night following withdrawal that appeared to be resolved by the second night. The use of the Benzodiazepine Withdrawal Symptom Questionnaire and examination of any other withdrawal-emergent events did not detect any other evidence for a withdrawal syndrome following abrupt discontinuation of Somna therapy in pre-marketing studies.

However, available data cannot provide a reliable estimate of the incidence of dependence during treatment at recommended doses of Somna. Other sedative/hypnotics have been associated with various signs and symptoms following abrupt discontinuation, ranging from mild dysphoria and insomnia to a withdrawal syndrome that may include abdominal and muscle cramps, vomiting, sweating, tremors, and convulsions. Seizures have been observed in two patients, one of which had a prior seizure, in clinical trials with Somna. Seizures and death have been seen following the withdrawal of zaleplon from animals at doses many times higher than those proposed for human use. Because individuals with a history of addiction to, or abuse of, drugs or alcohol are at risk of habituation and dependence, they should be under careful surveillance when receiving Somna or any other hypnotic.

Tolerance

Possible tolerance to the hypnotic effects of Somna 10 mg and 20 mg was assessed by evaluating time to sleep onset for Somna compared with placebo in two 28-night placebo-controlled studies and latency to persistent sleep in one 35-night placebo-controlled study where tolerance was evaluated on nights 29 and 30. No development of tolerance to Somna was observed for time to sleep onset over 4 weeks.

DRUG INTERACTIONS

As with all drugs, the potential exists for interaction with other drugs by a variety of mechanisms.

CNS-Active Drugs

Ethanol: Somna 10 mg potentiated the CNS-impairing effects of ethanol 0.75 g/kg on balance testing and reaction time for 1 hour after ethanol administration and on the digit symbol substitution test (DSST), symbol copying test, and the variability component of the divided attention test for 2.5 hours after ethanol administration. The potentiation resulted from a CNS pharmacodynamic interaction; zaleplon did not affect the pharmacokinetics of ethanol.

Imipramine: Coadministration of single doses of Somna 20 mg and imipramine 75 mg produced additive effects on decreased alertness and impaired psychomotor performance for 2 to 4 hours after administration. The interaction was pharmacodynamic with no alteration of the pharmacokinetics of either drug.

Paroxetine: Coadministration of a single dose of Somna 20 mg and paroxetine 20 mg daily for 7 days did not produce any interaction on psychomotor performance. Additionally, paroxetine did not alter the pharmacokinetics of Somna, reflecting the absence of a role of CYP2D6 in zaleplon's metabolism.

Thioridazine: Coadministration of single doses of Somna 20 mg and thioridazine 50 mg produced additive effects on decreased alertness and impaired psychomotor performance for 2 to 4 hours after administration. The interaction was pharmacodynamic with no alteration of the pharmacokinetics of either drug.

Venlafaxine: Coadministration of a single dose of zaleplon 10 mg and multiple doses of venlafaxine ER (extended release) 150 mg did not result in any significant changes in the pharmacokinetics of either zaleplon or venlafaxine. In addition, there was no pharmacodynamic interaction as a result of coadministration of zaleplon and venlafaxine ER.

Promethazine: Coadministration of a single dose of zaleplon and promethazine (10 and 25 mg, respectively) resulted in a 15% decrease in maximal plasma concentrations of zaleplon, but no change in the area under the plasma concentration-time curve. However, the pharmacodynamics of coadministration of zaleplon and promethazine have not been evaluated. Caution should be exercised when these 2 agents are coadministered.

Drugs That Induce CYP3A4

Rifampin: CYP3A4 is ordinarily a minor metabolizing enzyme of zaleplon. Multiple-dose administration of the potent CYP3A4 inducer rifampin (600 mg every 24 hours, q24h, for 14 days), however, reduced zaleplon Cmax and AUC by approximately 80%. The coadministration of a potent CYP3A4 enzyme inducer, although not posing a safety concern, thus could lead to ineffectiveness of zaleplon. An alternative non-CYP3A4 substrate hypnotic agent may be considered in patients taking CYP3A4 inducers such as rifampin, phenytoin, carbamazepine, and phenobarbital.

