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Bear Grylls Ultimate Fine Edge Knife
Since its release, the excitement surrounding the Bear Grylls Ultimate Knife has been overwhelming. In 2011 the Ultimate was the best-selling knife in world. Fans and collectors, however, clamored for a non-serrated version and we listened. We now make the Ultimate Knife with a fine-edge from the top of the handle to the tip of the blade. Using the same high carbon, stainless steel drop-point blade and texturized rubber handle this is equally tough and unmistakably Bear-inspired. Housed in a nylon and hard rubber military-grade sheath, a diamond-coated knife sharpener, emergency whistle, fire starter and survival guide are all integrated. This is the Ultimate Knife that you asked for, the pinnacle of Bear's signature line.
- Open length: 25.4 cm
- Blade Length: 12.2 cm
- Weight: (with sheath): 416.8 g
- Weight (no sheath): 317.6 g
- Knife Features:
- Full Fine Edge High Carbon Stainless Steel Drop Point Blade - Ideal for edge retention
- Ergonomic Textured Rubber Grip - Maximizes comfort and reduces slippage
- Stainless Steel Pommel - At base of handle for hammering
- Emergency Whistle - Integrated into lanyard cord
- Sheath Features:
- Fire Starter - Ferrocerium rod locks into sheath, striker notch incorporated into back of knife blade
- Nylon Sheath - Lightweight, military-grade, mildew resistant
- Land to air rescue instructions
- Diamond Sharpener - Integrated into sheath for on-the-go sharpening
- Priorities of Survival - Pocket guide contains Bear's survival essentials
Reviews Press
It's great I'm on scouting and iTS pretty handy
Received my knife the other day, It's great! Took it out to the woods and put it to work. No issues to report
I had the serrated version, but I was wondering which one is more recommended for the uses of camping/recreation that isn't as extremely hardcore as the tasks Bear performs? In simpler terms, would you recommend the fine edge or serrated version?
yeeer , i wish to get all your product but they all so expensive ... :(
is it that hard to sharpen a knife even if it comes out of the box a little dull? people are so afraid to open a box and find the knife a little dull. people are getting lazier and lazier.
This knife looks real good, is it?
Does the blade bend?
How sharp is it when opened?
Please tell!!!!
when will it come to europe(germany)?
Should i get this one or the serrated version, for survival, i already have a non serrated pocket knife so i don't need another.
the tang does extend through the length of the handle many of those reviews mistakenly attributed the problems they experienced with the pommel breaking to the knife not having a full tang when the actual problem (which has been fixed in both the serrated and fine edge versions of the knife btw) was that the pommel was not attached to the tang of the knife hope this helps
i think you guess really improved this knife by making it a plain edge because now i wont have to worry about damaging serrations on my knife, it is so solid and very well built good job guess.
Knife is great every thing you would expect for £60 very happy with it, fire starter works well, as does the sharperning stone, would of paid slot more for a knife like this
I saw some bad reviews on the serrated version about the tang not extending all the way through the handle, does the same go for this version?
I'm thru-hiking the Appalachian trail starting in June after I graduate high school this year. I'd love to be able to confidently take this knife with me on my journey.
This Knife is awsome I've been hoping for a fine edge version of the ultimate knife. I really liked the ultimate knife when it came out but was dissapointed with the serrations that took up half the blade which makes it extremely difficult to do detailed work with the knife. but now that this is out this truly is the best knife and a great deal.
This is a great, great knife. To answer the question, you can get these in the UK from Greenman Bushcraft. Google them. I got mine within 24 hours of ordering.
cant decide if i want this for my birthday or the lmf ll both look like great knives, i already have the serrated version and LOVE it... would also love it if it came in black and grey instead of orange...
Best thought out and constructed field knife I've owned!
I go this knife for Xmas and have taken it on 3 camping trips so for. I LOVE THIS KNIFE!!!! It handles everything I throw at it and wants more.
Going to buy a new knife soon. Would like it to be this one. When is it going to be for sale?
can anyone tell me when this knife will be availiable in the uk?
would love to see a saw on the back part of the blade for sawing does not have to be the full part of the blade just about 2" still leaves 2.8" for batoning wood so that u can have the best of both knifes a nice fine edge for cleaning game and have a saw to saw
FDF/rapid response
I think that is a good idea of a "military" version, but if you guys do make one keeps the BG on it, and add a camouflage sheath too!
my name is Tifrea,and i like very very much your survival's:D,and i want to say thanks to learn us how to survive in the wild,in any place...i wish always to be with you in a mission,in a desert,or somewhere,i don't know:D...you're great,and what are you doing is great...thanks one more time Bear. I respect you and your team:)
Does anyone know when this knife is going to be vailable through gerber or through walmart or canadian tire??
When will be for sale of this knife? When will can i buy this knife in europe?
I like the knife and the idea of having the fire starter in the sheath. A very good option even for one who's more used to the traditional Scandinavian knives.
Good balance between usability as a bushcraft tool and a hacking tool (blade width).
The only thing I would really love is a military version of this knife. Military as in not rescue orange.
Make a black one or Black/OD instead of Black/Orange, and I'll be sure to carry one next rotation.
Hey kid just because you cant live your dream, doesn't mean I cant so dont comment unless you actually have a comment, and my friend got the knife and loved it, thanks for making amazing quality knifes!!! Wilderness survival (young survivalists!!!)
who ever is this "young survivalist with the co-survivalist" is a giant knob. So Colten you can stop saying you are some expert survivalist, cause your not! grow up!
love this knife. would recomend it to any outdoorsman looking for protection cutting ability and warmth when there no matches or lighters. and for the price its hard to beat
It would be a nice idea to make an ultimate folding knife with every feature of the original ultimate knife, but it folds I will totally buy if it came out
I just bought this knife a week ago and I love it, but I wish Gerber made an ultimate folding knife without serrations, that would include a fire starter and a whistle.
I hope gerber makes a ultimate folding knife with every features but instead it folds
I'm very impressed that Gerber listened to the customers and produced the Bear Grylls knife WITHOUT serrations! I was one of the many who sent an e-mail asking for it, and here it is!
Still not available in my area though, but you can bet your ass when this comes my way I'll be upgrading for sure!
Just another example of why I always choose Gerber.
I have the serrated version, but I hate serrations. Good job Gerber for making the plain edge!!!!!!!!
finally a fine edge knife,
i am so getting one
I got this knife as a christmas present and went right out to test it in the wild. The knife chopped cut and pried. I was able to make shelter and start a nice fire. I did not have a problem with it. I added some 550 para cord by wrapping the handle because I use it alot. Overall it did what it said I`m pleased with it
It would be nice if i had known that there was a straight bladed version, i hate knives with serrated blades, but oh well its still nice
Just got the knife in the mail today, so far i really like it. It feels good in my hand..has a good weight to it. the flint rod works very good. the sheath is comfortable sometimes the knife is a little snug coming out but its ok. the sharpener works good - had to use it because the knife came a little dull but i got it sharpened up real nice and its razor sharp.
The original serrated bear grylls knife was in my opinion, great. And all that gerber did was take all of the complaints (not many) of the customers and basicly made a newer better model. They didnt just change the serration they also changed the grind of the blade and fixed the problem with the pomel. And as far as im concerned, for this price, they dont come any better than this.
i loved the designe of the ultamite knife but the steel is to soft. the first time that i used the knife for any hard cutting i distroyed the serration part of the blade and the edge didn't last very long. i think if you were to up the rc of the steel to rc 57 - 58 would make the perfect knife. Also the sheath needs to be more like the LMF sheath.
Love the knife me and my co-friend survivalist are hopping to get a few for our FB survival shows!!!
I mostly like the design, and have been a big fan of gerber since I got the River Shorty dive knife when I was 6. I carried a model 400 folder EVERYWHERE from the time I was 8 til I was about 12. Now I am a serious survivalist and very honest about what I believe to be true. I wanna see 2 main things before I would buy one. 1) A better blade steel, one you can be proud of and mark on the knife instead of "mystery steel". 2) The other, as has been metioned before, a good survival knife would benifit greatly from a reflective surface. Thanks for listening, best wishes to Gerber.
Great kit for survival and general use. But the edge is week i bent and broke the seration part of mine just by cuting litle branches.
I saw that your new knife came out, and i really want to be a survivalist like BG when i get older. my friends and i are very big fans of what you do, my mom never trusted me with an open knife, but now that I have proven to her that I have never and never will injure myself with a knife, she is going to let me buy the knife.
yo i love the knive great work bear n gerber tough knife im tired of all the morons complaining about the blade i have beat the heck out of mine n not 1 problem its a great design just wish i coud get the fine edge version for the collection i personaly love serrations its great lookin very comfortable to use easy to sharpen and an all around great deal for a survival knife
this is a great knif love it probally the best knife i have i dont like the velcrow on the sheath the sewwing comes loose from hard use
I recently purchased one of your survival kits and the knife wasn't reflective. For survival purposes that's rather useless for signaling. Unless you can come up with a good answer I will toucher myself by not watching any Bear Grylls Man vs Wild this week and it's only monday!
Great looking knife but what type of hi-carbon stainless steal is it exactly? Also what is the weight? Not being available in the UK is pants. 3 stars because i look at it or even buy it..
Great! I hope , I can buy the knife in Germany too.
From AUSTRALIA, just picked this knife up.. brilliant solid quality, amazingly made..looks like it will meet any challenge and last forever.
I only buy knifes made in the USA and the gerber lmf was always a favorite of mine and I decided to take a leap and buy the Bear Grylls ultimate knife. It seemed perfect except 4 things. The pommel broke way too easy, it was not USA made, the "High carbon stainless steel" doesn't tell me exactly what the knife is made of and the serations bent/broke with minor use. Seeing as how Gerber is a company that listens to its customers they have changed it so the pommel doesn't break and it doesn't have serations. Which makes it as close to perfect as possible besides not being USA made and the mystery material it is made from. Gerber is a great company and will continue to be one as long as it listens to its customers.
That knife is piece of junk. Lots of my friends lost their money buying this -4 of those knives got broke on handle or pommel!
Bear can come to Australia, but his knife can't...?
É uma pena não haver este produto´disponivél na Europa pois ele seria o sonho para muita gente .
Why on earth can't you send it to the UK, where Bear is from!
