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We've all heard the statistics about childhood obesity; rates of unhealthy body weight among children and adolescents have tripled since the 1980s. But new studies show it's a problem that Americans are concerned with and support action against.
Respondents in a study published in January's American Journal of Preventive Medicine considered childhood obesity as serious of a problem as tobacco use and violence. Respondents also supported most school-, community- and media-based strategies that include offering health information, limiting unhealthy food promotion, and increasing healthy nutrition and physical activity choices. Here's the not-so-good news: They were generally opposed to regulatory and tax or cost-based interventions, and they did not think that childhood obesity was as big of a problem as drug abuse. Of those surveyed, women in general and individuals with higher levels of education showed greater support for these interventions while parents with children at home were less supportive.
So, just what are the fitness community, government and the public doing to help? One example of ongoing efforts comes from Louisiana. The Louisiana Department of Health and Hospitals launched a four-month competition in February to get young Louisianans moving. The Lighten Up Louisiana Kids program urges 5 to 17 year olds to group into teams of 10 to 30 and track their miles of activity on a wall chart. By the end of the program, teams that average 200 miles per person qualify for awards including medals, special recognition at the state capitol with Governor Kathleen Babineaux Blanco before state legislators and a picture of the team featured on a billboard in the team's hometown. Teams can be made of school classes, youth church groups, after-school groups, 4-H clubs, etc.
"The purpose of the Lighten Up Louisiana Kids program is to fight the obesity epidemic we are facing in Louisiana and nationwide," Gov. Blanco said in a letter to Louisiana residents. "The program is a positive way to teach kids about the importance of being physically active and to show them that fitness can be fun."
Teams are run by a team captain, who is an adult with access to the Internet (which is necessary to report miles, ask questions and download activity and nutritional resources for the group). The program is free for all participants and is in addition to Lighten Up Louisiana, a similar program for adults.
Over on the East Coast, Chelsea Piers in New York City opened a Kids Fitness Center in January complete with Fun Fit, a 90-minute class that combines strength training, cardio, flexibility and rock-climbing activities for children from 5 to 12 with kid-friendly equipment and exercises.
"Not every child will want to participate in competitive sports. This class gives them another outlet," Peter Kormann, director of gymnastics at Chelsea Piers, said in a release about the class. "Additionally, this is the age, 5 to 12 years old, when life-long habits are formed. A child who is taught about fitness early will have a better chance of becoming an adult who cares about fitness."
Finally, national, state and local organizations are trying to get more fitness into schools.
The Washington Action for Healthy Kids, a state team of the national nonprofit Action for Healthy Kids, released "The Learning Connection: The Value of Improving Nutrition and Physical Activity in our Schools." The report shows how improving nutrition and physical activity in schools may not only help schools academically but also financially.
"Schools alone cannot solve the problem of childhood obesity, but they can and should have a positive influence on children's eating and physical activity behaviors," Shelley Curtis of Children's Alliance and Action for Healthy Kids subcommittee co-chair, said.
The organization is also helping schools to develop local wellness policies — a policy now mandatory since Congress passed The Child Nutrition and WIC Reauthorization Act of 2004 in June 2004.


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We are delighted to welcome our young magicians who will be competing in the Arthur Setterington Close-Up Competition. Hull Magicians' Circle members will not only form part of the audience with the friends and family of competitors, they will also vote for this year's winner! With close up magic being very popular among the current crop of youngsters, the standards are expected to be high and will make a great show.
After the break we will be holding our own competition - the third round of the Simpson Shield with 'a trick with a wallet'.

subset: commoncrawl


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Javier Hernandez is unsure whether he will remain at Manchester United next year, but Atletico Madrid are willing to offer the Mexican an escape route from Old Trafford should he decide to leave.
Hernandez flew out to the United States to join the club's pre-season tour, but he has so far only made two brief substitute appearances.
Even though new manager Louis van Gaal likes to play with two strikers, Hernandez still faces stiff competition from Robin van Persie, Wayne Rooney, Danny Welbeck and Wilfried Zaha for a first-team place.
In a rushed interview following United's penalty shoot-out win over Inter Milan on Tuesday night, Hernandez was asked if he saw his future at Old Trafford.
"The future, only god knows," he said.
When pressed on his limited match time under Van Gaal, the striker responded: "There is competition here and I will continue to work hard as I always do."
Hernandez was an instant hit at United following his surprise move from home-town club Guadalajara in 2011.
But the signing of Van Persie and the emergence of Welbeck has caused the Mexican to start just 15 Premier League games in the last two seasons.
Van Gaal was asked after the friendly win in Washington whether he would consider selling Hernandez.
He replied: "That I cannot answer because he is a player of Manchester United at this moment."
The latter part of the answer seemed to suggest Hernandez could be on his way out of United.
There are plenty of interested parties, chief among them Atletico.
The Spanish champions have already brought in forwards Mario Mandzukic and Antoine Griezmann this summer to compensate for the departures of Diego Costa, David Villa and Adrian Lopez, but Diego Simeone revealed he is still looking for an extra forward.
The Atletico coach thinks Hernandez would be an asset for his side.
"He's a vertical player, he's great in one-on-one situations and he's someone who could be useful to any team," the Atletico coach told a press conference in Mexico, ahead of his team's pre-season friendly with Club America.
"We are speaking to the sporting directors about the type of player we want and then it's up to them to bring the player in. With Javier Hernandez and lots of other great players, anything is possible. We can't close any door until the transfer window shuts."
Inter are also reported to be interested in Hernandez's signature.
Their defender Nemanja Vidic, who played alongside Hernandez at Old Trafford for three years, appears open to the idea of 'Chicharito' coming to Inter.
"He is a great player," Vidic said after Tuesday's game, which went to penalties after a goalless stalemate over 90 minutes.
"He is a Manchester United player but he can play in any team. He is a great professional. That is all I can say."
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Yoichi Wada is a controversial figure in the game industry. That's why when his resigning as President and Representative Director of Square Enix was hailed by many with Joy and by a few with a bit of melancholy.
Looks like, despite his resignation, he didn't go too far, and will be able to watch from an executive position the rebirth of Final Fantasy XIV, that he stubbornly supported.
@Abriael, Do you spend all day on GAF or what? Haha.
Disagrees are from Wada.
I'm ok with this as long as he's not making major decisions. Keep that man away from 15 and KH3.


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Captain's ReportQuite the Boat: Everglades 350CC
By Capt. Ron SvobodaWOW, what a boat! Invoking this kind of emotion out of me is complex. After all, I am a little jaded from having the good fortune of working as a professional boat tester. And in my opinion there are only a handful of boat builders that stand above the norm and produce a truly outstanding product. The Everglades 350 Center Console (CC) is definitely one of them. From the sleek yet brawny silhouette to the prominent hard top, this fish boat is different. And after spending an afternoon with her, what's clear to me is the impeccable quality and relentless attention to detail.Hardcore FishboatThe North-East Florida builder's flagship is a hardcore fish boat unlike any other. She's loaded to the gills with standard features, but available with few options. (There isn't much else to put on her that the company hasn't already thought of!) But if you ask, I'm sure they would be happy to oblige. A bow thruster, some canvas, hull side colors and different engines are some of the available choices.Innovations AboundThe front of the boat includes several innovative items that I really like. There is a plush front seat with side grab-handles, cup holders and head rests just forward of the center console. Forward, a raised deck casting platform incorporates an electric table that rises up from the deck to offer a snack table large enough to accommodate everyone on board. There are also massive storage lockers in the bow's deck with lockable storage compartments in the gunwales for your rods and reels. Finally, the forepeak has an anchor hatch with access to the windlass, control switches and fresh or raw water wash-down hose. Helping to keep the boat organized are six gunwale storage lockers, perfect for storing lines and PFD's. A wide gunwale cap includes long, powder coated bow railing for safety while thick coaming pads, rod storage and toe rails complete the boat's sides.At the HelmBest of all, the command center of the 350 is high-tech and comfortable, with digital instrumentation on top and anti-fatigue matting below. (My feet and joints love this item.) The dash features a state-of-the-art digital switch panel for the DC accessories and a motorized security panel which hides all of your navigation gear. But the Kingfish of the helm station is the electric bolster seats which are mounted atop a compartment dedicated to the battery banks and main power switches.Directly above the helm, a fiberglass hardtop is supported by a powder coated frame, providing mountings for outriggers, antennae, rocket launchers and even a tuna tower if you choose. The frame also has a ladder so climbing to the tower will be simplified. The underside of the top possess a wrap-around windshield with side vents, a radio box, courtesy lights, speakers and spreader lights.More FeaturesAs you might expect the center console integrates a head compartment, but also has a small quarter berth too. The berth is cramped but is enough to get a person out of the weather for a nap in air conditioned comfort. Otherwise the head grants more than enough space for taking care of business, plus a sink and shower to boot. Several lockers can also be found here, making for dry storage and access to the back of the helm's dash.Working your way to the cockpit is a baiter's dream station just under the t-top. This ultra-functional counter is inclusive with livewell, sink, cutting board, tackle drawers and a magnificent fighting chair that quickly deploys and stows. In the sole of the cockpit is an access hatch to tend to bilge pumps, trim pumps and the boats water manifold system. That's not all, at the stern, the transom presents a second livewell, a frozen bait box and a refrigerated fish box. On the back, a molded swim platform offers engine access from the starboard side transom gate and some room for swimming or diving fun.SpecificationsAt a hefty 9,260 pounds (w/o engines), the 10'8" wide hull has a razor sharp 41 degree deadrise at the bow, and draws a scant 24" of water. The boat is also virtually unsinkable thanks to a meticulously installed urethane foam structure system sandwiched between the hull and deck. In order to propel this beauty to her best speed, a trio of outboard engines is required from either Suzuki or Honda. With such few decisions to make on the 350, the toughest one is whether you're worthy of a boat like this: of course you are, just don't tell your wife what you spent on it!
Test Result Highlights
- Top speed for the Everglades 350 CC (2007-) is 50.3 mph (81 kph), burning 63.9 gallons per hour (gph) or 241.86 liters per hour (lph).
- Best cruise for the Everglades 350 CC (2007-) is 20.4 mph (32.8 kph), and the boat gets 1.66 miles per gallon (mpg) or 0.71 kilometers per liter (kpl), giving the boat a cruising range of 613 miles (986.53 kilometers).
- Tested power is 3 x 225-hp Honda 4-Stroke Outboards.
Standard and Optional Features
|CD Stereo
|Head: Fixed
|Shore Power
|Trim Tabs
|Washdown: Fresh Water
|Washdown: Raw Water
Exterior Features
|Ice Chest
|Outlet: 12-Volt Acc
|Swim Ladder
|Swim Platform
|Cockpit Cover
|Standard Isenglass enclosure
Boats More Than 30 Feet
|Bow Thruster
Hull Warranty
10 year
|NMMA Certification
(It's quick and FREE!)


