LEUKERAN

Genel Bilgiler

  • Ticaret Unvanı:
  • LEUKERAN 2 MG 25 TABLET
  • Reçete türü:
  • Normal
  • İçin kullanmak:
  • İnsanlar
  • İlaç türü:
  • allopatik ilaç

Belgeler

Yerelleştirme

  • Bulunduğu ülkeler::
  • LEUKERAN 2 MG 25 TABLET
    Türkiye
  • Dil:
  • Türkçe

Terapötik bilgiler

  • Terapötik alanı:
  • biyolojik

Diğer bilgiler

Durum

  • Kaynak:
  • TİTCK - TÜRKİYE İLAÇ VE TIBBİ CİHAZ KURUMU - Türkiye
  • Yetkilendirme durumu:
  • Aktif
  • Yetkilendirme numarası:
  • 6091403210039
  • Yetkilendirme tarihi:
  • 29-01-2013
  • Son Güncelleme:
  • 24-05-2018

Hasta Bilgi broşürü: Ürün Özellikleri Özeti - kompozisyon, endikasyonlar, yan etkiler, dozaj, etkileşimleri, advers reaksiyonlar, gebelik, laktasyon

KISA ÜRÜN BİLGİSİ

1.

BEŞERİ TIBBİ ÜRÜNÜN ADI

LEUKERAN 2 mg Film Tablet

2.

KALİTATİF VE KANTİTATİF BİLEŞİM

Etkin madde:

Her tablette:

Klorambusil (INN)

2 mg

Yardımcı maddeler:

Susuz Laktoz

67.65 mg

Yardımcı maddeler için bölüm 6.1’e bakınız.

3.

FARMASÖTİK FORM

Film tablet

Bir yüzünde “GX EG3”, diğer yüzünde “L” baskısı olan, kahve renkli, yuvarlak, bikonveks

tabletlerdir

4.

KLİNİK ÖZELLİKLER

4.1.

Terapötik endikasyonlar

LEUKERAN aşağıdaki hastalıkların tedavisinde endikedir:

Hodgkin lenfoma

Non-Hodgkin lenfoma

Kronik lenfositik lösemi

Waldenström makroglobulinemisi

4.2.

Pozoloji ve uygulama şekli

KULLANILAN

TEDAVİ

ŞEMALARININ

AYRINTILARI

İÇİN

KONUDAKİ

ÇALIŞMALARDAN YARARLANILMALIDIR.

LEUKERAN, AKTİF BİR SİTOTOKSİK AJANDIR VE SADECE UYGULAMA SIRASINDA

VE SONRASINDA KLİNİK, BİYOKİMYASAL VE HEMATOLOJİK ETKİLERİN DÜZENLİ

OLARAK İZLENEBİLECEĞİ TESİSLERE SAHİP ONKOLOJİ SERVİSLERİNDEKİ UZMAN

HEKİMLERİN KONTROLÜ ALTINDA UYGULANMALIDIR.

Pozoloji/Uygulama Sıklığı ve Süresi

Yetişkinlerde:

Hodgkin lenfoma:

İlerlemiş hastalığın palyatif tedavisinde tek ajan olarak kullanılmaktadır tipik dozu 4 - 8 hafta süre

ile 0.2 mg/kg/gün’dür.

LEUKERAN genellikle kombinasyon tedavisi ve birkaç rejim içinde kullanılmaktadır.

LEUKERAN nitrojen mustarda alternatif olarak kullanılmaktadır, toksisitede azalma ile birlikte

benzer terapötik sonuçlar vermektedir.

Non-Hodgkin lenfoma:

Başlangıçta, 4 - 8 hafta için genel doz tek ajan olarak 0.1 - 0.2 mg/kg/gündür, idame tedavide ise

azaltılmış günlük doz veya aralıklı doz olarak verilir.

LEUKERAN ilerlemiş yaygın lenfositik lenfomalı ve radyoterapi sonrası nüks görülen hastaların

tedavisinde yararlıdır.

İleri

non-hodgkin

lenfositik

lenfomalı

hastalarda

LEUKERAN

yapılan

ajan

kombinasyon kemoterapisinde, tedaviye cevap oranlarında önemli bir farklılık yoktur.

Kronik lenfositik lösemi:

LEUKERAN tedavisine genellikle belirtiler başladıktan sonra veya periferal kan sayımı ile

gösterilmiş kemik iliği fonksiyon bozukluğu ortaya çıktığında (ama kemik iliği yetmezliğinde

değil) başlanmalıdır.

Başlangıçta LEUKERAN toplam lökosit sayısı mikrolitre başına 10.000’e düşene kadar 0.15

mg/kg/gün dozunda verilir.

İlk kürden sonra tedaviye 0.1 mg/kg/gün dozu ile 4 hafta boyunca devam edilebilir.

Genellikle yaklaşık 2 yıl süren tedaviden sonra hastaların bir kısmında, kan lökosit sayısı normal

düzeylere iner, büyüyen dalak ve lenf nodülleri hissedilemez durumda olur ve kemik iliğindeki

lenfositlerin oranı % 20’nin altına iner.

Kemik iliği yetmezliği olan hastalar önce prednizolon ile tedavi edilmeli ve LEUKERAN ile

tedaviye başlanmadan önce kemik iliğinin yeniden oluşmaya başlaması sağlanmalıdır.

Aralıklı yüksek doz tedavisi günlük LEUKERAN tedavisi ile karşılaştırılmıştır. Ancak her iki

tedavi grubu arasında terapötik yanıt veya yan etki sıklığında anlamlı bir fark gözlenmemiştir.

Waldenstromun makroglobulinemisi:

LEUKERAN bu endikasyonda tedavi seçeneklerinden biridir.

Lökopeni görülene kadar 6 - 12 mg başlangıç dozları tavsiye edilmektedir, bunu takiben de bir

müddet günde 2 - 8 mg verilmelidir.

Özel popülasyonlara ilişkin ek bilgiler:

Böbrek yetmezliği:

LEUKERAN’ın üriner atılımı son derece düşüktür. Bu yüzden klorambusilin eliminasyonunda

renal atılım önemli bir yolak olarak değerlendirilmez. Böbrek yetmezliği olan hastalarda doz

ayarlamasına gerek yoktur. Ancak, böbrek yetmezliği durumunda klorambusilin farmakokinetiği

üzerine uygun şekilde yapılmış çalışmalar yoktur.

Karaciğer yetmezliği:

Karaciğer

yetmezliği

olan

hastalar

toksisite

belirtileri

bulguları

açısından

yakından

izlenmelidir. Klorambusil başlıca karaciğerde metabolize edilir. Ağır karaciğer yetmezliği olan

hastalarda doz azaltılması düşünülmelidir. Ancak, karaciğer yetmezliği olan hastalara özgü bir

dozlama önermek için yeterli veri yoktur.

Pediyatrik popülasyon:

LEUKERAN çocuklarda Hodgkin lenfoma ve non-Hodgkin lenfoma tedavisinde kullanılabilir.

Doz rejimleri yetişkinlerdekine benzerdir.

Geriyatrik popülasyon:

Yaşlı hastalara spesifik çalışmalar yürütülmemiştir. Ancak, böbrek ve karaciğer fonksiyonlarının

izlenmesi tavsiye edilir ve yetmezlik durumunda dikkatli olunmalıdır.

Klinik deneyim yanıtta yaşa bağlı farklılıklar ortaya çıkarmamış olsa da, yaşlılarda genel olarak doz

dikkatli şekilde ayarlanmalı, çoğunlukla en düşük doz aralığından tedavi başlatılmalıdır.

Uygulama şekli:

LEUKERAN oral yoldan uygulanır. Yüksek gastrik pH’nın LEUKERAN biyoyararlanımını

belirgin şekilde azalttığı gösterilmiş olduğundan aç karna (yemeklerden önce veya yemeklerden 3

saat sonra) alınması önerilir.

4.3.

Kontrendikasyonlar

LEUKERAN, klorambusil veya içeriğindeki maddelere karşı aşırı duyarlılığı olan kişilerde

kontrendikedir.

4.4.

Özel kullanım uyarıları ve önlemleri

Canlı organizma aşısı ile immunizasyon, bağışıklığı baskılanmış hastalarda enfeksiyon oluşturma

potansiyeli taşır. Bu nedenle canlı organizma aşılarıyla immünizasyon tavsiye edilmemektedir.

Otolog kök hücre transplantasyonu alma ihtimali olan hastalara uzun süreli klorambusil tedavisi

verilmemelidir.

LEUKERAN Tablet’lerin güvenli kullanımı:

Bölüm 6.6’ya bakınız.

İzleme

LEUKERAN geri dönüşümsüz kemik iliği baskılanması meydana getirebileceğinden, tedavi olan

hastalarda kan sayımları dikkatle kontrol edilmelidir. Toplam dozaj 6.5 mg/kg vücut ağırlığı

civarında olduğunda geri dönüşümsüz kemik iliği hasarı ile ilişkilidir.