I would never buy a knife that does not tell the buyer what kind of hi-carbon stainless or the RC hardness of the blade temper. In my experience 440C stainless, 5160 and 1095 steel is the best for edge retention and durability if quenched and tempered correctly. If a cutlery can't list the exact type of blade material than the knife is not worth your money, there is a lot of cheap hi-carbon stainless steel types that make crappy but somewhat sharp blades, 440A is one of them.
Please make it available in the UK. One start lost for that.
Bear you tease us with this knife in the UK. We can't get hold of it!!
My BG. GERBER has helped me in many a tight spot!
Is It possible to perfect it even more!
"Never leave home without your Bear!"
would love to have it but as with most bg gerber products hard to get in bears home country. sad. please can you try and resolve this or add to gerber uk pages
haha, I just purchased the classic Ultimate Knife yesterday!
and it is AWESOME
Well,this knife is an ultimate one as described by the users(I'm not yet).But I think,the price is a little much ! Isn't it? $62 for just a knife.I'm not a survival expert,or any kind of scout,so for me it isn't worth it.Maybe,for people who trek n go for
REALLY like this knife! Don't have the money for it but I might just have to get it anyway
i am very disapointed that the fine edged knife isn't available in the UK please can u try and sort this out loses 1 star for not being in UK
I've been scouting for a good fine edged knife and when I read the announcement on Facebook. I just had to get one! Sadly though I am in the UK and I cant purchase and get this shipped here. So this knife loses two stars for not being available in the cou
Great Knife! Don't have the $ now--hope you make it for sale later again.
You know him from Discovery's "Man vs. Wild" television show. But did you know Brit survivalist star Bear Grylls, 37, once crossed the North Atlantic in an inflatable boat, or that he circumnavigated the United Kingdom on a jet ski? Grylls, who served three years in the British Special Air Service, has more recently worked with Gerber Legendary Blades on a namesake line of knives and survival products. We caught up with Grylls late last month to talk machetes, snare wires, and the debate around serration on blades built for survival situations in the jungle or woods.
The first version of this knife (with a partly serrated edge) was insanely successful, due to its high quality, practical design, and very reasonable price. I like this version better. Gerber did everything right, including putting the knife in reach of even the humblest at around $52. Now you, too, can parachute into some loathsome part of the world, eat stuff that makes you puke, and return home little worse for the experience.


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iPad, iPhone, Android
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subset: commoncrawl


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Marking Sixteen Years Since Princess Diana Passed
Princess Diana July 01, 1961 to August 31, 1997
Wow, time goes so quickly and it just seems like yesterday I heard about the death of Princess Diana. Of course it was a big shock at the time because of her enormous popularity worldwide. Any magazine that put her on the cover, when she was alive, always sold more than normal. She was an icon during her life and after. Her legacy has continued and she is still loved deeply by many.
Princess Diana Princess Diana will long be remembered for her kindness, gentleness, beauty, and humanitarianism. Let's celebrate her life and what she gave to so many.
Here is an amazing and inspiring quote from a beautiful woman and an inspiration to so many…..
"Carry out random acts of kindness with no expectation of reward; safe in the knowledge that one day, someone might do the same for you." – Princess Diana
This is so true. Whenever you do kindnesses expect nothing in return and that is how the blessings come in to your life.
In 2007, marking the tenth anniversary of her death, her sons, Princes William and Harry, honored their beloved mother with a special concert to be held on what would have been her 46th birthday. The proceeds of the event went to charities supported by Diana and her sons.
Continuing her charitable efforts is the Diana, Princess of Wales Memorial Fund. Established after her death, the fund provides grants to numerous organizations and supports initiatives to provide care to the sick in Africa, help refugees, and stop the use of land mines.
So here are a few facts on Princess Diana's effect on the world.
• Diana shook up the British monarchy and speeded its modernization.
• She helped to tear down prejudices about AIDS.
• She raised awareness of eating disorders.
• She promoted opposition to land mines.
These are pretty hefty achievements for a woman of little education who mocked herself for being "thick as a plank." Add to these a more dubious accomplishment — her skillful manipulation of media images — and it's clear why, so many years after her death, Diana remains an inescapable presence in British life: mostly, but not always, benign; a restless and seductive ghost. It's time to peer into the many corners she still haunts.
In her charitable work, Diana set a standard that's hard to equal. She ignored the prevailing prejudices and fears about AIDS to clasp the hands of sufferers, and embraced leprosy patients in Indonesia. Arbiter remembers a visit to a home for the blind where Diana noticed that an old resident was crying: "She asked what was the matter and he said, 'I can't see you.' So she took his hand and put it on her face."
Her beautiful spirit will always live on. She will always be the Queen of Hearts!


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Do you ever wonder what it would be like to live in Warsaw, Berlin, Paris, or even Tel Aviv in the 1920s and 30s? Or what the late night cabaret music scene would be like? Piven Theatre's Cities of Light provides a glimpse into just this world. Rebecca Joy Fletcher's uniquely written cabaret takes audience members on a ride back into Jewish history as they follow the provocative and persistent Chanteuse and her younger counterpart /accompanist, Jimmi. Writer Fletcher and Director Marti Lyons take the standard cabaret to a new level, transforming the typical plot-less cabaret into a historically relevant and character driven performance. For the 80 minutes inside the small and intimate Piven Theatre on opening night, audiences got to transport themselves back several decades to the musical world of Jewry in Europe and Israel, and were able to shed a few laughs along the way.
Interestingly, when the play began, I thought I might have come to the wrong place! Jimmi (played by Allison Hendrix), Fletcher's sidekick and pianist, opened the theatre welcoming audience members to her lecture and as such began discussing Europe in the 1920s, genuinely confusing me and making me second guess what I had signed up to see. When Chanteuse (Rebecca Joy Fletcher) boldly and rather abruptly appeared begging Jimmi (AllisonHendrix) to stop lecturing and instead follow her along on the trains, streets, and music halls of Eastern and Western Europe, the fourth wall began to disappear. I must admit that at the beginning I was bit a disenlightened by the trite pedagogic introduction and Hendrix's overly exaggerated theatricality upon meeting Chanteuse, a woman of a different time. Hendrix might have overdone it a bit in expressing her perturbance at Chanteuse's intervening her "lecture," but thankfully, once the introduction was over, the ride down memory lane and into the exciting world of Jewish history was a genuine enjoyable adventure.
As the audience got to experience Berlin, a place submerged in Jewish stereotypes at the brink of World War II, Chanteuse's songs expressed Jewish desires to reclaim their own story and take control for themselves over those otherwise hurtful stereotypes. The mockful songs like "Life's a Swindle" and "A Jew to Blame!" were two songs presented, emblematic of that self-deprecation. When Chanteuse and Jimmi made it to Warsaw, the songs became a bit more provocative and sexy, and Chanteuse even brought a sweet old man from the audience up to join her in her romantic lovey-dovey Yiddish songs. In Paris, life turned a bit richer and dark, replete with undesirables, prostitutes, and big boulevards. By the time the duo arrived in Tel Aviv, life was brighter, the beach was near, and cafes were brimming with sun-tanned customers. Throughout this journey, Fletcher and Hendrix made a perfect pair. As they travelled along these adventures together, they made the sceneries seem incredibly authentic, even though on stage nothing really changed. From German sirens to bumpy train rides to stormy days, the two enabled the audience to enter the world of their imagination and join them on their exciting and sometimes frightful journey.
Furthermore, while most of the cabaret was in English and would likely not have worked well with audiences had it had been in any other language, Fletcher incorporated a sufficient amount of Yiddish, Hebrew, German, and Polish into her pieces. This added just the right amount of authenticity to the performance.
The majority of "Cities of Light's" story on cabaret theatre in the 20s and 30s was told through song. Thankfully, Fletcher and Hendrix both had strong voices. Rebecca Joy Fletcher's voice was operatic, filled with resonance and vibrato, and fitting for the cabarets of the times and places she represented. In addition to her strong voice, she was incredibly animated and proved she has quite the knack for schtick. Her rendition of song "Titina" in which she played the characters of pioneering couple Titina and Ephraim, who bicker back and forth, like most married couples do, over the type of life they want to make for themselves inside British Palestine was hilarious. Fletcher's good-natured parody of hardworking, laborious Ephraim and his nagging wife Titina provided a fun and light-hearted look at Tel Aviv cabaret. It also showed off Fletcher's malleability as an actor and singer. Similarly, her "Oy, Madagaskar!" 1937 song she sang in Warsaw also brought out her animated and comedic nature. A song highlighting the desire for the world to rid the Jews by shipping them off to Madagascar, Chanteuse jovially played an observant Jew caught in the middle of this discussion, and played the Jew complete with the religious payes and black top hat. These highly comedic, farcical songs were what I would consider to be Fletcher's strongest suit.
Overall, I was very impressed by the writing of "Cities of Light." The lectures Hendrix gave to the audience seamlessly blended in with the cabarets and historical scenes that were played onstage. This historical information gave audience members a chance to contextualize what was going on amidst the cabaret venues, and did so in a creative way, albeit breaking down the fourth wall. While I was skeptical of this method at first and was sometimes distracted by Hendrix's dramatic telling as she escaped the present "real" world and became privy to Chanteuse's adventures, I believe this type of lecture-imaginative world convergence worked for this show.
In sum, Piven Theatre's "Cities of Light" provides a very creative look at Jewish history, one presented in a very different way than most plays go, and one presented in a very different way than most cabarets go. The adventures of Chanteuse and Jimmi through the cabaret scene are entertaining, informative, and imaginative. In the end, it was hard to believe that on such a bare and minimalist stage, the audience could be so seamlessly transported back to Europe and Israel just after the turn of the century.
Cities of Light (World Premiere)
Written by Rebecca Joy Fletcher
Directed by Marti Lyons
November 7 - December 11, 2010
More information can be found here http://www.piventheatre.org/current.htm
Tickets are $15 for preview performances and start at $25 for regular run performances.
Student, Senior and group rates are available.
Tickets are available at the Box Office, 927 Noyes Street, Evanston, by calling 847.866.8049


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All ideas are made of other ideas
If you want to find new ideas, start by breaking existing ideas down into smaller ones. Only then can you see how to build your own.
It's a little mantra you can say: Ideas are made of other ideas.