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SALE ENDS SOON! Get 20% off all rings with code AUTUMN20 *excludes custom rings
Often overlooked and undervalued, your worth is much more subtle than most. But when things get bad, you hold your own alongside your more flashy comrades. On the water, or on land, you're a true king, and you need a ring that shows it.
** NOTE - there is a 4-5 week LEAD TIME on these rings** (more below)
Founder's Line Policies:
Each ring in this collection is made entirely in the U.S.A. and handcrafted to order by our ferocious team of artisan Manly Band jewelers.
Not exactly the drone you're looking for? Find out how to do a custom ring here. Fill out the form at the bottom of the page and one of our customer service agents will get back to you with ideas in 24-48 hours.
How long will it take to get to me?
Lead time is about 4-5 weeks. This ring is made to order. Rush orders available for an extra fee. Email us with your rush request at: firstname.lastname@example.com for an estimate. Fed Ex Ground shipping, with signature confirmation, is complimentary. If you need to expedite, let us know!
Sizing - can I pick a quarter size?
Absolutely! We actually send you a complimentary sizer after you order - just to make double sure that we're selecting the right size for you with our jeweler. Sizes shift depending on comfort fit and width, so let our sizing experts lead the way after you get your sizer and determine your standard size. And yes - we can do quarter sizes in Founder's Line and Custom rings.
Yes indeed! We offer complimentary engraving on this ring, up to 35 characters (including spaces). It also comes with the Manly Bands logo and a small notation with the kind of metal used - ex. "14K Gold" "Cobalt"
Financing options?
Yes - we offer a great "3 easy payments" deal with Affirm. It's 3 payments over 3 months with 0% interest! So gives you a little more wiggle room to get what you really want :) You can select this option by clicking "Affirm" near the credit card options at checkout to get more information and sign up to take advantage of that hot deal.
A size exchange on a Founder's Line ring can be processed for a 15% original price fee. Please note exchanges can take 3-4 weeks. If you're wanting to change styles, your best bet is to return the current ring and repurchase the new style.
**Don't worry we're going to send you a sizer and instructions - nothing a man can't handle (but for serious, read the instructions this time). ALWAYS try on your ring BEFORE the wedding. We promise it's not bad luck. You want a little resistance in taking it off. See our video here for more on that (scroll down a smidge).
On most Founder's Line rings, we will accept a return within 30 days of delivery date for a 25% restocking fee. The exception to this rule is if you choose any customizations or engraving options. We will not be able to accept a return on customized rings, as we cannot resell your ring.
Founder's Line rings are covered, at no extra charge, under your FREE Lifetime "no hassle" warranty. If you have any issues after that time, reach out and we will see how we can help and let you know if there are any fees associated with your repairs.
The order process for your Founder's Line ring:
1. You've decided on the Founder's Line ring of your dreams! You place your order on the website.
2. Your complimentary Manly Ring Sizer ships out to you first. Please follow the instructions with it to determine your proper size. We've even got a fun little "how to" video here.
3. You'll get another email from us asking for your size. Hold onto that until you get your Manly Ring Sizer and have a chance to follow the instructions. To properly size yourself, it may take a couple days - we get it. Once we have your size, your order is officially placed and we start making your handcrafted ring. No one likes to get married with the wrong sized wedding ring - so save yourself the stress and fees, and give us the right standard size please :)
4. About 3 weeks later, you will get an email that your ring has shipped!
5. At about the 4-5 week mark, your ring arrives and you realize it is possible to love two things - also you live happily ever after!
Have other questions? Just ask! firstname.lastname@example.com
Like we mentioned, Bro, getting your size right is free and easy - So opt in to get the free sizer. It's a no brainer and you'll be glad you did it.
If you already have a sizer/want to opt out of the free sizer, no problem. After you purchase, you'll get an email from us in about 5 days, asking for your size. Alternatively, you can email us early to confirm your size and wedding date and we can get this party started.


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A local veterans organization is skeptical about a recent decision by the Department of Veterans Affairs to target claims older than a year for completion by 2015.
A local veterans organization is skeptical about a recent decision by the Department of Veterans Affairs to target claims older than a year for completion by 2015.
Veterans whose claims fall in that time frame will be given a provisional rating and will have one year after receiving the rating to provide additional information before the VA issues a final decision.
"Too many veterans wait too long for a decision, and this has never been acceptable," said VA secretary Eric Shinseki in a release announcing the backlog initiative. "That is why we are implementing an aggressive plan to eliminate the backlog in 2015. This initiative is the right thing to do now for veterans who have waited the longest."
One veteran service officer sees a flaw in the VA plan.
"First off, all of their system is not intact yet," said Jim Foyil, the veteran service officer for the Military Order of the Purple Heart. "They aren�t fully funded and if it is fully funded people won�t be trained in time to start it on time. You have to go through development, coaching, the rating process, etc. I don�t think they can do it.
"It�s a valiant effort, but they wont have it done by 2015 because the claims that are still pending are still going to take anywhere from 12, 18 or 24 months unless they start changing the rating schedule tomorrow."
U.S. Senator Kay Hagan, D-N.C., says she welcomes the news.
"I welcome any action by the VA to reduce the unacceptable backlog of claims that have prevented our brave men and women from accessing the benefits they�ve earned," Hagan said in a press release on the announcement. "While this initiative marks a step in the right direction for the VA, more must be done to reduce the wait times North Carolina veterans face."
More than 7,000 veterans have been waiting at least a year for the Winston-Salem Regional Office to rule on their disability claims � with more than 700 waiting more than two years � according to information from Hagan�s office. The average claim takes 341 days to process through the office in Winston-Salem, the second longest wait time in the VA�s southeastern region, according to Hagan�s office.
"I will continue to monitor the VA�s efforts to reduce the backlog at the Winston-Salem Regional Office and do everything I can to ensure this problem is properly addressed," Hagan said.
The VA is stuck in a vicious cycle where it can�t get an efficient group of adjudicating rating officers, Foyil said.
"(The VA) can�t catch up," he said. "Each one of those claims our modern veteran is filing, these guys have 13 or 14 claims on one file. By the time a QTC examination is done, it adds another 30, 45 or 60 days. It�s a very complex thing and people are not being educated."
Veteran service organizations have begun increasing staff members due to the military drawdown and a heavy influx of claims.
"The service organizations are trying to do everything they can, but the VA is about two years behind everything, which slows everything down," Foyil said. "The VA has a tough and tedious job to get all these claims done properly, but we as veterans service organizations have faith things will eventually work out."


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Posted on September 2, 2013 in Shoes and Apparel
The Bryan Brothers are always the team to watch in any major, but being on US soil, you know the twins want to add another US Open title to their already amazing career. Let's take a look at what Mike and Bob are wearing and using during this year's US Open.
Their apparel: Mike and Bob are the perfect ambassadors for the California grown company, KSwiss. This year at Flushing Meadows, they are flourishing on court in lots of color in the KSwiss Fall Spliced Crew in the bright yellow color. This 100% polyester crew is lightweight and keeps them cool on the court. They pair this crew with the KSwiss Basic Training Woven Short which are lightweight and comfortable on court. Under their shorts, they are wearing a compression short from Under Armour that keeps their muscles warm and helps with a quick recovery. They round out their look with the KSwiss BigShot II in the black and yellow colorway. This durable, yet lightweight shoe is more stable, more breathable and more comfortable than its predecessor.
Their equipment: When it comes to finding a racquet that serves the twins aggressive net play, solid returns, and dynamic doubles play, the Bryan brothers find the Prince EXO3 Rebel 95 to do just that. The tight 18×20 string pattern provides control from all areas of the court with a stable feel. At net, this racquet helps provide precise control with quick access to touch; while on serve, this faster feeling racquet is easy to generate both pace and spin. They keep their hands nice and dry with Tourna Grip Original Overgrip. They string it up with Prince Beast XP 17 blended with Prince Natural Gut 16 for the perfect feel for this doubles duo.
Enjoy the Open! And play with heart,


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Sapphire HD6670 Ultimate, HD6750 & HD6770 Review
Price: HD6750 - $105.99
Price: HD6770 - $127.99
Are you looking for a new video card for your current setup? Maybe you have been waiting for a decently priced card to come out that has some good features and supports DirectX 11. Heck, maybe you are building a new computer that is going to be used for light gaming but you still want to be able to have some of the higher graphics settings that a majority of the new games support such as DX 11's Tessellation. Well, whatever your reason for wanting to pick up a new graphics card for either a future build or upgrading your current solution, Sapphire has released the HD6750 and HD6770 as well as added a new cooler to the HD6670 as the Ultimate edition. I am curious to see exactly how these three cards are going to be able to perform when they are put up against some of the other cards on the market, so let's get into the testing and see.
Closer Look:
When you first look at the packaging for the Sapphire HD6750 and HD6770, you are going to see that they have a bunch of similarities, the woman depicted on the front of each package is not the same. However, they are both ready for battle! The Sapphire HD6750's packaging is going to have a greenish background with a redhead woman holding a pistol that is in a sexy warrior outfit while the woman pictured on the Sapphire HD6770 has a red background and has a sword on her back. On both of the packages you will find the Sapphire logo in the upper left hand corner of the package with the 1GB GDDR5 badge in the upper right hand corner. Along the bottom of each package, you will find the name of the card, be it the HD6750 or HD6770. Listed across the bottom of the package you will find a list of badges that let you know the more important highlighted features of each card, which happen to be the same. You will find the Radeon Graphics, AMD Black Vision, AMD Eyefinity, Onboard HDMI and DisplayPort, CrossFireX Ready, and AMD Accelerated Parallel Processing Technology badges listed here. You are also going to see along the bottom under the list of badges Microsoft DirectX 11, PCI Express 2.1 and CrossFireX Ready printed to give you a little more information about the card. When you flip the package over and look at the back, you are going to find a more detailed list of the features that each card has with a nice quick description of each if you are not familiar with them. You are also going to find an introduction paragraph off to the left side of the package that lets you know what to expect from each card.
The packaging for the Sapphire HD6670 Ultimate does look quite different than the HD6750 and HD6770 we just looked at. The front of the package does not include the typical image of a woman on the front, however you will find her on the back side of the package. The top left hand corner of the package displays the Sapphire logo with the "Get Radeon in your system" tag in the top right hand corner of the package. In the center of the package you will find the Ultimate logo with Radeon HD6670 printed below. There is a 1GB GDDR5 badge in the upper right hand corner with the Dirt 3 Game Code sticker next to that as well. Towards the bottom of the package, you will find the HDMI extension cable badge. You will also find a picture of a fan with the tag saying "Enjoy the silence No Fan!" next to it, letting you know that there is no active cooling installed on the HD6670 Ultimate. When you take a look at the back of the package, you will find a list of the highlighted features as well as a nice little description of each.
Once you get the packages opened up to reveal what is inside, you are going to find that they are both packaged almost identically and have the just about the exact same contents with the exception of the cards themselves being different. The Sapphire HD6750 is pictured on top and the HD6770 on the bottom. You are going to find all of the documentation sitting on top of the graphics card with the VESA to DVI dongle and the 4pin molex to 6pin PCI-E dongle resting under the card. In each package, you will find a drivers CD, a Sapphire Select Club invite, and a user manual. In the Sapphire HD6750 package, you are going to find one extra piece of paper, this is a warning that lets you know that there is a protective film on the cooler that you need to remove before you begin to use the card as it will hinder the cooling performance of the card.
Once you get the packaging opened for the Sapphire HD6670 ultimate, you are going to find that the inner brown packaging is separated into two sections, one has the card itself while the other has a section that holds the HDMI cable and the VESA to DVI dongle. Other than the HDMI cable and the dongle, you are going to find the drivers CD, Sapphire Select Club invite, as well as a user manual. The Sapphire HD6670 Ultimate also comes with a free Dirt 3 code.
Well now we know exactly how the Sapphire HD6750, HD6770, and HD6670 Ultimate are packaged and what comes with them. Let's take a closer look at the cards themselves.


