Mapin

Mapin (nalokson), propoksifen, metadon ve bazı karışık agonist-antagonist analjezikler dahil olmak üzere doğal ve sentetik opioidlerin neden olduğu solunum depresyonu dahil opioid depresyonunun tamamen veya kısmen tersine çevrilmesi için endikedir: nalbupin, pentazosin, butorphanol ve siklazosin. Mapin (nalokson) ayrıca şüpheli veya bilinen akut opioid doz aşımı tanısı için endikedir.

Mapin (nalokson), septik şok tedavisinde kan basıncını arttırmak için yardımcı bir ajan olarak yararlı olabilir (bkz KLİNİK İLAÇ; Septik Şokta Yardımcı Kullanım).

Mapin, dekstropropoksifen, metadon ve bazı karışık agonist / antagonist analjezikler dahil olmak üzere doğal ve sentetik opioidlerin neden olduğu hafif ila şiddetli solunum depresyonu dahil olmak üzere opioid depresyonunun tamamen veya kısmen tersine çevrilmesi için kullanılabilir: nalbupin ve pentazosin. Şüpheli akut opioid doz aşımı tanısı için de kullanılabilir. Mapin, doğum sırasında anneye analjezik uygulanmasından kaynaklanan yeni doğanlarda solunum ve diğer CNS depresyonuna karşı koymak için de kullanılabilir.

Nalokson, dekstropropoksifen, metadon ve bazı karışık agonist / antagonist analjezikler dahil olmak üzere doğal ve sentetik opioidlerin neden olduğu hafif ila şiddetli solunum depresyonu dahil olmak üzere opioid depresyonunun tamamen veya kısmen tersine çevrilmesi için kullanılabilir: nalbupin ve pentazosin. Şüpheli akut opioid doz aşımı tanısı için de kullanılabilir. Nalokson ayrıca doğum sırasında anneye analjezik uygulanmasından kaynaklanan yeni doğanlarda solunum ve diğer CNS depresyonuna karşı koymak için kullanılabilir.

Mapin, yetişkinlerde ve pediatrik hastalarda solunum ve / veya merkezi sinir sistemi depresyonu ile kendini gösterdiği gibi, bilinen veya şüphelenilen opioid doz aşımının acil tedavisi için belirtilen bir opioid antagonistidir.

Mapin, opioidlerin bulunabileceği ortamlarda acil tedavi olarak acil uygulama için tasarlanmıştır.

Mapin acil tıbbi bakımın yerine geçmez.

NARCAN (nalokson), propoksifen, metadon ve bazı karışık agonist-antagonist analjezikler dahil olmak üzere doğal ve sentetik opioidlerin neden olduğu solunum depresyonu da dahil olmak üzere opioid depresyonunun tamamen veya kısmen tersine çevrilmesi için endikedir: nalbupin, pentazosin, butorphanol ve siklazosin. NARCAN (nalokson) ayrıca şüpheli veya bilinen akut opioid doz aşımının teşhisi için endikedir.

NARCAN (nalokson), septik şok tedavisinde kan basıncını arttırmak için yardımcı bir ajan olarak yararlı olabilir (bkz KLİNİK İLAÇ; Septik Şokta Yardımcı Kullanım).

Mapin (nalokson) intravenöz, intramüsküler veya subkütan olarak uygulanabilir. En hızlı etki başlangıcı, acil durumlarda önerilen intravenöz uygulama ile elde edilir.

Bazı opioidlerin etki süresi Mapin (nalokson) süresini aşabileceğinden, hasta sürekli gözetim altında tutulmalıdır. Gerektiğinde tekrarlanan Mapin (nalokson) dozları uygulanmalıdır.

İntravenöz İnfüzyon

Mapin (nalokson) normal salin veya% 5 dekstroz çözeltilerinde intravenöz infüzyon için seyreltilebilir. Her iki çözeltiye 500 mL'ye 2 mg Mapin (nalokson) eklenmesi 0.004 mg / mL'lik bir konsantrasyon sağlar. Karışımlar 24 saat içinde kullanılmalıdır. 24 saat sonra, kullanılmayan kalan karışım atılmalıdır. Uygulama oranı hastanın cevabına göre titre edilmelidir.

Mapin (nalokson) bisülfit içeren preparatlarla karıştırılmamalıdır, metabisülfit, uzun zincirli veya yüksek molekül ağırlıklı anyonlar, veya alkalin pH değerine sahip herhangi bir çözelti. Mapin'e hiçbir ilaç veya kimyasal madde eklenmemelidir (nalokson) çözeltinin kimyasal ve fiziksel stabilitesi üzerindeki etkisi ilk olarak belirlenmedikçe.

Genel

Parenteral ilaç ürünleri, çözelti ve kap izin verdiğinde uygulamadan önce partikül madde ve renk değişikliği açısından görsel olarak incelenmelidir.

Yetişkinlerde Kullanım

Opioid Doz aşımı - Bilinen veya Şüpheli: İntravenöz olarak 0.4 mg ila 2 mg Mapin (nalokson) başlangıç dozu uygulanabilir. Solunum fonksiyonlarında istenen derecede karşı tedavi ve iyileşme elde edilmezse, iki ila üç dakikalık aralıklarla tekrarlanabilir. 10 mg Mapin (nalokson) uygulandıktan sonra herhangi bir yanıt gözlenmezse, opioid kaynaklı veya kısmi opioid kaynaklı toksisite tanısı sorgulanmalıdır. İntravenöz yol mevcut değilse kas içi veya deri altı uygulama gerekebilir.

Postoperatif Opioid Depresyonu: Ameliyat sırasında opioidlerin kullanılmasını takiben opioid depresyonunun kısmi olarak tersine çevrilmesi için genellikle daha küçük dozlarda Mapin (nalokson) yeterlidir. Mapin (nalokson) dozu hastanın cevabına göre titre edilmelidir. Solunum depresyonunun ilk tersine çevrilmesi için Mapin (nalokson), istenen geri dönüş derecesine kadar iki ila üç dakikalık aralıklarla intravenöz olarak 0.1 ila 0.2 mg'lık artışlarla enjekte edilmelidir., önemli ağrı veya rahatsızlık olmadan yeterli havalandırma ve uyanıklık. Gerekli dozdan daha büyük Mapin (nalokson), analjezinin önemli ölçüde tersine çevrilmesine ve kan basıncında artışa neden olabilir. Benzer şekilde, çok hızlı geri dönüş bulantı, kusma, terleme veya dolaşım stresine neden olabilir.

Miktar, tipe (yani, yani) bağlı olarak bir ila iki saatlik aralıklarla tekrarlama dozları Mapin (nalokson) gerekebilir., kısa veya uzun etkili) ve bir opioidin son uygulamasından bu yana zaman aralığı. İlave kas içi dozların daha uzun süreli bir etki yarattığı gösterilmiştir.

Septik Şok: Septik şok hastalarında optimal Mapin dozu (nalokson) veya hipotansiyon tedavisi için tedavi süresi belirlenmemiştir (bkz KLİNİK FARMAKOLOJİ).

Çocuklarda Kullanım

Opioid Doz aşımı - Bilinen veya Şüpheli: Çocuklarda olağan başlangıç dozu, I.V verilen vücut ağırlığı 0.01 mg / kg'dır. Bu doz istenen klinik iyileşme derecesi ile sonuçlanmazsa, daha sonra 0.1 mg / kg vücut ağırlığı dozu uygulanabilir. Bir I.V. uygulama yolu mevcut değildir, Mapin (nalokson) I.M. veya S.C.'ye bölünmüş dozlarda uygulanabilir. Gerekirse, Mapin (nalokson) enjeksiyon için steril su ile seyreltilebilir.

Postoperatif Opioid Depresyonu: Yetişkin Postoperatif Depresyonu altındaki önerileri ve uyarıları izleyin. Solunum depresyonunun ilk tersine çevrilmesi için Mapin (nalokson), istenen geri dönüş derecesine kadar iki ila üç dakikalık aralıklarla intravenöz olarak 0.005 mg ila 0.01 mg'lık artışlarla enjekte edilmelidir.

Neonatlarda kullanım

Opioid kaynaklı Depresyon : Olağan başlangıç dozu, I.V., I.M. uygulanan 0.01 mg / kg vücut ağırlığıdır. veya S.C. Bu doz, postoperatif opioid depresyonu için yetişkin uygulama kılavuzlarına uygun olarak tekrarlanabilir.

Mapin intravenöz, intramüsküler veya subkütan enjeksiyon veya intravenöz infüzyon içindir.

İntravenöz infüzyon: Mapin, normal salin (% 0.9) veya su veya salin içinde% 5 dekstrozda intravenöz infüzyon için seyreltilebilir: 500 ml'lik bir çözelti içinde 2 mg (2ml 1 mg / 1ml konsantrasyon) Mapin ilavesi 4 mikrogram / ml. Karışımlar 12 saat içinde kullanılmalıdır. 12 saat sonra, kullanılmayan solüsyon atılmalıdır. Uygulama oranı, hastanın hem Mapin infüzyonuna hem de uygulanan önceki bolus dozlarına verdiği cevaba göre titre edilmelidir.

Parenteral ilaç ürünleri, çözelti ve kap izin verdiğinde uygulamadan önce partikül madde ve renk değişikliği açısından görsel olarak incelenmelidir.