LEUKERAN terapötik dozlarında lenfositleri azaltır, nötrofil ve trombosit sayıları ile hemoglobin

düzeyleri

üzerindeki

etkisi

daha

azdır.

Nötrofillerdeki

düşüş

belirtisinde

LEUKERAN

kullanımını kesmek gerekmez, ancak bu düşüşün son dozdan sonra 10 gün ya da daha uzun süre

devam edebileceği unutulmamalıdır.

Yakın

zamanda

radyoterapi

uygulanmış

başka

sitotoksik

ajan

almış

olan

hastalara

LEUKERAN verilmemelidir. LEUKERAN sadece kemik iliği fonksiyonu baskılanmış ya da

lenfotik infiltrasyonu aynı olan hastalara dikkatle verilmelidir.

Kemik iliğinin lenfositik infiltrasyonunda veya kemik iliği hipoplazisinde günlük 0.1 mg/kg vücut

ağırlığı dozu aşılmamalıdır.

Nefrotik sendromlu çocuklar, aralıklı yüksek doz rejim uygulanan hastalar ve nöbet hikayesi

olanlar, nöbet riski artabileceğinden LEUKERAN uygulamasını takiben yakından izlenmelidir.

Mutajenite ve karsinojenite

LEUKERAN’ın insanlarda kromatid ya da kromozom hasarına neden olduğu gösterilmiştir.

Hastanın

uzun

süreli

tedavisi

planlandığında

benzer

etkilerin

olabileceği

ihtimali

akılda

tutulmalıdır.

Özellikle uzun süreli tedavilerin ardından akut ikincil hematolojik maligniteler (özellikle lösemi

ve miyelodisplastik sendrom) bildirilmiştir (

bkz

. İstenmeyen etkiler).

Over kanserli hastalar arasında alkilleyici ajan almış olanların ve olmayanların karşılaştırıldığı bir

çalışma, LEUKERAN da dahil alkilleyici ajan kullanımının akut lösemi insidansını anlamlı

derecede arttırdığını göstermiştir.

Meme kanseri için LEUKERAN ile uzun süreli adjuvan tedavi gören hastaların küçük bir kısmında

akut miyelojen lösemi bildirilmiştir.

LEUKERAN kullanımı söz konusu olduğunda potansiyel terapötik yarara karşılık lösemi gelişme

riski dengelenmelidir.

Klorambusil alan hastalarda Steven-Johnson Sendromu rapor edildiğinden eğer döküntü gelişirse

klorambusil ile devamlı tedavi değerlendirilmelidir.

Şeker intoleransı

LEUKERAN laktoz içermektedir. Nadir kalıtımsal galaktoz intoleransı, Lapp laktoz yetmezliği ya

da glikoz-galaktoz malabsorpsiyon problemi olan hastaların bu ilacı kullanmamaları gerekir. Her

bir LEUKERAN 2 mg tablet 67.65 mg laktoz içerir.

4.5.

Diğer tıbbi ürünlerle etkileşim ve diğer etkileşim şekilleri

Bağışıklığı baskılanmış kişilerde canlı organizma aşıları ile aşılama tavsiye edilmemektedir (

bkz

Bölüm 4.1: Özel kullanım uyarıları ve önlemleri)

Pürin

nükleozid

analogları

(fludarabin,

pentostatin

kladribin)

vivo

klorambusil’in

sitotoksisitesini artırmıştır. Klinik olarak pürin nükleozid analogları ve alkilleyici ajanların

kombinasyonu daha yüksek yanıt oranları meydana getirmiştir. Ancak, kombinasyonlar aynı

zamanda daha yüksek oranda hematolojik toksisitelerle sonuçlanmıştır. Hayvanlar üzerinde

yapılan

çalışmalar,

klorambusil

toksisitesinde

artış

olasılığından

dolayı

fenilbutazon

alan

hastalarda standart LEUKERAN dozları azaltılmalıdır.

4.6.

Gebelik ve laktasyon

Genel tavsiye

Gebelik kategorisi D.

Çocuk doğurma potansiyeli olan kadınlar/Doğum kontrolü (Kontrasepsiyon)

Diğer sitotoksik ajanlarda olduğu gibi eşlerden herhangi biri LEUKERAN alıyorsa uygun doğum

kontrol önlemlerinin alınması tavsiye edilmektedir. Eşler ilacın üreme hücrelerine olan etkisi

hakkında bilgilendirilmelidir.

Gebelik dönemi

Gebelik sırasında kullanılmamalıdır; özellikle ilk trimesterde hekim ilacın elzem olduğunu

belirtmediği sürece LEUKERAN kullanımından kaçınılmalıdır. Her bireysel durumda anneye

sağlaması beklenen fayda ile fetus için oluşturduğu potansiyel tehlike dengelenmelidir.

Laktasyon dönemi

LEUKERAN alan anneler emzirmemelidir.

Üreme yeteneği/Fertilite

Klorambusil over fonksiyonunu baskılayabilir ve LEUKERAN tedavisinden sonra amenore

bildirilmiştir.

LEUKERAN ile tedavi sonucu azospermi görülmüştür; ancak bunun için toplam dozun en az 400

mg olması gerektiği düşünülmektedir. Lenfomalı hastalarda toplam 400 - 2600 mg dozlarda

uygulanan

LEUKERAN

tedavisinden

sonra

spermatogenezde

değişik

derecelerde

düzelme

bildirilmiştir.

Teratojenite

Diğer toksik ilaçlarda olduğu gibi klorambusil potansiyel olarak teratojeniktir (Bkz. bölüm 5.3)

4.7.

Araç ve makine kullanımı üzerindeki etkiler

Bildirilmemiştir.

4.8.

İstenmeyen etkiler

ürün

için

istenmeyen

etkilerin

sıklığını

belirlemek

için

kullanılan

modern

klinik

dökümantasyon bulunmamaktadır. Beklenmeyen etkilerin insidansı alınan doza ve diğer terapötik

ajanlarla kombinasyon şeklinde verilmesine bağlı olarak değişiklik gösterebilir.

Aşağıda, advers etkiler sıklık sınıflandırmasına göre sıralanmıştır:

Çok yaygın (≥1/10); yaygın (≥1/100 ila <1/10); yaygın olmayan (≥1/1000 ila <1/100); seyrek

(≥1/10 000 ila <1/1000); çok seyrek (<1/10 000), bilinmiyor (eldeki verilerden hareketle tahmin

edilemiyor).

Vücut Sistemi

Yan etkiler

İyi huylu ve kötü huylu

neoplazmalar (Kist ve

polipler dahil olmak

üzere)

Yaygın

Özellikle uzun süreli tedaviden sonra akut

sekonder hematolojik maligniteler (başta lösemi

ve miyelodisplastik sendrom).

Kan ve lenf sistemi

hastalıkları

Çok yaygın

Lökopeni, nötropeni, trombositopeni, pansitopeni

veya kemik iliği baskılanması

Yaygın

Anemi.

Çok seyrek

Geri dönüşsüz kemik iliği yetmezliği.

Bağışıklık sistemi

hastalıkları

Seyrek

İlk dozdan veya sonraki dozlardan sonra ürtiker

ve anjiyonörotik ödem gibi aşırı duyarlılık.

Sinir sistemi hastalıkları

Yaygın

Nefrotik sendromu olan pediyatrik popülasyonda

konvülsiyonlar.

Seyrek

Klorambusilin terapötik günlük dozlarını veya

yüksek puls dozlam rejimini alan pediyatrik

popülasyon ve erişkinlerde kısmi ve/veya

jeneralize konvülsiyonlar

Çok seyrek

Konvülsiyonlar olmadan tremor, kas seğirmesi

ve miyoklonus dahil hareket bozuklukları.

Periferik nöropati.

Solunum, göğüs

bozuklukları ve

mediyastinal hastalıklar

Çok seyrek

İnterstisyel pulmoner fibroz

, interstisyel

pnömoni.

Gastrointestinal

hastalıklar

Yaygın

Bulantı ve kusma, diyare ve oral ülserasyon gibi

gastro intestinal hastalıklar.

Hepatobiliyer hastalıklar

Seyrek

Hepatotoksisite, sarılık.

Deri ve derialtı doku

hastalıkları

Yaygın

olmayan

Döküntü.

Seyrek

Stevens-Johnson sendromu, toksik epidermal

nekroliz

Böbrek ve idrar yolu

hastalıkları

Çok seyrek

Steril sistit.

Üreme sistemi ve meme

bozuklukları

Bilinmiyor

Amenore, azoospermi.

Genel bozukluklar ve

uygulama bölgesine ilişkin

hastalıklar

Seyrek

Pireksi.

1. Kemik iliği baskılanması sıklıkla meydana gelse de, klorambusil yeterince erken kesilirse genellikle geri

dönüşümlüdür.

2. Nöbet bozukluğu öyküsü olan hastalar özellikle duyarlı olabilir.

3. Uzun süreli klorambusil tedavisinde kronik lenfositik lösemili hastalarda ara sıra şiddetli interstisyel pulmoner

fibroz bildirilmiştir. Pulmoner fibroz, klorambusilin kesilmesiyle giderilebilir.