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MILI and CIBER to Present 'Medical Industry Innovation in China' on May 30
Gain insight into China's booming medical device industry at this free seminar.
Gain insight into China's booming medical device industry by attending "Medical Industry Innovation in China," a seminar presented by the Medical Industry Leadership Institute (MILI) and the Center for International Business Education and Research (CIBER). This free event is taking place Wednesday, May 30, from 8:00 to 11:30 a.m. in the 3M Auditorium.
Universities, government agencies, and private companies all play a role in fostering medical innovation in China. This seminar will identify opportunities in this developing market for U.S. companies, and experts from the U.S. and China will share lessons for mutual learning and collaboration. This program will also showcase the new multi-disciplinary approach to medical innovation used by the University of Shanghai for Science and Technology.
The keynote speaker will be Professor Chengli Song, executive director, Shanghai Institute for Minimally Invasive Therapy, University of Shanghai Science and Technology.
Panelists will include:
• Susan Alpert, principal, SFA Consulting LLC and MILI Executive in Residence
• Stephen Parente, MILI director and professor
• Ken Paulus, president and CEO, Allina Hospitals and Clinic
• Randy Schiestl, vice president, Research and Development, Boston Scientific
Registration for this event is available online.


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Dartmouth cross-country skier dies at Vermont event
CRAFTSBURY, Vt. – Dartmouth College says that a 20-year-old member of its cross-country ski team died at an event in Vermont.
Dartmouth spokesman Rick Bender says that Torin Tucker died while competing at the Vermont Carnival Saturday. Tucker is a junior from Sun Valley, Idaho.
Bender says that the junior died at the scene after attempts to resuscitate him failed. The cause of his death is still under investigation.
The team returned to campus and won't complete in the rest of the Vermont Carnival.
Dartmouth President Philip Hanlon shared the news through a campus-wide email and urged students, faculty and staff to contact the school's safety and security department if they or someone they know needs to speak with a counselor or chaplain.


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Photos: Elmo Goes to Work in Times Square
Costumed characters working in Times Square have come under increasing pressure in recent weeks after a number of incidents led some to campaign for regulation of their work.
New York City mayor Bill de Blasio said people working in costumes should be licensed, wrote WSJ's Mara Gay.
On Wednesday, Reuters photographer Eduardo Munoz spent time with Jorge, an immigrant from Mexico who collects tips from tourists eager to take pictures with the beloved Sesame Street character, Elmo.


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We've all probably heard Oh Christmas Tree many times, it's one of the most popular and famous Christmas Carols, originally named "O Tannenbaum" in German, and dating back to the 16st century.
This is a smooth jazz rendition of that carol, arranged with an acoustic trio of piano, acoustic bass, and brush drums – creating a cosy and warm atmosphere, as if we're next to the fireplace during Christmas time.
Feel free to contact me if you need any changes or edits. If you need it looped let me know.
Thanks for your interest.


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OXON HILL, Maryland — Officials have lifted mandatory water restrictions for some 200,000 residents and businesses in the suburbs of Washington, D.C., as repairs were completed on a failing transmission main.
The Washington Suburban Sanitary Commission lifted the restrictions in southern Prince George's County Friday afternoon. Officials said repairs to the 54-inch main began Tuesday and progressed smoothly.
Commission president Jerry N. Johnson said residents used less water during the restrictions, which began at 9 p.m. Tuesday.
Residents were initially told that water would run out during repairs on the pipe. Temperatures soared above 90 degrees in the region each day during the repairs.


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It is possible that the main title of the report Syphilis, Acquired is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.
Syphilis is a chronic infectious disease caused by the bacterium (microorganism) treponema pallidum. It is transmitted by direct contact with an infected lesion, usually through sexual intercourse. When untreated, syphilis progresses through primary, secondary and latent stages. The early stages of syphilis may not have any detectable symptoms. In some cases, symptoms can remain dormant for years. Eventually any tissue or vascular organ in the body may be affected.
Syphilis may also be acquired by the fetus in the uterus (congenital syphilis). Syphilis, especially when detected early, may be cured with appropriate treatment.
Sexuality Information and Education Council of the U.S.
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Tel: (212)819-9770
Fax: (212)819-9776
Email: firstname.lastname@example.com
Internet: http://www.siecus.org
Center for Disease Control and Prevention
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Atlanta, GA 30333
Tel: (404)639-3534
Tel: (800)232-4636
Email: firstname.lastname@example.com
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Office of Communications and Government Relations
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Email: http://rarediseases.info.nih.gov/GARD/EmailForm.aspx
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Buddhist Meditation, Buddhism | Nottingham, UKThe Buddha lived 2,500 years ago in India and taught love, generosity and awareness. The Nottingham Buddhist Centre is dedicated to the spread of the Buddha's message in a way that is relevant to us here and now, yet remains faithful to the essentials of the Buddhist Tradition.
For those new to the centre, we have a weekly meditation class, suitable for beginners. For those with some experience of meditation we run Buddhism and meditation courses several times a year for those who want to learn something of the Buddha's message.
The Centre is located in the lace market district of Nottingham city centre. We have Nottingham's best-stocked Buddhist bookshop, which sells books on most Buddhist topics, cards, postcards and incense and some CDs. We also have some resources for the visually impaired in the form of CD recordings of some books.
The centre is run by a small team from the Triratna Buddhist Order, assisted by those who attend the centre regularly. It is affiliated to the Triratna Buddhist Community, a Buddhist movement founded by Sangharakshita in the late 1960's and originally known in the west as the Friends of the Western Buddhist Order (FWBO).This name was changed recently to more truly reflect the international nature of the movement. The name Triratna also reminds us of our central ideals, meaning "Three Jewels" which refers to the Buddha, Dharma and Sangha (see About Buddhism page).
Donating to The Buddhist Centre


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[ Mobile users click here for video ]
With the flurry of new videos that have released today with Mobile World Congress 2011, it just wouldn't be complete without a BB Messenger news update from RIM. As announced recently by RIM, BlackBerry Messenger will have a mobile gifting platform in which users will be able to integrate with BlackBerry App World and carrier billing systems to allow BlackBerry subscribers to instantly gift airtime, apps and other carrier services from one subscriber to another using BBM. Not much of a cosmetic change going on, but some other new features discussed in the video will be:
- More freedom and ability to send files of larger sizes and video to BBM contacts.
- BBM chat within 3rd party applications with the ability to interact with other users in games, media, ect.
Developer Tools are suppose to be released by RIM sometime by March, and BlackBerry users will see the new BlackBerry Messenger 6.0 roll out sometime around May of this year.
Any else you would like to see in BBM 6.0? Leave us a comment below.