Drugs That Inhibit CYP3A4

CYP3A4 is a minor metabolic pathway for the elimination of zaleplon because the sum of desethylzaleplon (formed via CYP3A4 in vitro) and its metabolites, 5-oxo-desethylzaleplon and 5-oxo-desethylzaleplon glucuronide, account for only 9% of the urinary recovery of a zaleplon dose. Coadministration of single, oral doses of zaleplon with erythromycin (10 mg and 800 mg respectively), a strong, selective CYP3A4 inhibitor, produced a 34% increase in zaleplon's maximal plasma concentrations and a 20% increase in the area under the plasma concentration-time curve. The magnitude of interaction with multiple doses of erythromycin is unknown. Other strong selective CYP3A4 inhibitors such as ketoconazole can also be expected to increase the exposure of zaleplon. A routine dosage adjustment of zaleplon is not considered necessary.

Drugs That Inhibit Aldehyde Oxidase

The aldehyde oxidase enzyme system is less well studied than the cytochrome P450 enzyme system.

Diphenhydramine: Diphenhydramine is reported to be a weak inhibitor of aldehyde oxidase in rat liver, but its inhibitory effects in human liver are not known. There is no pharmacokinetic interaction between zaleplon and diphenhydramine following the administration of a single dose (10 mg and 50 mg, respectively) of each drug. However, because both of these compounds have CNS effects, an additive pharmacodynamic effect is possible.

Drugs That Inhibit Both Aldehyde Oxidase And CYP3A4

Cimetidine: Cimetidine inhibits both aldehyde oxidase (in vitro) and CYP3A4 (in vitro and in vivo), the primary and secondary enzymes, respectively, responsible for zaleplon metabolism. Concomitant administration of Somna (10 mg) and cimetidine (800 mg) produced an 85% increase in the mean Cmax and AUC of zaleplon. An initial dose of 5 mg should be given to patients who are concomitantly being treated with cimetidine (see DOSAGE AND ADMINISTRATION).

Drugs Highly Bound To Plasma Protein

Zaleplon is not highly bound to plasma proteins (fraction bound 60%±15%); therefore, the disposition of zaleplon is not expected to be sensitive to alterations in protein binding. In addition, administration of Somna to a patient taking another drug that is highly protein bound should not cause transient increase in free concentrations of the other drug.

Drugs With A Narrow Therapeutic Index

Digoxin: Somna (10 mg) did not affect the pharmacokinetic or pharmacodynamic profile of digoxin (0.375 mg q24h for 8 days).

Warfarin: Multiple oral doses of Somna (20 mg q24h for 13 days) did not affect the pharmacokinetics of warfarin (R+)- or (S-)-enantiomers or the pharmacodynamics (prothrombin time) following a single 25-mg oral dose of warfarin.

Drugs That Alter Renal Excretion

Ibuprofen:

WARNINGS

Because sleep disturbances may be the presenting manifestation of a physical and/or psychiatric disorder, symptomatic treatment of insomnia should be initiated only after a careful evaluation of the patient. The failure of insomnia to remit after 7 to 10 days of treatment may indicate the presence of a primary psychiatric and/or medical illness that should be evaluated.

Worsening of insomnia or the emergence of new thinking or behavior abnormalities may be the consequence of an unrecognized psychiatric or physical disorder. Such findings have emerged during the course of treatment with sedative/hypnotic drugs, including Somna. Because some of the important adverse effects of Somna appear to be dose-related, it is important to use the lowest possible effective dose, especially in the elderly (see DOSAGE AND ADMINISTRATION).

A variety of abnormal thinking and behavior changes have been reported to occur in association with the use of sedative/hypnotics. Some of these changes may be characterized by decreased inhibition (e.g., aggressiveness and extroversion that seem out of character), similar to effects produced by alcohol and other CNS depressants. Other reported behavioral changes have included bizarre behavior, agitation, hallucinations, and depersonalization.