No genius invented their parents. No legendary artist created the idea of art or language. Mozart didn't invent the piano and Picasso didn't invent paint. We have always borrowed, reused, and remade, standing on the shoulders of ideas that came before us and we always will.
It's impossible to find any idea that can't be broken down into smaller ideas. Pick a song, an invention, a philosophy… they are all recombinations of other ideas. Sometimes the grandest ideas, once you ditch the romance, are the easiest to dissect. Until you can see the fact that all ideas are made of other ideas as an immutable law, you're unlikely to create, since you see ideas in the world as fixed when in truth they are always in motion.
I wrote about this at length in The Myths of Innovation, and it's also in my Creative Thinking Hacks essay:
[use] the following simple definition: an idea is a combination of other ideas. Say it five times out loud. Say it to your cat. Yell it out you car window at strangers waiting for the bus. Every amazing creative thing you've ever seen, or idea you've ever heard can be broken down into smaller ideas that existed before.
An automobile? An engine + wheels. A telephone? Electricity and sound. Reese's peanut butter cups? Peanut butter and chocolate. All great creative ideas, inventions, and theories are comprised of other ideas.
Why should you care? Here's why: if you want to be a creator instead of a mere consumer you must see ideas currently in the world as fuel for your mind. You must stop seeing them as objects or functional things: they are combinations of ingredients waiting for reuse.


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Candidates often say they write their own speeches, but in the case of Mitt Romney's convention address, it is a claim more plausible than most. It was highly personal, rhetorically unambitious and perfectly imaginable as the product of Romney's iPad.
Assuming this to be the case, we have been handed an interesting artifact. Setting aside aesthetic and partisan judgments, what do his preferred arguments and illustrations reveal about Romney himself?
First, at least stylistically, Romney is the retro candidate. His stories are sentimental, his jokes are corny, his parents are his heroes and his family is aggressively nuclear. There is an admirable defiance about it all. You want authenticity? You got it. In your heart you know he's square.
Not that there is anything wrong with that. Some of my best friends - and me - are squares. But this is a change from recent presidents. Both Bill Clinton and George W. Bush were baby boomer archetypes - one a story of indiscipline, the other of repentance. In his 2000 convention address, Bush said, "I believe ... in forgiveness, because I needed it." The need itself was humanizing and typical of his times.
Romney, in contrast, inhabits the world before Mrs. Robinson. Some deny it ever existed. Romney proves them wrong. This is not nostalgia; it is a lifestyle choice. Some on the cultural left have little tolerance for this particular alternative lifestyle. But millions of Americans, including many Mormons and evangelicals, practice it without shame. It may even help explain Romney's strong appeal to seniors - a group he leads by double digits, for example, in Florida. Former Gov. Jeb Bush hypothesizes cultural affinity may be a "secret weapon" in Romney's outreach to the elderly. What's not to like about an upstanding, earnest man prone to reciting "The Ballad of Davy Crockett" in public?
In this case, anachronism is also a kind of armor. No man so grounded, so stable, so religious, so endearingly square can also be the heartless, lawless villain of President Obama's hyperbolic negative ads.
A second self-revelation contained in Romney's speech: He is not really ideological. He did not engage a debate on the role of government, or America's place in the world, or the future of entitlements. He proclaimed policies instead of arguing for them. He offered five points instead of first principles.
Romney's policy instincts, particularly on the economy, are broadly conservative - a general preference for free markets over planning. But he is not a cause politician, driven to inspire or convert. Problems, in Romney's presentation, require data, analysis and decisions, not ideological abstraction. And Romney views himself, above all, as a businessman. In his speech, he purposely deflated Republican ideological ambitions. Let the word go forth: "My promise is to help you and your family." And he made a virtue of this modesty by comparing it to Obama's intergalactic ambitions of four years ago.
This approach has limitations. It makes it harder for Romney to explain how and why his policies would actually work. Ronald Reagan, for example, offered theories about the causes of inflation, the effect of lowering marginal tax rates, the importance of stable monetary policy. If you accepted his worldview, you accepted his policies. Romney's proposals can seem like dots in search of a crayon.
But there are advantages as well. It is harder to attack Romney as an ideologue when he doesn't have a particularly vivid ideology. In his convention speech, he managed to distance himself from the worst excesses and hardest edges of his party - from Ron Paul to Todd Akin - without picking any direct fights with the GOP base. Instead of advancing a more moderate ideology, he dismissed the importance of ideology in mastering current challenges. This can only be reassuring to middle-ground voters, distrustful of ideological fevers on both sides.
Romney has often been dinged for lacking authenticity. Whatever its faults, his convention speech was relentlessly authentic. Romney is a solid, sentimental, not particularly ideological, highly respected businessman. This is not the normal profile of a transformative leader. But in a country where a little public competence and responsibility are distant dreams, it is probably enough.
Michael Gerson's email address is michaelgersonwashpost .com.


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Chef Decor offers a collection of hundreds of paintings perfect for any
home kitchen or restaurant. From our humorous Fat Chef series, to the
more classic Country Kitchen collection, you will find the perfect
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Emergency Preparation
Let's Get Ready
Preparing for emergencies is something the whole family and community can do together! Help children remember important information, and create a family emergency kit and plan. These steps will go a long way in keeping children safe and secure.
Explore the Tools in the Kit:Read quick facts, download resource guides, and more!
For Providers
For Caregivers
For Providers
You are one of the special grown-ups with whom children feel most comfortable. This gives you a unique opportunity to help them learn about emergencies in a calm and reassuring environment. Sesame Street created the Educator Guide to help you prepare your children for emergencies with activities that can complement school safety drills. You can find an additional Community Guide to get everyone in your neighborhood ready!
For Caregivers
You and your family help one another every day by getting ready for work and school. You also do things to keep one another safe, such as buckling up in the car. Preparing for emergencies is another great way to get ready and keep your family safe. Here you'll find videos, an app, and a family guide to help the whole family prepare for emergencies — together!
#1 Emergency Signals
Notice emergency signs and signals. Hear the siren or see the flashing lights of an ambulance, a fire truck, or a police car. They mean that help is on the way!
#2 What's An Emergency?
Talk with your child about emergencies in a calm way. You could explain, "An emergency is when something happens that we don't expect and we have to act quickly to keep ourselves safe."
#3 Whole Names
Help your child learn her whole name and the whole names of her caregivers. If you and your child ever get separated, she can share these names with trusted adults to reach you.
#4 Phone and Address
Helping your child learn your phone number and address can help reunite your family quickly in an emergency.
#5 Special Helpers
Help your child learn about the people who help keep you safe, like firefighters, police officers, doctors, and emergency responders so he is more comfortable with them in an emergency.
#6 Creating a Kit
Create a family emergency kit. Reuse an old box or bag and let your child decorate it with drawings or stickers. Let your child put some of the items into the kit.
#7 Emergency Contacts
Choose two emergency contacts. An out-of-town emergency contact can make sure you're all OK. A local emergency contact can help you with tasks such as picking up your child from child care.
#8 Our Meeting Place
Select an emergency meeting place. This is the safe place where your family will meet if you can't get home during an emergency.
More Kit Components
About This Project
Sesame Street Let's Get Ready: Planning Together for Emergencies, created with support provided by PSEG, is a bilingual (English and Spanish) multiple media resource designed to help entire families, especially those with young children, to plan and prepare together for emergencies. Through simple strategies and tips that can be incorporated into everyday routines, Let's Get Ready helps children, families, and caregivers to prepare ahead of time in age-appropriate and engaging ways.
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You are here: Home > Prescription(RX) Drugs > A > Anastrozole (App Pharmaceuticals, Llc)
anastrozole tablet
1.1 Adjuvant Treatment
Anastrozole tablets 1 mg is indicated for adjuvant treatment of postmenopausal women with hormone receptor-positive early breast cancer.
1.2 First-Line Treatment
Anastrozole tablets 1 mg is indicated for the first-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor unknown locally advanced or metastatic breast cancer.
1.3 Second-Line Treatment
Anastrozole tablets 1 mg is indicated for the treatment of advanced breast cancer in postmenopausal women with disease progression following tamoxifen therapy. Patients with ER-negative disease and patients who did not respond to previous tamoxifen therapy rarely responded to anastrozole.
2.1 Recommended Dose
The dose of anastrozole is one 1 mg tablet taken once a day. For patients with advanced breast cancer, anastrozole tablets 1 mg should be continued until tumor progression. Anastrozole tablets 1 mg can be taken with or without food.
For adjuvant treatment of early breast cancer in postmenopausal women, the optimal duration of therapy is unknown. In the ATAC trial anastrozole tablets 1 mg were administered for five years. [see Clinical Studies (14.1)]
No dosage adjustment is necessary for patients with renal impairment or for elderly patients. [see Use in Specific Populations (8.6)]
2.2 Patients with Hepatic Impairment
No changes in dose are recommended for patients with mild-to-moderate hepatic impairment. Anastrozole tablets have not been studied in patients with severe hepatic impairment. [see Use in Specific Populations (8.7)]
The tablets are white to off white circular, film-coated biconvex tablets, debossed with 'DB02' on one side and plain on other side, supplied in bottles of 30 tablets.
4.1 Pregnancy and Premenopausal Women
Anastrozole may cause fetal harm when administered to a pregnant woman and offers no clinical benefit to premenopausal women with breast cancer. Anastrozole is contraindicated in women who are or may become pregnant. There are no adequate and well-controlled studies in pregnant women using anastrozole tablets. If anastrozole tablets are used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to a fetus or potential risk for loss of the pregnancy. [see Use in Specific Populations (8.1)]
4.2 Hypersensitivity
Anastrozole tablets are contraindicated in any patient who has shown a hypersensitivity reaction to the drug or to any of the excipients. Observed reactions include anaphylaxis, angioedema, and urticaria. [see Adverse Reactions (6.2)]
5.1 Ischemic Cardiovascular Events
In women with pre-existing ischemic heart disease, an increased incidence of ischemic cardiovascular events was observed with anastrozole in the ATAC trial (17% of patients on anastrozole tablets and 10% of patients on tamoxifen). Consider risk and benefits of anastrozole therapy in patients with pre-existing ischemic heart disease. [see Adverse Reactions (6.1)]
5.2 Bone Effects
Results from the ATAC trial bone substudy at 12 and 24 months demonstrated that patients receiving anastrozole tablets had a mean decrease in both lumbar spine and total hip bone mineral density (BMD) compared to baseline. Patients receiving tamoxifen had a mean increase in both lumbar spine and total hip BMD compared to baseline [see Adverse Reactions, (6.1)].