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Label: GAMMAGARD S/D- human immunoglobulin g
- NDC Code(s): 0338-0001-37, 0944-2620-04
- Packager: Baxter Healthcare Corporation
- Category: PLASMA DERIVATIVE
- DEA Schedule: None
- Marketing Status: Biologic Licensing Application
Drug Label Information
Updated December 16, 2011
If you are a consumer or patient please visit this version.
- Download DRUG LABEL INFO: PDF XML
- Official Label (Printer Friendly)
- BOXED WARNING(What is this?)
- Intravenous use of human immune globulin (IGIV) products, particularly those containing sucrose, has been reported to be associated with renal dysfunction, acute renal failure, osmotic nephropathy, and death. Patients at risk of acute renal failure include those with any degree of pre-existing renal insufficiency, diabetes mellitus, advanced age (above 65 years of age), volume depletion, sepsis, paraproteinemia, or those receiving known nephrotoxic drugs. GAMMAGARD S/D does not contain sucrose.
- For patients at risk of renal dysfunction or failure, administer GAMMAGARD S/D at the minimum concentration available and the minimum rate of infusion practicable.
These highlights do not include all the information needed to use GAMMAGARD S/D safely and effectively. See full prescribing information for GAMMAGARD S/D
GAMMAGARD S/D, Immune Globulin Intravenous (Human)
Solvent Detergent Treated
IgA less than or equal to 2.2 µg/mL in a 5% Solution
Initial U.S. Approval: 1994
See full prescribing information for complete boxed warning
- Renal dysfunction, acute renal failure, osmotic nephropathy, and death may occur with the intravenous administration of human immune globulin products, particularly those products that contain sucrose. GAMMAGARD S/D does not contain sucrose.
- For patients at risk of renal dysfunction or failure, administer GAMMAGARD S/Dat the minimum rate of infusion practicable.
GAMMAGARD S/D is an Immune Globulin Intravenous (Human), indicated for:
- Treatment of Primary Immunodeficiency (PI) in adults and pediatric patients two years of age or older. (1.1)
- Prevention of bacterial infections in hypogammaglobulinemia and/or recurrent bacterial infections associated with B-cell Chronic Lymphocytic Leukemia (CLL). (1.2)
- Prevention and/or control of bleeding in adult Chronic Idiopathic Thrombocytopenic Purpura (ITP) patients. (1.3)
- Prevention of coronary artery aneurysms associated with Kawasaki syndrome in pediatric patients. (1.4)
Intravenous Use Only
- *
- Administer concomitant aspirin therapy: 80-100 mg/kg/day in four divided doses
Indication Recommended Dosage Duration PI (2.1) 300-600 mg/kg Every 3 to 4 weeks CLL (2.2) 400 mg/kg Every 3 to 4 weeks ITP (2.3) 1g/kg Maximal 3 doses on alternate days Kawasaki Syndrome (2.4) Single 1g/kg or 400 mg/kg for 4 consecutive days Begin within 7 days of onset of fever*
Freeze-dried preparation containing 2.5g, 5 g and 10g IgG. (3)
- IgA deficient patients with antibodies to IgA are at greater risk of severe hypersensitivity reactions and anaphylactic reactions. (5.1)
- Monitor renal function, including blood urea nitrogen, serum creatinine, and urine output in patients at risk of acute renal failure. (5.2)
- Thrombotic and thromboembolic events have been reported with GAMMAGARD S/D. Monitor patients with known risk factors for thrombotic events; consider baseline assessment of blood viscosity for those at risk for hyperviscosity. (5.3)
- Aseptic Meningitis Syndrome (AMS) has been reported with GAMMAGARD S/D. (5.4)
- Hemolytic anemia can develop. Monitor patients for clinical signs and symptoms of hemolysis and hemolytic anemia. (5.5)
- Monitor patients for pulmonary adverse reactions (transfusion-related acute lung injury, TRALI). (5.6)
- Product is made from human plasma and may contain infectious agents, e.g., viruses and theoretically, Creutzfeldt-Jacob disease agent. (5.7)
- Hyperproteinemia, increased serum viscosity and hyponatremia may occur may occur. (5.8)
- The most common adverse reactions observed in ≥ 5% of patients during the clinical trials were headache, nausea, chills, fatigue, pyrexia, upper abdominal pain, diarrhea, back pain, infusion site pain, hyperhidrosis and flushing (6.1).
- Severe adverse reactions reported postmarketing include renal failure, thrombotic events (myocardial infarction, cerebrovascular accidents, and pulmonary embolism), anaphylactic shock, aseptic meningitis and hemolysis.(6.2)
To report SUSPECTED ADVERSE REACTIONS, contact Baxter Healthcare Corporation at 1-866-888-2472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch
Passive transfer of antibodies may interfere with the immune response to live vaccines, such as measles, mumps, and rubella. (7)
See 17 for PATIENT COUNSELING INFORMATION.
Revised: 7/2010Close
1.1 Primary Immunodeficiency (PI)
1.2 B-cell Chronic Lymphocytic Leukemia (CLL)
1.3 Idiopathic Thrombocytopenic Purpura (ITP)
1.4 Kawasaki Syndrome
2.1 Preparation and Handling
2.2 Dose
2.3 Administration
5.1 Hypersensitivity
5.2 Renal Dysfunction Failure
5.3 Thromboembolic Events
5.4 Aseptic Meningitis Syndrome (AMS)
5.5 Hemolysis
5.6 Transfusion-Related Acute Lung Injury (TRALI)
5.7 Transmissible Infectious Agents
5.8 Hyperproteinemia, Increased Serum Viscosity, and Hypernatremia
5.9 Monitoring: Laboratory Tests
5.10 Interference with Laboratory Tests
5.11 Rubber Latex Sensitivity
6.1 Clinical Trials Experience
6.2 Postmarketing Experience
8.1 Pregnancy
8.3 Nursing Mothers
8.4 Pediatric Use
8.5 Geriatric Use
12.1 Mechanism of Action
12.3 Pharmacokinetics
14.1 Primary Immunodeficiency (PI)
14.2 B-cell Chronic Lymphocytic Leukemia (CLL)
14.3 Idiopathic Thrombocytopenic Purpura (ITP)
14.4 Kawasaki Syndrome
- *
- Sections or subsections omitted from the full prescribing information are not listed.
1.1 Primary Immunodeficiency (PI)
GAMMAGARD S/D is indicated for the treatment of primary immunodeficiency (PI) associated with defects in humoral immunity, in adults and children two years and older. This includes, but is not limited to, congenital agammaglobulinemia, common variable immunodeficiency, Wiskott-Aldrich syndrome, and severe combined immunodeficiencies.1,2,3
1.2 B-cell Chronic Lymphocytic Leukemia (CLL)
GAMMAGARD S/D is indicated for prevention of bacterial infections in patients with hypogammaglobulinemia and/or recurrent bacterial infections associated with B-cell Chronic Lymphocytic Leukemia (CLL).4
1.3 Idiopathic Thrombocytopenic Purpura (ITP)
GAMMAGARD S/D is indicated for the treatment of adult Chronic Idiopathic Thrombocytopenic Purpura to increase platelet count and to prevent and/or to control bleeding.
1.4 Kawasaki Syndrome
GAMMAGARD S/D is indicated for the prevention of coronary artery aneurysms associated with Kawasaki syndrome in pediatric patients.5
For Intravenous Use Only
2.1 Preparation and Handling
Instruction for Reconstitution:
Allow GAMMAGARD S/D and diluent to reach room temperature before reconstitution and administration if refrigerated.
1. Remove caps from concentrate and diluent bottles to expose central portion of rubber stoppers, and cleanse stoppers with germicidal solution.
To make a 5% solution: Use the full volume of the diluent bottle
To make a 10% solution: Remove half of the volume of the diluent bottle
Table 1 indicates the volume of diluent that should be removed from the vial before attaching the transfer device to produce a 10% concentration. Using aseptic technique, withdraw the unnecessary volume of diluent using a sterile hypodermic syringe and needle. Discard the filled syringe into a suitable puncture proof container (Sharps Container).
Table 1. Required Diluent Volume to be Removed Concentration 2.5 g bottle 5 g bottle 10 g bottle 5% Do not remove any diluent for reconstitution of 5% Solution 10% 25 ml 48 mL 96 mL
2. Remove spike cap from one end of the transfer device. Do not touch spike.
3a. Place the diluent bottle on a flat surface and hold the bottle to prevent slipping. Use exposed end of transfer device to spike diluent bottle perpendicularly through center of the stopper.
CAUTION: Failure to insert spike into center of the stopper may result in dislodging of the stopper.
3b. Ensure that the collar collapses fully into the device by pushing down on the transfer device firmly.
While holding onto transfer device, remove remaining spike cover from the other end of the transfer device. Do not touch spike.
4. Hold diluent bottle with attached transfer device at an angle to the concentrate bottle to prevent spilling the diluent.
Note: Do not hold diluent bottle upside down, for this can lead to diluent spillage.
5a. Spike concentrate bottle through center of the stopper while quickly inverting the diluent bottle to minimize spilling out diluent.
CAUTION: Failure to insert the spike into the center of the stopper may result in dislodging of the stopper and loss of vacuum.
5b. Ensure that the collar collapses fully into the device by pushing down on the diluent bottle firmly.
6. After transfer of diluent is complete, remove transfer device and empty diluent bottle. Immediately swirl the concentrate bottle gently to thoroughly mix contents. Repeat gentle rotation as long as undissolved product is observed.
CAUTION: Do not shake. Avoid foaming.
Discard transfer device after single use per local guidelines.
Reconstituted GAMMAGARD S/D is a clear to slightly opalescent and colorless to pale yellow solution. Visually inspect parenteral drug product for particulate matter and discoloration prior to administration. Do not use if particulate matter and/or discoloration is observed.
Follow directions for use which accompany the administration set provided. If another administration set is used, ensure that the set contains a similar filter.
Begin administration as soon as possible within 2 hours if reconstitution is performed aseptically outside of a sterile laminar air flow hood.
Administer within 24 hours if reconstitution is performed aseptically inside of a sterile laminar flow hood and stored in the original glass container or pooled into ViaFlex bags under constant refrigeration (2 °C to 8 °C). Record the date and time of reconstitution/pooling. Discard partially used vials.
2.2 Dose
Primary Immunodeficiency (PI)
The recommended dose of GAMMAGARD S/D for patients with PI is 300-600 mg/kg infused at 3 to 4 week intervals.1,2,6 Adjust dose according to the clinical response; the frequency and dose of immunoglobulin may vary from patient to patient. No randomized controlled clinical trials are available to determine an optimum target trough serum IgG level.
B-cell Chronic Lymphocytic Leukemia (CLL)
The recommended dose of GAMMAGARD S/D for patients with hypogammaglobulinemia and/or recurrent bacterial infections due to B-cell CLL is 400 mg/kg body weight infused at every 3 to 4 week intervals.4
Idiopathic Thrombocytopenic Purpura (ITP)
The recommended dose of GAMMAGARD S/D for patients with chronic ITP is 1 g/kg. The need for additional doses can be determined by clinical response and platelet count. Up to three separate doses may be given on alternate days if required.
Kawasaki Syndrome
The recommended dose of GAMMAGARD S/D for patients with Kawasaki Syndrome is either a single 1 g/kg dose or a dose of 400 mg/kg for four consecutive days beginning within seven days of the onset of fever, administered concomitantly with appropriate aspirin therapy (80-100 mg/kg/day in four divided doses) is recommended.5,7,8
