Saturday, November 30, 2013
Friday, November 29, 2013
Wal-Mart protesters arrested at Black Friday rallies - Nov. 29, 2013
In a tradition that's becoming as much a part of Black Friday as the shopping, protesters gathered outside a number of Wal-Mart locations Friday calling for higher wages at the country's largest private retailer.
Wal-Mart protesters arrested at Black Friday rallies - Nov. 29, 2013
SPIEGEL Series on Winners and Losers of Economic Boom in Africa - SPIEGEL ONLINE
In roughly a decade, Africa has gone from being labeled "the hopeless continent" to enjoying an unprecedented boom. In a three-part series, SPIEGEL explores this transformation -- its drivers, winners and losers -- and asks if it can last.
SPIEGEL Series on Winners and Losers of Economic Boom in Africa - SPIEGEL ONLINE
SPIEGEL Series on Winners and Losers of Economic Boom in Africa - SPIEGEL ONLINE
$9M Bitcoin haul buried in U.K. rubbish tip - Nov. 29, 2013
Hoarders everywhere may be feeling smug after a British man threw a hard drive containing more than $9 million in bitcoin into the trash.
$9M Bitcoin haul buried in U.K. rubbish tip - Nov. 29, 2013
Here's what Wal-Mart's U.S. CEO has to say about early Thanksgiving Day store openings - Nov. 29, 2013
Wal-Mart opened its stores at 6 p.m. this year, two hours earlier than last year and smack in the middle of most families' Thanksgiving dinners. So what does one of its top executives have to say?
Here's what Wal-Mart's U.S. CEO has to say about early Thanksgiving Day store openings - Nov. 29, 2013
Bitcoin worth almost as much as gold - Nov. 29, 2013
Bitcoins are now worth nearly as much as an ounce of gold.
Bitcoin worth almost as much as gold - Nov. 29, 2013
Holiday shopping season kicks off with fights, arrests - Nov. 29, 2013
The start of the holiday shopping season Thursday included reports of fights among shoppers at several Wal-Marts nationwide.
Holiday shopping season kicks off with fights, arrests - Nov. 29, 2013
Rabbit abuse video prompts retailers to halt angora production - Nov. 29, 2013
Fashion giant H&M has stopped making angora products after an animal rights group released a video that appears to show Chinese farmers plucking fur from live rabbits.
Rabbit abuse video prompts retailers to halt angora production - Nov. 29, 2013
The Busiest Day in the 40 Year History of FedEx is Monday, December 2
FedEx Press Release:
HOW DOES FEDEX MANAGE ALL THOSE PACKAGES IN ONE DAY?
MEDIA OPPORTUNITIES:
B-ROLL:
The Busiest Day in the 40 Year History of FedEx is Monday, December 2
November 29 2013
WHAT: The Busiest Day in FedEx history is Monday, December 2. On this day FedEx will handle 22 million packages in one day – the most out of any one day in the 40 year history of the company! December 2 also kicks off the Busiest Week for FedEx, during which the company will be handling more than 85 million packages.
WHEN: Monday, December 2 – also known as Cyber Monday
FUN FACTS ABOUT THE FEDEX BUSIEST DAY:
- FedEx is shipping 11% more packages this year than last year’s Busiest Day
- Package volumes on Busiest Day have almost doubled since 2007 when we shipped 11.5MM packages on that day
- More than 125 packages per second will be handled on Busiest Day
- This is the earliest Busiest Day in the company’s history, a testament to the growing power of eCommerce in the holiday season
HOW DOES FEDEX MANAGE ALL THOSE PACKAGES IN ONE DAY?
The FedEx network is vast and well-equipped to manage the high package volumes. The network includes:
- 300,000+ team members
- 90,000+ vehicles
- 630+ aircraft
- 1,800+ FedEx Office locations
- More than 1,200 FedEx Express and 500 FedEx Ground facilities
- Many modes of transportation, including boats and gondolas, electric tricycles, all-electric delivery vans and hybrid-electric delivery vans
- The Memphis World Hub that, when working at peak capacity, sorts 500,000 packages per hour across 42 miles of conveyor belt
MEDIA OPPORTUNITIES:
To learn more about the FedEx Busiest Day or schedule an interview, call the FedEx Media Relations Hotline at 901-434-8100 or email mediarelations@fedex.com.