5.3 Cholesterol
During the ATAC trial, more patients receiving anastrozole tablets were reported to have elevated serum cholesterol compared to patients receiving tamoxifen (9% versus 3.5%, respectively) [see Adverse Reactions, (6.1)].
Serious adverse reactions with anastrozole occurring in less than 1 in 10,000 patients, are: 1) skin reactions such as lesions, ulcers, or blisters; 2) allergic reactions with swelling of the face, lips, tongue, and/or throat. This may cause difficulty in swallowing and/or breathing; and 3) changes in blood tests of the liver function, including inflammation of the liver with symptoms that may include a general feeling of not being well, with or without jaundice, liver pain or liver swelling [see Adverse Reactions, (6.2)].
Common adverse reactions (occurring with an incidence of >10%) in women taking anastrozole tablets included: hot flashes, asthenia, arthritis, pain, arthralgia, pharyngitis, hypertension, depression, nausea and vomiting, rash, osteoporosis, fractures, back pain, insomnia, pain, headache, bone pain, peripheral edema, increased cough, dyspnea, pharyngitis and lymphedema.
In the ATAC trial, the most common reported adverse reaction (>0.1%) leading to discontinuation of therapy for both treatment groups was hot flashes, although there were fewer patients who discontinued therapy as a result of hot flashes in the anastrozole group.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
6.1 Clinical Trials Experience
Adjuvant Therapy
Adverse reaction data for adjuvant therapy are based on the ATAC trial [see Clinical Studies (14.1)]. The median duration of adjuvant treatment for safety evaluation was 59.8 months and 59.6 months for patients receiving anastrozole tablets 1 mg and tamoxifen 20 mg, respectively.
Adverse reactions occurring with an incidence of at least 5% in either treatment group during treatment or within 14 days of the end of treatment are presented in Table 1.
Certain adverse reactions and combinations of adverse reactions were prospectively specified for analysis, based on the known pharmacologic properties and side effect profiles of the two drugs (see Table 2).
Ischemic Cardiovascular Events
Between treatment arms in the overall population of 6186 patients, there was no statistical difference in ischemic cardiovascular events (4% anastrozole vs. 3% tamoxifen). In the overall population, angina pectoris was reported in 71/3092 (2.3%) patients in the anastrozole arm and 51/3094 (1.6%) patients in the tamoxifen arm; myocardial infarction was reported in 37/3092 (1.2%) patients in the anastrozole arm and 34/3094 (1.1%) patients in the tamoxifen arm.
In women with pre-existing ischemic heart disease 465/6186 (7.5%), the incidence of ischemic cardiovascular events was 17% in patients on anastrozole and 10% in patients on tamoxifen. In this patient population, angina pectoris was reported in 25/216 (11.6%) patients receiving anastrozole tablets and 13/249 (5.2%) patients receiving tamoxifen; myocardial infarction was reported in 2/216 (0.9%) patients receiving anastrozole tablets and 8/249 (3.2%) patients receiving tamoxifen.
Bone Mineral Density Findings
Results from the ATAC trial bone substudy at 12 and 24 months demonstrated that patients receiving anastrozole tablets had a mean decrease in both lumbar spine and total hip bone mineral density (BMD) compared to baseline. Patients receiving tamoxifen had a mean increase in both lumbar spine and total hip BMD compared to baseline.
Because anastrozole tablets lowers circulating estrogen levels it may cause a reduction in bone mineral density.
A post-marketing trial assessed the combined effects of anastrozole tablets and the bisphosphonate risedronate on changes from baseline in BMD and markers of bone resorption and formation in postmenopausal women with hormone receptor-positive early breast cancer. All patients received calcium and vitamin D supplementation. At 12 months, small reductions in lumbar spine bone mineral density were noted in patients not receiving bisphosphonates. Bisphosphonate treatment preserved bone density in most patients at risk of fracture.
Postmenopausal women with early breast cancer scheduled to be treated with anastrozole tablets should have their bone status managed according to treatment guidelines already available for postmenopausal women at similar risk of fragility fracture.
During the ATAC trial, more patients receiving anastrozole tablets were reported to have an elevated serum cholesterol compared to patients receiving tamoxifen (9% versus 3.5%, respectively).
A post-marketing trial also evaluated any potential effects of anastrozole tablets on lipid profile. In the primary analysis population for lipids (anastrozole tablet alone), there was no clinically significant change in LDL-C from baseline to 12 months and HDL-C from baseline to 12 months
In secondary population for lipids (anastrozole tablets+risedronate), there also was no clinically significant change in LDL-C and HDL-C from baseline to 12 months.
In both populations for lipids, there was no clinically significant difference in total cholesterol (TC) or serum triglycerides (TG) at 12 months compared with baseline.
In this trial, treatment for 12 months with anastrozole tablets alone had a neutral effect on lipid profile. Combination treatment with anastrozole tablets and risedronate also had a neutral effect on lipid profile.
The trial provides evidence that postmenopausal women with early breast cancer scheduled to be treated with anastrozole tablets should be managed using the current National Cholesterol Education Program guidelines for cardiovascular risk-based management of individual patients with LDL elevations.
Other Adverse Reactions
Patients receiving anastrozole tablets had an increase in joint disorders (including arthritis, arthrosis and arthralgia) compared with patients receiving tamoxifen. Patients receiving anastrozole tablets had an increase in the incidence of all fractures (specifically fractures of spine, hip and wrist) [315 (10%)] compared with patients receiving tamoxifen [209 (7%)].
Patients receiving anastrozole tablets had a higher incidence of carpal tunnel syndrome [78 (2.5%)] compared with patients receiving tamoxifen [22 (0.7%)].
Vaginal bleeding occurred more frequently in the tamoxifen-treated patients versus the anastrozole tablets-treated patients 317 (10%) versus 167 (5%), respectively.
Patients receiving anastrozole tablets had a lower incidence of hot flashes, vaginal bleeding, vaginal discharge, endometrial cancer, venous thromboembolic events and ischemic cerebrovascular events compared with patients receiving tamoxifen.
First-Line Therapy
Adverse reactions occurring with an incidence of at least 5% in either treatment group of trials 0030 and 0027 during or within 2 weeks of the end of treatment are shown in Table 3.
Table 3 – Adverse Reactions Occurring with an Incidence of at Least 5% in Trials 0030 and 0027
Less frequent adverse experiences reported in patients receiving Anastrozole tablets 1 mg in either Trial 0030 or Trial 0027 were similar to those reported for second-line therapy.
Based on results from second-line therapy and the established safety profile of tamoxifen, the incidences of 9 pre-specified adverse event categories potentially causally related to one or both of the therapies because of their pharmacology were statistically analyzed. No significant differences were seen between treatment groups.
Table 4 – Number of Patients with Pre-specified Adverse Reactions in Trials 0030 and 0027
Second-Line Therapy
Anastrozole tablets were tolerated in two controlled clinical trials (i.e., Trials 0004 and 0005), with less than 3.3% of the anastrozole tablets-treated patients and 4% of the megestrol acetate-treated patients withdrawing due to an adverse reaction.
The principal adverse reaction more common with anastrozole tablets than megestrol acetate was diarrhea. Adverse reactions reported in greater than 5% of the patients in any of the treatment groups in these two controlled clinical trials, regardless of causality, are presented below:
Table 5 - Number (n) and Percentage of Patients with Adverse Reactions in Trials 0004 and 0005
Other less frequent (2% to 5%) adverse reactions reported in patients receiving Anastrozole tablets l mg in either Trial 0004 or Trial 0005 are listed below. These adverse experiences are listed by body system and are in order of decreasing frequency within each body system regardless of assessed causality.
Body as a Whole: Flu syndrome; fever; neck pain; malaise; accidental injury; infection
Cardiovascular: Hypertension; thrombophlebitis
Hepatic: Gamma GT increased; SGOT increased; SGPT increased
Hematologic: Anemia; leukopenia
Metabolic and Nutritional: Alkaline phosphatase increased; weight loss
Mean serum total cholesterol levels increased by 0.5 mmol/L among patients receiving Anastrozole tablets. Increases in LDL cholesterol have been shown to contribute to these changes.
Musculoskeletal: Myalgia; arthralgia; pathological fracture
Nervous: Somnolence; confusion; insomnia; anxiety; nervousness
Respiratory: Sinusitis; bronchitis; rhinitis
Skin and Appendages: Hair thinning (alopecia); pruritus
Urogenital: Urinary tract infection; breast pain
The incidences of the following adverse event groups potentially causally related to one or both of the therapies because of their pharmacology, were statistically analyzed: weight gain, edema, thromboembolic disease, gastrointestinal disturbance, hot flushes, and vaginal dryness. These six groups, and the adverse reactions captured in the groups, were prospectively defined. The results are shown in the table below.
6.2 Post-Marketing Experience
Hepatobiliary events including increases in alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase have been reported (>1% and <10%) and gamma-GT, bilirubin and hepatitis have been reported (>0.1% and <1%) in patients receiving anastrozole tablets.
Anastrozole tablets may also be associated with rash including cases of mucocutaneous disorders such as erythema multiforme and Stevens-Johnson syndrome.
Cases of allergic reactions including angioedema, urticaria and anaphylaxis have been reported in patients receiving anastrozole tablets. [see Contraindications (4.2)]
Trigger finger has been reported (>0.1% and <1%) in patients receiving anastrozole tablets.
7.1 Tamoxifen
Co-administration of anastrozole and tamoxifen in breast cancer patients reduced anastrozole plasma concentration by 27%. However, the coadministration of anastrozole and tamoxifen did not affect the pharmacokinetics of tamoxifen or N-desmethyltamoxifen. At a median follow-up of 33 months, the combination of anastrozole tablets and tamoxifen did not demonstrate any efficacy benefit when compared with tamoxifen in all patients as well as in the hormone receptor-positive subpopulation. This treatment arm was discontinued from the trial. [see Clinical Studies (14.1)]. Based on clinical and pharmacokinetic results from the ATAC trial, tamoxifen should not be administered with anastrozole.