2.3 Administration
Administer GAMMAGARD S/D as soon after reconstitution as possible and administer the reconstituted material at room temperature.
The recommended initial 5% solution infusion rate is 0.5 mL/kg/hour. The infusion rate may be gradually increased to a maximum rate of 4 mL/kg/hour as tolerated for patients with no history of adverse reactions to IGIV and no significant risk factors for renal dysfunction or thrombotic complications. Patients who tolerate the 5% concentration at 4 mL/kg/hour can be infused with the 10% concentration starting at 0.5 mL/kg/hour. The rate can be increased gradually up to a maximum of 8 mL/kg/hour if no adverse effects occur.9
Monitor patient vital signs throughout the infusion. Certain adverse reactions such as headaches, flushing and changes in pulse rate and blood pressure may be related to the rate of infusion. Slow or stop the infusion if adverse reactions occur. If symptoms subside promptly, the infusion may be resumed at a lower rate that does not result in reoccurrence of the symptoms.
It is recommended that, if possible, the antecubital veins are used, especially for 10% solutions, to reduce the likelihood of discomfort at the infusion site (see ADVERSE REACTIONS [6]).
Adverse reactions may occur more frequently in patients who receive human IGIV for the first time, upon switching brands, or if there has been a long hiatus since the previous infusion. In such cases, start at a lower rate and gradually increase as tolerated.
There are no prospective studies demonstrating that any concentration or rate of infusion is completely safe. However, the risk may be decreased at lower rates of infusion.10 For patients who are judged to be at risk of renal dysfunction or thrombotic complications, administer GAMMAGARD S/D at the minimum allowable rate of infusion and gradually titrated up to a more conservative maximal rate of less than 3.3 mg/kg/min (< 2mL/kg/hour of a 10% or < 4mL/kg/hour of a 5% solution) (see WARNINGS AND PRECAUTIONS [5.3]).
GAMMAGARD S/D is a freeze-dried preparation containing 2.5 g, 5 g or 10 g IgG.Close
GAMMAGARD S/D is contraindicated in patients who have had a history of anaphylactic or severe systemic hypersensitivity reactions to the administration of human immunoglobulin.
GAMMAGARD S/D is contraindicated in IgA deficient patients with antibodies to IgA and a history of hypersensitivity.Close
5.1 Hypersensitivity
Severe hypersensitivity reactions and anaphylactic reactions with a fall in blood pressure have occurred in patients receiving GAMMAGARD S/D, including patients who tolerated previous treatments with GAMMAGARD S/D, even though it contains low levels of IgA. If hypersensitivity reaction develops, discontinue GAMMAGARD S/D infusion immediately and institute appropriate treatment.
GAMMAGARD S/D contains trace amounts of IgA (≤ 2.2 µg/mL in a 5% solution). Patients with IgA deficiency and antibodies to IgA have a greater risk of developing potentially severe hypersensitivity and anaphylactic reactions. GAMMAGARD S/D is contraindicated in patients with antibodies against IgA and a history of hypersensitivity reaction (see CONTRAINDICATIONS [4]).
5.2 Renal Dysfunction Failure
Acute renal failure has been reported in association with GAMMAGARD S/D. Acute renal dysfunction/failure, acute tubular necrosis, proximal tubular nephropathy, osmotic nephrosis and death have been reported in patients receiving IGIV, particularly those products containing sucrose.10 GAMMAGARD S/D does not contain sucrose.
Assure that patients are not volume depleted prior to the initiation of the infusion of GAMMAGARD S/D. In patients who are at risk of developing renal dysfunction, because of pre-existing renal insufficiency or predisposition to acute renal failure (such as diabetes mellitus, age greater than 65, volume depletion, sepsis, paraproteinemia, or patients receiving known nephrotoxic drugs, etc.), administer GAMMAGARD S/D at an infusion rate less than 4 mL/kg/hour (< 3.3 mg IG/kg/min) for a 5% solution or at a rate less than 2 mL/kg/hour (< 3.3 mg IG/kg/min) for a 10 % solution (see DOSAGE AND ADMINISTRATION [2]).
Periodic monitoring of renal function and urine output is particularly important in patients judged to be at increased risk for developing acute renal failure. Assess renal function, including measurement of blood urea nitrogen (BUN) and serum creatinine, before the initial infusion of GAMMAGARD S/D and again at appropriate intervals thereafter. If renal function deteriorates, consider discontinuation of GAMMAGARD S/D.
5.3 Thromboembolic Events
Thromboembolic events, including myocardial infarction, cerebral vascular accident, deep vein thrombosis, and pulmonary embolism, have been reported in association with IGIV therapy, including GAMMAGARD S/D (see ADVERSE REACTIONS [6]).10,11 Patients at risk for thromboembolic events include those with a history of atherosclerosis, multiple cardiovascular risk factors, advanced age, impaired cardiac output, known or suspected hyperviscosity, hypercoagulable disorders, prolonged periods of immobilization, obesity, diabetes mellitus, acquired or inherited thrombophilic disorder, a history of vascular diseases, and a history of a previous thrombotic or thromboembolic event (see WARNINGS AND PRECAUTIONS [5.9]).
Consider baseline assessment of blood viscosity in patients at risk for hyperviscosity, including those with cryoglobulins, fasting chylomicronemia/markedly high triacylglycerols (triglycerides), or monoclonal gammopathies (see WARNINGS AND PRECAUTIONS [5.9]). For patients judged to be at risk of developing thrombotic events, administer GAMMAGARD S/D at the minimum rate of infusion practicable (see DOSAGE AND ADMINISTRATION [2.3]).
5.4 Aseptic Meningitis Syndrome (AMS)
AMS has been reported to occur in association with IGIV therapy, including GAMMAGARD S/D. Discontinuation of IGIV treatment has resulted in remission of AMS within several days without sequelae. The syndrome of AMS usually begins within several hours to two days following IGIV treatment.
AMS is characterized by the following symptoms and signs: severe headache, nuchal rigidity, drowsiness, fever, photophobia, painful eye movements, nausea and vomiting. Cerebrospinal fluid (CSF) studies are frequently positive with pleocytosis up to several thousand cells per cubic mm, predominantly from the granulocytic series, and with elevated protein levels up to several hundred mg/dL, but negative culture results. Conduct a thorough neurological examination on patients exhibiting such symptoms and signs, including CSF studies, to rule out other causes of meningitis.
AMS may occur more frequently with high dose (2 g/kg) IGIV treatment.12
5.5 Hemolysis
Hemolytic anemia can develop subsequent to IGIV therapy, including GAMMAGARD S/D. (see ADVERSE REACTIONS (6.2)) GAMMAGARD S/D contains blood group antibodies which may act as hemolysins and induce in vivo coating of red blood cells (RBC) with immunoglobulin, causing a positive direct antiglobulin reaction and, rarely, hemolysis. Acute intravascular hemolysis has been reported, and delayed hemolytic anemia can develop subsequent to IGIV therapy due to enhanced RBC sequestration (see ADVERSE REACTIONS (6.2)).
Monitor patients for clinical signs and symptoms of hemolysis. If signs and/or symptoms of hemolysis are present after GAMMAGARD S/D infusion, perform appropriate confirmatory laboratory testing.
5.6 Transfusion-Related Acute Lung Injury (TRALI)
Non-cardiogenic pulmonary edema (TRALI) has been reported in patients following the administration of gammaglobulin products, including GAMMAGARD S/D therapy (see ADVERSE REACTIONS (6.2)). TRALI is characterized by severe respiratory distress, pulmonary edema, hypoxemia, normal left ventricular function, and fever. Symptoms typically occur within 1 to 6 hours after treatment.
Monitor patients for pulmonary adverse reactions. If TRALI is suspected, perform appropriate tests for the presence of anti-neutrophil and anti-HLA antibodies in both the product and patient serum. TRALI may be managed using oxygen therapy with adequate ventilatory support.
5.7 Transmissible Infectious Agents
Because GAMMAGARD S/D is made from human plasma, it may carry a risk of transmitting infectious agents, e.g., viruses, and theoretically, the Creutzfeldt-Jakob disease (CJD) agent. This also applies to unknown or emerging viruses and other pathogens. No cases of transmission of viral diseases or CJD have ever been identified for GAMMAGARD S/D. All infections thought by a physician possibly to have been transmitted by this product should be reported by the physician or other healthcare provider to Baxter Healthcare Corporation at 1-800-423-2862 (in the U.S.) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. The physician should discuss the risks and benefits of this product with the patient.
5.8 Hyperproteinemia, Increased Serum Viscosity, and Hypernatremia
Hyperproteinemia and increased serum viscosity may occur in patients receiving GAMMAGARD S/D.
The amount of sodium in the product may add materially to the recommended daily allowance of dietary sodium for patients on a low sodium diet. In these patients, calculate the amount of sodium from the product and use it when determining dietary sodium intake. GAMMAGARD S/D contains approximately 0.85% NaCI or approximately 3340 mg sodium/liter at a 5% concentration. A 70 kg patient receiving 1g/kg (1.4 L) of the product would receive 4676 mg of sodium.
5.9 Monitoring: Laboratory Tests
- Periodic monitoring of renal function and urine output should be considered in patients judged to be at increased risk of developing acute renal failure. Assess renal function, including measurement of BUN and serum creatinine, before the initial infusion of GAMMAGARD S/D and at appropriate intervals thereafter.10
- Consider baseline assessment of blood viscosity in patients at risk for hyperviscosity, including those with cryoglobulins, fasting chylomicronemia/markedly high triacylglycerols (triglycerides), or monoclonal gammopathies because of the potentially increased risk of thrombosis.
- If signs and/or symptoms of hemolysis are present after an infusion of GAMMAGARD S/D, perform appropriate laboratory testing for confirmation.
- If TRALI is suspected, perform appropriate tests for the presence of anti-neutrophil antibodies and anti-HLA antibodies in both the product and patient's serum.
5.10 Interference with Laboratory Tests
After infusion of IgG, the transitory rise of the various passively transferred antibodies in the patient's blood may yield false positive serological testing results, with the potential for misleading interpretation. Passive transmission of antibodies to erythrocyte antigens (e.g., A, B, and D) may cause a positive direct or indirect antiglobulin (Coombs') test.
5.11 Rubber Latex Sensitivity
Certain components used in the packaging of this product contain natural rubber latex. Use GAMMAGARD S/D cautiously in patients with sensitivity to rubber latex.
The most common adverse reactions reported in ≥ 5% of clinical trial subjects occurring during or within 48 hours of an infusion were headache, nausea, chills, asthenia (fatigue), pyrexia, upper abdominal pain, diarrhea, back pain, hyperhidrosis, and flushing.