B-ROLL:
B-roll is available for download upon request. Satellite feeds are also scheduled daily. Please contact us at 901-434-8100 or mediarelations@fedex.com for details. This footage is made available free for unrestricted use. If used, please courtesy FedEx.
###
This year's early start to Black Friday proves Thanksgiving as you know it is gone. - Nov. 29, 2013
American consumerism has triumphed. For all the talk of boycotting stores that opened on Thanksgiving Day, the crowds showed up anyway.
This year's early start to Black Friday proves Thanksgiving as you know it is gone. - Nov. 29, 2013
Toys "R" Us deals are fleeting on Black Thanksgiving - Nov. 29, 2013
Black Friday? More like Black Thanksgiving.
Toys "R" Us deals are fleeting on Black Thanksgiving - Nov. 29, 2013
J.C. Penney shows signs of life on Black Friday - Nov. 29, 2013
After a tough year, Black Friday is J.C. Penney's do-or-die moment, and so far, the retailer is showing mild signs of life.
J.C. Penney shows signs of life on Black Friday - Nov. 29, 2013
Target's Black Friday deals draw crowds on Thanksgiving - Nov. 29, 2013
Qiana Roberts admits she has a Black Friday addiction.
Target's Black Friday deals draw crowds on Thanksgiving - Nov. 29, 2013
Thursday, November 28, 2013
Angela Merkel Open to Ukraine Cooperation After Trade Deal Collapse - SPIEGEL ONLINE
Despite Ukraine's rejection of a planned Association Agreement trade deal with the European Union, German Chancellor Angela Merkel is holding the door open. She says Moscow should stop pressuring former Soviet satellite states.
Angela Merkel Open to Ukraine Cooperation After Trade Deal Collapse - SPIEGEL ONLINE
Angela Merkel Open to Ukraine Cooperation After Trade Deal Collapse - SPIEGEL ONLINE
German Press Criticizes Social Spending in New Government Platforms - SPIEGEL ONLINE
Germany's next government is expected to shower the country with goodies including a minimum wage and an earlier retirement age. Editorialists warn the extra spending sends the wrong message and will be costly for the next generation.
German Press Criticizes Social Spending in New Government Platforms - SPIEGEL ONLINE
German Press Criticizes Social Spending in New Government Platforms - SPIEGEL ONLINE
U.K. moves to tame property bubble risks - Nov. 28, 2013
The U.K. is ending cheap bank funding for new mortgages in a bid to control the growing risk of a property bubble.
U.K. moves to tame property bubble risks - Nov. 28, 2013
Regulatory Update - GSK receives positive CHMP opinion for Cervarix™ two-dose schedule
GSK Press Release:
Regulatory Update - GSK receives positive CHMP opinion for Cervarix™ two-dose schedule
Today, GlaxoSmithKline plc (GSK) announced that the European Medicines Agency's Committee for Medicinal Products for Human Use (CHMP) is recommending marketing authorisation for a two-dose schedule in 9-14 year old girls for its cervical cancer vaccine, Cervarix™ [Human papillomavirus bivalent (types 16 and 18) vaccine, recombinant].
“We are delighted by the positive opinion issued by CHMP on a two-dose schedule for Cervarix. It represents another major milestone in our commitment to reducing the global burden of cervical cancer which remains high. Many countries are unable to implement national immunisation programmes in young adults with high coverage. A two-dose vaccine schedule has the potential to be easier to deliver than a three-dose schedule, thereby expanding the population that could benefit from protection.” said Thomas Breuer, Senior Vice President and Lead Physician, GSK Vaccines.
The EU licence application is based on the results of a Phase III study (HPV-070) which showed that two doses of the vaccine in girls aged nine to fourteen years provide an immunogenicity matching the currently licensed three-dose schedule in fifteen to twenty five year olds.
A CHMP positive opinion is one of the final steps before marketing authorisation is granted by the European Commission, but does not always result in marketing authorisation.
The vaccine is currently approved in the EU for use in females from the age of 9 years, administered according to a three-dose schedule (vaccination at months 0,1 and 6) for the prevention of premalignant genital (cervical, vulvar and vaginal) lesions and cervical cancer causally related to certain oncogenic Human Papillomavirus (HPV) types. The two-dose schedule will only apply to vaccination of girls aged 9-14. The three-dose schedule remains recommended for girls and women aged 15 years and above.