7.2 Estrogen
Estrogen-containing therapies should not be used with anastrozole as they may diminish its pharmacological action.
7.3 Warfarin
In a study conducted in 16 male volunteers, anastrozole did not alter the exposure (as measured by Cmax and AUC) and anticoagulant activity (as measured by prothrombin time, activated partial thromboplastin time, and thrombin time) of both R- and S-warfarin.
7.4 Cytochrome P450
Based on in vitro and in vivo results, it is unlikely that co-administration of anastrozole tablets 1 mg will affect other drugs as a result inhibition of cytochrome P450 [see Clinical Pharmacology (12.3)].
8.1 Pregnancy
PREGNANCY CATEGORY X [see Contraindications (4.1)]
Anastrozole may cause fetal harm when administered to a pregnant woman and offers no clinical benefit to premenopausal women with breast cancer. Anastrozole is contraindicated in women who are or may become pregnant. In animal studies, anastrozole caused pregnancy failure, increased pregnancy loss, and signs of delayed fetal development. There are no studies of anastrozole use in pregnant women. If anastrozole is used during pregnancy, or if the patient becomes pregnant while receiving this drug, the patient should be apprised of the potential hazard to the fetus and potential risk for pregnancy loss.
In animal reproduction studies, pregnant rats and rabbits received anastrozole during organogenesis at doses equal to or greater than 1 (rats) and 1/3 (rabbits) the recommended human dose on a mg/m2basis. In both species, anastrozole crossed the placenta, and there was increased pregnancy loss (increased pre-and/or post-implantation loss, increased resorption, and decreased numbers of live fetuses). In rats, these effects were dose related, and placental weights were significantly increased. Fetotoxicity, including delayed fetal development (i.e., incomplete ossification and depressed fetal body weights), occurred in rats at anastrozole doses that produced peak plasma levels 19 times higher than serum levels in humans at the therapeutic dose (AUC0-24hr 9 times higher). In rabbits, anastrozole caused pregnancy failure at doses equal to or greater than 16 times the recommended human dose on a mg/m2basis. [see Animal Toxicology and/or Pharmacology (13.2)]
8.3 Nursing Mothers
It is not known if anastrozole is excreted in human milk. Because many drugs are excreted in human milk and because of the tumorigenicity shown for anastrozole in animal studies, or the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
8.4 Pediatric Use
The efficacy of anastrozole tablets in the treatment of pubertal gynecomastia in adolescent boys and in the treatment of precocious puberty in girls with McCune-Albright Syndrome has not been demonstrated.
Labeling describing clinical trials and pharmacokinetic studies of anastrozole in pubertal boys of adolescent age with gynecomastia and in girls with McCune-Albright Syndrome and progressive precocious puberty is approved for AstraZeneca Pharmaceuticals LP's Arimidex®. However, due to AstraZeneca Pharmaceuticals LP's marketing exclusivity rights, a description of those trials and studies is not approved for this anastrozole labeling.
8.5 Geriatric Use
In studies 0030 and 0027 about 50% of patients were 65 or older. Patients ≥ 65 years of age had moderately better tumor response and time to tumor progression than patients < 65 years of age regardless of randomized treatment. In studies 0004 and 0005 50% of patients were 65 or older. Response rates and time to progression were similar for the over 65 and younger patients.
In the ATAC study 45% of patients were 65 years of age or older. The efficacy of anastrozole compared to tamoxifen in patients who were 65 years or older (N=1413 for anastrozole and N=1410 for tamoxifen, the hazard ratio for disease-free survival was 0.93 (95% CI: 0.8, 1.08)) was less than efficacy observed in patients who were less than 65 years of age (N=1712 for anastrozole and N=1706 for tamoxifen, the hazard ratio for disease-free survival was 0.79 (95% CI: 0.67, 0.94)).
The pharmacokinetics of anastrozole are not affected by age.
8.6 Renal Impairment
Since only about 10% of anastrozole is excreted unchanged in the urine, the renal impairment does not influence the total body clearance. Dosage adjustment in patients with renal impairment is not necessary [see Dosage and Administration (2.1) and Clinical Pharmacology (12.3)].
8.7 Hepatic Impairment
The plasma anastrozole concentrations in the subjects with hepatic cirrhosis were within the range of concentrations seen in normal subjects across all clinical trials. Therefore, dosage adjustment is also not necessary in patients with stable hepatic cirrhosis. Anastrozole has not been studied in patients with severe hepatic impairment [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)].
Clinical trials have been conducted with anastrozole tablets, up to 60 mg in a single dose given to healthy male volunteers and up to 10 mg daily given to postmenopausal women with advanced breast cancer; these dosages were tolerated. A single dose of anastrozole tablets that results in life-threatening symptoms has not been established. There is no specific antidote to overdosage and treatment must be symptomatic. In the management of an overdose, consider that multiple agents may have been taken. Vomiting may be induced if the patient is alert. Dialysis may be helpful because anastrozole is not highly protein bound. General supportive care, including frequent monitoring of vital signs and close observation of the patient, is indicated.
Anastrozole tablets for oral administration contain 1 mg of anastrozole, a non-steroidal aromatase inhibitor. It is chemically described as 1,3-Benzenediacetonitrile, a, a, a', a'-tetramethyl-5-(1H-1,2,4-triazol-1-ylmethyl). Its molecular formula is C17H19N5and its structural formula is:
Anastrozole is an off-white powder with a molecular weight of 293.4. Anastrozole has moderate aqueous solubility (0.5 mg/mL at 25°C); solubility is independent of pH in the physiological range. Anastrozole is freely soluble in methanol, acetone, ethanol, and tetrahydrofuran, and very soluble in acetonitrile.
Each tablet contains as inactive ingredients: lactose monohydrate, magnesium stearate, povidone, sodium starch glycolate and opadry white (methylhydroxypropyl cellulose, polyethylene glycol and titanium dioxide).
12.1 Mechanism of Action
The growth of many cancers of the breast is stimulated or maintained by estrogens. Treatment of breast cancer thought to be hormonally responsive (i.e., estrogen and/or progesterone receptor positive or receptor unknown) has included a variety of efforts to decrease estrogen levels (ovariectomy, adrenalectomy, hypophysectomy) or inhibit estrogen effects (antiestrogens and progestational agents). These interventions lead to decreased tumor mass or delayed progression of tumor growth in some women.
In postmenopausal women, estrogens are mainly derived from the action of the aromatase enzyme, which converts adrenal androgens (primarily androstenedione and testosterone) to estrone and estradiol. The suppression of estrogen biosynthesis in peripheral tissues and in the cancer tissue itself can therefore be achieved by specifically inhibiting the aromatase enzyme.
Anastrozole is a potent and selective non-steroidal aromatase inhibitor. It significantly lowers serum estradiol concentrations and has no detectable effect on formation of adrenal corticosteroids or aldosterone.
12.2 Pharmacodynamics
Effect on Estradiol
Mean serum concentrations of estradiol were evaluated in multiple daily dosing trials with 0.5, 1, 3, 5, and 10 mg of anastrozole tablets in postmenopausal women with advanced breast cancer. Clinically significant suppression of serum estradiol was seen with all doses. Doses of 1 mg and higher resulted in suppression of mean serum concentrations of estradiol to the lower limit of detection (3.7 pmol/L). The recommended daily dose, anastrozole tablets 1 mg, reduced estradiol by approximately 70% within 24 hours and by approximately 80% after 14 days of daily dosing. Suppression of serum estradiol was maintained for up to 6 days after cessation of daily dosing with anastrozole tablets 1 mg.
The effect of anastrozole tablets in premenopausal women with early or advanced breast cancer has not been studied. Because aromatization of adrenal androgens is not a significant source of estradiol in premenopausal women, anastrozole would not be expected to lower estradiol levels in premenopausal women.
Effect on Corticosteroids
In multiple daily dosing trials with 3, 5, and 10 mg, the selectivity of anastrozole was assessed by examining effects on corticosteroid synthesis. For all doses, anastrozole did not affect cortisol or aldosterone secretion at baseline or in response to ACTH. No glucocorticoid or mineralocorticoid replacement therapy is necessary with anastrozole.
Other Endocrine Effects
In multiple daily dosing trials with 5 and 10 mg, thyroid stimulating hormone (TSH) was measured; there was no increase in TSH during the administration of anastrozole tablets. Anastrozoledoes not possess direct progestogenic, androgenic, or estrogenic activity in animals, but does perturb the circulating levels of progesterone, androgens, and estrogens.
12.3 Pharmacokinetics
Inhibition of aromatase activity is primarily due to anastrozole, the parent drug. Absorption of anastrozole is rapid and maximum plasma concentrations typically occur within 2 hours of dosing under fasted conditions. Studies with radiolabeled drug have demonstrated that orally administered anastrozole is well absorbed into the systemic circulation. Food reduces the rate but not the overall extent of anastrozole absorption. The mean Cmaxof anastrozole decreased by 16% and the median Tmax was delayed from 2 to 5 hours when anastrozole was administered 30 minutes after food. The pharmacokinetics of anastrozole are linear over the dose range of 1 to 20 mg, and do not change with repeated dosing. The pharmacokinetics of anastrozole were similar in patients and healthy volunteers.
Steady-state plasma levels are approximately 3- to 4-fold higher than levels observed after a single dose of anastrozole tablets. Plasma concentrations approach steady-state levels at about 7 days of once daily dosing. Anastrozole is 40% bound to plasma proteins in the therapeutic range.
Metabolism of anastrozole occurs by N-dealkylation, hydroxylation and glucuronidation. Three metabolites of anastrozole (triazole, a glucuronide conjugate of hydroxy-anastrozole, and a glucuronide conjugate of anastrozole itself) have been identified in human plasma and urine. The major circulating metabolite of anastrozole, triazole, lacks pharmacologic activity.
Anastrozole inhibited reactions catalyzed by cytochrome P450 1A2, 2C8/9, and 3A4 in vitro with Ki values which were approximately 30 times higher than the mean steady-state Cmaxvalues observed following a 1 mg daily dose. Anastrozole had no inhibitory effect on reactions catalyzed by cytochrome P450 2A6 or 2D6 in vitro. Administration of a single 30 mg/kg or multiple 10 mg/kg doses of anastrozole to healthy subjects had no effect on the clearance of antipyrine or urinary recovery of antipyrine metabolites.