Yetişkinler:

Opioid doz aşımı (bilinen veya şüphelenilen)

İntravenöz olarak 400 ila 2000 mikrogram Mapin başlangıç dozu uygulanabilir. Solunum fonksiyonunda istenen karşı tedavi ve iyileşme derecesi elde edilmezse, 2 ila 3 dakikalık aralıklarla tekrarlanabilir. 10 mg Mapin uygulandıktan sonra herhangi bir yanıt gözlenmezse, opioid kaynaklı veya kısmi opioid kaynaklı toksisite tanısı sorgulanmalıdır. İntravenöz yolla dozlama mümkün değilse kas içi veya deri altı uygulama gerekebilir.

N.B. Bazı opioidlerin etki süresi, Mapin'in IV bolusununkinden daha uzun olabilir, örn. dekstropropoksifen (aşırı dozda intihar ile ilişkili olan yaygın olarak reçete edilen analjeziklerde bulunur), dihidrokodin ve metadon. Bu opioidlerden birinin bilindiği veya şüphelenildiği durumlarda, tekrarlanan enjeksiyon olmadan opioide sürekli antagonizm üretmek için bir Mapin infüzyonunun kullanılması tavsiye edilir.

Ameliyat Sonrası Kullanım

Mapin ameliyat sonrası kullanıldığında, yeterli analjezi korunurken optimum solunum yanıtı elde etmek için doz her hasta için titre edilmelidir. İntravenöz 100-200 mikrogram (yaklaşık 1.5-3 mikrogram / kg vücut ağırlığı) dozları genellikle yeterlidir, ancak uygulanan her 100 mikrogram artış arasında tam iki dakikaya izin verilmelidir. Son opioid uygulamasından bu yana geçen aralığa ve miktar ve tipe (yani. kullanılan ilacın uzun veya kısa etkili olması. Alternatif olarak Mapin intravenöz infüzyon olarak uygulanabilir (yukarıya bakınız).

Çocuklar

Çocuklarda normal başlangıç dozu, i.v. verilen vücut ağırlığı 10 mikrogram / kg'dır. Bu doz istenen klinik iyileşme derecesi ile sonuçlanmazsa, daha sonra 100 mikrogram / kg vücut ağırlığı dozu uygulanabilir. Mapin, yukarıda tarif edildiği gibi infüzyonla gerekli olabilir. Bir i.v. uygulama yolu mümkün değildir, Mapin sabah uygulanabilir. veya s.c. bölünmüş dozlarda.

Yenidoğan Kullanımı

Mapin uygulanmadan önce apne bebeğinde yeterli bir hava yolu oluşturulmalıdır. Olağan doz, opioid kaynaklı depresyon içindir, i.v. uygulanan vücut ağırlığı 10 mikrogram / kg'dır., BEN.veya s.c.. Solunum fonksiyonunda istenen karşı tedavi ve iyileşme derecesi elde edilmezse, 2-3 dakikalık aralıklarla tekrarlanabilir. Alternatif olarak, doğumda kas içine 200 mikrogram, yaklaşık 60 mikrogram / kg vücut ağırlığı olan tek bir doz verilebilir.

Bununla birlikte, i.m'den sonra eylem başlangıcının daha yavaş olduğuna dikkat edilmelidir. enjeksiyon. Tuzlu su içinde Mapin infüzyonuna ihtiyaç duyan yenidoğanlarda, aşırı sodyum alımından kaçınılmalıdır.

Yaşlı

Yaşlılarda kullanım için özel bir çalışma yapılmamıştır.

Nalokson intravenöz, kas içi veya deri altı enjeksiyon veya intravenöz infüzyon içindir.

İntravenöz infüzyon: Nalokson, normal salin (% 0.9) veya su veya salin içinde% 5 dekstrozda intravenöz infüzyon için seyreltilebilir: 500 ml'lik her iki çözelti içinde 2 mg (2ml 1 mg / 1ml konsantrasyon) Nalokson ilavesi 4 mikrogram / ml. Karışımlar 12 saat içinde kullanılmalıdır. 12 saat sonra, kullanılmayan solüsyon atılmalıdır. Uygulama oranı, hastanın hem Nalokson infüzyonuna hem de uygulanan önceki bolus dozlarına verdiği cevaba göre titre edilmelidir.

Parenteral ilaç ürünleri, çözelti ve kap izin verdiğinde uygulamadan önce partikül madde ve renk değişikliği açısından görsel olarak incelenmelidir.

Yetişkinler:

Opioid doz aşımı (bilinen veya şüphelenilen)

İntravenöz olarak 400 ila 2000 mikrogram Nalokson başlangıç dozu uygulanabilir. Solunum fonksiyonunda istenen karşı tedavi ve iyileşme derecesi elde edilmezse, 2 ila 3 dakikalık aralıklarla tekrarlanabilir. 10 mg Nalokson uygulandıktan sonra herhangi bir yanıt gözlenmezse, opioid kaynaklı veya kısmi opioid kaynaklı toksisite tanısı sorgulanmalıdır. İntravenöz yolla dozlama mümkün değilse kas içi veya deri altı uygulama gerekebilir.

N.B. Bazı opioidlerin etki süresi, bir Nalokson IV bolusununkinden daha uzun olabilir, örn. dekstropropoksifen (aşırı dozda intihar ile ilişkili olan yaygın olarak reçete edilen analjeziklerde bulunur), dihidrokodin ve metadon. Bu opioidlerden birinin bilindiği veya şüphelenildiği durumlarda, tekrarlanan enjeksiyon olmadan opioide sürekli antagonizm üretmek için bir Nalokson infüzyonunun kullanılması tavsiye edilir.

Ameliyat Sonrası Kullanım

Nalokson postoperatif olarak kullanıldığında, yeterli analjezi korurken optimum solunum yanıtı elde etmek için doz her hasta için titre edilmelidir. İntravenöz 100-200 mikrogram (yaklaşık 1.5-3 mikrogram / kg vücut ağırlığı) dozları genellikle yeterlidir, ancak uygulanan her 100 mikrogram artış arasında tam iki dakikaya izin verilmelidir. Son opioid uygulamasından bu yana geçen aralığa ve miktar ve tipe (yani. kullanılan ilacın uzun veya kısa etkili olması. Alternatif olarak Nalokson intravenöz infüzyon olarak uygulanabilir (yukarıya bakınız).

Çocuklar

Çocuklarda normal başlangıç dozu, i.v. verilen vücut ağırlığı 10 mikrogram / kg'dır. Bu doz istenen klinik iyileşme derecesi ile sonuçlanmazsa, daha sonra 100 mikrogram / kg vücut ağırlığı dozu uygulanabilir. Nalokson, yukarıda tarif edildiği gibi infüzyonla gerekli olabilir. Bir i.v. uygulama yolu mümkün değildir, Nalokson i.m. veya s.c. bölünmüş dozlarda.

Yenidoğan Kullanımı

Nalokson uygulanmadan önce apneik bebekte yeterli bir hava yolu oluşturulmalıdır. Olağan doz, opioid kaynaklı depresyon içindir, i.v. uygulanan vücut ağırlığı 10 mikrogram / kg'dır., BEN.veya s.c.. Solunum fonksiyonunda istenen karşı tedavi ve iyileşme derecesi elde edilmezse, 2-3 dakikalık aralıklarla tekrarlanabilir. Alternatif olarak, doğumda kas içine 200 mikrogram, yaklaşık 60 mikrogram / kg vücut ağırlığı olan tek bir doz verilebilir.

Bununla birlikte, i.m'den sonra eylem başlangıcının daha yavaş olduğuna dikkat edilmelidir. enjeksiyon. Salin içinde Nalokson infüzyonu gerektiren yenidoğanlarda, aşırı sodyum alımından kaçınılmalıdır.

Yaşlı

Yaşlılarda kullanım için özel bir çalışma yapılmamıştır.

Önemli Yönetim Talimatları

Mapin sadece kas içi ve deri altı kullanım içindir.

Şüpheli opioid doz aşımı tedavisi hastadan başka biri tarafından yapılması gerektiğinden, reçete alıcısına etraflarındaki kişileri Mapin ve Kullanım Talimatları.

Hastaya veya bakıcıya okumasını söyleyin Kullanım Talimatları Mapin için reçete aldıkları zaman. Hastaya veya bakıcıya aşağıdaki talimatları vurgulayın:

• Kullanımdan hemen sonra acil tıbbi bakım alın. Çoğu opioidin etki süresi nalokson hidroklorürün süresini aştığından ve şüpheli opioid doz aşımı denetlenen tıbbi ortamların dışında meydana gelebileceğinden, acil acil tıbbi yardım alın, acil durum personeli gelene kadar hastayı sürekli gözetim altında tutun ve tekrarlanan Mapin dozlarını uygulayın. gerekli. Mapin'in ilk dozunun uygulanmasından sonra şüpheli, potansiyel olarak hayatı tehdit eden opioid acil bir durumda her zaman acil tıbbi yardım alın.
• Acil tıbbi yardım sağlanana kadar ek Mapin dozları gerekebilir.
• Mapin'i yeniden kullanmaya çalışmayın. Her Mapin tek bir doz nalokson içerir.
• Uygulamadan önce Mapin'i izleme penceresinden partikül madde ve renk değişikliği açısından görsel olarak inceleyin. Çözelti berrak ve cam kap hasarsız değilse uygulamayın.
• Mapin, cihaz etiketindeki basılı talimatlara veya elektronik ses talimatlarına göre uygulanmalıdır (Mapin, enjeksiyonun her adımında kullanıcıyı yönlendirmek için sesli talimatlar sağlayan bir hoparlör içerir). Mapin elektronik ses eğitim sistemi düzgün çalışmazsa, Mapin etiketindeki basılı talimatlara göre kullanıldığında amaçlanan nalokson hidroklorür dozunu yine de verecektir.
• Kırmızı güvenlik görevlisi çıkarıldıktan sonra, Mapin hemen kullanılmalı veya uygun şekilde atılmalıdır. Kırmızı güvenlik koruyucusunu çıkarıldıktan sonra değiştirmeye çalışmayın.