Cervarix™ is also approved in the US. For the full US Prescribing Information and EU Patient Information Leaflet, which includes information on the approved use of Cervarix, please visit http://www.gsk.com/products.html.
GlaxoSmithKline Vaccines - is active in vaccine research and development. Headquartered in Belgium, GSK Vaccines has 13 manufacturing sites strategically positioned around the globe. Of the 883 million doses of our vaccines we distributed in 2012, over 80% went to developing countries, which include the least developed, low- and middle-income countries.
GSK – one of the world’s leading research-based pharmaceutical and healthcare companies – is committed to improving the quality of human life by enabling people to do more, feel better and live longer. For further information please visit www.gsk.com.
Corruption and Poverty Cause India to Fall Behind - SPIEGEL ONLINE
Two decades after the start of its economic miracle, India is falling behind its rival China. Corruption is rampant, and investors are pulling out of the country. Will parliamentary elections next year offer a fresh start?
Corruption and Poverty Cause India to Fall Behind - SPIEGEL ONLINE
Corruption and Poverty Cause India to Fall Behind - SPIEGEL ONLINE
Wednesday, November 27, 2013
Sriracha factory ordered to put a lid on smell after locals pepper city with complaints - Nov. 27, 2013
A Sriracha hot sauce factory is getting a chilly reception in Southern California.
Sriracha factory ordered to put a lid on smell after locals pepper city with complaints - Nov. 27, 2013
Disgusted shoppers threaten to boycott Black Friday (Thursday) - Nov. 27, 2013
Black Friday has morphed into Black Thursday, and a lot of shoppers aren't happy. They're lashing out at major retailers online, threatening to boycott stores that are opening early on Thanksgiving.
Disgusted shoppers threaten to boycott Black Friday (Thursday) - Nov. 27, 2013
Black Friday: Is it worth it? - Nov. 27, 2013
Black Friday's encroachment into Thanksgiving Day has stirred debate about whether scoring deep discounts is worth sacrificing time with family. But even those who decide to hit the stores early may not end up getting the best deals this Black Friday.
Black Friday: Is it worth it? - Nov. 27, 2013
American US Air cleared to land merger - Nov. 27, 2013
A federal bankruptcy court judge has cleared the way for American Airlines and US Airways to merge into the world's largest airline company, dismissing a final objection from a group of airline passengers trying to block the deal.
American US Air cleared to land merger - Nov. 27, 2013
Black Friday 2013: What to expect - Nov. 27, 2013
Black Friday has become the most storied shopping day, filled with big deals and even bigger crowds.
Black Friday 2013: What to expect - Nov. 27, 2013
Report linking Bitcoin and Silk Road retracted - Nov. 27, 2013
After suggesting earlier this week that a link existed between the creators of Silk Road and Bitcoin, two Israeli computer researchers have retracted their report.
Report linking Bitcoin and Silk Road retracted - Nov. 27, 2013
RBS in hot water over lending practices - Nov. 27, 2013
Pressure on the Royal Bank of Scotland is intensifying over allegations it forced small companies out of business to boost profits.
RBS in hot water over lending practices - Nov. 27, 2013
SEC expands probe into overseas hiring by U.S. banks - Nov. 27, 2013
The SEC is broadening a probe into the overseas hiring practices of U.S. banks, according to a person familiar with the matter.
SEC expands probe into overseas hiring by U.S. banks - Nov. 27, 2013
Bitcoin prices top $1,000 - Nov. 27, 2013
Bitcoin prices crossed $1,000, as the virtual currency continues its spectacular rise this year.
Bitcoin prices top $1,000 - Nov. 27, 2013
Sony files patent for a "SmartWig" - Nov. 27, 2013
Sony is taking wearable technology to a whole new level.
Sony files patent for a "SmartWig" - Nov. 27, 2013
Charmin Provides Relief to Tailgaters During a Treasured American Pastime, Thanksgiving Football
News Release:
| Charmin Provides Relief to Tailgaters During a Treasured American Pastime, Thanksgiving Football |
The Charmin Relief Project Rolls into
Watching football on
While tailgating can be a fun part of fans’ football experience, there is nothing fun about the inevitable trips to portable potties.