Eighty-five percent of radiolabeled anastrozole was recovered in feces and urine. Hepatic metabolism accounts for approximately 85% of anastrozole elimination. Renal elimination accounts for approximately 10% of total clearance. The mean elimination half-life of anastrozole is 50 hours.
Effect of Gender and Age
Anastrozole pharmacokinetics have been investigated in postmenopausal female volunteers and patients with breast cancer. No age related effects were seen over the range <50 to >80 years.
Effect of Race
Estradiol and estrone sulfate serum levels were similar between Japanese and Caucasian postmenopausal women who received 1 mg of anastrozole daily for 16 days. Anastrozole mean steady-state minimum plasma concentrations in Caucasian and Japanese postmenopausal women were 25.7 and 30.4 ng/mL, respectively.
Effect of Renal Impairment
Anastrozole pharmacokinetics have been investigated in subjects with renal impairment. Anastrozole renal clearance decreased proportionally with creatinine clearance and was approximately 50% lower in volunteers with severe renal impairment (creatinine clearance < 30 mL/min/1.73 m2) compared to controls. Total clearance was only reduced 10%. No dosage adjustment is needed for renal impairment. [see Dosage and Administration (2.1) and Use in Specific Populations (8.6)]
Effect of Hepatic Impairment
Anastrozole pharmacokinetics have been investigated in subjects with hepatic cirrhosis related to alcohol abuse. The apparent oral clearance (CL/F) of anastrozole was approximately 30% lower in subjects with stable hepatic cirrhosis than in control subjects with normal liver function. However, these plasma concentrations were still with the range of values observed in normal subjects. The effect of severe hepatic impairment was not studied. No dose adjustment is necessary for stable hepatic cirrhosis. [see Dosage and Administration (2.2) and Use in Specific Populations (8.7)]
13.1 Carcinogenesis & Mutagenesis & Impairment Of Fertility
A conventional carcinogenesis study in rats at doses of 1 to 25 mg/kg/day (about 10 to 243 times the daily maximum recommended human dose on a mg/m2basis) administered by oral gavage for up to 2 years revealed an increase in the incidence of hepatocellular adenoma and carcinoma and uterine stromal polyps in females and thyroid adenoma in males at the high dose. A dose related increase was observed in the incidence of ovarian and uterine hyperplasia in females. At 25 mg/kg/day, plasma AUC0-24 hrlevels in rats were 110 to 125 times higher than the level exhibited in postmenopausal volunteers at the recommended dose. A separate carcinogenicity study in mice at oral doses of 5 to 50 mg/kg/day (about 24 to 243 times the daily maximum recommended human dose on a mg/m2 basis) for up to 2 years produced an increase in the incidence of benign ovarian stromal, epithelial and granulosa cell tumors at all dose levels. A dose related increase in the incidence of ovarian hyperplasia was also observed in female mice. These ovarian changes are considered to be rodent-specific effects of aromatase inhibition and are of questionable significance to humans. The incidence of lymphosarcoma was increased in males and females at the high dose. At 50 mg/kg/day, plasma AUC levels in mice were 35 to 40 times higher than the level exhibited in postmenopausal volunteers at the recommended dose.
Anastrozole has not been shown to be mutagenic in in vitro tests (Ames and E. coli bacterial tests, CHO-K1 gene mutation assay) or clastogenic either in vitro (chromosome aberrations in human lymphocytes) or in vivo (micronucleus test in rats).
Oral administration of anastrozole to female rats (from 2 weeks before mating to pregnancy day 7) produced significant incidence of infertility and reduced numbers of viable pregnancies at 1 mg/kg/day (about 10 times the recommended human dose on a mg/m2 basis and 9 times higher than the AUC0-24 hr found in postmenopausal volunteers at the recommended dose). Pre-implantation loss of ova or fetus was increased at doses equal to or greater than 0.02 mg/kg/day (about one-fifth the recommended human dose on a mg/m2 basis). Recovery of fertility was observed following a 5-week non-dosing period which followed 3 weeks of dosing. It is not known whether these effects observed in female rats are indicative of impaired fertility in humans.
Multiple-dose studies in rats administered anastrozole for 6 months at doses equal to or greater than 1 mg/kg/day (which produced plasma anastrozole Cssmax and AUC0-24 hrthat were 19 and 9 times higher than the respective values found in postmenopausal volunteers at the recommended dose) resulted in hypertrophy of the ovaries and the presence of follicular cysts. In addition, hyperplastic uteri were observed in 6-month studies in female dogs administered doses equal to or greater than 1 mg/kg/day (which produced plasma anastrozole Cssmax and AUC0-24 hr that were 22 times and 16 times higher than the respective values found in postmenopausal women at the recommended dose). It is not known whether these effects on the reproductive organs of animals are associated with impaired fertility in premenopausal women.
13.2 Animal Pharmacology & Or Toxicology
Reproductive Toxicology
Anastrozole has been found to cross the placenta following oral administration of 0.1 mg/kg in rats and rabbits (about 1 and 1.9 times the recommended human dose, respectively, on a mg/m2 basis). Studies in both rats and rabbits at doses equal to or greater than 0.1 and 0.02 mg/kg/day, respectively (about 1 and 1/3, respectively, the recommended human dose on a mg/m2 basis), administered during the period of organogenesis showed that anastrozole increased pregnancy loss (increased pre- and/or post-implantation loss, increased resorption, and decreased numbers of live fetuses); effects were dose related in rats. Placental weights were significantly increased in rats at doses of 0.1 mg/kg/day or more.
Evidence of fetotoxicity, including delayed fetal development (i.e., incomplete ossification and depressed fetal body weights), was observed in rats administered doses of 1 mg/kg/day (which produced plasma anastrozole Cssmax and AUC0-24 hr that were 19 times and 9 times higher than the respective values found in postmenopausal volunteers at the recommended dose). There was no evidence of teratogenicity in rats administered doses up to 1 mg/kg/day. In rabbits, anastrozole caused pregnancy failure at doses equal to or greater than 1 mg/kg/day (about 16 times the recommended human dose on a mg/m2 basis); there was no evidence of teratogenicity in rabbits administered 0.2 mg/kg/day (about 3 times the recommended human dose on a mg/m2 basis).
14.1 Adjuvant Treatment of Breast Cancer in Postmenopausal Women
A multicenter, double-blind trial (ATAC) randomized 9,366 postmenopausal women with operable breast cancer to adjuvant treatment with anastrozoletablets 1 mg daily, tamoxifen 20 mg daily, or a combination of the two treatments for five years or until recurrence of the disease.
The primary endpoint of the trial was disease-free survival (i.e., time to occurrence of a distant or local recurrence, or contralateral breast cancer or death from any cause). Secondary endpoints of the trial included distant disease-free survival, the incidence of contralateral breast cancer and overall survival. At a median follow-up of 33 months, the combination of anastrozoletablets and tamoxifen did not demonstrate any efficacy benefit when compared with tamoxifen in all patients as well as in the hormone receptor positive subpopulation. This treatment arm was discontinued from the trial. Based on clinical and pharmacokinetic results from the ATAC trial, tamoxifen should not be administered with anastrozole. [see Drug Interactions (7.1)]
Demographic and other baseline characteristics were similar among the three treatment groups (see Table 7).
Table 7 - Demographic and Baseline Characteristics for ATAC Trial
Patients in the two monotherapy arms of the ATAC trial were treated for a median of 60 months (5 years) and followed for a median of 68 months. Disease-free survival in the intent-to-treat population was statistically significantly improved [Hazard Ratio (HR) = 0.87, 95% CI: 0.78, 0.97, p=0.0127 in the anastrozolearm compared to the tamoxifen arm. In the hormone receptor-positive subpopulation representing about 84% of the trial patients, disease-free survival was also statistically significantly improved (HR =0.83, 95% CI: 0.73, 0.94, p=0.0049) in the anastrozolearm compared to the tamoxifen arm.
Figure 1 — Disease-Free Survival Kaplan Meier Survival Curve for all Patients Randomized to AnastrozoleTablets or Tamoxifen Monotherapy in the ATAC trial (Intent-to-Treat)
Figure 2 — Disease-free Survival for Hormone Receptor-Positive Subpopulation of Patients Randomized to AnastrozoleTablets or Tamoxifen Monotherapy in the ATAC Trial
The survival data with 68 months follow-up is presented in Table 9.
In the group of patients who had previous adjuvant chemotherapy (N=698 for anastrozoleand N=647 for tamoxifen), the hazard ratio for disease-free survival was 0.91 (95% CI: 0.73 to 1.13) in the anastrozolearm compared to the tamoxifen arm.
The frequency of individual events in the intent-to-treat population and the hormone receptor-positive subpopulation are described in Table 8.
Table 8- All Recurrence and Death Events*
A summary of the study efficacy results is provided in Table 9.
Table 9 - ATAC Efficacy Summary*
14.2 First-Line Therapy in Postmenopausal Women with Advanced Breast Cancer
Two double-blind, controlled clinical studies of similar design (0030, a North American study and 0027, a predominately European study) were conducted to assess the efficacy of anastrozolecompared with tamoxifen as first-line therapy for hormone receptor positive or hormone receptor unknown locally advanced or metastatic breast cancer in postmenopausal women. A total of 1021 patients between the ages of 30 and
Demographics and other baseline characteristics, including patients who had measurable and no measurable disease, patients who were given previous adjuvant therapy, the site of metastatic disease and ethnic origin were similar for the two treatment groups for both trials. The following table summarizes the hormone receptor status at entry for all randomized patients in trials 0030 and 0027.
Table 10 – Demographic and Other Baseline Characteristics
For the primary endpoints, trial 0030 showed that anastrozolehad a statistically significant advantage over tamoxifen (p=0.006) for time to tumor progression; objective tumor response rates were similar for anastrozoleand tamoxifen. Trial 0027 showed that anastrozoleand tamoxifen had similar objective tumor response rates and time to tumor progression (see Table 11 and Figure 3 and 4)
Table 11 below summarizes the results of trial 0030 and trial 0027 for the primary efficacy endpoints.