4.Döküntünün Stevens-Johnson sendromu ve toksik epidermal nekroliz gibi ciddi koşullara ilerlediği bildirilmiştir.

Şüpheli advers reaksiyonların raporlanması

Ruhsatlandırma

sonrası

şüpheli

ilaç

advers

reaksiyonlarının

raporlanması

büyük

önem

taşımaktadır. Raporlama yapılması, ilacın yarar/risk dengesinin sürekli olarak izlenmesine olanak

sağlar.

Sağlık

mesleği

mensuplarının

herhangi

şüpheli

advers

reaksiyonu

Türkiye

Farmakovijilans Merkezi (TÜFAM)’ne bildirilmesi gerekmektedir (www.titck.gov.tr; e-posta:

tufam@titck.gov.tr; tel: 0 800 314 00 08; faks: 0 312 218 35 99).

4.9.

Doz aşımı ve tedavisi

Semptomlar ve belirtiler:

LEUKERAN’ın

yanlışlıkla

uygulanan

yüksek

dozlarının

başlıca

bulgusu

geri

dönüşümlü

pansitopenidir. Ajite davranış ve ataksiden, grand mal nöbetlere kadar değişen nörolojik toksisite

meydana gelmiştir.

Tedavi:

Bilinen bir antidotu olmadığından kan tablosu yakından izlenmeli ve gerekirse uygun kan

transfüzyonlarıyla birlikte genel destekleyici önlemler alınmalıdır.

5.

FARMAKOLOJİK ÖZELLİKLER

5.1.

Farmakodinamik özellikler

Farmakoterapötik grubu: Antineoplastik ve immünomodülatör ajanlar, antineoplastik ajanlar,

alkilleyici ajanlar, nitrojen mustard analogları

ATC Kodu: L01AA02

Etki mekanizması:

Klorambusil, bifonksiyonel alkilleyici ajan olarak görev yapan bir aromatik azotlu hardal türevidir.

DNA replikasyonuna girişimin yanısıra klorambusil sitozolik p53’ün birikmesi ve bunu takiben

bir apoptoz tetikleyicinin (Bax) aktive olması suretiyle selüler apoptozu uyarır.

Farmakodinamik etkiler:

Klorambusilin sitotoksik etkisi klorambusilin majör metaboliti fenilasetik asit mustarddan (hardal)

kaynaklanır (Bkz. bölüm 5.2)

Direnç mekanizması:

Klorambusil bir aromatik azotlu hardal türevidir ve azotlu hardallara karşı dirençte ikincil

derecedeki etkiler bildirilmiştir: çeşitli çoklu ilaç direnci ilişkili proteinler yoluyla bu ajanların ve

metabolitlerinin

aktarılmasında

değişiklikler,

ajanlarla

oluşan

çapraz

bağlarının

kinetiklerinde

değişiklikler

apostoz

değişiklikleri

değişen

onarım

aktivitesi.

Klorambusil çoklu ilaç direnci ilişkili proteinin (MRP1 veya ABCC1) substratı değildir, ancak

glutatyon konjugatları MRP1 (ABCC1) ve MRP2 (ABCC2)’nin konjugatlarıdır.

5.2.

Farmakokinetik özellikler

Genel özellikler

Emilim:

Klorambusil gastrointestinal kanaldan pasif difüzyon ile iyi emilir ve uygulamadan 15-30 dakika

sonra tayin edilebilir. Oral klorambusilinin biyoyararlanımı tek doz 10-200 mg uygulamadan sonra

%70 ila %100’dür. 12 hastaya 0.2 mg/kg dozunda klorambusilin oral yolla verildiği bir çalışmada,

maksimum

plazma

konsantrasyonuna

(492

ng/ml)

uygulamadan

0.25-2

saat

sonra

ulaşılmıştır.

Hızlı,

tahmin

edilebilir

klorambusil

absorpsiyonunun,

klorambusilin

plazma

farmakokinetiklerinde bireyler arası değişkenlikle uyumlu olarak 15 ve 70 mg arasındaki dozların

ağızdan verilmesini takiben nispeten küçük olduğu gösterilmiştir

(EAA’da

2 kat hasta-içi

değişkenlik ve 2-4 kat hastalar arası değişkenlik).

Klorambusil absorpsiyonu yemekten sonra alındığında azalır. On hastanın katıldığı bir çalışmada

yiyecek alımı C

maks

’a erişmede medyan zamanını %100’den daha fazla artırmış, pik plazma

konsantrasyonunu %50’den fazla azaltmış ve ortalama EAA

(0- ∞ )

’yı yaklaşık %27 azaltmıştır.

Dağılım:

Klorambusilin dağılım hacmi yaklaşık 0.14-0.24 L/kg’dır. Klorambusil plazma proteinlerine,

başlıca albümine (%98) kovalan olarak bağlanır. Kırmızı kan hücrelerine de kovalan olarak

bağlanır.

Biyotransformasyon:

Klorambusil monodikloroetilasyon ve β-oksidasyon ile geniş çapta karaciğerde metabolize edilir;

hayvanlarda alkilasyonu aktive eden fenilasetik asit mustard (PAAM) ana metabolit olarak oluşur.

Klorambusil

PAAM in vivo monohidroksi

ve dihidroksi

türevlerine parçalanır. Ayrıca

klorambusil mono- ve diglutatyonil konjugatlarını oluşturmak üzere glutatyon ile reaksiyona girer.

Klorambusil oral yoldan yaklaşık 0.2 mg/kg vücut ağırlığı dozunda verilmesini takiben bazı

hastaların plazmasında henüz 15. dakikada tespit edilmiştir ve 306 ± 73 nanogram/ml’nin ortalama

doz ayarlanmış plazma konsantrasyonu (C

maks

) 1 ila 3 saatte görülmüştür.

Eliminasyon:

Ortalama plazma terminal eliminasyon yarı ömrü 1.3-1.5 saat aralığındadır ve PAAM için yaklaşık

1.8 saattir.

Değişmemiş klorambusilin veya PAAM’nin renal atılım oranı çok düşüktür; uygulana her bir

dozun 24 saat içinde idrara atılımı %1’den azdır. Dozun kalanı esas olarak monohidroksi ve

dihidroksi türevleri olarak atılır.

5.3.

Klinik öncesi güvenlilik verileri

Mutajenite ve karsinojenite:

Diğer

sitotoksik

ajanlar

gibi

klorambusil

in

vitro

in

vivo

genotoksisite

testlerine

göre

mutajeniktir, insanlarda ve hayvanlarda karsinojeniktir.

Fertiliteye etkisi:

Sıçanlarda, klorambusilin spermatogeneze zarar verdiği ve testiküler atrofiye neden olduğu

gösterilmiştir.

Teratojenite:

Klorambusil 4 - 20 mg/kg tek bir doz oral uygulamasının ardından; kısa veya kıvrımlı kuyruk,

mikrosefali ve eksensefali gibi gelişim anormallikleri, ektrodaktili, brakidaktili, sindaktili ve

polidaktili dahil parmak anormallikleri ve kemik boyunda kısalma, bir veya bir kaç bileşeninde

eksiklik ayrıca fare ve sıçan embriyolarında ossifikasyon bölgelerinde bütünsel eksiklikler gibi

uzun kemik anormalliklerini indüklediği gösterilmiştir Ayrıca klorambusilin sıçanlarda 3-6

mg/kg’lık tek doz intraperitonal enjeksiyonu takiben yavrularda renal bozukluklara neden olduğu

gösterilmiştir.

Beyin ve plazma farmakokinetiği

işaretli

klorambusilin

sıçanlara

oral

yoldan

uygulanmasını

takiben,

radyoaktif

işaretli

materyalin en yüksek konsantrasyonları plazma, karaciğer ve böbreklerde tespit edilmiştir.

Klorambusilin intravenöz yoldan uygulanmasından sonra sıçanların serebral dokusunda yalnızca

düşük konsantrasyonlarda tespit edilmiştir.

6.

FARMASÖTİK ÖZELLİKLER

6.1.

Yardımcı maddelerin listesi

Çekirdek:

Mikrokristalize selüloz

Susuz laktoz

Kolloidal susuz silika

Stearik asit

Kaplama:

Hipromelloz

Titanyum dioksit

Sentetik sarı demir oksit

Sentetik kırmızı demir oksit

Makrogol

6.2.

Geçimsizlikler

Bilinen bir geçimsizliği bulunmamaktadır.

6.3.

Raf ömrü

36 ay.

6.4.

Saklamaya yönelik özel tedbirler

2°-8°C arasında saklanmalıdır.

6.5.

Ambalajın niteliği ve içeriği

LEUKERAN tabletler, çocuk kilidi olan amber renkli cam şişeler içinde 25 ve 100 tablet olarak

bulunur.

6.6.