There were no serious adverse events that were attributed to GAMMAGARD S/D in the clinical trials.
In postmarketing surveillance, serious adverse reactions reported with GAMMAGARD S/D were anaphylaxis, acute renal failure, myocardial infarction, cerebral vascular accident, transient ischemic attack, deep vein thrombosis, pulmonary embolism; aseptic meningitis, acute hemolysis, and TRALI.
6.1 Clinical Trials Experience
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 clinical practice.
Primary Immunodeficiency (PI)
In 17 patients receiving GAMMAGARD (5% solution) for 56 to 77 months, 12 (71%) were adults, and 5 (29%) were children (16 years or younger).3 Adverse reactions are those adverse events (AEs) that were deemed by the investigators as causally related to the infusion of GAMMAGARD. Twenty-one adverse reactions occurred in 6 of the 17 subjects of the total 341 infusions (6%). There was one death in a woman from a cerebral vascular hemorrhage secondary to thrombocytopenia and was considered unrelated to study product. Of the 5 subjects who received an infusion with 600 mg/kg at a rate of 0.3 g/kg/hour, two subjects experienced adverse reactions, with an adverse reaction rate of 40%.
The adverse reactions occurred in ≥ 5% of subjects during or within 48 hours of infusion are listed in Table 2.
Table 2. Adverse Reactions that Occurred in ≥ 5% of Subjects During or within 48 Hours of Infusion Adverse Reaction
By Subjects (%)Total number of subjects: 17
By Infusions (%)Total number of infusions: 341
Headache 3 (17.6) 3 (0.9) Chills 2 (11.8) 6 (1.8) Backache 2 (11.8) 2 (0.6) Emesis 1 (5.9) 1 (0.3) Flushing 1 (5.9) 1 (0.3) Fatigue 1 (5.9) 4 (1.2) Dizziness 1 (5.9) 1 (0.3)
In a double blind, crossover study, 36 subjects with PI were treated for 6 months with GAMMAGARD S/D and 6 months with Gamimune N. One hundred AEs were considered to be possibly or probably related to treatment with GAMMAGARD S/D. Of these, 72 were mild, 24 were moderate, and 4 were severe. The numbers and percentages of AEs were similar for GAMMAGARD S/D and Gamimune-N. There were no deaths during the study. The adverse reactions that occurred during GAMMAGARD S/D treatment in ≥ 5% of subjects in the study are shown in Table 3.
Table 3. Adverse Reactions that Occurred in ≥ 5% of Subjects Treated with GAMMAGARD S/D Adverse Reactions
By Subject (%)Total number of subjects: 36
By Infusion (%)Total number of infusions: 211
Headache 11 (30.56) 23 (10.9) Nausea 8 (22.22) 14 (6.64) Chills 7 (19.44) 14 (6.64) Fatigue 4 (11.11) 11 (5.21) Pyrexia 4 (11.11) 6 (2.84) Upper Abdominal Pain 3 (8.33) 3 (1.42) Diarrhea 3 (8.33) 3 (1.42) Back Pain 3 (8.33) 4 (1.90) Infusion Site Pain 2 (5.56) 3 (1.42) Hyperhidrosis 2 (5.56) 4 (1.90) Flushing 2 (5.56) 2 (0.95)
In 10 subjects who participated in a PK crossover study of GAMMAGARD and GAMMAGARD S/D 5 adverse reactions were reported to be associated with the total 28 infusions (17.5%). Three of the adverse reactions were associated with 10 GAMMAGARD infusions and 2 were associated with 18 GAMMAGARD S/D infusions. Two subjects withdrew from the study. One subject developed a recurrence of chronic cellulitis and was hospitalized and the event was not considered to be related to study drug. The other subject withdrew due to the experience of moderate severe adverse reactions such as chills, anxiety and increased temperature after infusion of GAMMAGARD.
Adverse reactions occurred in the PK study and in the safety study are shown in Table 4.
Table 4. Adverse Reactions that Occurred During or Within 48 hours of an Infusion of GAMMAGARD S/D Event
By Infusion (%)Total number: 394
Headache 20 (5.1) Chills 11 (2.7) Elevated Temperature 7 (1.8) Nausea 6 (1.5) Emesis 5 (1.3) Hypertension 4 (1.0) Fatigue 4 (1.0) Flushing 4 (1.0) Leg Cramps 3 (0.8) Flu-Like Symptoms 2 (0.5) Exanthema 2 (0.5) Loss of Appetite 2 (0.5) Anxiety 1 (0.25) Backache 1 (0.25) Urticaria 1 (0.25)
The tolerability and viral safety of GAMMAGARD S/D were evaluated in a study of 38 subjects, who were treated with GAMMAGARD S/D for an average of 7.7 months. Adverse reactions were reported from 20 of the 38 subjects (52.6%) in 50 of the total 394 infusions (12.7%) during or within 48 hours of an infusion. Twenty-four (48%) of the adverse reactions occurred in 3 subjects and 26 occurred in the other 35 subjects in 350 infusions. No subject withdrew during the study. Five subjects had a transient borderline elevation in liver enzyme (AST). No subject developed a positive serologic response to Hepatitis C or HIV. There were no other significant laboratory abnormalities.
The adverse experiences of GAMMAGARD S/D reconstituted as a 10% solution and the maximal tolerated infusion rate were examined in a post-marketing study of 27 subjects. Local pain and/or irritation occurred in 42 of the total 276 infusions (15.2%). Ninety percent of the reactions occurred when the patients received the 10% solution compared to the 5% control. These local reactions tended to be more common following hand vein infusions and their incidence may be reduced by infusions via the antecubital vein. Application of a warm compress to the infusion site alleviated local symptoms. Twenty-six subjects were able to achieve the maximal infusion rate of 8 mL/kg/hour with the GAMMAGARD S/D reconstituted to a 10% solution.
B-cell Chronic Lymphocytic Leukemia (CLL)
In the study of 81 patients with B-cell CLL, the incidence of adverse reactions following GAMMAGARD infusions was approximately 1.3% compare to the rate of the placebo (normal saline) group which was 0.6%.3 There were 23 adverse reactions associated with the 1235 infusions in the study. Sixteen of the adverse reactions occurred in the GAMMAGARD group (1.6%) and 7 in the control group (0.6%). The most common reactions were fever and chills. Sleepiness was noted during 4 infusions. One subject had a myocardial infarction which was considered to be unrelated to the GAMMAGARD. Twenty-four of the subjects did not complete all 17 infusions. Three subjects in each group died during the study, five of whom were due to infection. The other 18 subjects withdrew for reasons unrelated to the treatment.
Idiopathic Thrombocytopenic Purpura (ITP)
During the clinical study of GAMMAGARD for the treatment of ITP, headache occurred in 12 of 16 subjects (75%) and was the only adverse reaction reported. Of these 12 subjects, 11 had chronic ITP (9 adults, 2 children), and one child had acute ITP. Oral antihistamines and analgesics alleviated the symptoms and were used as pretreatment for those subjects requiring additional IGIV therapy.
Kawasaki Syndrome
In a study of 51 subjects with Kawasaki syndrome, no hypersensitivity-type reactions (urticaria, bronchospasm or generalized anaphylaxis) were reported in subjects receiving either a single 1g/kg dose or 400 mg/kg of GAMMAGARD for four consecutive days. Adverse reactions, including chills, flushing, cramping, headache, hypotension, nausea, rash and wheezing, were reported with both dose regimens. These adverse reactions occurred in 7 of the 51 (13.7%) subjects associated with 7 of the 129 (5.4%) infusions. Of the 25 subjects who received a single 1 g/kg dose, 4 subjects (16%) experienced adverse reactions. Of the 26 subjects who received 400 mg/kg/day over 4 days, 3 (11.5%) experienced adverse reactions.
6.2 Postmarketing Experience
Because adverse reactions are reported voluntarily post-approval from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to product exposure.
The following adverse reactions have been reported during postmarketing use of GAMMAGARD S/D (Table 5).
Table 5. Adverse Reactions from Postmarketing Experience
- *
- non-infectious hepatitis
Infections and Infestations Aseptic Meningitis Syndrome Blood and Lymphatic System Disorders Anemia, Hemolysis, Lymphadenopathy, Thrombocytopenia Immune System Disorders
Anaphylactic Shock, Anaphylactic/Anaphylactoid Reaction, Hypersensitivity
Psychiatric Disorders Restlessness Nervous System Disorders Cerebrovascular Accident, Transient Ischemic Attack, Convulsion, Dizziness, Migraine, Paresthesia, Syncope, Tremor Eye Disorders Retinal Vein Thrombosis, Eye Pain, Photophobia, Visual Disturbance Cardiac Disorders Myocardial Infarction, Cyanosis, Tachycardia, Bradycardia Vascular Disorders Vena Cava Thrombosis, Arterial Thrombosis, Deep Vein Thrombosis, Hypotension, Hypertension, Pallor, Thrombophlebitis Respiratory, Thoracic And Mediastinal Disorders Pulmonary Embolism, Pulmonary Edema, Bronchospasm, Wheezing, Cough, Hyperventilation, Hypoxia, Throat Tightness Gastrointestinal Disorders Abdominal Pain, Dyspepsia Hepatobiliary Disorders Hepatitis* Skin and Subcutaneous Tissue Disorders Angioedema, Dermatitis, Erythema, Rash Musculoskeletal And Connective Tissue Disorders Arthralgia, Myalgia Renal and Urinary Disorders Renal Failure General Disorders and Administration-Site Conditions Infusion Site Reaction, Asthenia, Edema, Rigors Investigations Positive Direct Coombs Test
In addition to the events listed above which were observed for GAMMAGARD S/D, the following events have been identified for IGIV products in general:
Renal Osmotic nephropathy Respiratory Cyanosis, Apnea, Acute Respiratory Distress Syndrome (ARDS) Integumentary Bullous dermatitis, Epidermolysis, Erythema multiforme, Stevens-Johnson Syndrome Cardiovascular Cardiac arrest, Vascular collapse Neurological Coma, Loss of consciousness
PancytopeniaHepatic dysfunction
Admixtures of GAMMAGARD S/D with other drugs and intravenous solutions have not been evaluated. It is recommended that GAMMAGARD S/D be administered separately from other drugs or medications which the patient may be receiving. Do not mix the product with human IGIV products from other manufacturers.
Passive transfer of antibodies may transiently impair the immune responses to live attenuated vaccines, such as measles, mumps, rubella, and varicella. Inform the immunizing physician of recent therapy with GAMMAGARD S/D so that appropriate precautions can be taken.
8.1 Pregnancy
Pregnancy Category C. Animal reproduction studies have not been conducted with GAMMAGARD S/D. It is also not known whether GAMMAGARD S/D can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Immunoglobulins cross the placenta from maternal circulation increasingly after 30 weeks of gestation. GAMMAGARD S/D should be given to a pregnant woman only if clearly needed.
8.3 Nursing Mothers
GAMMAGARD S/D has not been evaluated in nursing mothers. GAMMAGARD S/D should be given to nursing women only if clearly indicated.
8.4 Pediatric Use
Clinical studies of GAMMAGARD S/D for the treatment of PI did not include sufficient numbers of subjects aged 16 and younger to determine whether they respond differently from adults. Five children under the age of 16 were treated in the initial trial of GAMMAGARD. The mean age of subjects in the phase 4 study was 17.8 years (range 1.7 to 55.3). Efficacy and safety of GAMMAGARD S/D in pediatric patients with chronic ITP has not been established.
Efficacy and safety of GAMMAGARD S/D in pediatric patients with Kawasaki disease has been established. Virtually all patients treated for Kawasaki's disease were less than 5 years of age, with approximately 20% under the age of 1 year.
8.5 Geriatric Use