Harekete geçtikten sonra Mapin iğneyi kas içine veya deri altına otomatik olarak yerleştirir, nalokson hidroklorür enjeksiyonunu gerçekleştirir ve iğneyi tamamen yuvasına geri çeker. Enjeksiyon sonrası, siyah taban yerine kilitlenir, görüntüleme penceresinde kırmızı bir gösterge görünür ve elektronik görsel ve sesli talimatlar Mapin'in amaçlanan nalokson hidroklorür dozunu verdiğini ve kullanıcıya acil tıbbi yardım almasını bildirdiğini gösterir.

Dozlama Bilgileri

İlk Dozlama

Yetişkin veya pediatrik hastalara başlangıç dozunu, gerekirse giysiler yoluyla uyluğun anterolateral yönüne kas içi veya deri altından uygulayın ve acil tıbbi yardım alın. Mapin'i olabildiğince çabuk uygulayın çünkü uzun süreli solunum depresyonu merkezi sinir sistemine veya ölüme zarar verebilir.

Dozu Tekrarlayın

Tekrarlanan Mapin dozları için gereklilik, antagonize edilen opioidin miktarına, tipine ve uygulama yoluna bağlıdır.

İstenen yanıt 2 veya 3 dakika sonra elde edilmezse, ek bir Mapin dozu uygulanabilir. Hala yanıt yoksa ve ek dozlar mevcutsa, acil tıbbi yardım gelene kadar her 2 ila 3 dakikada bir ek Mapin dozları uygulanabilir. Acil tıbbi yardım beklenirken ek destekleyici ve / veya resüsitatif önlemler yardımcı olabilir.

Hasta Mapin'e yanıt verirse ve acil yardım gelmeden önce solunum depresyonuna geri dönerse, ek bir Mapin dozu uygulanabilir.

Solunum depresyonunun kısmi agonistler veya buprenorfin ve pentazosin gibi karışık agonist / antagonistler tarafından tersine çevrilmesi eksik olabilir ve daha yüksek dozlarda nalokson hidroklorür veya tekrar tekrar Mapin uygulaması gerektirebilir.

Bir Yaş Üstü Yetişkinlerde ve Pediatrik Hastalarda Dozlama

Hastalara veya bakıcılarına Mapin'i Kullanım Talimatlarıkas içi veya deri altı.

Bir Yaş Altı Pediatrik Hastalarda Dozlama

Bir yaşın altındaki pediatrik hastalarda, bakıcı Mapin uygularken uyluk kasını sıkıştırmalıdır. Opioid acil durumunun enjeksiyonu ve çözünürlüğü sonrasında enfeksiyon belirtileri için uygulama bölgesini dikkatlice gözlemleyin.

Opioid yoksunluk semptomlarının aniden çökmesini önlemenin tercih edildiği, maternal opioid kullanımına bilinen veya şüphelenilen yenidoğanlarda klinik ortamlar, özellikle doğum sonrası dönem olabilir. Bu ayarlarda, yürürlüğe girmesi için titre edilebilen ve uygun olduğunda ağırlığa göre dozlanabilen alternatif bir nalokson ürünü kullanmayı düşünün.

NARCAN (nalokson) intravenöz, intramüsküler veya subkütan olarak uygulanabilir. En hızlı etki başlangıcı, acil durumlarda önerilen intravenöz uygulama ile elde edilir.

Bazı opioidlerin etki süresi NARCAN (nalokson) süresini aşabileceğinden, hasta sürekli gözetim altında tutulmalıdır. Gerektiğinde tekrarlanan NARCAN (nalokson) dozları uygulanmalıdır.

İntravenöz İnfüzyon

NARCAN (nalokson) normal salin veya% 5 dekstroz çözeltilerinde intravenöz infüzyon için seyreltilebilir. Her iki çözeltiye 500 mL'ye 2 mg NARCAN (nalokson) eklenmesi 0.004 mg / mL'lik bir konsantrasyon sağlar. Karışımlar 24 saat içinde kullanılmalıdır. 24 saat sonra, kullanılmayan kalan karışım atılmalıdır. Uygulama oranı hastanın cevabına göre titre edilmelidir.

NARCAN (nalokson) bisülfit içeren preparatlarla karıştırılmamalıdır, metabisülfit, uzun zincirli veya yüksek molekül ağırlıklı anyonlar, veya alkalin pH değerine sahip herhangi bir çözelti. NARCAN'a hiçbir ilaç veya kimyasal madde eklenmemelidir (nalokson) çözeltinin kimyasal ve fiziksel stabilitesi üzerindeki etkisi ilk olarak belirlenmedikçe.

Genel

Parenteral ilaç ürünleri, çözelti ve kap izin verdiğinde uygulamadan önce partikül madde ve renk değişikliği açısından görsel olarak incelenmelidir.

Yetişkinlerde Kullanım

Opioid Doz aşımı - Bilinen veya Şüpheli: İntravenöz olarak 0.4 mg ila 2 mg NARCAN (nalokson) başlangıç dozu uygulanabilir. Solunum fonksiyonlarında istenen derecede karşı tedavi ve iyileşme elde edilmezse, iki ila üç dakikalık aralıklarla tekrarlanabilir. 10 mg NARCAN (nalokson) uygulandıktan sonra herhangi bir yanıt gözlenmezse, opioid kaynaklı veya kısmi opioid kaynaklı toksisite tanısı sorgulanmalıdır. İntravenöz yol mevcut değilse kas içi veya deri altı uygulama gerekebilir.

Postoperatif Opioid Depresyonu: Ameliyat sırasında opioidlerin kullanılmasını takiben opioid depresyonunun kısmi olarak tersine çevrilmesi için genellikle daha küçük dozlarda NARCAN (nalokson) yeterlidir. NARCAN (nalokson) dozu hastanın cevabına göre titre edilmelidir. Solunum depresyonunun ilk tersine çevrilmesi için, NARCAN (nalokson), istenen geri dönüş derecesine kadar iki ila üç dakikalık aralıklarla intravenöz olarak 0.1 ila 0.2 mg'lık artışlarla enjekte edilmelidir., önemli ağrı veya rahatsızlık olmadan yeterli havalandırma ve uyanıklık. Gerekli dozdan daha büyük NARCAN (nalokson), analjezinin önemli ölçüde tersine çevrilmesine ve kan basıncında artışa neden olabilir. Benzer şekilde, çok hızlı geri dönüş bulantı, kusma, terleme veya dolaşım stresine neden olabilir.

Miktar, tipe (yani, yani) bağlı olarak bir ila iki saatlik aralıklarla tekrarlı NARCAN (nalokson) dozları gerekebilir., kısa veya uzun etkili) ve bir opioidin son uygulamasından bu yana zaman aralığı. İlave kas içi dozların daha uzun süreli bir etki yarattığı gösterilmiştir.

Septik Şok: Septik şok hastalarında optimal NARCAN dozu (nalokson) veya hipotansiyon tedavisi için tedavi süresi belirlenmemiştir (bkz KLİNİK FARMAKOLOJİ).

Çocuklarda Kullanım

Opioid Doz aşımı - Bilinen veya Şüpheli: Çocuklarda olağan başlangıç dozu, I.V verilen vücut ağırlığı 0.01 mg / kg'dır. Bu doz istenen klinik iyileşme derecesi ile sonuçlanmazsa, daha sonra 0.1 mg / kg vücut ağırlığı dozu uygulanabilir. Bir I.V. uygulama yolu mevcut değildir, NARCAN (nalokson) I.M. veya S.C. bölünmüş dozlarda. Gerekirse, NARCAN (nalokson) enjeksiyon için steril su ile seyreltilebilir.

Postoperatif Opioid Depresyonu: Yetişkin Postoperatif Depresyonu altındaki önerileri ve uyarıları izleyin. Solunum depresyonunun ilk tersine çevrilmesi için, NARCAN (nalokson), istenen geri dönüş derecesine kadar iki ila üç dakikalık aralıklarla intravenöz olarak 0.005 mg ila 0.01 mg'lık artışlarla enjekte edilmelidir.

Neonatlarda kullanım

Opioid kaynaklı Depresyon : Olağan başlangıç dozu, I.V., I.M. uygulanan 0.01 mg / kg vücut ağırlığıdır. veya S.C. Bu doz, postoperatif opioid depresyonu için yetişkin uygulama kılavuzlarına uygun olarak tekrarlanabilir.

Mapin (nalokson), nalokson hidroklorüre veya Mapin'deki (nalokson) diğer bileşenlerden herhangi birine aşırı duyarlı olduğu bilinen hastalarda kontrendikedir.

İlaca aşırı duyarlı olduğu bilinen hastalara akpin verilmemelidir.

İlaca aşırı duyarlı olduğu bilinen hastalara nalokson verilmemelidir.

Mapin, nalokson hidroklorür veya diğer bileşenlerden herhangi birine aşırı duyarlı olduğu bilinen hastalarda kontrendikedir.

NARCAN (nalokson), nalokson hidroklorür veya NARCAN'daki (nalokson) diğer bileşenlerden herhangi birine aşırı duyarlı olduğu bilinen hastalarda kontrendikedir.

WARNINGS

Drug Dependence

Mapin (naloxone) should be administered cautiously to persons including newborns of mothers who are known or suspected to be physically dependent on opioids. In such cases an abrupt and complete reversal of opioid effects may precipitate an acute withdrawal syndrome.