Table 11 – Efficacy Results of First-line Treatment
Figure 4 - Kaplan-Meier probability of time to progression for all randomized patients (intent-to-treat) in Trial 0027
Results from the secondary endpoints were supportive of the results of the primary efficacy endpoints. There were too few deaths occurring across treatment groups of both trials to draw conclusions on overall survival differences.
14.3 Second-Line Therapy in Postmenopausal Women with Advanced Breast Cancer who had Disease Progression following Tamoxifen Therapy
Anastrozole was studied in two controlled clinical trials (0004, a North American study; 0005, a predominately European study) in postmenopausal women with advanced breast cancer who had disease progression following tamoxifen therapy for either advanced or early breast cancer. Some of the patients had also received previous cytotoxic treatment. Most patients were ER-positive; a smaller fraction were ER-unknown or ER-negative; the ER-negative patients were eligible only if they had a positive response to tamoxifen. Eligible patients with measurable and non-measurable disease were randomized to receive either a single daily dose of 1 mg or 10 mg of anastrozoleor megestrol acetate 40 mg four times a day. The studies were double-blinded with respect to anastrozole. Time to progression and objective response (only patients with measurable disease could be considered partial responders) rates were the primary efficacy variables. Objective response rates were calculated based on the Union Internationale Contre le Cancer (UICC) criteria. The rate of prolonged (more than 24 weeks) stable disease, the rate of progression, and survival were also calculated.
Both trials included over 375 patients; demographics and other baseline characteristics were similar for the three treatment groups in each trial. Patients in the 0005 trial had responded better to prior tamoxifen treatment. Of the patients entered who had prior tamoxifen therapy for advanced disease (58% in Trial 0004; 57% in Trial 0005), 18% of these patients in Trial 0004 and 42% in Trial 0005 were reported by the primary investigator to have responded. In Trial 0004, 81% of patients were ER-positive, 13% were ER-unknown, and 6% were ER-negative. In Trial 0005, 58% of patients were ER-positive, 37% were ER-unknown, and 5% were ER-negative. In Trial 0004, 62% of patients had measurable disease compared to 79% in Trial 0005. The sites of metastatic disease were similar among treatment groups for each trial. On average, 40% of the patients had soft tissue metastases; 60% had bone metastases; and 40% had visceral (15% liver) metastases.
Efficacy results from the two studies were similar as presented in Table 12. In both studies there were no significant differences between treatment arms with respect to any of the efficacy parameters listed in the table below.
Table 12– Efficacy Results of Second-line Treatment
When data from the two controlled trials are pooled, the objective response rates and median times to progression and death were similar for patients randomized to anastrozoletablets 1 mg and megestrol acetate. There is, in this data, no indication that anastrozoletablets 10 mg is superior to anastrozoletablets 1 mg.
Table 13 – Pooled Efficacy Results of Second-line Treatment
Anastrozole Tablets is supplied as follows:
Product NDC
No. No. Strength
129030 63323-129-30 1 mg 30 tablets per bottle.
Store at 20º to 25ºC (68º to 77ºF) [see USP Controlled Room Temperature].
17.1 Pregnancy
Patients should be advised that anastrozole tablets may cause fetal harm. They should also be advised that anastrozole tablets are not for use in premenopausal women; therefore, if they become pregnant they should stop taking anastrozole tablets and immediately contact their doctor.
17.2 Allergic (Hypersensitivity) Reactions
Patients should be informed of the possibility of serious allergic reactions with swelling of the face, lips, tongue and/or throat (angioedema) which may cause difficulty in swallowing and/or breathing and to immediately report this to their doctor.
17.3 Ischemic Cardiovascular Events
Patients with pre-existing ischemic heart disease should be informed that an increased incidence of cardiovascular events has been observed with use of anastrozole tablets compared to tamoxifen use.
17.4 Bone Effects
Patients should be informed that anastrozole tablet lowers the level of estrogen. This may lead to a loss of the mineral content of bones, which might decrease bone strength. A possible consequence of decreased mineral content of bones is an increase in the risk of fractures.
17.5 Cholesterol
Patients should be informed that an increased level of cholesterol might be seen while receiving anastrozole tablets.
17.7 FDA-Approved Patient Labeling
Read the information that comes with anastrozole tablets before you start taking it and each time you get a refill. The information may have changed. This leaflet does not take the place of talking with your doctor about your medical condition or treatment. Talk with your doctor about anastrozole tablets when you start taking it and at regular checkups.
What is Anastrozole tablets?
Anastrozole tablets is a prescription medicine used in women who have finished menopause ("the change of life") for:
Anastrozole tablets do not work in women with breast cancer who have not finished menopause (premenopausal women).
Who should not take Anastrozole tablets?
Do not take anastrozole tablets if you:
What is the most important information I should know about Anastrozole tablets?
Anastrozole tablets may cause serious side effects including:
What should I tell my doctor before taking Anastrozole tablets?
Anastrozole tablets may not be right for you. Before taking anastrozole tablets, tell your doctor about all your medical conditions, including if you:
Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:
Know the medicines you take. Keep a list of them and show it to your doctor and pharmacist each time you get a new medicine.
How should I take Anastrozole tablets?
Talk with your doctor about any health changes you have while taking anastrozole tablets.
What are possible side effects of Anastrozole tablets?
Anastrozole tablets can cause serious side effects including:
Common side effects in women taking anastrozole tablets include:
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
General information about Anastrozole tablets.
Medicines are sometimes prescribed for conditions that are not mentioned in patient information leaflets. Do not take anastrozole tablets for a condition for which it was not prescribed. Do not give anastrozole tablets to other people, even if they have the same symptoms you have. It may harm them.
This patient information leaflet summarizes the most important information about anastrozole tablets. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about anastrozole tablets that is written for health professionals.
What are the ingredients in Anastrozole tablet?
Active ingredient: anastrozole
Inactive ingredients: lactose monohydrate, magnesium stearate, povidone, sodium starch glycolate and opadry white (methylhydroxypropyl cellulose, polyethylene glycol and titanium dioxide).
Manufactured for:
APP Pharmaceuticals, LLC
Schaumburg, IL 60173
Made in India
For Product Inquiry:
1-800-551-7176 or www.APPpharma.com
Anastrozole Tablets 1 mg Container Label
1 mg
Rx only
30 Tablets
Revised: 04/2010 APP Pharmaceuticals, LLC
Reproduced with permission of U.S. National Library of Medicine
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text:
SAN FRANCISCO (Reuters) - Facebook Inc, stung by doubts that advertising on the social network delivers enough bang for the buck, is preparing to unveil data to counter its critics and show that "clicks," the current metric of choice, tell only half the story.
The world's No. 1 social network, embarrassed just days before its initial public offering in May when General Motors declared it was pulling the plug on all paid advertising on its network, will argue that big-brand marketers should abandon the industry's obsession with numbers of clicks and focus on more effective advertising techniques.
Fewer than 1 percent of in-store sales tied to brand advertising campaigns on Facebook come from people who clicked on an ad, according to a new study that Facebook has conducted through a partnership with Datalogix, a data mining firm that tracks real-world retail sales.
"We ended up in this world where the click is king," said Brad Smallwood, Facebook's head of measurement and insights, who will present some of Facebook's findings at one of the advertising industry's biggest conferences in New York on Monday.
While designing online ads to garner clicks makes sense for certain types of companies - such as e-commerce firms trying to ring up immediate online sales - clicks are not relevant to brand marketers, Smallwood said.
Through its partnership with Datalogix, Facebook says it can now give brand marketers data on the actual in-store sales that their ad campaigns on Facebook have generated - a more useful piece of feedback than total clicks. Datalogix tracks the relationship between ads on Facebook and real-world spending by compiling consumer purchasing information from retail stores and matching it with data about Facebook ad impressions.
Facebook's push to provide marketers with more feedback comes as the company's revenue growth slows and the effectiveness of its ads remains a hotly debated topic. Facebook, whose stock by the end of the third quarter was down 43 percent since its IPO, has unveiled a variety of new advertising capabilities in recent months, including ads designed to be viewed on smartphones.
"Advertisers have been increasingly vocal about concerns regarding effectiveness of Facebook," said Pivotal Research Group analyst Brian Wieser.
Clicks became a metric of choice in part because they had become tied to Google Inc's performance. The world's No. 1 Web search engine offers an effective and easy-to-measure form of advertising because it lets marketers reach consumers at the moment they are searching for a particular product.
If a consumer clicks on the search ad, the job is done.
Facebook argues that for brand advertisers, fine-tuning the number of times a consumer sees an ad as well as ensuring that the ad has reached all of its target audience are far more effective techniques.
According to Smallwood, marketers can increase the return on investment from their ads by 40 percent by focusing on an ad's so-called frequency. Instead of one Facebook user seeing an ad 100 times and another user seeing the ad only twice, for example, Facebook says it will soon offer advertisers' insight on the ideal number of ad impressions for a particular campaign.
"Using the Datalogix tool, we'll able to understand what that sweet spot is," Smallwood said, adding that Facebook will then control how often each user sees the ad.
Many large brand advertising campaigns are not even hitting half their target audience, he said. But ad campaigns that focus on getting the optimal reach are 88 percent more effective at improving their return on investment, Facebook says its studies have shown.
Getting online advertisers to break their focus on clicks will not be easy, but Facebook says the techniques it is advocating are standard in the television advertising world.
Vik Kathuria, a managing partner at GroupM, the parent company of WPP's media agencies, said there has been a longstanding desire in the industry for different ways to measure the effectiveness of online display ads.
The click-through rate "as a metric was probably irrelevant five or six years ago," said Kathuria, who said his firm has talked with Facebook about this.
"What (Smallwood) is doing is what we have been saying all along. Let's talk about bigger brand dollars and in that context how you measure the efficacy, not click-through rates."
Still, persuading the online brand advertising industry to change its habits could take time, said eMarketer analyst Debra Aho Williamson.
"For an advertiser, the click is a powerful indication that somebody is at least possibly interested in learning more about their brand," said Williamson. "It becomes easy to focus on the click as a metric of success."
As Facebook strives to persuade marketers to think differently, it also is attempting to assuage privacy concerns.
Facebook's partnership with Datalogix has raised complaints from privacy advocates, who say the social networking company could be violating the terms of a privacy settlement with the U.S. Federal Trade Commission by not obtaining the express consent of users to share their personal information.