Beşeri tıbbi üründen arta kalan maddelerin imhası ve diğer özel önlemler

LEUKERAN tabletlerin güvenli kullanımı:

LEUKERAN tabletler, sitotoksik ilaçların kullanımı ile ilgili yürürlükteki talimatlara ve/veya

düzenlemelere uygun şekilde kullanılmalıdır.

Tablet kaplaması sağlamdır, LEUKERAN tabletlerin elle tutulmasında bir sakınca yoktur. Hamile

personel sitotoksik maddelere dokunmamalıdır.

LEUKERAN tabletler bölünmemelidir.

İmha:

Kullanılmamış olan ürünler ya da atık materyaller “Tıbbi Atıkların Kontrolü Yönetmeliği” ve

“Ambalaj ve Ambalaj Atıklarının Kontrolü Yönetmeliği”ne uygun olarak imha edilmelidir.

7.

RUHSAT SAHİBİ

VLD Danışmanlık, Tıbbi Ürünler ve Tanıtım Hizmetleri Ltd. Şti.

Büyükdere Cad. No. 127 Astoria İş Merkezi A Blok K9 Esentepe 34394 İstanbul

Telefon

: +90 – 212 – 3407684

: +90 – 212 – 3407601

e-posta

: info@vldpharma.com

8.

RUHSAT NUMARASI

132/12

9.

İLK RUHSAT TARİHİ/RUHSAT YENİLEME TARİHİ

04.10.2011

10.

KÜB’ÜN YENİLENME TARİHİ

8-12-2018

Annual assessment of Echinococcus multilocularis surveillance reports submitted in 2018 in the context of Commission Regulation (EU) No 1152/2011

Annual assessment of Echinococcus multilocularis surveillance reports submitted in 2018 in the context of Commission Regulation (EU) No 1152/2011

Published on: Fri, 07 Dec 2018 This report is part of the `Echinococcus multilocularis surveillance’ scientific reports which are presented annually by EFSA to the European Commission and are intended to assess the sampling strategy, data collection and detection methods used by Finland, Ireland, Malta, the United Kingdom (UK) and Norway in their respective surveillance programmes. The surveillance programmes of these five countries were evaluated by checking the information submitted by each of them an...

Europe - EFSA - European Food Safety Authority Publications

7-12-2018

Strawberry-flavoured acetaminophen infant oral drops in 24 mL bottles recalled because of defective child-resistant safety caps

Strawberry-flavoured acetaminophen infant oral drops in 24 mL bottles recalled because of defective child-resistant safety caps

Laboratoire RivaInc. and Laboratoires Trianon Inc. are voluntarily recalling five over-the-counter strawberry-flavoured acetaminophen oral drops for infants. The products are labeled as Biomedic, Option, Personnelle, Selection, or Laboratoires Trianon Inc. The products are packaged in 24 mL bottles and are used for pain and fever relief. They are being recalled because the child-resistant safety cap may be defective. This recall is in addition to previous recalls of children’s acetaminophen syrups for th...

Health Canada

7-12-2018

Magnesium citrate malate as a source of magnesium added for nutritional purposes to food supplements

Magnesium citrate malate as a source of magnesium added for nutritional purposes to food supplements

Published on: Thu, 06 Dec 2018 The present scientific opinion deals with the assessment of the bioavailability of magnesium, from the proposed nutrient source, magnesium citrate malate (MgCM), when added for nutritional purposes to food supplements. MgCM is a mixed salt consisting of magnesium cations and citrate and malate anions, and with a magnesium content of 12–15%. MgCM is proposed to be used in food supplements that are intended to provide up to 300–540 mg/day magnesium. The data provided demonst...

Europe - EFSA - European Food Safety Authority Publications

7-12-2018

Re‐evaluation of propane‐1,2‐diol esters of fatty acids (E 477) as a food additive

Re‐evaluation of propane‐1,2‐diol esters of fatty acids (E 477) as a food additive

Published on: Thu, 06 Dec 2018 The EFSA Panel on Food Additives and Flavourings (FAF) provides a scientific opinion re‐evaluating the safety of propane‐1,2‐diol esters of fatty acids (E 477) when used as a food additive. The Scientific Committee on Food (SCF) in 1978 endorsed the acceptable daily intake (ADI) of 25 mg/kg body weight (bw) per day, expressed as propane‐1,2‐diol, established by the Joint FAO/WHO Expert Committee on Food Additives (JECFA) in 1974. No adverse effects were observed in short‐t...

Europe - EFSA - European Food Safety Authority Publications

5-12-2018

Public health risks associated with food‐borne parasites

Public health risks associated with food‐borne parasites

Published on: Tue, 04 Dec 2018 Parasites are important food‐borne pathogens. Their complex lifecycles, varied transmission routes, and prolonged periods between infection and symptoms mean that the public health burden and relative importance of different transmission routes are often difficult to assess. Furthermore, there are challenges in detection and diagnostics, and variations in reporting. A Europe‐focused ranking exercise, using multicriteria decision analysis, identified potentially food‐borne ...

Europe - EFSA - European Food Safety Authority Publications

1-12-2018

Safety evaluation of the food enzyme endo‐1,4‐β‐xylanase from a genetically modified Trichoderma reesei (strain DP‐Nzd22)

Safety evaluation of the food enzyme endo‐1,4‐β‐xylanase from a genetically modified Trichoderma reesei (strain DP‐Nzd22)

Published on: Fri, 30 Nov 2018 The food enzyme endo‐1,4‐β‐xylanase (EC 3.2.1.8) is produced with a genetically modified Trichoderma reesei (strain DP‐Nzd22) by DuPont. The genetic modifications do not give rise to safety concerns. The food enzyme is free from viable cells of the production organism and recombinant DNA. The endo‐1,4‐β‐xylanase is intended to be used in distilled alcohol production, bakery and brewery. Residual amounts of total organic solids (TOS) are removed during the production of dis...

Europe - EFSA - European Food Safety Authority Publications

1-12-2018

Safety assessment of the process ‘RecyPET Hungária’, based on RecyPET Hungária technology, used to recycle post‐consumer PET into food contact materials

Safety assessment of the process ‘RecyPET Hungária’, based on RecyPET Hungária technology, used to recycle post‐consumer PET into food contact materials

Published on: Fri, 30 Nov 2018 The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of the recycling process RecyPET Hungária (EU register number RECYC0146). The input is hot caustic washed and dried poly(ethylene terephthalate) (PET) flakes originating from collected post‐consumer PET containers, containing no more than 5% of PET from non‐food applications. The flakes are dried and extruded. The output of the extrusion step is cut into pellets in an underwater...

Europe - EFSA - European Food Safety Authority Publications

30-11-2018

Understanding ASF spread and emergency control concepts in wild boar populations using individual‐based modelling and spatio‐temporal surveillance data

Understanding ASF spread and emergency control concepts in wild boar populations using individual‐based modelling and spatio‐temporal surveillance data

Published on: Thu, 29 Nov 2018 African swine fever (ASF) infection is circulating in Eurasia since a decade within wild boar populations without a demonstrated vector host. Further the infection was recurrently translocated by spatio‐temporal dynamics that is incompatible with wild boar movement characteristics. Management actions are required in areas affected by ASF. Control measures address areas with recent focal introduction and areas with ASF circulating several seasons or endemic occurrence. In v...

Europe - EFSA - European Food Safety Authority Publications

30-11-2018

Data collection for the estimation of ecological data (specific focal species, time spent in treated areas collecting food, composition of diet), residue level and residue decline on food items to be used in the risk assessment for birds and mammals

Data collection for the estimation of ecological data (specific focal species, time spent in treated areas collecting food, composition of diet), residue level and residue decline on food items to be used in the risk assessment for birds and mammals

Published on: Thu, 29 Nov 2018 The study described in this report was conducted with the aim of developing an unified database of ecological data and residue data to be used for the risk assessment of plant protection products for birds and mammals. The main sources of data were the information submitted in the context of approval of active substances and authorization of products and and additional information retrieved through a systematic literature review. The data were screened and organised in thr...

Europe - EFSA - European Food Safety Authority Publications

29-11-2018

FDA warns company for selling e-liquids that resemble kid-friendly foods as part of the agency’s ongoing Youth Tobacco Prevention Plan

FDA warns company for selling e-liquids that resemble kid-friendly foods as part of the agency’s ongoing Youth Tobacco Prevention Plan

FDA issued a warning letter to Electric Lotus LLC for selling nicotine-containing e-liquids used in e-cigarettes with labeling and/or advertising that cause them to resemble kid-friendly food products.

FDA - U.S. Food and Drug Administration

28-11-2018

FDA approves first biosimilar for treatment of adult patients with non-Hodgkin’s lymphoma

FDA approves first biosimilar for treatment of adult patients with non-Hodgkin’s lymphoma

The FDA approved Truxima (rituximab-abbs) as the first biosimilar to Rituxan (rituximab) for the treatment of adult patients with CD20-positive, B-cell non-Hodgkin’s lymphoma (NHL) to be used as a single agent or in combination with chemotherapy.