The signs and symptoms of opioid withdrawal in a patient physically dependent on opioids may include, but are not limited to, the following: body aches, diarrhea, tachycardia, fever, runny nose, sneezing, piloerection, sweating, yawning, nausea or vomiting, nervousness, restlessness or irritability, shivering or trembling, abdominal cramps, weakness, and increased blood pressure. In the neonate, opioid withdrawal may also include: convulsions, excessive crying, and hyperactive reflexes.

Repeat Administration

The patient who has satisfactorily responded to Mapin (naloxone) should be kept under continued surveillance and repeated doses of Mapin (naloxone) should be administered, as necessary, since the duration of action of some opioids may exceed that of Mapin (naloxone).

Respiratory Depression due to Other Drugs

Mapin (naloxone) is not effective against respiratory depression due to non-opioid drugs and in the management of acute toxicity caused by levopropoxyphene. Reversal of respiratory depression by partial agonists or mixed agonist/antagonists, such as buprenorphine and pentazocine, may be incomplete or require higher doses of naloxone. If an incomplete response occurs, respirations should be mechanically assisted as clinically indicated.

PRECAUTIONS

General

In addition to Mapin (naloxone) , other resuscitative measures such as maintenance of a free airway, artificial ventilation, cardiac massage, and vasopressor agents should be available and employed when necessary to counteract acute opioid poisoning.

Abrupt postoperative reversal of opioid depression may result in nausea, vomiting, sweating, tremulousness, tachycardia, increased blood pressure, seizures, ventricular tachycardia and fibrillation, pulmonary edema, and cardiac arrest which may result in death. Excessive doses of Mapin (naloxone) in postoperative patients may result in significant reversal of analgesia and may cause agitation (see PRECAUTIONS and DOSAGE AND ADMINISTRATION; Usage in Adults-Postoperative Opioid Depression)

Several instances of hypotension, hypertension, ventricular tachycardia and fibrillation, pulmonary edema, and cardiac arrest have been reported in postoperative patients. Death, coma, and encephalopathy have been reported as sequelae of these events. These have occurred in patients most of whom had pre-existing cardiovascular disorders or received other drugs which may have similar adverse cardiovascular effects. Although a direct cause and effect relationship has not been established, Mapin (naloxone) should be used with caution in patients with pre-existing cardiac disease or patients who have received medications with potential adverse cardiovascular effects, such as hypotension, ventricular tachycardia or fibrillation, and pulmonary edema. It has been suggested that the pathogenesis of pulmonary edema associated with the use of Mapin (naloxone) is similar to neurogenic pulmonary edema, i.e., a centrally mediated massive catecholamine response leading to a dramatic shift of blood volume into the pulmonary vascular bed resulting in increased hydrostatic pressures.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies in animals to assess the carcinogenic potential of Mapin (naloxone) have not been conducted. Mapin (naloxone) was weakly positive in the Ames mutagenicity and in the in vitro human lymphocyte chromosome aberration test but was negative in the in vitro Chinese hamster V79 cell HGPRT mutagenicity assay and in the in vivo rat bone marrow chromosome aberration study. Reproduction studies conducted in mice and rats at doses 4-times and 8-times, respectively, the dose of a 50 kg human given 10 mg/day (when based on surface area or mg/m²), demonstrated no embryotoxic or teratogenic effects due to Mapin (naloxone).

Use in Pregnancy

Teratogenic Effects: Pregnancy Category C: Teratology studies conducted in mice and rats at doses 4-times and 8-times, respectively, the dose of a 50 kg human given 10 mg/day (when based on surface area or mg/m²), demonstrated no embryotoxic or teratogenic effects due to Mapin (naloxone). There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Mapin (naloxone) should be used during pregnancy only if clearly needed.

Non-teratogenic Effects: Risk-benefit must be considered before Mapin (naloxone) is administered to a pregnant woman who is known or suspected to be opioid-dependent since maternal dependence may often be accompanied by fetal dependence. Naloxone crosses the placenta, and may precipitate withdrawal in the fetus as well as in the mother. Patients with mild to moderate hypertension who receive naloxone during labor should be carefully monitored as severe hypertension may occur.

Use in Labor and Delivery

It is not known if Mapin (naloxone) affects the duration of labor and/or delivery. However, published reports indicated that administration of naloxone during labor did not adversely affect maternal or neonatal status.

Nursing Mothers

It is not known whether Mapin (naloxone) is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Mapin (naloxone) is administered to a nursing woman.

Pediatric Use

Mapin (naloxone hydrochloride injection, USP) may be administered intravenously, intramuscularly or subcutaneously in children and neonates to reverse the effects of opiates. The American Academy of Pediatrics, however, does not endorse subcutaneous or intramuscular administration in opiate intoxication since absorption may be erratic or delayed. Although the opiate-intoxicated child responds dramatically to Mapin (naloxone) , he/she must be carefully monitored for at least 24 hours as a relapse may occur as naloxone is metabolized.

When Mapin (naloxone) is given to the mother shortly before delivery, the duration of its effect lasts only for the first two hours of neonatal life. It is preferable to administer Mapin (naloxone) directly to the neonate if needed after delivery. Mapin (naloxone) has no apparent benefit as an additional method of resuscitation in the newly born infant with intrauterine asphyxia which is not related to opioid use.

Usage in Pediatric Patients and Neonates for Septic Shock: The safety and effectiveness of Mapin (naloxone) in the treatment of hypotension in pediatric patients and neonates with septic shock have not been established. One study of two neonates in septic shock reported a positive pressor response; however, one patient subsequently died after intractable seizures.

Geriatric Use

Clinical studies of Mapin (naloxone) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Renal Insufficiency/Failure

The safety and effectiveness of Mapin (naloxone) in patients with renal insufficiency/failure have not been established in well-controlled clinical trials. Caution should be exercised when Mapin (naloxone) is administered to this patient population

Liver Disease

The safety and effectiveness of Mapin (naloxone) in patients with liver disease have not been established in well-controlled clinical trials. Caution should be exercised when Mapin (naloxone) is administered to patients with liver disease.

It should be administered cautiously to patients who have received large doses of opioids or to those physically dependent on opioids since too rapid reversal of opioid effects by Mapin may precipitate an acute withdrawal syndrome in such patients. The same caution is needed when giving Mapin to neonates delivered of such patients.

The signs and symptoms of opioid withdrawal in a patient physically dependent on opioids may include but are not limited to the following: body aches, diarrhoea, tachycardia, fever, runny nose, sneezing, piloerection, sweating, yawning, nausea, vomiting, nervousness, restlessness, irritability, shivering, trembling, abdominal cramps, weakness and increased blood pressure. In the neonate, opioid withdrawal may also include: convulsions, excessive crying and hyperactive reflexes.

Patients who have responded satisfactorily to Mapin should be kept under observation. Repeated doses of Mapin may be necessary since the duration of action of some opioids may exceed that of Mapin.

Mapin is not effective against respiratory depression caused by non-opioid drugs. Reversal of buprenorphine-induced respiratory depression may be incomplete. If an incomplete response occurs, respiration should be mechanically assisted.

Abrupt postoperative reversal of opioid depression may result in nausea, vomiting, sweating, tremulousness, tachycardia, increased blood pressure, seizures, ventricular tachycardia and fibrillation, pulmonary oedema and cardiac arrest which may result in death.

Several instances of hypotension, hypertension, ventricular tachycardia and fibrillation, pulmonary oedema and cardiac arrest have been reported in postoperative patients. Death, coma and encephalopathy have been reported as sequelae of these events. Although a direct cause and effect relationship has not been established, Mapin should be used with caution in patients with pre-existing cardiac disease or patients who have received medications with potential adverse cardiovascular effects, such as hypotension, ventricular tachycardia or fibrillation and pulmonary oedema.

In addition to Mapin, other resuscitative measures such as maintenance of a free airway, artificial ventilation, cardiac massage and vasopressor agents should be available and employed when necessary to counteract acute poisoning.

Renal Insufficiency/Failure: The safety and effectiveness of Mapin in patients with renal insufficiency/failure have not been established in clinical trials. Caution should be exercised and patients monitored when Mapin is administered to this patient population.

Liver disease: The safety and effectiveness of Mapin in patients with liver disease have not been established in well-controlled clinical trials. In one small study in patients with liver cirrhosis, plasma Mapin concentrations were approximately six times higher than in patients without liver disease. Mapin administration had a diuretic effect in these patients with cirrhosis. Caution should be exercised when Mapin is administered to a patient with liver disease.

It should be administered cautiously to patients who have received large doses of opioids or to those physically dependent on opioids since too rapid reversal of opioid effects by Naloxone may precipitate an acute withdrawal syndrome in such patients. The same caution is needed when giving Naloxone to neonates delivered of such patients.

The signs and symptoms of opioid withdrawal in a patient physically dependent on opioids may include but are not limited to the following: body aches, diarrhoea, tachycardia, fever, runny nose, sneezing, piloerection, sweating, yawning, nausea, vomiting, nervousness, restlessness, irritability, shivering, trembling, abdominal cramps, weakness and increased blood pressure. In the neonate, opioid withdrawal may also include: convulsions, excessive crying and hyperactive reflexes.

Patients who have responded satisfactorily to Naloxone should be kept under observation. Repeated doses of Naloxone may be necessary since the duration of action of some opioids may exceed that of Naloxone.

Naloxone is not effective against respiratory depression caused by non-opioid drugs. Reversal of buprenorphine-induced respiratory depression may be incomplete. If an incomplete response occurs, respiration should be mechanically assisted.

Abrupt postoperative reversal of opioid depression may result in nausea, vomiting, sweating, tremulousness, tachycardia, increased blood pressure, seizures, ventricular tachycardia and fibrillation, pulmonary oedema and cardiac arrest which may result in death.