“Thanksgiving is a time for families to gather together and celebrate and for many families in
The tailgating potties kicked off in
In conjunction with the program, Charmin recently launched CharminReliefProject.com, for all fans to “enjoy the go” by entering a sweepstakes to win weekly and monthly prizes, with a grand prize of a bathroom makeover. On the site, fans can see a rolling count of how many people the
Charmin is part of P&G’s overall sponsorship of the
To learn more about Charmin, visit Facebook.com/Charmin or @Charmin.
About Charmin
Charmin has been America’s most popular toilet paper for more than 25 years. In the U.S., P&G offers Charmin Ultra Soft and Charmin Ultra Strong - premium two-ply toilet paper; Charmin Basic - a one-ply toilet paper; Charmin Sensitive - with gentle and soothing lotion with a touch of aloe & E; and Charmin Freshmates - flushable moist wipes. For more information on Charmin, visit http://www.charmin.com/.
About
P&G serves approximately 4.8 billion people around the world with its brands. The Company has one of the strongest portfolios of trusted, quality, leadership brands, including Ace®, Always®, Ambi Pur®, Ariel®, Bounty®, Charmin®, Crest®, Dawn®, Downy®, Duracell®, Fairy®, Febreze®, Fusion®, Gain®, Gillette®, Head & Shoulders®, Iams®, Lenor®, Mach3®, Olay®, Oral-B®, Pampers®, Pantene®, Prestobarba®, SK-II®, Tide®, Vicks®, Wella®, and Whisper®. The P&G community includes operations in approximately 70 countries worldwide. Please visit http://www.pg.com for the latest news and in-depth information about P&G and its brands. 
Source:
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Additional legal costs for big banks could top $100 billion - Nov. 27, 2013
U.S. banks might still be on the hook for more than $100 billion in additional fines and legal costs over bad mortgage loans sold during the financial crisis, according to a new estimate from credit rating agency Standard & Poor's.
Additional legal costs for big banks could top $100 billion - Nov. 27, 2013
5 Black Friday tricks to avoid - Nov. 27, 2013
Black Friday is often billed as the best day of the year to find deals. But, in many cases, shoppers are either being enticed to spend more or to buy lower-quality products.
5 Black Friday tricks to avoid - Nov. 27, 2013
Europe's golden visas lure Chinese investors - Nov. 26, 2013
A growing number of wealthy foreigners are buying their way into Europe as hard-pressed countries trade their passports for cash.
Europe's golden visas lure Chinese investors - Nov. 26, 2013
Tuesday, November 26, 2013
Merck Announces Increased Quarterly Dividend
Merck Press Release:
Merck Announces Increased Quarterly Dividend
Category:
Tuesday, November 26, 2013 2:18 pm EST
Public Company Information:
NYSE:
MRK
"This increase in our dividend reflects our focus on creating value for shareholders and our confidence in Merck’s future as we increase productivity and invest in our most promising R&D opportunities"
WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced that the Board of Directors has increased the company’s quarterly dividend to $0.44 per outstanding share of the company’s common stock, up $0.01 from $0.43 per outstanding share paid last quarter. Payment will be made on January 8, 2014, to stockholders of record at the close of business on December 16, 2013.
”This increase in our dividend reflects our focus on creating value for shareholders and our confidence in Merck’s future as we increase productivity and invest in our most promising R&D opportunities,” said Kenneth C. Frazier, chairman and chief executive officer, Merck.
Merck last announced a dividend increase in November 2012, when the Board raised the dividend from $0.42 to $0.43 per common share.
About Merck
Today's Merck is a global healthcare leader working to help the world be well. Merck is known as MSD outside the United States and Canada. Through our prescription medicines, vaccines, biologic therapies, and consumer care and animal health products, we work with customers and operate in more than 140 countries to deliver innovative health solutions. We also demonstrate our commitment to increasing access to healthcare through far-reaching policies, programs and partnerships. For more information, visit www.merck.com and connect with us on Twitter, Facebookand YouTube.
Take-Two Interactive, Grand Theft Auto maker, buys back Carl Icahn's stake - Nov. 26, 2013
Take-Two Interactive, the company behind the Grand Theft Auto game series, is calling it quits with Carl Icahn after nearly four years together.