FDA - U.S. Food and Drug Administration

28-11-2018

EFSA Scientific Colloquium 24 – 'omics in risk assessment: state of the art and next steps

EFSA Scientific Colloquium 24 – 'omics in risk assessment: state of the art and next steps

Published on: Tue, 27 Nov 2018 In recent years, the development of innovative tools in genomics, transcriptomics, proteomics and metabolomics (designated collectively as 'omics technologies) has opened up new possibilities for applications in scientific research and led to the availability of vast amounts of analytical data. The interpretation and integration of 'omics data can provide valuable information on the functional status of an organism and on the effect of external factors such as stressors. T...

Europe - EFSA - European Food Safety Authority Publications

27-11-2018

Database of processing techniques and processing factors compatible with the EFSA food classification and description system FoodEx 2 Objective 1: Compendium of Representative Processing Techniques investigated in regulatory studies for pesticides

Database of processing techniques and processing factors compatible with the EFSA food classification and description system FoodEx 2 Objective 1: Compendium of Representative Processing Techniques investigated in regulatory studies for pesticides

Published on: Mon, 26 Nov 2018 EFSA is conducting pan‐European dietary exposure and risk assessments related to actual levels of pesticide residues in food commodities. These assessments use the pesticide occurrence data generated under the official monitoring programs of Member States, the consumption data from EFSA's comprehensive food consumption database and pesticide‐specific information such as processing factors. Currently no harmonised list of processing factors is available within Europe and wo...

Europe - EFSA - European Food Safety Authority Publications

27-11-2018

Database of processing techniques and processing factors compatible with the EFSA food classification and description system FoodEx 2 Objective 3: European database of processing factors for pesticides in food

Database of processing techniques and processing factors compatible with the EFSA food classification and description system FoodEx 2 Objective 3: European database of processing factors for pesticides in food

Published on: Mon, 26 Nov 2018 EFSA is conducting pan‐European dietary exposure and risk assessments related to actual levels of pesticide residues in food commodities. These assessments use the pesticide occurrence data generated under the official monitoring programs of Member States, the consumption data from EFSA's comprehensive food consumption database and pesticide‐specific information such as processing factors. Currently no harmonised list of processing factors is available within Europe and wo...

Europe - EFSA - European Food Safety Authority Publications

27-11-2018

Database of processing techniques and processing factors compatible with the EFSA food classification and description system FoodEx2 related to pesticide residues Objective 2: Linking the processing techniques investigated in regulatory studies with the E

Database of processing techniques and processing factors compatible with the EFSA food classification and description system FoodEx2 related to pesticide residues Objective 2: Linking the processing techniques investigated in regulatory studies with the E

Published on: Mon, 26 Nov 2018 In the framework of the project ‘Database of processing techniques and processing factors compatible with the EFSA food classification and description system FoodEx2’ a compendium of representative processing techniques was prepared as a result of Objective 1. In Objective 2 the food / feed items and processes as described in the compendium of Objective 1 were coded using the FoodEx2 coding system. The coding covers the raw agricultural commodities and the food / feed item...

Europe - EFSA - European Food Safety Authority Publications

27-11-2018

INNUENDO: A cross‐sectoral platform for the integration of genomics in the surveillance of food‐borne pathogens

INNUENDO: A cross‐sectoral platform for the integration of genomics in the surveillance of food‐borne pathogens

Published on: Mon, 26 Nov 2018 Abstract In response to the EFSA call New approaches in identifying and characterizing microbial and chemical hazards, the project INNUENDO (https://sites.google.com/site/theinnuendoproject/) aimed to design an analytical platform and standard procedures for the use of whole‐genome sequencing in surveillance and outbreak investigation of food‐borne pathogens. The project firstly attempted to identify existing flaws and needs, and then to provide applicable cross‐sectorial ...

Europe - EFSA - European Food Safety Authority Publications

24-11-2018

The EFSA‐funded collection of dietary and related data in the general population aged 10‐74 years in Greece

The EFSA‐funded collection of dietary and related data in the general population aged 10‐74 years in Greece

Published on: Fri, 23 Nov 2018 The Hellenic Health Foundation received support from the European Food Safety Authority in order to organise a national nutrition survey according to the methodology described in the EFSA Guidance document and to collect food consumption and related information among 780 adolescents, adults and elderly residing permanently in Greece. The EFSA‐funded data collection was largely based on the protocol of a large scale Greek national nutrition and health survey, called HYDRIA....

Europe - EFSA - European Food Safety Authority Publications

24-11-2018

Lumpy skin disease: Workshop on risk assessment and data collection for epidemiology, control and surveillance

Lumpy skin disease: Workshop on risk assessment and data collection for epidemiology, control and surveillance

Published on: Fri, 23 Nov 2018 Abstract The epidemics of lumpy skin disease in EU has been controlled mainly thanks to the coordinated control measures taken in the Balkan region, based above all on regional vaccination campaign. Since before the epidemics EFSA has been performing risk assessment on LSD to support the decision making process both for EC and also for the national authorities. Periodical meetings with representatives from affected and at risk countries have been organised by EFSA in order...

Europe - EFSA - European Food Safety Authority Publications

24-11-2018

Hazard identification and ranking for poultry at slaughter

Hazard identification and ranking for poultry at slaughter

Published on: Fri, 23 Nov 2018 The Hellenic Health Foundation received support from the European Food Safety Authority in order to organise a national nutrition survey according to the methodology described in the EFSA Guidance document and to collect food consumption and related information among 780 adolescents, adults and elderly residing permanently in Greece. The EFSA‐funded data collection was largely based on the protocol of a large scale Greek national nutrition and health survey, called HYDRIA....

Europe - EFSA - European Food Safety Authority Publications

22-11-2018

Safety and efficacy of Monteban® G100 (narasin) for ducks for fattening

Safety and efficacy of Monteban® G100 (narasin) for ducks for fattening

Published on: Wed, 21 Nov 2018 Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of Monteban® G100 for ducks. Monteban® G100, containing narasin, is intended for the prevention of coccidiosis in ducks for fattening at a dose range of 60–70 mg/kg of complete feed. Narasin from Monteban® G100 is safe for ducks for fattening at a level of 70 mg/kg complete feed...

Europe - EFSA - European Food Safety Authority Publications

21-11-2018

FDA approves new treatment for patients with acute myeloid leukemia

FDA approves new treatment for patients with acute myeloid leukemia

The FDA approved Daurismo (glasdegib) tablets to be used in combination with low-dose cytarabine (LDAC), a type of chemotherapy, for the treatment of newly-diagnosed acute myeloid leukemia (AML) in adults who are 75 years of age or older or who have other chronic health conditions or diseases (comorbidities) that may preclude the use of intensive chemotherapy.

FDA - U.S. Food and Drug Administration

21-11-2018

Implementation and verification of PBPK modelling codes of TCDD in rats and humans into Berkeley Madonna

Implementation and verification of PBPK modelling codes of TCDD in rats and humans into Berkeley Madonna

Published on: Tue, 20 Nov 2018 The goal of the current work was to implement and verify previously published rat and human PBPK modelling codes for TCDD into Berkeley Madonna. The US‐EPA has used these PBPK models in the reassessment of TCDD. A procurement contract has been set up to explore the possibilities to adequately run the models and reproduce previously published results. The implementation of the available codes in Berkeley Madonna was carried out at RIKILT‐WUR under the framework agreement wi...

Europe - EFSA - European Food Safety Authority Publications

21-11-2018

Safety and efficacy of Monteban® G100 (narasin) for chickens for fattening

Safety and efficacy of Monteban® G100 (narasin) for chickens for fattening

Published on: Tue, 20 Nov 2018 The feed additive Monteban® G100, containing the active substance narasin, an ionophore anticoccidial, is intended to control coccidiosis in chickens for fattening at a dose of 60–70 mg/kg complete feed. Narasin is produced by fermentation. Limited data on the taxonomic identification of the production strain did not allow the proper identification of strain NRRL 8092 as Streptomyces aureofaciens. The FEEDAP Panel cannot conclude on the absence of genetic determinants for ...

Europe - EFSA - European Food Safety Authority Publications

21-11-2018

Extensive literature search, selection for relevance and data extraction of studies related to the toxicity of PCDD/Fs and DL‐PCBs in humans

Extensive literature search, selection for relevance and data extraction of studies related to the toxicity of PCDD/Fs and DL‐PCBs in humans

Published on: Tue, 20 Nov 2018 To enable the hazard identification and characterisation in the risk assessment for humans related to the seventeen 2,3,7,8‐substituted dioxins (PCCDs) and furans (PCDFs) and the twelve dioxin‐like polychlorinated biphenyls (DL‐PCBs), EFSA outsourced an extensive literature search (ELS), followed by selection for relevance and extraction of relevant data for consideration in the risk assessment. Two tailored search strategies for Web of Science (WoS) and PubMed for identif...