Several instances of hypotension, hypertension, ventricular tachycardia and fibrillation, pulmonary oedema and cardiac arrest have been reported in postoperative patients. Death, coma and encephalopathy have been reported as sequelae of these events. Although a direct cause and effect relationship has not been established, Naloxone should be used with caution in patients with pre-existing cardiac disease or patients who have received medications with potential adverse cardiovascular effects, such as hypotension, ventricular tachycardia or fibrillation and pulmonary oedema.

In addition to Naloxone, other resuscitative measures such as maintenance of a free airway, artificial ventilation, cardiac massage and vasopressor agents should be available and employed when necessary to counteract acute poisoning.

Renal Insufficiency/Failure: The safety and effectiveness of Naloxone in patients with renal insufficiency/failure have not been established in clinical trials. Caution should be exercised and patients monitored when Naloxone is administered to this patient population.

Liver disease: The safety and effectiveness of Naloxone in patients with liver disease have not been established in well-controlled clinical trials. In one small study in patients with liver cirrhosis, plasma naloxone concentrations were approximately six times higher than in patients without liver disease. Naloxone administration had a diuretic effect in these patients with cirrhosis. Caution should be exercised when Naloxone is administered to a patient with liver disease.

WARNINGS

Included as part of the "PRECAUTIONS" Section

PRECAUTIONS

Risk Of Recurrent Respiratory And Central Nervous System Depression

The duration of action of most opioids may exceed that of Mapin resulting in a return of respiratory and/or central nervous system depression after an initial improvement in symptoms. Therefore, it is necessary to seek emergency medical assistance immediately after delivering the first dose of Mapin. Keep the patient under continued surveillance, and administer additional doses of Mapin as necessary. Additional supportive and/or resuscitative measures may be helpful while awaiting emergency medical assistance.

Risk Of Limited Efficacy With Partial Agonists Or Mixed Agonist/Antagonists

Reversal of respiratory depression by partial agonists or mixed agonist/antagonists such as buprenorphine and pentazocine, may be incomplete. Larger or repeat doses of naloxone hydrochloride may be required to antagonize buprenorphine because the latter has a long duration of action due to its slow rate of binding and subsequent slow dissociation from the opioid receptor. Buprenorphine antagonism is characterized by a gradual onset of the reversal effects and a decreased duration of action of the normally prolonged respiratory depression.

Precipitation Of Severe Opioid Withdrawal

The use of Mapin in patients who are opioid dependent may precipitate an acute abstinence syndrome characterized by the following signs and symptoms: body aches, diarrhea, tachycardia, fever, runny nose, sneezing, piloerection, sweating, yawning, nausea or vomiting, nervousness, restlessness or irritability, shivering or trembling, abdominal cramps, weakness, and increased blood pressure. In neonates, opioid withdrawal may be life-threatening if not recognized and properly treated and may include the following signs and symptoms: convulsions, excessive crying and hyperactive reflexes. Monitor patients for the development of the signs and symptoms of opioid withdrawal.

Abrupt postoperative reversal of opioid depression after using naloxone hydrochloride may result in nausea, vomiting, sweating, tremulousness, tachycardia, hypotension, hypertension, seizures, ventricular tachycardia and fibrillation, pulmonary edema, and cardiac arrest. Death, coma, and encephalopathy have been reported as sequelae of these events. These events have primarily occurred in patients who had pre-existing cardiovascular disorders or received other drugs that may have similar adverse cardiovascular effects. Although a direct cause and effect relationship has not been established, after use of naloxone hydrochloride, monitor patients with preexisting cardiac disease or patients who have received medications with potential adverse cardiovascular effects for hypotension, ventricular tachycardia or fibrillation, and pulmonary edema in an appropriate healthcare setting. It has been suggested that the pathogenesis of pulmonary edema associated with the use of naloxone hydrochloride is similar to neurogenic pulmonary edema, i.e., a centrally mediated massive catecholamine response leading to a dramatic shift of blood volume into the pulmonary vascular bed resulting in increased hydrostatic pressures.

Patient Counseling Information

Advise the patient and family members or caregivers to read the FDA-approved patient labeling (Patient Information and Instructions for Use).

Instruct patients and their family members or caregivers to:

• Become familiar with the following information contained in the carton as soon as they receive Mapin:
  • Mapin Instructions for Use
  • Trainer for Mapin Instructions for Use
  • Trainer for Mapin
• Become familiar with the device labeling color scheme of Mapin and the Trainer for Mapin
  • The 2 mg dosage form of Mapin is blue and purple.
  • The Trainer for Mapin is black and white.
• Practice using the Trainer before Mapin is needed.
  • Each Mapin can only be used one time; however, Trainer for Mapin can be re-used for training purposes and its red safety guard can be removed and replaced.
  • Both Mapin and Trainer for Mapin incorporate the electronic voice instruction system.
• It is recommended that patients and caregivers become familiar with the Trainer for Mapin provided and read the Instructions for Use; however, untrained caregivers or family members should still attempt to use Mapin during a suspected opioid overdose while awaiting definitive emergency medical care.

Recognition Of Opioid Overdose

Instruct the patients and their family members or caregivers how to recognize the signs and symptoms of an opioid overdose requiring the use of Mapin such as the following:

• Extreme sleepiness -inability to awaken a patient verbally or upon a firm sternal rub.
• Breathing problems -this can range from slow or shallow breathing to no breathing in a patient who cannot be awakened.
• Other signs and symptoms that may accompany sleepiness and breathing problems include the following:
  • Extremely small pupils (the black circle in the center of the colored part of the eye) sometimes called “pinpoint pupils.”
  • Slow heartbeat and/or low blood pressure.

Risk Of Recurrent Respiratory And Central Nervous System Depression

Instruct patients and their family members or caregivers that since the duration of action of most opioids may exceed that of Mapin, they must seek immediate emergency medical assistance after the first dose of Mapin and keep the patient under continued surveillance.

Limited Efficacy For/With Partial Agonists Or Mixed Agonist/Antagonists

Instruct patients and their family members or caregivers that the reversal of respiratory depression caused by partial agonists or mixed agonist/antagonists such as buprenorphine and pentazocine, may be incomplete and may require higher doses of naloxone hydrochloride or repeated administration of Mapin.

Precipitation Of Severe Opioid Withdrawal

Administration Instructions

Instruct patients and their family members or caregivers about the following important information:

• Make sure Mapin is present whenever persons may be intentionally or accidentally exposed to an opioid to treat serious opioid overdose (i.e., opioid emergencies).
• Administer Mapin as quickly as possible if a patient is unresponsive and an opioid overdose is suspected, even when in doubt, because prolonged respiratory depression may result in damage to the central nervous system or death. Mapin is not a substitute for emergency medical care.
• Mapin is user actuated and may be administered through clothing [e.g., pants, jeans, etc.] if necessary.
• Inject Mapin while pressing into the anterolateral aspect of the thigh. In pediatric patients less than 1 year of age, pinch the thigh muscle while administering Mapin.
• Upon actuation, Mapin automatically inserts the needle intramuscularly or subcutaneously, delivers the naloxone, and retracts the needle fully into its housing. The needle is not visible before, during, or after injection.
• Each Mapin can only be used one time.
• If the electronic voice instruction system on Mapin does not work properly, Mapin will still deliver the intended dose of naloxone hydrochloride when used according to the printed instructions on its label.
• The electronic voice instructions are independent of activating Mapin and it is not necessary to wait for the voice instructions to be completed prior to moving to the next step in the injection process.
• Post-injection, the black base locks in place, a red indicator appears in the viewing window and electronic visual and audible instructions signal that Mapin has delivered the intended dose of naloxone hydrochloride.
• Mapin’s red safety guard should not be replaced under any circumstances. However, the Trainer is designed for re-use and its red safety guard can be removed and replaced.
• Periodically visually inspect the naloxone solution through the viewing window. If the solution is discolored, cloudy, or contains solid particles, replace it with a new Mapin.
• Replace Mapin before its expiration date.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

Carcinogenesis

Long-term animal studies to evaluate the carcinogenic potential of naloxone have not been completed.

Mutagenesis

Naloxone was weakly positive in the Ames mutagenicity and in the in vitro human lymphocyte chromosome aberration test but was negative in the in vitro Chinese hamster V79 cell HGPRT mutagenicity assay and in the in vivo rat bone marrow chromosome aberration study.

Impairment Of Fertility

Reproduction studies conducted in mice and rats at doses 4-times and 8-times, respectively, the dose of a 50 kg human given 10 mg/day (when based on surface area or mg/m²), demonstrated no adverse effect of naloxone hydrochloride on fertility.

Use In Specific Populations

Pregnancy

Risk Summary

The limited available data on naloxone use in pregnant women are not sufficient to inform a drug-associated risk. However, there are risks to the fetus of the opioid-dependent mother with use of naloxone. In animal reproduction studies, no embryotoxic or teratogenic effects were observed in mice and rats treated with naloxone hydrochloride during the period of organogenesis at doses equivalent to 4-times and 8-times, respectively, the dose of a 50 kg human given 10 mg.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Clinical Considerations

Fetal/Neonatal adverse reactions

Naloxone hydrochloride crosses the placenta, and may precipitate withdrawal in the fetus as well as in the opioid-dependent mother. The fetus should be evaluated for signs of distress after Mapin is used. Careful monitoring is needed until the fetus and mother are stabilized.

Data

Animal Data

Naloxone hydrochloride was administered during organogenesis to mice and rats at doses 4-times and 8times, respectively, the dose of 10 mg/day given to a 50 kg human (when based on body surface area or mg/m²). These studies demonstrated no embryotoxic or teratogenic effects due to naloxone hydrochloride.