Smallwood said the only information given to Datalogix is that people were exposed to certain marketing messages. He added that Facebook is not receiving any personal consumer information from Datalogix.
Reporting By Alexei Oreskovic with additional reporting by Jennifer Saba in New York; Editing by Edwin Chan, Gary Crosse and Douglas Royalty


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A small shrine on the path through Fushimi-Inari shrine, in Kyoto, Japan. Fushimi Inari Taisha (伏見稲荷大社) is a large shrine dedicated to the Kami Inari.
Many businesses pay their respects to Inari in order to achieve wealth and business success. The hill that Fushimi Inari is located on is crossed with paths lined with thousands of torii (鳥居) gates, painted in bright vermillion. These torii are donated by business and business people from across Japan. Each gate bears the name of the business or person that donated it.
The eight islands of Japan sprang into existence through Divine Intervention.The first two gods who came into existence were Izanagi no Mikoto and Izanami no Mikoto, the Exalted Male and Exalted Female. It was their job to make the land for people to live on.They went to the bridge between heaven and earth and, using a jewel-encrusted halberd, Izanagi and Izanami churned up the sea into a frothy foam. As salty drips of water fell from the tip of the halberd the first island was formed. Its name was Onogoro.So far, so good. But when Izanagi and Izanami first met on their island, Izanami spoke to Isanagi without being spoken to first. Since she was the female, and this was improper, their first union created badly-formed offspring who were sent off into the sea in boats.The next time they met, Izanagi was sure to speak first, ensuring the proper rules were followed, and this time they produced eight children, which became the islands of Japan.I'm sure you did not fail to miss the significance of this myth for the establishment of Japanese formal society.At present, Japan is the financial capital of Asia. It has the second largest economy in the world and the largest metropolitan area (Tokyo.)Technically there are three thousand islands making up the Japanese archipelago. Izanagi and Izanami must have been busy little devils with their jewelled halberd...Japan's culture is highly technical and organized. Everything sparkles and swooshes on silent, miniaturized mechanisms.They're a world leader in robotics, and the Japanese have the longest life-expectancy on earth.Text by Steve Smith.


text:
Manage bookings
If you're an Airpoints™ member, you can view all your flight bookings in one place. Simply sign into your account and choose My Flight Bookings under My Bookings. If you haven't yet registered, register now.
To add future bookings to your account, please sign in, select See my bookings then Add a missing booking. You can either enter your Air New Zealand reference or flight information.
Alternatively you can view and manage your booking online if the booking was made with Air New Zealand through our website or over the telephone.
Whichever way you retrieve your booking, you will see range of options depending on the booking type. These may include requesting a copy of your electronic ticket, requesting seats, changing your booking and cancelling your booking. Details of which booking types can be changed and cancelled are below.
Please note - not all bookings are able to be accessed online. Your Airpoints membership number must be in your booking to view it in your account.
Changing a booking
Domestic and international bookings can be changed online, subject to the fare rules. Please note, any changes or cancellations will apply to all travellers in the same booking.
Check change fees and fare rules
If you cannot change your booking online, please contact us. Service fees will apply for changes made via the Contact Centre.
Cancelling a booking
Bookings for domestic and international travel may be cancelled online, subject to the following considerations:
- Flexi fares and Business fares may be cancelled up until departure and are fully refundable with the exception of Flexitime and Business Saver fares
- A booking must be cancelled in full, i.e. both the outbound and return flights if a round trip
When cancelling online, a refund will be credited to the original form of payment you used to make the booking. For further assistance, please call us on 800-8523380.
If you are eligible for a refund of your Seat Select or Extra Bags purchases, please fill out this form to start the refund process.


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Boosey & Hawkes
Welcome to our World of Music
Boosey & Hawkes is the largest specialist classical music publishing company in the world. We own an unrivalled catalogue of music copyrights including the works of such distinguished 20th century composers as Stravinsky, Bartók, Copland, Britten,Prokofieff, Strauss and Rachmaninoff. In the 21st century, we continue to publish the very best in new music and have exclusive agreements with many of the leading international classical composers of today, including John Adams, Steve Reich, James MacMillan, Mark-Anthony Turnage and Karl Jenkins, as well as a growing roster ofjazz composers.
Boosey & Hawkes is a global publisher, with offices in New York, London, and Berlin and a network of agents in every major country. We promote our repertoire throughout the music world and seek to lead artistic and creative taste.
Our extensive catalogue of printed music for the professional, student and leisure markets ranges from instrumental and choral to market-leading tutor books and creative teaching materials for schools and colleges. For these and publications from other music publishers, please visit our shop.
The catalogue can be heard in a variety of audio-visual media, including film, television, advertising, videogames and on the internet. Through partnerships with several specialty labels, our global licensingteam is often able to offer music and master recordings for our works. Moreover, the 'recorded music' library started by Ralph Hawkes in the 1930s has been transformed into Boosey & Hawkes Production Music, providing original, high quality recordings for use in all media. Our Cavendish brand, one of the top independent production music libraries, has been joined by Abaco, a recently-purchased American catalogue, both serviced through our state-of-the-art recording studio in London.
Further information about Boosey & Hawkes is contained in the following pages. For a lively and detailed history of the company we recommend you read Boosey & Hawkes: The publishing story by Helen Wallace.
Thank you for taking the time to find out about our organisation.
John Minch


text:
Chicago P.D. - S05
Year: 2015
Duration: 43 min
IMDb: 8.2
Country: USA
Actors: Jason Beghe, Jesse Lee Soffer, Patrick John Flueger, Marina Squerciati, Elias Koteas, LaRoyce Hawkins, Amy Morton, Sophia Bush, Jon Seda, Brian Geraghty
District 21 of the Chicago Police Department is made up of two distinctly different groups. There are the uniformed cops who patrol the beat and go head-to-head with the city's street crimes. And there's the Intelligence Unit, the team that combats the city's major offenses - organized crime, drug trafficking, high profile murders and beyond.


text:
N° 23–2007: Celebrating Space with ESA in Paris
31 May 2007
The French capital has been chosen to host a celebration of space, "Paris fête l'Espace", to be held on the place du Trocadéro on 15 June starting at 9.30pm.
With its "Night of the Astronauts" in Cologne/Germany in 2004 and then in Barcelona/Spain in 2006, the European Space Agency introduced a new kind of attraction designed to inform the public of and share with it advances to date in the conquest of space.
In order to cater for the huge public interest in space demonstrated by these repeatedly successful events, ESA decided to organise, in partnership with the Centre National d'Etudes Spatiales and with the support of the City of Paris, an altogether novel celebration of space on the place du Trocadéro.
The stage specially set up for the purpose will be graced by many distinguished guests. Astronauts and experts from the world of science will in turn appear before the public from 9.30pm onwards, in what promises to be a richly eventful evening.
TV presenter Jérôme Bonaldi and ESA astronaut Jean-François Clervoy of France will host the show. Together with their guests, they will tackle various topics, such as the huge importance of application satellite operations, for telecommunications as well as for observing climate change, with Pascale Ultré-Guérard of CNES; there will then be a session on "How to become an astronaut" featuring ESA astronaut Léopold Eyharts of France, who is due to fly to the International Space Station at the end of the year on a mission to install Europe's Columbus space laboratory.
Space exploration programmes geared to discovering planets in our solar system will also be highlighted. Then will come the official presentation to ESA of an original first edition of the Jules Verne classic From the Earth to the Moon. This is due to be carried to the ISS onboard the European supply vessel, the Automated Transfer Vehicle. For the inaugural flight, the first ATV has been named Jules Verne in honour of this visionary writer.
At 10.30pm, the public will be treated to a son et lumière laser spectacular, featuring special effects, space music and images produced from science satellite data projected onto a giant 350m2 screen.
Private reception, Eiffel Tower first level
As a prelude to this public event, a private reception starting at 7pm will be held on the first level of the Eiffel Tower, arranged by Jean-Jacques Dordain, ESA Director General, and Yannick d'Escatha, CNES President.
Reception programme:
•Inauguration of the corresponding space exhibition on the first level of the Eiffel Tower
•Official handing-over to ESA of the first-edition Jules Verne classic From the Earth to the Moon
After cocktails and a buffet dinner, the evening's proceedings will continue with the public festivities starting at 9.30pm.
Guests arriving are asked to make their way to the ESA/CNES stand located at the Eiffel Tower north base, as from 6pm.
To obtain accreditation, please complete and return the attached form by fax to:
ESA, Media Relations Office, Paris, France
Fax. no.: +33 (0)1 53 69 76 90
ESA/CNES reception, Eiffel Tower first level
Friday 15 June 2007, from 6pm onwards
Surname:______________________First Name:_________________
Media Oganisation:_______________________________________
Passport no./Identity card no.: ___________________________
Issued by:_________________________________________________
Expiry date:_______________________________________________
Nationality: _______________________________________________
Date of birth:______________________________________________
Office tel.:_________________ Fax:__________________________
Mobile: ___________________ Email :________________________
( ) will be attending the 15 June reception on the first level of the Eiffel Tower
Please return this form to:
ESA, Media Relations Office, Paris, France
Tel: +33(0)1 53 69 72 99
Fax: +33 (0)1 53 69 76 90
Email: email@example.com
For further information:
ESA - Media Relations Service
Tel: +33.(0)1.5369.7299
Fax: +33.(0)1.5369.7690


text:
Holle Organic Fruit Bar Apple & Banana is suitable as a snack for babies aged from 12 months to nibble and chew. Its handy, practical size makes it easy for even small baby hands to grasp. The fruit bar has a wholegrain spelt wafer-base, ensuring that children won't get sticky hands when holding them.
More info on use, ingredients, nutritional values & more
Apple juice concentrate* 44 %, bananas dried* 41 %, rice flour*, wholegrain spelt wafer* 5 % (wholegrain spelt flour*,
potato starch*)
*from organic farming.
May contain traces of nuts (no peanut), soy, milk and sesame.
Only carefully selected organic ingredients are used to make Holle Organic Fruit Bar Apple & Banana.
Please do not let your baby chew unattended. Due to risk of choking, do not let your baby chew on the fruit bar while lying down or walking.
Make sure to follow a regular dental hygiene routine from the baby's first tooth.