Take-Two Interactive, Grand Theft Auto maker, buys back Carl Icahn's stake - Nov. 26, 2013
HCA Appoints Gregory R. Angle Mountain Division President
HCA Press Release:
| HCA Appoints Gregory R. Angle Mountain Division President |
Current Division President
As
“Greg is a healthcare industry veteran and a skilled hospital operator who has held several facility and multi-facility senior leadership roles throughout his 30-year career,” said
Angle joined HCA in 2009 when he was appointed CEO of 343-bed
Angle has a bachelor’s degree in business administration from the
Hanshaw has been President of the Mountain Division since 2005. Hanshaw served as CEO of
Hanshaw earned a bachelor’s degree in business administration/accounting from the
“John has provided strong leadership throughout his tenure with HCA, and the Mountain Division has experienced significant growth under his direction during the last eight years,” said Hall. “We appreciate John’s many contributions and years of service to the company, and we wish him the best in this next phase of his life.”
All references to “Company” and “HCA” as used throughout this release refer to
Source:
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Union Pacific Railroad Adds Intermodal Service between Monterrey and Chicago
Union Pacific News Release:
Union Pacific Railroad Adds Intermodal Service between Monterrey and Chicago
UNION PACIFIC INTERMODAL
Omaha, Neb., November 26, 2013 – Union Pacific Railroad recently introduced a new intermodal service offering between Chicago and Monterrey, Mexico, giving companies another reliable transportation option to move goods across the border six days a week. Trains carrying intermodal containers will interchange at Eagle Pass, Texas, to and from Ferromex, Mexico's largest railroad, which will operate trains between the border and Monterrey. Union Pacific and Ferromex have made significant terminal, track and equipment investments to optimize the operating success of this new service.
Intermodal shipping incorporates multiple modes of transportation - in this case, truck and rail - to capitalize on the advantages of each mode. The versatile form of transportation allows consumer and manufactured goods, such as clothing and appliances, to be transported across the border in a cost-effective and timely way. This new international service will provide companies with opportunities for growth in the ever-expanding Mexico market.
"Union Pacific's network provides a competitive advantage to companies importing and exporting with Mexico and recent investments made across our network are providing safe and efficient transportation that helps the bottom line for our current and future customers," said Bernardo Ayala, vice president - Mexico Markets for Union Pacific Railroad.
Union Pacific is the only railroad serving all six Mexico gateways: Laredo, Eagle Pass, El Paso and Brownsville in Texas; Calexico, Calif.; and Nogales, Ariz.
About Union Pacific
Union Pacific Railroad is the principal operating company of Union Pacific Corporation (NYSE: UNP). One of America's most recognized companies, Union Pacific Railroad links 23 states in the western two-thirds of the country by rail, providing a critical link in the global supply chain. From 2007-2012, Union Pacific invested $18 billion in its network and operations to support America's transportation infrastructure, including a record $3.7 billion in 2012. The railroad's diversified business mix includes Agricultural Products, Automotive, Chemicals, Coal, Industrial Products and Intermodal. Union Pacific serves many of the fastest-growing U.S. population centers, operates from all major West Coast and Gulf Coast ports to eastern gateways, connects with Canada's rail systems and is the only railroad serving all six major Mexico gateways. Union Pacific provides value to its roughly 10,000 customers by delivering products in a safe, reliable, fuel-efficient and environmentally responsible manner.
Greece Plans Frugal Presidency of Council of the European Union - SPIEGEL ONLINE
Greece has announced it will offer fewer perks and spend considerably less than other countries on the rotating presidency of the Council of the European Union when it assumes the role in January. Doing otherwise would send the wrong message, Athens stressed.
Greece Plans Frugal Presidency of Council of the European Union - SPIEGEL ONLINE
Greece Plans Frugal Presidency of Council of the European Union - SPIEGEL ONLINE
Switzerland: The best country for top talent - Nov. 26, 2013
Which country is the best at developing, attracting and retaining top talent?
Switzerland: The best country for top talent - Nov. 26, 2013
Home prices continue to climb - Nov. 26, 2013
Home prices continued to climb in third quarter, rising 11% from a year earlier.