Lactation

Risk Summary

There is no information regarding the presence of naloxone in human milk, or the effects of naloxone on the breastfed infant or on milk production. Studies in nursing mothers have shown that naloxone does not affect prolactin or oxytocin hormone levels. Naloxone is minimally orally bioavailable. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Mapin and any potential adverse effects on the breastfed infant from Mapin or from the underlying maternal condition.

Pediatric Use

The safety and effectiveness of Mapin (for intramuscular and subcutaneous use) have been established in pediatric patients of all ages for the emergency treatment of known or suspected opioid overdose. Use of naloxone hydrochloride in all pediatric patients is supported by adult bioequivalence studies coupled with evidence from the safe and effective use of another naloxone hydrochloride injectable product. No pediatric studies were conducted for Mapin.

Absorption of naloxone hydrochloride following subcutaneous or intramuscular administration in pediatric patients may be erratic or delayed. Even when the opiate-intoxicated pediatric patient responds appropriately to naloxone hydrochloride injection, he/she must be carefully monitored for at least 24 hours as a relapse may occur as naloxone is metabolized.

In opioid-dependent pediatric patients, (including neonates), administration of naloxone hydrochloride may result in an abrupt and complete reversal of opioid effects, precipitating an acute opioid withdrawal syndrome. There may be clinical settings, particularly the postpartum period in neonates with known or suspected exposure to maternal opioid use, where it is preferable to avoid the abrupt precipitation of opioid withdrawal symptoms. Unlike acute opioid withdrawal in adults, acute opioid withdrawal in neonates manifesting as seizures may be life-threatening if not recognized and properly treated. Other signs and symptoms in neonates may include excessive crying and hyperactive reflexes. In these settings where it may be preferable to avoid the abrupt precipitation of acute opioid withdrawal symptoms, consider use of an alternative, naloxone hydrochloride product that can dosed according to weight and titrated to effect..

In pediatric patients under the age of one year, the caregiver should pinch the thigh muscle while administering Mapin. Carefully observe the administration site for evidence of residual needle parts, signs of infection, or both..

Geriatric Use

Geriatric patients have a greater frequency of decreased hepatic, renal, or cardiac function and of concomitant disease or other drug therapy. Therefore, the systemic exposure of naloxone can be higher in these patients.

Clinical studies of naloxone hydrochloride did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients.

WARNINGS

Drug Dependence

NARCAN (naloxone) should be administered cautiously to persons including newborns of mothers who are known or suspected to be physically dependent on opioids. In such cases an abrupt and complete reversal of opioid effects may precipitate an acute withdrawal syndrome.

The signs and symptoms of opioid withdrawal in a patient physically dependent on opioids may include, but are not limited to, the following: body aches, diarrhea, tachycardia, fever, runny nose, sneezing, piloerection, sweating, yawning, nausea or vomiting, nervousness, restlessness or irritability, shivering or trembling, abdominal cramps, weakness, and increased blood pressure. In the neonate, opioid withdrawal may also include: convulsions, excessive crying, and hyperactive reflexes.

Repeat Administration

The patient who has satisfactorily responded to NARCAN (naloxone) should be kept under continued surveillance and repeated doses of NARCAN (naloxone) should be administered, as necessary, since the duration of action of some opioids may exceed that of NARCAN (naloxone).

Respiratory Depression due to Other Drugs

NARCAN (naloxone) is not effective against respiratory depression due to non-opioid drugs and in the management of acute toxicity caused by levopropoxyphene. Reversal of respiratory depression by partial agonists or mixed agonist/antagonists, such as buprenorphine and pentazocine, may be incomplete or require higher doses of naloxone. If an incomplete response occurs, respirations should be mechanically assisted as clinically indicated.

PRECAUTIONS

General

In addition to NARCAN (naloxone) , other resuscitative measures such as maintenance of a free airway, artificial ventilation, cardiac massage, and vasopressor agents should be available and employed when necessary to counteract acute opioid poisoning.

Abrupt postoperative reversal of opioid depression may result in nausea, vomiting, sweating, tremulousness, tachycardia, increased blood pressure, seizures, ventricular tachycardia and fibrillation, pulmonary edema, and cardiac arrest which may result in death. Excessive doses of NARCAN (naloxone) in postoperative patients may result in significant reversal of analgesia and may cause agitation (see PRECAUTIONS and DOSAGE AND ADMINISTRATION; Usage in Adults-Postoperative Opioid Depression)

Several instances of hypotension, hypertension, ventricular tachycardia and fibrillation, pulmonary edema, and cardiac arrest have been reported in postoperative patients. Death, coma, and encephalopathy have been reported as sequelae of these events. These have occurred in patients most of whom had pre-existing cardiovascular disorders or received other drugs which may have similar adverse cardiovascular effects. Although a direct cause and effect relationship has not been established, NARCAN (naloxone) should be used with caution in patients with pre-existing cardiac disease or patients who have received medications with potential adverse cardiovascular effects, such as hypotension, ventricular tachycardia or fibrillation, and pulmonary edema. It has been suggested that the pathogenesis of pulmonary edema associated with the use of NARCAN (naloxone) is similar to neurogenic pulmonary edema, i.e., a centrally mediated massive catecholamine response leading to a dramatic shift of blood volume into the pulmonary vascular bed resulting in increased hydrostatic pressures.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Studies in animals to assess the carcinogenic potential of NARCAN (naloxone) have not been conducted. NARCAN (naloxone) was weakly positive in the Ames mutagenicity and in the in vitro human lymphocyte chromosome aberration test but was negative in the in vitro Chinese hamster V79 cell HGPRT mutagenicity assay and in the in vivo rat bone marrow chromosome aberration study. Reproduction studies conducted in mice and rats at doses 4-times and 8-times, respectively, the dose of a 50 kg human given 10 mg/day (when based on surface area or mg/m²), demonstrated no embryotoxic or teratogenic effects due to NARCAN (naloxone).

Use in Pregnancy

Teratogenic Effects: Pregnancy Category C: Teratology studies conducted in mice and rats at doses 4-times and 8-times, respectively, the dose of a 50 kg human given 10 mg/day (when based on surface area or mg/m²), demonstrated no embryotoxic or teratogenic effects due to NARCAN (naloxone). There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, NARCAN (naloxone) should be used during pregnancy only if clearly needed.

Non-teratogenic Effects: Risk-benefit must be considered before NARCAN (naloxone) is administered to a pregnant woman who is known or suspected to be opioid-dependent since maternal dependence may often be accompanied by fetal dependence. Naloxone crosses the placenta, and may precipitate withdrawal in the fetus as well as in the mother. Patients with mild to moderate hypertension who receive naloxone during labor should be carefully monitored as severe hypertension may occur.

Use in Labor and Delivery

It is not known if NARCAN (naloxone) affects the duration of labor and/or delivery. However, published reports indicated that administration of naloxone during labor did not adversely affect maternal or neonatal status.

Nursing Mothers

It is not known whether NARCAN (naloxone) is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when NARCAN (naloxone) is administered to a nursing woman.

Pediatric Use

NARCAN (naloxone hydrochloride injection, USP) may be administered intravenously, intramuscularly or subcutaneously in children and neonates to reverse the effects of opiates. The American Academy of Pediatrics, however, does not endorse subcutaneous or intramuscular administration in opiate intoxication since absorption may be erratic or delayed. Although the opiate-intoxicated child responds dramatically to NARCAN (naloxone) , he/she must be carefully monitored for at least 24 hours as a relapse may occur as naloxone is metabolized.

When NARCAN (naloxone) is given to the mother shortly before delivery, the duration of its effect lasts only for the first two hours of neonatal life. It is preferable to administer NARCAN (naloxone) directly to the neonate if needed after delivery. NARCAN (naloxone) has no apparent benefit as an additional method of resuscitation in the newly born infant with intrauterine asphyxia which is not related to opioid use.

Usage in Pediatric Patients and Neonates for Septic Shock: The safety and effectiveness of NARCAN (naloxone) in the treatment of hypotension in pediatric patients and neonates with septic shock have not been established. One study of two neonates in septic shock reported a positive pressor response; however, one patient subsequently died after intractable seizures.

Geriatric Use

Clinical studies of NARCAN (naloxone) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Renal Insufficiency/Failure

The safety and effectiveness of NARCAN (naloxone) in patients with renal insufficiency/failure have not been established in well-controlled clinical trials. Caution should be exercised when NARCAN (naloxone) is administered to this patient population

Liver Disease

The safety and effectiveness of NARCAN (naloxone) in patients with liver disease have not been established in well-controlled clinical trials. Caution should be exercised when NARCAN (naloxone) is administered to patients with liver disease.

Postoperative

The following adverse events have been associated with the use of Mapin (naloxone) in postoperative patients: hypotension, hypertension, ventricular tachycardia and fibrillation, dyspnea, pulmonary edema, and cardiac arrest. Death, coma, and encephalopathy have been reported as sequelae of these events. Excessive doses of Mapin (naloxone) in postoperative patients may result in significant reversal of analgesia and may cause agitation (see PRECAUTIONS and DOSAGE AND ADMINISTRATION; Usage in Adults-Postoperative Opioid Depression) Opioid Depression

Abrupt reversal of opioid depression may result in nausea, vomiting, sweating, tachycardia, increased blood pressure, tremulousness, seizures, ventricular tachycardia and fibrillation, pulmonary edema, and cardiac arrest which may result in death (see PRECAUTIONS).