Europe - EFSA - European Food Safety Authority Publications

20-11-2018

Modification of the existing maximum residue levels for pyraclostrobin in soyabean

Modification of the existing maximum residue levels for pyraclostrobin in soyabean

Published on: Mon, 19 Nov 2018 In accordance with Article 6 of Regulation (EC) No 396/2005, the applicant BASF SE submitted a request to the competent national authority in France to modify the existing maximum residue level (MRL) for the active substance pyraclostrobin in soyabean. The data submitted in support of the request were found to be sufficient to derive MRL proposals for soyabean. The applicant provided a new validated analytical method to control residues of pyraclostrobin on the commodity u...

Europe - EFSA - European Food Safety Authority Publications

17-11-2018

Review of the existing maximum residue levels for tau‐fluvalinate according to Article 12 of Regulation (EC) No 396/2005

Review of the existing maximum residue levels for tau‐fluvalinate according to Article 12 of Regulation (EC) No 396/2005

Published on: Fri, 16 Nov 2018 According to Article 12 of Regulation (EC) No 396/2005, EFSA has reviewed the maximum residue levels (MRLs) currently established at European level for the pesticide active substance tau‐fluvalinate. To assess the occurrence of tau‐fluvalinate residues in plants, processed commodities, rotational crops and livestock, EFSA considered the conclusions derived in the framework of Commission Regulation (EC) No 33/2008 as well as the European authorisations reported by Member St...

Europe - EFSA - European Food Safety Authority Publications

17-11-2018

Safety evaluation of the food enzyme endo‐1,4‐β‐xylanase from a genetically modified Aspergillus oryzae (strain NZYM‐FA)

Safety evaluation of the food enzyme endo‐1,4‐β‐xylanase from a genetically modified Aspergillus oryzae (strain NZYM‐FA)

Published on: Fri, 16 Nov 2018 The food enzyme is an endo‐1,4‐β‐xylanase (EC 3.2.1.8) produced with a genetically modified strain of Aspergillus oryzae by Novozymes A/S. The genetic modifications do not give rise to safety concerns. The food enzyme is free from viable cells of the production organism and recombinant DNA. This xylanase is intended to be used in baking and cereal‐based processes. Based on the proposed maximum use levels, dietary exposure to the food enzyme–total organic solids (TOS) was e...

Europe - EFSA - European Food Safety Authority Publications

16-11-2018

FDA approves new drug to treat travelers’ diarrhea

FDA approves new drug to treat travelers’ diarrhea

FDA approved Aemcolo (rifamycin), an antibacterial drug indicated for the treatment of adult patients with travelers’ diarrhea caused by noninvasive strains of Escherichia coli (E. coli), not complicated by fever or blood in the stool.

FDA - U.S. Food and Drug Administration

16-11-2018

FDA approves first-line treatment for peripheral T-cell lymphoma under new review pilot

FDA approves first-line treatment for peripheral T-cell lymphoma under new review pilot

The FDA expanded the approved use of Adcetris (brentuximab vedotin) injection in combination with chemotherapy for adult patients with certain types of peripheral T-cell lymphoma (PTCL). This is the first FDA approval for treatment of newly diagnosed PTCL, and the agency used a new review program to complete the approval more quickly.

FDA - U.S. Food and Drug Administration

15-11-2018

Safety evaluation of the food enzyme maltogenic amylase from a genetically modified Bacillus subtilis (strain NZYM‐OC)

Safety evaluation of the food enzyme maltogenic amylase from a genetically modified Bacillus subtilis (strain NZYM‐OC)

Published on: Wed, 14 Nov 2018 The food enzyme maltogenic amylase (glucan 1,4‐a‐maltohydrolase; EC 3.2.1.133) is produced with a genetically modified Bacillus subtilis strain NZYM‐OC by Novozymes A/S. The genetic modifications do not give rise to safety concerns. The food enzyme is free from viable cells of the production microorganism and recombinant DNA. This maltogenic amylase is intended to be used in baking processes. Based on the maximum use levels recommended, dietary exposure to the food enzyme–...

Europe - EFSA - European Food Safety Authority Publications

15-11-2018

Recommendations on the use of the proportionality approach in the framework of risk assessment for pesticide residues

Recommendations on the use of the proportionality approach in the framework of risk assessment for pesticide residues

Published on: Wed, 14 Nov 2018 The technical report reflects the outcome of the discussions and agreements that were reached in the pesticides peer review meeting on residues and maximum residue levels regarding the principles and guidance for application of the proportionality concept in the risk assessment methodologies used at European level for the estimation of the maximum residue levels for pesticides. In addition, practical experiences on the use of the proportionality approach gained by EFSA hav...

Europe - EFSA - European Food Safety Authority Publications

15-11-2018

Safety evaluation of the food enzyme maltogenic amylase from a genetically modified Bacillus subtilis (strain NZYM‐SO)

Safety evaluation of the food enzyme maltogenic amylase from a genetically modified Bacillus subtilis (strain NZYM‐SO)

Published on: Wed, 14 Nov 2018 The food enzyme maltogenic amylase (glucan 1,4‐α‐maltohydrolase; EC 3.2.1.133) is produced with a genetically modified Bacillus subtilis strain NZYM‐SO by Novozymes A/S. The genetic modifications do not give rise to safety concerns. The food enzyme is free from viable cells of the production microorganism and recombinant DNA. This maltogenic amylase is intended to be used in baking processes. Based on the maximum use levels, dietary exposure to the food enzyme–total organi...

Europe - EFSA - European Food Safety Authority Publications

15-11-2018

Safety evaluation of the food enzyme acetolactate decarboxylase from a genetically modified Bacillus licheniformis (strain NZYM‐JB)

Safety evaluation of the food enzyme acetolactate decarboxylase from a genetically modified Bacillus licheniformis (strain NZYM‐JB)

Published on: Wed, 14 Nov 2018 The food enzyme acetolactate decarboxylase (α‐acetolactate decarboxylase; EC 4.1.1.5) is produced with a genetically modified Bacillus licheniformis strain NZYM‐JB by Novozymes A/S. The genetic modifications do not give rise to safety concerns. The food enzyme is free from viable cells of the production organism and recombinant DNA. This acetolactate decarboxylase is intended to be used in distilled alcohol production and brewing processes. Residual amounts of total organi...

Europe - EFSA - European Food Safety Authority Publications

14-11-2018

FDA alerts doctors, patients about risk of complications when certain implanted pumps are used to deliver pain medications not approved for use with the devices

FDA alerts doctors, patients about risk of complications when certain implanted pumps are used to deliver pain medications not approved for use with the devices

FDA alerted health care providers and patients about the serious complications that can occur when using medications not approved for use with implanted pumps that deliver medication into the spinal fluid to treat or manage pain.

FDA - U.S. Food and Drug Administration

14-11-2018

Several children's strawberry-flavoured acetaminophen syrups recalled because of defective child-resistant safety caps on the bottles

Several children's strawberry-flavoured acetaminophen syrups recalled because of defective child-resistant safety caps on the bottles

Laboratoire RivaInc. and Laboratoires Trianon Inc. are voluntarily recalling several over-the-counter children’s strawberry-flavoured acetaminophen syrups labeled as Biomedic, Option, or Laboratoires Trianon Inc. The products, which are used for pain and fever relief, are being recalled because the child-resistant safety cap may be defective.

Health Canada

9-11-2018

Safety assessment of the active substance polyacrylic acid, sodium salt, cross‐linked, for use in active food contact materials

Safety assessment of the active substance polyacrylic acid, sodium salt, cross‐linked, for use in active food contact materials

Published on: Thu, 08 Nov 2018 00:00:00 +0100 The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP) assessed the safety of polyacrylic acid, sodium salt, cross‐linked, FCM substance No 1015, which is intended to be used as a liquid absorber in the packaging of fresh or frozen foods such as meat, poultry and seafood as well as fresh fruits and vegetables. Specific migration tests were not performed due to the high absorption of liquids by the substance. The Panel noted that if polya...

Europe - EFSA - European Food Safety Authority Publications

9-11-2018

Safety assessment of the substance Ln 1,4‐benzene dicarboxylic acid (with Ln = La, Eu, Gd, Tb) for use in food contact materials

Safety assessment of the substance Ln 1,4‐benzene dicarboxylic acid (with Ln = La, Eu, Gd, Tb) for use in food contact materials

Published on: Wed, 07 Nov 2018 00:00:00 +0100 The EFSA Panel on Food Contact Materials, Enzymes and Processing Aids (CEP Panel) assessed the safety of the additive Ln 1,4‐benzene dicarboxylic acid (with Ln = La, Eu, Gd, Tb) for use in food contact materials. It is a family of mixtures combining the four lanthanides lanthanum (La), europium (Eu), gadolinium (Gd) and/or terbium (Tb) in different proportions as their 1,4‐benzene dicarboxylate complexes, used as a taggant in plastics for authentication and ...