Limited information is available for the geriatric use of GAMMAGARD S/D. Clinical studies of GAMMAGARD S/D for the treatment of PI did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Use caution when administering GAMMAGARD S/D to patients age 65 and over who are judged to be at increased risk for developing thromboembolic events or renal insufficiency. Do not exceed recommended dose, and administer GAMMAGARD S/D at the minimum infusion rate practicable (seeBOXED WARNING, WARNINGS AND PRECAUTIONS [5.2, 5.4] and DOSAGE AND ADMINISTRATION[2.2])
Overdose may lead to fluid overload and hyperviscosity. Patients at particular risk of complications of fluid overload and hyperviscosity include elderly patients and patients with cardiac or renal impairment.Close
GAMMAGARD S/D, Immune Globulin Intravenous (Human) [IGIV] is a solvent/ detergent treated, sterile, freeze-dried preparation of purified immunoglobulin G (IgG) derived from large pools of human plasma. IgG preparations are purified from plasma pools using a modified Cohn-Oncley cold ethanol fractionation process, as well as cation and anion exchange chromatography. The distribution of IgG subclasses present in this product is similar to that in normal plasma. The Fc portion is maintained intact. When reconstituted with the total volume of diluent (Sterile Water for Injection, USP) supplied, reconstituted to 5% solution, the product contains approximately 50 mg/mL of protein, of which at least 90% is gamma globulin. GAMMAGARD S/D contains trace amounts of IgA (≤ 2.2µg/mL in a 5% solution) and IgM is present in trace amounts. GAMMAGARD S/D contains all of the IgG antibody activities which are present in the donor population.The product, after reconstituted to 5% solution, contains a physiological concentration of sodium chloride (approximately 8.5 mg/mL) and has a pH of 6.8 ± 0.4. Stabilizing agents and additional components are present in the following maximum amounts for a 5% solution: 3 mg/mL Albumin (Human), 22.5 mg/mL glycine, 20 mg/mL glucose, 2 mg/mL polyethylene glycol (PEG), 1 µg/mL tri-n-butyl phosphate, 1 µg/mL octoxynol 9, and 100 µg/mL polysorbate 80. GAMMAGARD S/D contains no preservative.
To prepare a 10% (100 mg/mL) solution for infusion, add half the volume of diluent, as described in DOSAGE AND ADMINISTRATION. The content of the stabilizing agents and other components, including IgA, for the 10% solution will be doubled compared to the 5% solution.
Screening against potentially infectious agents in the product begins with the donor selection process and continues throughout plasma collection and plasma preparation. Each individual plasma donation used in the manufacture of GAMMAGARD S/D is collected only at FDA approved blood establishments and is tested by FDA licensed serological tests for Hepatitis B Surface Antigen (HBsAg), and for antibodies to Human Immunodeficiency Virus (HIV-1/HIV-2) and Hepatitis C Virus (HCV) in accordance with U.S. regulatory requirements. As an additional safety measure, mini-pools of the plasma are tested for the presence of HIV-1 and HCV by FDA licensed Nucleic Acid Testing (NAT) and found negative.
The manufacturing process includes treatment with an organic solvent/detergent mixture, composed of tri-n-butyl phosphate, octoxynol 9 and polysorbate 80. The GAMMAGARD S/D manufacturing process provides a significant viral reduction in in vitro viral reduction studies. These studies, summarized in Table 6 demonstrate virus clearance during GAMMAGARD S/D manufacturing using infectious human immunodeficiency virus, Type 1 (HIV-1), as the relevant virus for HIV-1 and HIV-2, bovine viral diarrhea virus (BVD); a model virus for enveloped RNA viruses such as hepatitis C virus (HCV), pseudorabies virus (PRV); a generic model virus for enveloped DNA viruses such as hepatitis B virus (HBV); hepatitis A virus (HAV), and mice minute virus (MMV), a model for small non-enveloped DNA viruses such as human parvovirus B19 (B19V)3. These reductions are achieved through a combination of process chemistry, partitioning and/or inactivation during cold ethanol fractionation and the solvent/detergent treatment.
Table 6. In Vitro Virus Clearance During GAMMAGARD S/D Manufacturing Process Step Evaluated Virus Clearance (log10) Enveloped Viruses Non- Enveloped Viruses BVD HIV-1 PRV HAV MMV Step 1: Processing of Cryo-Poor Plasma to Fraction I+II+III Precipitate 0.6* 5.6 1.0* 0.5* NT† Step 2 - 3 2.6 > 5.7 > 5.2 > 5.2 > 5.3 Step 4: Solvent/Detergent Treatment >4.9 >3.7 >4.1 NA‡ NA Cumulative Reduction of Virus (log10) >7.5 >15.0 >9.3 > 5.2 > 5.3
12.1 Mechanism of Action
GAMMAGARD S/D, Immune Globulin Intravenous (Human), supplies a broad spectrum of opsonizing and neutralizing IgG antibodies against a wide variety of bacterial and viral agents. GAMMAGARD S/D also contains a spectrum of antibodies capable of reacting with cells such as erythrocytes. The role of these antibodies and the mechanisms of action of IgG in GAMMAGARD S/D have not been fully elucidated.
12.3 Pharmacokinetics
Following infusion, IGIV products show a biphasic decay curve. The initial (α) phase is characterized by an immediate post-infusion peak in serum IgG and is followed by rapid decay due to equilibration between the plasma and extravascular fluid compartments. The second (β) phase is characterized by a slower and constant rate of decay. As a class, IgG survives longer in vivo than other serum proteins. Peak levels of IgG reached within 30 minutes after an intravenous infusion of GAMMAGARD S/D. In previous studies, where radio-labeled IgG was injected to subjects, the IgG half-life was 21 to 25 days in healthy individuals or 17.7 to 37.6 days in immunodeficient patients. The half-life of IgG can vary considerably from person to person, however. In particular, high serum concentrations of IgG and hypermetabolism associated with fever and infection have been seen to coincide with a shortened half-life of IgG.
The pharmacokinetics of GAMMAGARD S/D was evaluated in 15 subjects with PI, 10 of them were previously treated. In the previously treated subjects, the half-life of GAMMAGARD S/D is approximately 37.7 ± 15 days compared to 34.1 ± 15.7 days for GAMMAGARD. The half lives of the IgG subclasses were similar, ranging from 28.1 ± 11.2 days for IgG4 to 42.3 ± 26.6 days for IgG1. The half life of pneumococcal antibody in these subjects was 41.4 ± 28.5 days. Pharmacokinetics did not differ between the previously licensed IGIV and GAMMAGARD S/D formulations administered to the previously treated patients. The pharmacokinetics of the GAMMAGARD S/D formulation in previously untreated patients was not significantly different from the results obtained in previously treated patients. The mean trough IgG concentration in the previously untreated patients was 1186 ± 614 mg/dL and the peak post infusion concentration was 1859 ± 872 mg/dL. The mean dose was 460 ± 194 mg/kg.
14.1 Primary Immunodeficiency (PI)
Intravenous use of GAMMAGARD was initially evaluated in a study of 17 subjects with PI. Twelve (71%) were adults and 5 (29%) were children 16 years or younger. Six subjects received a series of 5 infusions at 4-week intervals, with the starting infusion does of 100 mg/kg and then increased to 200, 300, and 400 mg/kg at rates of 0.1 to 0.2 mg/kg/hour. Five of the 6 subjects completed the 5 infusions and received another 6 monthly infusions with the following doses each administered twice: 200-400 mg/kg at 0.1 to 0.2 g/kg/hour, 400 mg/kg at 0.1 to 0.4 g/kg/hour and 400-800 mg/kg at 0.1 to 0.4 g/ kg/hour. Then all of the 17 subjects received GAMMAGARD at 400 mg/kg every 4 weeks at a rate of 0.1 to 0.4 g/kg/hour. Fifteen of the subjects were treated for 56 to 77 weeks in this study. There were no instances of pneumonia or other infections that would qualify as an acute bacterial infection. The overall rate of non-serious bacterial infections was 4.4 per subject per year.
In a study of 15 subjects with PI to compare the pharmacokinetics of GAMMAGARD S/D with GAMMAGARD, the subjects received a total of 28 infusions, half with GAMMAGARD S/D and half with GAMMAGARD. Five systemic AEs were reported during the study and 2 occurred with GAMMAGARD S/D treatment. The study then enrolled an additional 38 patients with the diagnosis of PI (8), ITP (13), CVID (5), CLL (2) and other miscellaneous diseases (3) to evaluate acute tolerability and the viral safety of GAMMAGARD S/D.
The mean age of the subjects was 12 years old (range 0.7 to 57.2 years); 17 were males and 21 were females. The subjects received an average of 10 (range 1-22) infusions over an average of 7.7 months (range 0.3-11 months). A total of 394 infusions were administered and all were completed. The average dose was 460 mg/kg (range: 188-1110 mg/kg). Incidence of infections was not recorded, though one subject had a recurrence of chronic cellulitis. Adverse events and viral safety data were analyzed (seeADVERSE REACTIONS [6]).
GAMMAGARD S/D was compared to Gamimune N in a double-blind, crossover study of 36 PI subjects. The mean age of subjects was 17.8 years (range 1.7 to 55.3 years); 22 subjects were male and 14 were female. Eighteen were naïve to IGIV therapy. Each subject received 6 infusions of both products. There were a total of 211 GAMMAGARD S/D infusions and 210 Gamimune N infusions. The dose of GAMMAGARD S/D administered was 300-600 mg/kg every 14 to 28 days for previously untreated subjects and the same as their pre-study dose and frequency for previously treated subjects. The infusions were started at 1.0 mL/kg/hour and increased every 30 minutes to a maximum of 4.8 mL/kg/hour as tolerated. The mean dose administered for both products was 440 mg/kg. The mean infusion rate was 2.35 ± 0.54 mL/kg/hour for GAMMAGARD S/D and 2.33 ± 0.71 for Gamimune N. Two subjects withdrew from the study. One subject was pregnant, and the other subject was withdrawn by his parents after the eighth infusion for reasons other than adverse events.
The use of GAMMAGARD S/D as a 10% solution and the maximal rate of infusion were evaluated in a postmarketing study of 27 subjects with PI. Subjects were treated with GAMMAGARD S/D at 400 mg/kg every 4 weeks for up to 12 months. Each subject received an initial infusion of GAMMAGARD S/D 5% solution at 4 mL/kg/hour. Subsequently, the concentration was increased to 7.5% and then to 10% as tolerated. Thereafter, the infusion rate was gradually increased to a maximal 8 mL/kg/hour as tolerated. There were 276 infusions administered and 26 of the 27 subjects were able to reach the maximum infusion rate and concentration.
14.2 B-cell Chronic Lymphocytic Leukemia (CLL)
The efficacy of GAMMAGARD in reducing bacterial infections of B-cell CLL patients has been demonstrated in a double-blind, placebo-controlled trial of 81 subjects.4 Subjects were treated with 400 mg/kg/dose of GAMMAGARD or saline solution every 3 weeks for a total of 17 infusions. Forty-one subjects received GAMMAGARD and 40 subjects received saline. The infection outcomes, including the frequency of bacterial/viral/fungal infections, mean time to first bacterial infections, were compared between the two groups and are shown in Table 7.
Table 7. Infection Outcomes of 81 B-Cell CLL Subjects with GAMMAGARD or Placebo Outcome GAMMAGARD S/D Placebo
SignificanceP value
Number of subjects 41 40 - Frequency of bacterial infections 56.1% 105% 0.01 Mean time to first bacterial infection > 365 192 0.026 Total Bacterial Infections 23 42 0.01 Total Viral Infections 40 37 0.65 Fungal or Candida infection 3 2 - Patients free of any infection 13 11 0.68