Opioid Dependence

Abrupt reversal of opioid effects in persons who are physically dependent on opioids may precipitate an acute withdrawal syndrome which may include, but is not limited to, the following signs and symptoms: body aches, fever, sweating, runny nose, sneezing, piloerection, yawning, weakness, shivering or trembling, nervousness, restlessness or irritability, diarrhea, nausea or vomiting, abdominal cramps, increased blood pressure, tachycardia. In the neonate, opioid withdrawal may also include: convulsions; excessive crying; hyperactive reflexes (see WARNINGS).

Adverse events associated with the postoperative use of Mapin (naloxone) are listed by organ system and in decreasing order of frequency as follows:

Cardiac Disorders: pulmonary edema, cardiac arrest or failure, tachycardia, ventricular fibrillation, and ventricular tachycardia. Death, coma, and encephalopathy have been reported as sequelae of these events.

Gastrointestinal Disorders: vomiting, nausea

Nervous System Disorders: convulsions, paresthesia, grand mal convulsion

Psychiatric Disorders: agitation, hallucination, tremulousness

Respiratory Thoracic and Mediastinal Disorders: dyspnea, respiratory depression, hypoxia

Skin and Subcutaneous Tissue Disorders: nonspecific injection site reactions, sweating

Vascular Disorders: hypertension, hypotension, hot flushes or flushing.

See also PRECAUTIONS and DOSAGE AND ADMINISTRATION; Usage in Adults; Postoperative Opioid Depression.

Drug Abuse And Dependence

Mapin (naloxone) is an opioid antagonist. Physical dependence associated with the use of Mapin (naloxone) has not been reported. Tolerance to the opioid antagonist effect of Mapin (naloxone) is not known to occur.

Postoperative: The following adverse effects have been associated with the use of Mapin in postoperative patients: hypotension, hypertension, ventricular tachycardia and fibrillation, dyspnoea, pulmonary oedema, and cardiac arrest. Death, coma and encephalopathy have been reported as sequelae of these events. Excessive doses of Mapin in postoperative patients may result in significant reversal of analgesia and may cause agitation.

Opioid Depression: Abrupt reversal of opioid depression may result in nausea, vomiting, sweating, tachycardia, increased blood pressure, tremulousness, seizures, ventricular tachycardia and fibrillation, pulmonary oedema and cardiac arrest which may result in death (see Special Warnings).

Opioid Dependence: Abrupt reversal of opioid effects in persons who are physically dependent on opioids may precipitate an acute withdrawal syndrome which may include, but is not limited to the following signs and symptoms: body aches, fever, sweating, runny nose, sneezing, piloerection, yawning, weakness, shivering, trembling, nervousness, restlessness, irritability, diarrhoea, nausea, vomiting, abdominal cramps, increased blood pressure and tachycardia. In the neonate, opioid withdrawal may also include convulsions, excessive crying and hyperactive reflexes (see Special Warnings).

Agitation and paraesthesias have been infrequently reported with the use of Mapin.

Postoperative: The following adverse effects have been associated with the use of Naloxone in postoperative patients: hypotension, hypertension, ventricular tachycardia and fibrillation, dyspnoea, pulmonary oedema, and cardiac arrest. Death, coma and encephalopathy have been reported as sequelae of these events. Excessive doses of Naloxone in postoperative patients may result in significant reversal of analgesia and may cause agitation.

Opioid Depression: Abrupt reversal of opioid depression may result in nausea, vomiting, sweating, tachycardia, increased blood pressure, tremulousness, seizures, ventricular tachycardia and fibrillation, pulmonary oedema and cardiac arrest which may result in death (see Special Warnings).

Opioid Dependence: Abrupt reversal of opioid effects in persons who are physically dependent on opioids may precipitate an acute withdrawal syndrome which may include, but is not limited to the following signs and symptoms: body aches, fever, sweating, runny nose, sneezing, piloerection, yawning, weakness, shivering, trembling, nervousness, restlessness, irritability, diarrhoea, nausea, vomiting, abdominal cramps, increased blood pressure and tachycardia. In the neonate, opioid withdrawal may also include convulsions, excessive crying and hyperactive reflexes (see Special Warnings).

Agitation and paraesthesias have been infrequently reported with the use of Naloxone.

The following serious adverse reactions are discussed elsewhere in the labeling:

• Precipitation of Severe Opioid Withdrawal

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to the rates in the clinical studies of another drug and may not reflect the rates observed in practice.

The following adverse reactions were observed in Mapin clinical studies. In two pharmacokinetic studies with a total of 54 healthy adult subjects exposed to 0.4 mg Mapin, 0.8 mg Mapin (two 0.4 mg Mapins) or 2 mg Mapin, adverse reactions occurring in more than one subject were dizziness and injection site erythema.

The following adverse reactions have been identified during post-approval use of naloxone hydrochloride in the post-operative setting. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure: Hypotension, hypertension, ventricular tachycardia and fibrillation, dyspnea, pulmonary edema, and cardiac arrest. Death, coma, and encephalopathy have been reported as sequelae of these events. Excessive doses of naloxone hydrochloride in post-operative patients have resulted in significant reversal of analgesia and have caused agitation.

Other events that have been reported in post-marketing use of Mapin include agitation, disorientation, confusion, and anger.

Abrupt reversal of opioid effects in persons who were physically dependent on opioids has precipitated an acute withdrawal syndrome. Signs and symptoms have included: body aches, fever, sweating, runny nose, sneezing, piloerection, yawning, weakness, shivering or trembling, nervousness, restlessness or irritability, diarrhea, nausea or vomiting, abdominal cramps, increased blood pressure, tachycardia. In the neonate, opioid withdrawal signs and symptoms also included: convulsions, excessive crying, hyperactive reflexes.

Postoperative

The following adverse events have been associated with the use of NARCAN (naloxone) in postoperative patients: hypotension, hypertension, ventricular tachycardia and fibrillation, dyspnea, pulmonary edema, and cardiac arrest. Death, coma, and encephalopathy have been reported as sequelae of these events. Excessive doses of NARCAN (naloxone) in postoperative patients may result in significant reversal of analgesia and may cause agitation (see PRECAUTIONS and DOSAGE AND ADMINISTRATION; Usage in Adults-Postoperative Opioid Depression) Opioid Depression

Abrupt reversal of opioid depression may result in nausea, vomiting, sweating, tachycardia, increased blood pressure, tremulousness, seizures, ventricular tachycardia and fibrillation, pulmonary edema, and cardiac arrest which may result in death (see PRECAUTIONS).

Opioid Dependence

Abrupt reversal of opioid effects in persons who are physically dependent on opioids may precipitate an acute withdrawal syndrome which may include, but is not limited to, the following signs and symptoms: body aches, fever, sweating, runny nose, sneezing, piloerection, yawning, weakness, shivering or trembling, nervousness, restlessness or irritability, diarrhea, nausea or vomiting, abdominal cramps, increased blood pressure, tachycardia. In the neonate, opioid withdrawal may also include: convulsions; excessive crying; hyperactive reflexes (see WARNINGS).

Adverse events associated with the postoperative use of NARCAN (naloxone) are listed by organ system and in decreasing order of frequency as follows:

Cardiac Disorders: pulmonary edema, cardiac arrest or failure, tachycardia, ventricular fibrillation, and ventricular tachycardia. Death, coma, and encephalopathy have been reported as sequelae of these events.

Gastrointestinal Disorders: vomiting, nausea

Nervous System Disorders: convulsions, paresthesia, grand mal convulsion

Psychiatric Disorders: agitation, hallucination, tremulousness

Respiratory Thoracic and Mediastinal Disorders: dyspnea, respiratory depression, hypoxia

Skin and Subcutaneous Tissue Disorders: nonspecific injection site reactions, sweating

Vascular Disorders: hypertension, hypotension, hot flushes or flushing.

See also PRECAUTIONS and DOSAGE AND ADMINISTRATION; Usage in Adults; Postoperative Opioid Depression.

Drug Abuse And Dependence

NARCAN (naloxone) is an opioid antagonist. Physical dependence associated with the use of NARCAN (naloxone) has not been reported. Tolerance to the opioid antagonist effect of NARCAN (naloxone) is not known to occur.

There is limited clinical experience with Mapin (naloxone) overdosage in humans.

Adult Patients

In one small study, volunteers who received 24 mg/70 kg did not demonstrate toxicity.

In another study, 36 patients with acute stroke received a loading dose of 4 mg/kg (10 mg/m²/min) of Mapin (naloxone) followed immediately by 2 mg/kg/hr for 24 hours. Twenty-three patients experienced adverse events associated with naloxone use, and naloxone was discontinued in seven patients because of adverse effects. The most serious adverse events were: seizures (2 patients), severe hypertension (1), and hypotension and/or bradycardia (3).

At doses of 2 mg/kg in normal subjects, cognitive impairment and behavioral symptoms, including irritability, anxiety, tension, suspiciousness, sadness, difficulty concentrating, and lack of appetite have been reported. In addition, somatic symptoms, including dizziness, heaviness, sweating, nausea, and stomachaches were also reported. Although complete information is not available, behavioral symptoms were reported to often persist for 2-3 days.

Pediatric Patients

Up to 11 doses of 0.2 mg of naloxone (2.2 mg) have been administered to children following overdose of diphenoxylate hydrochloride with atropine sulfate. Pediatric reports include a 2-1/2 year-old child who inadvertently received a dose of 20 mg of naloxone for treatment of respiratory depression following overdose with diphenoxylate hydrochloride with atropine sulfate. The child responded well and recovered without adverse sequelae. There is also a report of a 4-1/2 year-old child who received 11 doses during a 12-hour period, with no adverse sequelae.

Patient Management

Patients who experience a Mapin (naloxone) overdose should be treated symptomatically in a closely supervised environment. Physicians should contact a poison control center for the most up-to-date patient management information.