Europe - EFSA - European Food Safety Authority Publications

7-11-2018

Several store-brand pain or sinus relief tablets recalled because consumers may be unable to access important safety information

Several store-brand pain or sinus relief tablets recalled because consumers may be unable to access important safety information

Vita Health Products is voluntarily recalling several store-brand (Care, Exact, Life, and Pharmasave) over-the-counter drugs used for pain or sinus relief because of a labelling issue. Consumers may be unable to peel open the wrap-around label on the bottle to access the warning statements, or the label may not peel off completely, which may make it difficult to read some of the important safety information.

Health Canada

6-11-2018

Duncan Hines Classic White, Classic Butter Golden, Signature Confetti and Classic Yellow Cake Mixes Recalled Due to Potential Presence of Salmonella

Duncan Hines Classic White, Classic Butter Golden, Signature Confetti and Classic Yellow Cake Mixes Recalled Due to Potential Presence of Salmonella

Conagra Brands is collaborating with health officials in connection with a positive finding of Salmonella in a retail sample of Duncan Hines Classic White cake mix that may be linked to a Salmonella outbreak that is currently being investigated by CDC and FDA. While it has not been definitively concluded that this product is linked to the outbreak and the investigation is still ongoing, Conagra has decided to voluntarily recall the specific Duncan Hines variety identified (Classic White) and three other ...

FDA - U.S. Food and Drug Administration

5-11-2018

Products containing metam-sodium: ANSES announces the withdrawal of marketing authorisations

Products containing metam-sodium: ANSES announces the withdrawal of marketing authorisations

Plant protection products containing metam-sodium are used in market gardening and horticulture to disinfect the soil. Following the substance's approval at European level, ANSES reassessed the dossiers and notified the industrial companies concerned of its intention to withdraw all marketing authorisations for metam-sodium products. ANSES is also taking this opportunity to reiterate the importance of phytopharmacovigilance and the requirement for professionals to report any adverse effects on humans or ...

France - Agence Nationale du Médicament Vétérinaire

1-11-2018

FDA warns patients and doctors about risk of inaccurate results from home-use device to monitor blood thinner warfarin

FDA warns patients and doctors about risk of inaccurate results from home-use device to monitor blood thinner warfarin

Roche Diagnostics issued voluntary recall of certain test strips used with CoaguChek meter devices; patients affected by the recall should seek alternative methods for testing.

FDA - U.S. Food and Drug Administration

1-11-2018

Safety evaluation of the food enzyme endo‐1,4‐β‐xylanase from a genetically modified Bacillus subtilis (strain LMG S‐24584)

Safety evaluation of the food enzyme endo‐1,4‐β‐xylanase from a genetically modified Bacillus subtilis (strain LMG S‐24584)

Published on: Wed, 31 Oct 2018 00:00:00 +0100 The food enzyme endo‐1,4‐β‐xylanase (EC 3.2.1.8) is produced with the genetically modified Bacillus subtilis strain LMG S‐24584 by Puratos N. V. The genetic modifications do not give rise to safety concerns. The Panel noted that, although the production strain was not detected in the food enzyme, recombinant DNA was present in all batches of the food enzyme tested. The food enzyme is intended to be used in baking processes. Based on the maximum use levels re...

Europe - EFSA - European Food Safety Authority Publications

1-11-2018

Safety evaluation of the food enzyme glucan 1,4‐α‐glucosidase from a genetically modified Aspergillus niger (strain NZYM‐BW)

Safety evaluation of the food enzyme glucan 1,4‐α‐glucosidase from a genetically modified Aspergillus niger (strain NZYM‐BW)

Published on: Wed, 31 Oct 2018 00:00:00 +0100 The food enzyme glucan 1,4‐α‐glucosidase (EC 3.2.1.3) is produced with the genetically modified Aspergillus niger strain NZYM‐BW by Novozymes A/S. The genetic modifications do not give rise to safety concerns. The food enzyme is free from viable cells of the production organism and recombinant DNA. The glucan 1,4‐α‐glucosidase food enzyme is intended to be used in distilled alcohol production and starch processing for the production of glucose syrups. Residu...

Europe - EFSA - European Food Safety Authority Publications

1-11-2018

Safety of the food enzyme glucoamylase from a genetically modified Aspergillus niger (strain NZYM‐BF)

Safety of the food enzyme glucoamylase from a genetically modified Aspergillus niger (strain NZYM‐BF)

Published on: Wed, 31 Oct 2018 00:00:00 +0100 The food enzyme glucoamylase (glucan 1,4‐α‐glucosidase; EC 3.2.1.3) is produced with the genetically modified strain of Aspergillus niger by Novozymes A/S. The genetic modifications do not give rise to safety concerns. The food enzyme is free from viable cells of the production organism and recombinant DNA. This glucoamylase is intended to be used in brewing processes and in starch processing for glucose syrups production. Residual amounts of total organic s...

Europe - EFSA - European Food Safety Authority Publications

1-11-2018

Safety evaluation of the food enzyme α‐amylase from a genetically modified Aspergillus niger (strain NZYM‐MC)

Safety evaluation of the food enzyme α‐amylase from a genetically modified Aspergillus niger (strain NZYM‐MC)

Published on: Wed, 31 Oct 2018 00:00:00 +0100 The food enzyme alpha‐amylase (4‐α‐d‐glucan glucanohydrolase; EC 3.2.1.1) is produced with the genetically modified strain of Aspergillus niger by Novozymes A/S. The genetic modifications do not give rise to safety concerns. The food enzyme is free from viable cells of the production organism and recombinant DNA. This α‐amylase is intended to be used in starch processing for glucose syrups production, beverage alcohol (distilling) processes and baking proces...

Europe - EFSA - European Food Safety Authority Publications

31-10-2018

Safety and efficacy of a super critical carbon dioxide extract of Humulus lupulus L. flos when used as a feed flavouring for all animal species

Safety and efficacy of a super critical carbon dioxide extract of Humulus lupulus L. flos when used as a feed flavouring for all animal species

Published on: Tue, 30 Oct 2018 00:00:00 +0100 Following a request from the European Commission, the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of a super critical carbon dioxide extract of Humulus lupulus L. flos (hop strobiles) when used as a sensory feed additive for all animal species. The additive is specified to containing 40% beta acids and less than 0.2% alpha acids. Known substances of conce...

Europe - EFSA - European Food Safety Authority Publications

31-10-2018

Efficacy of Bergazym® P100 (endo‐1,4‐β‐xylanase) as a feed additive for chickens for fattening and weaned piglets

Efficacy of Bergazym® P100 (endo‐1,4‐β‐xylanase) as a feed additive for chickens for fattening and weaned piglets

Published on: Tue, 30 Oct 2018 00:00:00 +0100 The product Bergazym® P100 contains a xylanase which is produced by a non‐genetically modified strain of Trichoderma reesei. The additive is available in a coated granular form and it is intended to be used as a zootechnical additive (functional group: digestibility enhancers) for chickens for fattening, and weaned piglets at the dose of 1,500 EPU/kg feed. The production strain and the additive were fully characterised in a previous assessment of the Panel o...

Europe - EFSA - European Food Safety Authority Publications

31-10-2018

Safety and efficacy of Lactobacillus hilgardii CNCM I‐4785 and Lactobacillus buchneri CNCM I‐4323/NCIMB 40788 as a silage additive for all animal species

Safety and efficacy of Lactobacillus hilgardii CNCM I‐4785 and Lactobacillus buchneri CNCM I‐4323/NCIMB 40788 as a silage additive for all animal species

Published on: Tue, 30 Oct 2018 00:00:00 +0100 Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed was asked to deliver a scientific opinion on the safety and efficacy of a strain of Lactobacillus hilgardii and of Lactobacillus buchneri when used as a technological additive intended to improve ensiling at a proposed application rate of 3.0 x 108 colony forming units (CFU)/kg fresh material. The two bacterial species are considered by EFS...

Europe - EFSA - European Food Safety Authority Publications

30-10-2018

FDA takes action to stop the use of lead acetate in hair dyes

FDA takes action to stop the use of lead acetate in hair dyes

FDA takes action to stop the use of lead acetate in hair dyes. FDA will no longer allow lead acetate to be used in certain hair coloring products based on data that demonstrate that there is no longer a reasonable certainty of no harm from the use of this color additive.

FDA - U.S. Food and Drug Administration

30-10-2018

Training courses on “Steering an Expert Knowledge Elicitation” and “Use of the Expert Knowledge Elicitation Guidance in Risk Assessments for EFSA Management” and “Conduct of the Sheffield protocol for an Expert Knowledge Elicitation”

Training courses on “Steering an Expert Knowledge Elicitation” and “Use of the Expert Knowledge Elicitation Guidance in Risk Assessments for EFSA Management” and “Conduct of the Sheffield protocol for an Expert Knowledge Elicitation”

Published on: Mon, 29 Oct 2018 00:00:00 +0100 This report presents the results from an exploratory study in 2016 on clear communication of scientific assessment results. It had a specific focus on the communication of scientific uncertainties in EFSA scientific opinions. Qualitative methods were applied to the design and communication of an opinion summary and uncertainty statements related to that opinion, and to collect evidence on how different stakeholder groups responded to them. The study tested t...