Abnormal Thinking And Behavioral Changes

Complex behaviors such as “sleep-driving” (i.e., driving while not fully awake after ingestion of a sedative-hypnotic, with amnesia for the event) have been reported. These events can occur in sedative-hypnotic-naive as well as in sedative-hypnotic-experienced persons. Although behaviors such as sleep-driving may occur with Somna alone at therapeutic doses, the use of alcohol and other CNS depressants with Somna appears to increase the risk of such behaviors, as does the use of Somna at doses exceeding the maximum recommended dose. Due to the risk to the patient and the community, discontinuation of Somna should be strongly considered for patients who report a “sleep-driving” episode. Other complex behaviors (e.g., preparing and eating food, making phone calls, or having sex) have been reported in patients who are not fully awake after taking a sedative-hypnotic. As with sleep-driving, patients usually do not remember these events. Amnesia and other neuropsychiatric symptoms may occur unpredictably. In primarily depressed patients, worsening of depression, including suicidal thoughts and actions (including completed suicides), has been reported in association with the use of sedative/hypnotics.

It can rarely be determined with certainty whether a particular instance of the abnormal behaviors listed above is drug induced, spontaneous in origin, or a result of an underlying psychiatric or physical disorder. Nonetheless, the emergence of any new behavioral sign or symptom of concern requires careful and immediate evaluation.

Following rapid dose decrease or abrupt discontinuation of the use of sedative/hypnotics, there have been reports of signs and symptoms similar to those associated with withdrawal from other CNS-depressant drugs (see Drug Abuse And Dependence).

Somna, like other hypnotics, has CNS-depressant effects. Because of the rapid onset of action, Somna should only be ingested immediately prior to going to bed or after the patient has gone to bed and has experienced difficulty falling asleep. Patients receiving Somna should be cautioned against engaging in hazardous occupations requiring complete mental alertness or motor coordination (e.g., operating machinery or driving a motor vehicle) after ingesting the drug, including potential impairment of the performance of such activities that may occur the day following ingestion of Somna. Somna, as well as other hypnotics, may produce additive CNS-depressant effects when coadministered with other psychotropic medications, anticonvulsants, antihistamines, narcotic analgesics, anesthetics, ethanol, and other drugs that themselves produce CNS depression. Somna should not be taken with alcohol. Dosage adjustment may be necessary when Somna is administered with other CNS-depressant agents because of the potentially additive effects.

Severe Anaphylactic And Anaphylactoid Reactions

Rare cases of angioedema involving the tongue, glottis or larynx have been reported in patients after taking the first or subsequent doses of sedative-hypnotics, including Somna. Some patients have had additional symptoms such as dyspnea, throat closing, or nausea and vomiting that suggest anaphylaxis. Some patients have required medical therapy in the emergency department. If angioedema involves the tongue, glottis or larynx, airway obstruction may occur and be fatal. Patients who develop angioedema after treatment with Somna should not be rechallenged with the drug.

PRECAUTIONS

General

Timing Of Drug Administration

Somna should be taken immediately before bedtime or after the patient has gone to bed and has experienced difficulty falling asleep. As with all sedative/hypnotics, taking Somna while still up and about may result in short-term memory impairment, hallucinations, impaired coordination, dizziness, and lightheadedness.

Use In The Elderly And/Or Debilitated Patients

Impaired motor and/or cognitive performance after repeated exposure or unusual sensitivity to sedative/hypnotic drugs is a concern in the treatment of elderly and/or debilitated patients. A dose of 5 mg is recommended for elderly patients to decrease the possibility of side effects (see DOSAGE AND ADMINISTRATION). Elderly and/or debilitated patients should be monitored closely.

Use In Patients With Concomitant Illness

Clinical experience with Somna in patients with concomitant systemic illness is limited. Somna should be used with caution in patients with diseases or conditions that could affect metabolism or hemodynamic responses.

Although preliminary studies did not reveal respiratory depressant effects at hypnotic doses of Somna in normal subjects, caution should be observed if Somna (zaleplon) is prescribed to patients with compromised respiratory function, because sedative/hypnotics have the capacity to depress respiratory drive. Controlled trials of acute administration of Somna 10 mg in patients with mild to moderate chronic obstructive pulmonary disease or moderate obstructive sleep apnea showed no evidence of alterations in blood gases or apnea/hypopnea index, respectively. However, patients with compromised respiration due to preexisting illness should be monitored carefully.

The dose of Somna should be reduced to 5 mg in patients with mild to moderate hepatic impairment (see DOSAGE AND ADMINISTRATION). It is not recommended for use in patients with severe hepatic impairment.

No dose adjustment is necessary in patients with mild to moderate renal impairment. Somna has not been adequately studied in patients with severe renal impairment.

Use In Patients With Depression

As with other sedative/hypnotic