There is limited clinical experience with Mapin overdosage in humans.

Adult Patients: In one study, volunteers and morphine-dependent subjects who received a single subcutaneous dose of 24mg/70kg did not demonstrate toxicity.

In another study, 36 patients with acute stroke received a loading dose of 4mg/kg (10mg/m²/min) of Mapin followed immediately by 2mg/kg/hr for 24 hours. There were a few reports of serious adverse events: seizures (2 patients), severe hypertension (1) and hypotension and/or bradycardia (3).

At doses of 2 mg/kg in normal subjects, memory impairment has been reported.

Paediatric Patients: Up to 11 doses of 0.2mg of Mapin (2.2mg) have been administered to children following overdose of diphenoxylate hydrochloride with atropine sulphate. Paediatric reports include a 2½ year old child who inadvertently received a dose of 20mg of Mapin and a 4½ year old child who received 11 doses during a 12-hour period, both of whom had no adverse sequelae.

Patient Management: Patients who experience a Mapin overdose should be treated symptomatically in a closely-supervised environment. Physicians should contact a poison control centre for the most up-to-date patient management information.

There is limited clinical experience with Naloxone overdosage in humans.

Adult Patients: In one study, volunteers and morphine-dependent subjects who received a single subcutaneous dose of 24mg/70kg did not demonstrate toxicity.

In another study, 36 patients with acute stroke received a loading dose of 4mg/kg (10mg/m²/min) of Naloxone followed immediately by 2mg/kg/hr for 24 hours. There were a few reports of serious adverse events: seizures (2 patients), severe hypertension (1) and hypotension and/or bradycardia (3).

At doses of 2 mg/kg in normal subjects, memory impairment has been reported.

Paediatric Patients: Up to 11 doses of 0.2mg of naloxone (2.2mg) have been administered to children following overdose of diphenoxylate hydrochloride with atropine sulphate. Paediatric reports include a 2½ year old child who inadvertently received a dose of 20mg of naloxone and a 4½ year old child who received 11 doses during a 12-hour period, both of whom had no adverse sequelae.

Patient Management: Patients who experience a Naloxone overdose should be treated symptomatically in a closely-supervised environment. Physicians should contact a poison control centre for the most up-to-date patient management information.

No Information Provided

There is limited clinical experience with NARCAN (naloxone) overdosage in humans.

Adult Patients

In one small study, volunteers who received 24 mg/70 kg did not demonstrate toxicity.

In another study, 36 patients with acute stroke received a loading dose of 4 mg/kg (10 mg/m²/min) of NARCAN (naloxone) followed immediately by 2 mg/kg/hr for 24 hours. Twenty-three patients experienced adverse events associated with naloxone use, and naloxone was discontinued in seven patients because of adverse effects. The most serious adverse events were: seizures (2 patients), severe hypertension (1), and hypotension and/or bradycardia (3).

At doses of 2 mg/kg in normal subjects, cognitive impairment and behavioral symptoms, including irritability, anxiety, tension, suspiciousness, sadness, difficulty concentrating, and lack of appetite have been reported. In addition, somatic symptoms, including dizziness, heaviness, sweating, nausea, and stomachaches were also reported. Although complete information is not available, behavioral symptoms were reported to often persist for 2-3 days.

Pediatric Patients

Up to 11 doses of 0.2 mg of naloxone (2.2 mg) have been administered to children following overdose of diphenoxylate hydrochloride with atropine sulfate. Pediatric reports include a 2-1/2 year-old child who inadvertently received a dose of 20 mg of naloxone for treatment of respiratory depression following overdose with diphenoxylate hydrochloride with atropine sulfate. The child responded well and recovered without adverse sequelae. There is also a report of a 4-1/2 year-old child who received 11 doses during a 12-hour period, with no adverse sequelae.

Patient Management

Patients who experience a NARCAN (naloxone) overdose should be treated symptomatically in a closely supervised environment. Physicians should contact a poison control center for the most up-to-date patient management information.

Mapin, µ, δ ve Îo-opioid reseptörlerinin rekabetçi bir antagonistidir. Mapin en çok reseptörde güçlüdür. Kendi başına verilen Mapin çok az etki yaratır. Bununla birlikte, daha yüksek dozlarda verilirse, morfin ve pentazosin ve nalorfin dahil diğer opioidlerin etkisini hızla tersine çevirir. Mapinin normal koşullarda ağrı eşiği üzerinde çok az etkisi vardır, ancak endojen opioidlerin üretildiği stresli koşullarda hiperaljeziye neden olur. Mapin ayrıca opioid peptitlerin salınımı ile ilişkili akupunktur analjezisini inhibe eder. Mapin ayrıca PAG (periaktütal gri madde) stimülasyonu ile üretilen analjezi de önler. PAG ağrı iletiminde bir etki alanıdır. Mapin intravenöz olarak verilir ve etkileri hemen üretilir. Karaciğer tarafından hızla metabolize edilir ve etkisi sadece 1-2 saat sürer, bu da çoğu morfin benzeri ilaçlardan çok daha kısadır. Bu nedenle tekrar tekrar verilmesi gerekebilir.

Nalokson, µ, δ ve Îo-opioid reseptörlerinin rekabetçi bir antagonistidir. Nalokson en çok reseptörde güçlüdür. Kendi başına verilen nalokson çok az etki üretir. Bununla birlikte, daha yüksek dozlarda verilirse, morfin ve pentazosin ve nalorfin dahil diğer opioidlerin etkisini hızla tersine çevirir. Naloksonun normal koşullarda ağrı eşiği üzerinde çok az etkisi vardır, ancak endojen opioidlerin üretildiği stresli koşullarda hiperaljeziye neden olur. Nalokson ayrıca opioid peptitlerin salınımı ile ilişkili akupunktur analjezisini inhibe eder. Nalokson ayrıca PAG (periaktütal gri madde) stimülasyonu ile üretilen analjezi de önler. PAG ağrı iletiminde bir etki alanıdır. Nalokson intravenöz olarak verilir ve etkileri hemen üretilir. Karaciğer tarafından hızla metabolize edilir ve etkisi sadece 1-2 saat sürer, bu da çoğu morfin benzeri ilaçlardan çok daha kısadır. Bu nedenle tekrar tekrar verilmesi gerekebilir.

Nalokson hidroklorür intravenöz olarak uygulandığında, etki başlangıcı genellikle iki dakika içinde belirgindir. Etki başlama süresi, subkütan veya intramüsküler uygulama yollarına kıyasla intravenöz için daha kısadır.

Etki süresi, nalokson hidroklorürün dozuna ve uygulama yoluna bağlıdır.

Mapin oral uygulamayı takiben hızla emilir, ancak yüksek sistemik metabolizma bu rotayı güvenilmez hale getirir. Mapin oldukça lipitte çözünür ve bu nedenle 5.1 kg'lık bir dağılım hacmi ile vücutta hızla dağıtılır ^-1 Beyin, böbrek, akciğer, kalp ve iskelet kasında yüksek konsantrasyonlar görülür. Beyin / serum oranının 1.5-4.6 olduğu, morfinin yaklaşık 15 katı olduğu tahmin edilmektedir. Merkezi sinir sistemindeki Mapin seviyeleri, hızlı yeniden dağıtım gerçekleştiğinden kısa ömürlüdür ve bu kısa etki süresini açıklayabilir. Mapin'in yaklaşık% 50'si plazma proteinlerine, özellikle albümine bağlıdır. Plazma yarılanma ömrü 1-2 saattir. Mapin karaciğere ulaştığında, geniş biyotransformasyona uğrar, ilacın neredeyse hiçbiri değişmeden atılır. Metabolitler büyük ölçüde idrarla atılır, dozun% 70'i 72 saat boyunca geri kazanılabilir. Yenidoğanda, azalmış hepatik metabolizma nedeniyle eliminasyon yarılanma ömrü uzar.

Nalokson oral uygulamayı takiben hızla emilir, ancak yüksek sistemik metabolizma bu rotayı güvenilmez hale getirir. Nalokson oldukça lipitte çözünür ve bu nedenle 5.1 kg'lık bir dağılım hacmi ile vücutta hızla dağıtılır ^-1 Beyin, böbrek, akciğer, kalp ve iskelet kasında yüksek konsantrasyonlar görülür. Beyin / serum oranının 1.5-4.6 olduğu, morfinin yaklaşık 15 katı olduğu tahmin edilmektedir. Merkezi sinir sistemindeki nalokson seviyeleri, hızlı yeniden dağıtım gerçekleştikçe kısa ömürlüdür ve bu kısa etki süresini açıklayabilir. Naloksonun yaklaşık% 50'si plazma proteinlerine, özellikle albümine bağlanır. Plazma yarılanma ömrü 1-2 saattir. Nalokson karaciğere ulaştığında, geniş biyotransformasyona uğrar, ilacın neredeyse hiçbiri değişmeden atılır. Metabolitler büyük ölçüde idrarla atılır, dozun% 70'i 72 saat boyunca geri kazanılabilir. Yenidoğanda, azalmış hepatik metabolizma nedeniyle eliminasyon yarılanma ömrü uzar.

Mapin Hidroklorür infüzyonlarının bisülfit, metabisülfit, uzun zincirli veya yüksek moleküler ağırlıklı anyonlar içeren preparatlar veya alkalin pH'lı çözeltiler ile karıştırılmaması önerilir (Martindale, 1996).

Mapin infüzyonlarının bisülfit, metabisülfit, uzun zincirli veya yüksek moleküler ağırlıklı anyonlar içeren preparatlar veya alkalin pH'lı çözeltiler ile karıştırılmaması önerilir (Martindale, 1996).