Patients receiving GAMMAGARD had fewer infections with Streptococcus pneumoniae and Haemophilus influenza, but the incidence of other gram negative infections was similar.
14.3 Idiopathic Thrombocytopenic Purpura (ITP)
The efficacy of GAMMAGARD has been demonstrated in a clinical study involving 16 patients: thirteen had chronic ITP (11 adults, 2 children), and 3 had acute ITP (one adult, 2 children). All 16 patients (100%) demonstrated a rise in platelet count to a level greater than 40,000/mm3 following the administration of GAMMAGARD. Ten of the 16 patients (62.5%) exhibited a platelets rise to greater than 80,000/mm3. Of these 10 patients, 7 had chronic ITP (5 adults, 2 children), and 3 had acute ITP (one adult, 2 children).
The rise in platelet count to greater than 40,000/mm3 occurred after a single 1 g/kg infusion of GAMMAGARD in 8 patients with chronic ITP (6 adults, 2 children), and in 2 patients with acute ITP (one adult, one child). A similar response was observed after two 1 g/kg infusions in 3 adult patients with chronic ITP, and one child with acute ITP. The remaining 2 adult patients with chronic ITP received more than two 1 g/kg infusions before achieving a platelet count greater than 40,000/mm3. The rise in platelet count occurred within 5 days. However, this rise was transient and not considered curative. Platelet count rises lasted 2 to 3 weeks, with a range of 12 days to 6 months. It should be noted that childhood ITP may resolve spontaneously without treatment.
14.4 Kawasaki Syndrome
The efficacy of GAMMAGARD S/D in reducing the incidence of coronary artery aneurysm in patients with Kawasaki syndrome has been demonstrated in a clinical study of 44 patients.7
The incidence of coronary artery aneurysm in patients with Kawasaki syndrome receiving GAMMAGARD either at a single dose of 1 g/kg (n=22) or at a dose of 400 mg/kg for four consecutive days (n=22), beginning within seven days of onset of fever, was 3/44 (6.8%). This was significantly different (p=0.008) from a comparable group of patients that received aspirin only in previous trials and of whom 42/185 (22.7%) experienced coronary artery aneurysms. All patients in the GAMMAGARD trial received concomitant aspirin therapy and none experienced hypersensitivity-type reactions (urticaria, bronchospasm or generalized anaphylaxis).
- Orange JS, Hossny EM, Weiler CR, Ballow M, Berger M, Bonilla FA, Buckley R, Chinen J, El-Gamal Y, Mazer BD, Nelson Jr. RP, Patel DD, Secord E, Sorenson RU, Wasserman RL, Cunningham-Rundles C. Use of Intravenous Immunoglobulin in Human Disease: A Review of Evidence by Members of the Primary Immunodeficiency Committee of the American Academy of Allergy, Asthma, and Immunology. J Allergy Clin Immunol 2006; 117:S525-53.
- Bonilla FA, Bernstein IL, Khan DA, Ballas ZK, Chinen J, Frank MM, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. Ann Allergy Asthma Immunol. 2005; 94(suppl 1):S1-63.
- Ochs HD, Lee ML, Fischer SH, et al. Efficacy of a New Intravenous Immunoglobulin Preparation in Primary Immunodeficient Patients. Clinical Therapeutics. 1987; 9:512-522.
- Cooperative Group for the Study of Immunoglobulin in Chronic Lymphocytic Leukemia: Intravenous immunoglobulin for the prevention of infection in Chronic Lymphocytic Leukemia: A randomized, controlled clinical trial. N Eng J Med. 1988; 319:902-907.
- Newburger J, Takahashi M, Burns JG, et al. The Treatment of Kawasaki Syndrome with Intravenous Gamma Globulin. New England Journal of Medicine. 1986; 315:341-347.
- Eijkhout HW, Der Meer JW, Kallenbert CG, et al. The effect of two different dosages of intravenous immunoglobulin on the incidence of recurrent infections in patients with primary hypogammaglobulinemia. A randomized, double-blind, multicenter crossover trial. Ann Intern Med. 2001; 135:165-174.
- Barron KS, Murphy DJ, Siverman ED, Ruttenberg HD, Wright GB, Franklin W, Goldberg SJ, Higashino SM, Cox DG, Lee M. Treatment of Kawasaki syndrome: a comparison of two dosage regimens of intravenously administered immune globulin. J Pediatr. 1990; 117:638-644.
- Engle MA, Fatica NS, Bussel JB, O'Laughlin JE, Snyder MS, Lesser ML. Clinical Trial of Single-Dose Intravenous Gammaglobulin in Acute Kawasaki Disease. AJDC. 1989; 143:1300-1304.
- Polmar SH, Smith TF, Pirofsky B, Cox DG, Rechtman D. Rapid infusion of intravenous immunoglobulin in patients with primary immunodeficiency disease. J Allergy Clin Immunol. 1992; 69:166.
- Pierce LR, Jain N. Risks associated with the use of intravenous immunoglobulin. Transfusion Med Rev. 2003; 17:241-251.
- Katz U, Sheonfeld Y. Review: intravenous immunoglobulin therapy and thromboembolic complications. Lupus 2005; 14:802-8.
- Hamrock DJ. Adverse events associated with intravenous immunoglobulin therapy. International Immunopharmacology 2006; 6:535-42.
- Daw Z, Padmore R, Neurath D, Cober N, Tokessy M, Desjardins D, et al. Hemolytic transfusion reactions after administration of intravenous immune (gamma) globulin: a case series analysis. Transfusion 2008; 48:1598-601.
GAMMAGARD S/D is supplied in single use bottles containing the labeled amount of functionally active IgG. The following presentation of GAMMAGARD S/D is available:
GramsProtein NDC 2.5g 0944-2620-02 5 g 0944-2620-03 10 g 0944-2620-04
Each bottle of GAMMAGARD S/D is furnished with a suitable volume of Sterile Water for Injection, USP, a transfer device and an administration set which contains an integral airway and a 15 micron filter.
GAMMAGARD S/D is to be stored at a temperature not to exceed 25ºC (77ºF) for 24 months.
Do not Freeze.Close
Inform patients to immediately report the following signs and symptoms to their healthcare provider:
- Decreased urine output, sudden weight gain, fluid retention/edema, and/or shortness of breath (seeWARNINGS AND PRECAUTIONS [5.2])
- Acute chest pain, shortness of breath, leg pain, and swelling of the legs/feet, numbness in the face or extremities, weakness or paralysis, severe headache, confusion, and visual disturbances (see WARNINGS AND PRECAUTIONS [5.3]).
- Severe headache, neck stiffness, drowsiness, fever, sensitivity to light, painful eye movements, nausea, and vomiting (seeWARNINGS AND PRECAUTIONS [5.4])
- Increased heart rate, fatigue, yellowing of the skin or eyes, and dark-colored urine (seeWARNINGS AND PRECAUTIONS [5.5])
- Trouble breathing, chest pain, blue lips or extremities, fever (seeWARNINGS AND PRECAUTIONS [5.6])
Inform patients that GAMMAGARD S/D is made from human plasma and may contain infectious agents that can cause disease (e.g., viruses and, theoretically, the vCJD agent). The risk of GAMMAGARD S/D transmitting an infectious agent has been reduced by screening plasma donors for prior exposure, testing donated plasma, and inactivating or removing certain viruses during manufacturing; patients should report any symptoms that concern them or that might be caused by infections ( see WARNINGS AND PRECAUTIONS [5.7]).
Inform patients that GAMMAGARD S/D can interfere with their immune response to live viral vaccines such as measles, mumps and rubella. Inform patients to notify their healthcare professional of this potential interaction when they are receiving vaccinations (seeDRUG INTERACTIONS [7]).
To enroll in the confidential, industry-wide Patient Notification System, call 1-888-UPDATE U (1-888-873-2838)
Baxter, Gammagard and Viaflex are trademarks of Baxter International Inc., registered in the U.S. Patent and Trademark Office.
Baxter Healthcare Corporation
Westlake Village, CA 91362 USA
U.S. License No. 140
Revised: December 2011Close
GAMMAGARD SD 10g IgA less than 2.2 µg/mL in a 5% solution unit carton
192 mL size dried
Immune Globulin Intravenous (Human)
IgA less than or equal to 2.2 µg/mL in a 5% solution
Single dose container. For Intravenous administration only.
Dosage and Administration: See enclosed package insert.
Reconstitution Expiry Information: See Dosage and Administration in enclosed package insert.
Storage temperature: Not to exceed (25°C (77°F). Do not freeze.
This product is prepared from large pools of human plasma. Human blood and its components may transmit infectious agents. The patient and physician should discuss the risks and benefits of this product.
Rx Only
Baxter Healthcare Corporation
Westlake Village, CA 91362 USA
U.S. License No. 140
GAMMAGARD SD 10g IgA less than 2.2 µg/mL in a 5% solution unit carton
192 mL size, dried
single dose container
Immune Globulin Intravenous (Human)
IgA less than or equal to 2.2 µg/mL in a 5% solution
Dosage and Administration: See enclosed package insert.
Storage temperature: not to exceed (25°C (77°F). Do not freeze.
Rx Only
Baxter and Gammagard are trademarks of Baxter International, Inc.
Baxter Healthcare Corporation, Westlake Village, CA 91362 USA
U.S. License No.140
192 mL Sterile Water for Injection vial label
192 mL
Nonpyrogenic Single-Dose Container NDC 0338-0001-37
Sterile Water for Injection, USP for reconstitution of accompanying product
See accompanying directions for use. Do not use unless clear. No antimicrobial agent or other substance has been added. Do not use for intravascular injection without making approximately isotonic by addition of suitable solute. Discard unused portion.
This Product Contains Dry Natural Rubber. Rx Only.
Manufactured by: Baxter Healthcare Corporation Deerfield, IL 60015 USA
Imported by Baxter Corporation Toronto, Ontario
Baxter is a trademark of Baxter International Inc.Close
human immunoglobulin g kit
Product Information Product Type PLASMA DERIVATIVE Item Code (Source) NDC:0944-2620 Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:0944-2620-04 1 in 1 CARTON Quantity of Parts Part # Package Quantity Total Product Quantity Part 1 1 BOTTLE 200 mL Part 2 1 BOTTLE 192 mL Part 1 of 2 GAMMAGARD S/D
human immunoglobulin g injection, powder, lyophilized, for solution
Product Information Route of Administration INTRAVENOUS Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength HUMAN IMMUNOGLOBULIN G (UNII: 66Y330CJHS) (HUMAN IMMUNOGLOBULIN G - UNII:66Y330CJHS) HUMAN IMMUNOGLOBULIN G 50 mg in 1 mL Inactive Ingredients Ingredient Name Strength ALBUMIN (HUMAN) (UNII: ZIF514RVZR) GLYCINE (UNII: TE7660XO1C) ANHYDROUS DEXTROSE (UNII: 5SL0G7R0OK) POLYETHYLENE GLYCOLS (UNII: 3WJQ0SDW1A) TRI-N-BUTYL PHOSPHATE (UNII: 95UAS8YAF5) OCTOXYNOL 9 (UNII: 7JPC6Y25QS) POLYSORBATE 80 (UNII: 6OZP39ZG8H) Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 1 in 1 CARTON 1 200 mL in 1 BOTTLE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date BLA BLA103133 05/10/1994 Part 2 of 2 STERILE WATER
water liquid
Product Information Item Code (Source) NDC:0338-0001 Route of Administration INTRAVENOUS Inactive Ingredients Ingredient Name Strength WATER (UNII: 059QF0KO0R) 192 mL in 192 mL Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:0338-0001-37 192 mL in 1 BOTTLE Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date BLA BLA103133 05/10/1994 Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date BLA BLA103133 05/10/1994 Labeler - Baxter Healthcare Corporation (039121363) Establishment Name Address ID/FEI Business Operations Baxter SA 370191025 MANUFACTURE Establishment Name Address ID/FEI Business Operations Baxter Healthcare Corporation 001728059 MANUFACTURE