Europe - EFSA - European Food Safety Authority Publications

30-10-2018

Pest categorisation of Aleurocanthus spp.

Pest categorisation of Aleurocanthus spp.

Published on: Mon, 29 Oct 2018 00:00:00 +0100 The Panel on Plant Health performed a pest categorisation of Aleurocanthus spp., a well‐defined insect genus of the whitefly family Aleyrodidae (Arthropoda: Hemiptera). Difficulties within the taxonomy of the genus give doubt about the ability to accurately identify some members to species level. Nevertheless, the genus is thought to currently include about ninety species mainly reported from tropical and subtropical areas. The genus is listed in Council Dir...

Europe - EFSA - European Food Safety Authority Publications

26-10-2018

Multi-country outbreak of Listeria monocytogenes sequence type 8 infections linked to consumption of salmon products

Multi-country outbreak of Listeria monocytogenes sequence type 8 infections linked to consumption of salmon products

Published on: Thu, 25 Oct 2018 00:00:00 +0200 A multi-country outbreak of 12 listeriosis cases caused by Listeria monocytogenes sequence type (ST) 8 has been identified through whole genome sequencing (WGS) analysis in three EU/EEA countries: Denmark (6 cases), Germany (5) and France (1). Four of these cases have died due to or with the disease. It is likely that the extent of this outbreak has been underestimated since the outbreak was identified through sequencing and only a subset of the EU/EEA count...

Europe - EFSA - European Food Safety Authority Publications

26-10-2018

Safety and efficacy of l‐threonine produced by fermentation using Escherichia coli CGMCC 7.232 for all animal species

Safety and efficacy of l‐threonine produced by fermentation using Escherichia coli CGMCC 7.232 for all animal species

Published on: Thu, 25 Oct 2018 00:00:00 +0200 The product subject of this assessment is l‐threonine produced by fermentation with a genetically modified strain of Escherichia coli (CGMCC 7.232). It is intended to be used in feed and water for drinking for all animal species and categories. The production strain and its recombinant DNA were not detected in the additive. The product l‐threonine, manufactured by fermentation with E. coli CGMCC 7.232, does not raise any safety concern with regard to the gen...

Europe - EFSA - European Food Safety Authority Publications

25-10-2018

Safety of zinc chelate of methionine sulfate for the target species

Safety of zinc chelate of methionine sulfate for the target species

Published on: Wed, 24 Oct 2018 00:00:00 +0200 Zinc chelate of methionine sulfate is intended to be used as a nutritional additive (functional group: compounds of trace elements). The additive is zinc chelated with methionine in a molar ratio 1:1. It is intended to supply zinc as a nutritional additive to all animal species/categories. In 2017, the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) adopted an opinion on the safety and efficacy of zinc chelate of methionine su...

Europe - EFSA - European Food Safety Authority Publications

24-10-2018

Safety and efficacy of Hostazym® X (endo‐1,4‐beta‐xylanase) as a feed additive for sows in order to have benefit in piglets

Safety and efficacy of Hostazym® X (endo‐1,4‐beta‐xylanase) as a feed additive for sows in order to have benefit in piglets

Published on: Tue, 23 Oct 2018 00:00:00 +0200 Following a request from the European Commission, the Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of HOSTAZYM® X as a feed additive for sows in order to have benefit in piglets. The additive HOSTAZYM® X contains endo‐1,4‐beta‐xylanase and is available in liquid and solid formulations. This product is authorised as a feed additive for chickens for fattening, tu...

Europe - EFSA - European Food Safety Authority Publications

20-10-2018

Scientific Opinion of Flavouring Group Evaluation 411 (FGE.411): 2‐(4‐methylphenoxy)‐N‐(1H‐pyrazol‐3‐yl)‐N‐(thiophen‐2‐ylmethyl)acetamide from chemical group 30 (miscellaneous substances)

Scientific Opinion of Flavouring Group Evaluation 411 (FGE.411): 2‐(4‐methylphenoxy)‐N‐(1H‐pyrazol‐3‐yl)‐N‐(thiophen‐2‐ylmethyl)acetamide from chemical group 30 (miscellaneous substances)

Published on: Fri, 19 Oct 2018 00:00:00 +0200 EFSA was requested to deliver a scientific opinion on the implications for human health of the flavouring substance 2‐(4‐methylphenoxy)‐N‐(1H‐pyrazol‐3‐yl)‐N‐(thiophen‐2‐ylmethyl)acetamide [FL‐no: 16.133], in the Flavouring Group Evaluation 411 (FGE.411), according to Regulation (EC) No 1331/2008 of the European Parliament and of the Council. The substance has not been reported to occur in natural source materials of botanical or animal origin. It is intende...

Europe - EFSA - European Food Safety Authority Publications

19-10-2018

Hy-Vee Voluntarily Recalls Several Meat and Potato Products

Hy-Vee Voluntarily Recalls Several Meat and Potato Products

Hy-Vee, Inc., based in West Des Moines, Iowa, is voluntarily recalling six of its meat and potato products across its eight-state region due to possible contamination with Salmonella and Listeria monocytogenes. The potential for contamination was discovered after Hy-Vee’s supplier, McCain Foods, announced it was recalling its caramelized mushrooms and fire-roasted tomatoes, which are ingredients that are used in six Hy-Vee products. To date, no illnesses have been reported in connection with these prod...

FDA - U.S. Food and Drug Administration

17-10-2018

Pest categorisation of Stagonosporopsis andigena

Pest categorisation of Stagonosporopsis andigena

Published on: Tue, 16 Oct 2018 00:00:00 +0200 The Panel on Plant Health performed a pest categorisation of Stagonosporopsis andigena, the causal agent of black blight of potato, for the EU. The pest is a well‐defined fungal species and reliable methods exist for its detection and identification. S. andigena is present in Bolivia and Peru. The pest is not known to occur in the EU and is listed in Annex IAI of Directive 2000/29/EC as Phoma andina, meaning its introduction into the EU is prohibited. The ma...

Europe - EFSA - European Food Safety Authority Publications

17-10-2018

Pest categorisation of Thecaphora solani

Pest categorisation of Thecaphora solani

Published on: Tue, 16 Oct 2018 00:00:00 +0200 The Panel on Plant Health performed a pest categorisation of the fungus Thecaphora solani, the causal agent of smut of potato, for the EU. The identity of the pest is well established and reliable methods exist for its detection and identification. T. solaniis present in Bolivia, Chile, Colombia, Ecuador, Mexico, Panama, Peru and Venezuela. The pathogen is not known to occur in the EU and is listed in Annex IAI of Directive 2000/29/EC, meaning its introducti...

Europe - EFSA - European Food Safety Authority Publications

26-11-2018

A stereotactic system used by neurosurgeons to more precisely determine where to perform their surgical procedure was intended to be MRI compatible but the older predicate it compared itself to was not, requiring additional performance testing.

A stereotactic system used by neurosurgeons to more precisely determine where to perform their surgical procedure was intended to be MRI compatible but the older predicate it compared itself to was not, requiring additional performance testing.

A stereotactic system used by neurosurgeons to more precisely determine where to perform their surgical procedure was intended to be MRI compatible but the older predicate it compared itself to was not, requiring additional performance testing.

FDA - U.S. Food and Drug Administration

26-11-2018

TWEETORIAL: Today we announced changes to modernize FDA’s 510(k) clearance pathway, used for clearance of low- to moderate-risk devices that are substantially equivalent to a device already on the market, known as a predicate device  https://go.usa.gov/xP

TWEETORIAL: Today we announced changes to modernize FDA’s 510(k) clearance pathway, used for clearance of low- to moderate-risk devices that are substantially equivalent to a device already on the market, known as a predicate device https://go.usa.gov/xP

TWEETORIAL: Today we announced changes to modernize FDA’s 510(k) clearance pathway, used for clearance of low- to moderate-risk devices that are substantially equivalent to a device already on the market, known as a predicate device https://go.usa.gov/xPHdE 

FDA - U.S. Food and Drug Administration

21-11-2018

EU/3/18/2089 (Dystrogen Therapeutics S.A.)

EU/3/18/2089 (Dystrogen Therapeutics S.A.)

EU/3/18/2089 (Active substance: Ex vivo fused normal allogeneic human myoblast with autologous human myoblast derived from Duchenne muscular dystrophy affected donor) - Orphan designation - Commission Decision (2018)7798 of Wed, 21 Nov 2018

Europe -DG Health and Food Safety

21-11-2018

EU/3/18/2088 (Dystrogen Therapeutics S.A.)

EU/3/18/2088 (Dystrogen Therapeutics S.A.)

EU/3/18/2088 (Active substance: Ex vivo fused normal allogeneic human myoblast with another normal allogeneic human myoblast) - Orphan designation - Commission Decision (2018)7797 of Wed, 21 Nov 2018 European Medicines Agency (EMA) procedure number: EMA/OD/134/18

Europe -DG Health and Food Safety