Home prices continue to climb - Nov. 26, 2013
FDA Approves Merck’s NOXAFIL® (posaconazole) Delayed-Release Tablets
Merck News Release:
FDA Approves Merck’s NOXAFIL® (posaconazole) Delayed-Release Tablets
Category:
Tuesday, November 26, 2013 9:00 am EST
Public Company Information:
NYSE:
MRK
"Prophylaxis against invasive Aspergillus and Candida infections plays a key role in the management of severely immunocompromised patients with hematologic malignancies or hematopoietic stem cell transplant recipients who are at high risk for these life-threatening fungal infections"
WHITEHOUSE STATION, N.J.--(BUSINESS WIRE)--Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced that the U.S. Food and Drug Administration (FDA) has approved NOXAFIL® (posaconazole) 100 mg delayed-release tablets. NOXAFIL delayed-release tablets are a new formulation with a loading dose of 300 mg (three 100 mg delayed-release tablets) twice daily on the first day, followed by a once-daily maintenance dose of 300 mg (three 100 mg delayed-release tablets) starting on the second day of therapy. Merck also markets NOXAFIL (40 mg/mL) oral suspension, which is dosed three times daily.
NOXAFIL delayed-release tablets and oral suspension are indicated for the prophylaxis of invasive Aspergillus and Candida infections in patients, 13 years of age and older, who are at high risk of developing these infections due to being severely immunocompromised, such as hematopoietic stem cell transplant (HSCT) recipients with graft-versus-host disease (GVHD) or those with hematologic malignancies with prolonged neutropenia (low white blood cell counts) from chemotherapy.
NOXAFIL should not be administered to persons allergic to posaconazole, any ingredients of NOXAFIL, or other azole antifungal medicines. The administration of NOXAFIL with sirolimus, pimozide, quinidine, atorvastatin, lovastatin, simvastatin and ergot alkaloids must be avoided. When administered with NOXAFIL, some drugs such as cyclosporine and tacrolimus required dosage adjustments and frequent monitoring of their levels in the blood as serious side effects of the kidney (nephrotoxicity) or brain (leukoencephalopathy) including deaths have been reported in patients with increased cyclosporine or tacrolimus blood levels. NOXAFIL should be administered with caution to patients who may develop an irregular heart rhythm as NOXAFIL has been shown to prolong the QT interval and cases of potentially fatal irregular heart rhythm (torsades de pointes) have been reported in patients taking NOXAFIL. (See Selected Safety Information below.)
“Prophylaxis against invasive Aspergillus and Candida infections plays a key role in the management of severely immunocompromised patients with hematologic malignancies or hematopoietic stem cell transplant recipients who are at high risk for these life-threatening fungal infections," said Daniel Couriel, M.D., professor of internal medicine and clinical program director, adult blood and marrow transplantation program, University of Michigan Comprehensive Cancer Center. “Posaconazole delayed-release tablets offer physicians a way to help protect these critically ill patients against invasive Aspergillus and Candida infections while they are in the hospital and once they return home.”
FDA approval of NOXAFIL (posaconazole) delayed-release tablets based on a pharmacokinetic study in patients
A non-comparative, multicenter study was performed to evaluate the pharmacokinetic properties, safety and tolerability of NOXAFIL delayed-release tablets in patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) who had developed or were anticipated to develop significant neutropenia, and in patients who had undergone HSCT and were receiving immunosuppressive therapy for prevention or treatment of GVHD. In the study, exposures of posaconazole within a pre-specified range were attained. The exposure levels achieved support a 300 mg (three 100 mg delayed-release tablets) once-daily dose of NOXAFIL delayed-release tablets, following a 300 mg (three 100 mg delayed-release tablets) twice-a-day loading dose on the first day of therapy. The most frequently reported adverse reactions (>25%) with NOXAFIL delayed-release tablets were diarrhea, fever and nausea. The type of adverse reactions reported for NOXAFIL delayed-release tablets were generally similar to that reported in trials of NOXAFIL oral suspension. (See Selected Safety Information below.)
The effect of food intake on the oral bioavailability of posaconazole following administration of NOXAFIL delayed-release tablets is not known. However, since the oral bioavailability of posaconazole is significantly increased when NOXAFIL oral suspension is administered with food or a nutritional supplement, or an acidic carbonated beverage (e.g., ginger ale) in patients who cannot eat a full meal, it is also recommended that NOXAFIL delayed-release tablets be taken with food. For patients who cannot eat a full meal, NOXAFIL delayed-release tablets should be used instead of NOXAFIL oral suspension for the prophylaxis indication. NOXAFIL delayed-release tablets provide higher plasma drug exposures than NOXAFIL oral suspension under fasted conditions.
NOXAFIL delayed-release tablets should be swallowed whole, and not be divided, crushed or chewed. Coadministration of drugs that can decrease the plasma concentrations of posaconazole should generally be avoided unless the benefit outweighs the risk. If such drugs are necessary, patients should be monitored closely for breakthrough fungal infections. Patients who have severe diarrhea or vomiting should be monitored closely for breakthrough fungal infections.
Clinical experience with NOXAFIL (posaconazole) oral suspension for antifungal prophylaxis
Two clinical studies of prophylaxis against invasive fungal infections were conducted with NOXAFIL oral suspension. Both studies demonstrated substantially fewer breakthrough infections caused by Aspergillus species in patients receiving posaconazole prophylaxis when compared to patients receiving fluconazole or itraconazole.
In one randomized, open-label study that compared posaconazole oral suspension (200 mg three times a day) with fluconazole suspension (400 mg once daily) or itraconazole oral solution (200 mg twice daily) as prophylaxis against invasive fungal infections in neutropenic patients receiving cytotoxic chemotherapy for AML or MDS (n=602), clinical failure in patients while receiving antifungal prophylaxis and for seven days following the last dose of therapy was lower for posaconazole (27% [82/304]) compared to fluconazole or itraconazole (42% [126/298]), (95% CI for the difference posaconazole-comparator -22.9% to -7.8%). Clinical failure at 100 days post-randomization was 52% (158/304]) for posaconazole compared to 64% (191/298) for fluconazole or itraconazole. All-cause mortality was lower at 100 days for patients receiving posaconazole (14% [44/304]) vs. fluconazole or itraconazole (21% [64/298]).
In a randomized, double-blind study that compared posaconazole oral suspension (200 mg three times a day) with fluconazole capsules (400 mg once daily) as prophylaxis against invasive fungal infections in allogeneic HSCT recipients with GVHD (n=600), the clinical failure rate on therapy plus 7 days was 17% (50/301) for posaconazole and 18% (55/299) for fluconazole. Clinical failure through 16 weeks post-randomization was similar for posaconazole (33% [99/301]) and fluconazole (37% [110/299]), (95% CI for the difference posaconazole-comparator -11.5% to 3.7%). All-cause mortality was similar at 16 weeks for both treatment arms 19% ([58/301] vs. 20% [59/299]), respectively.
Clinical failure in these studies represented a composite endpoint of breakthrough invasive fungal infections, mortality and use of systemic antifungal therapy.
The most frequently reported adverse reactions (>30%) in these prophylaxis studies with NOXAFIL oral suspension were fever, diarrhea and nausea.
NOXAFIL delayed-release tablets and oral suspension are not to be used interchangeably due to the differences in the dosing of each formulation.
Selected Safety Information
NOXAFIL (posaconazole) is contraindicated in persons with known hypersensitivity to posaconazole, any component of NOXAFIL, or other azole antifungal agents.
NOXAFIL is contraindicated with sirolimus. Concomitant administration of NOXAFIL with sirolimus increases the sirolimus blood concentrations by approximately 9-fold and can result in sirolimus toxicity.
NOXAFIL is contraindicated with CYP3A4 substrates that prolong the QT interval. Concomitant administration of NOXAFIL with the CYP3A4 substrates, pimozide and quinidine may result in increased plasma concentrations of these drugs, leading to QT prolongation and cases of torsades de pointes.
NOXAFIL is contraindicated with HMG-CoA reductase inhibitors that are primarily metabolized through CYP3A4 (e.g., atorvastatin, lovastatin and simvastatin) as increased plasma concentration of these drugs can lead to rhabdomyolysis.
NOXAFIL is contraindicated with ergot alkaloids. NOXAFIL may increase the plasma concentrations of ergot alkaloids (ergotamine and dihydroergotamine) which may lead to ergotism.
Concomitant administration of NOXAFIL with cyclosporine or tacrolimus increases the whole blood trough concentrations of these calcineurin inhibitors. Nephrotoxicity and leukoencephalopathy (including deaths) have been reported in clinical efficacy studies in patients with elevated cyclosporine or tacrolimus concentrations. Frequent monitoring of cyclosporine or tacrolimus whole blood trough concentrations should be performed during and at discontinuation of NOXAFIL treatment and the tacrolimus or cyclosporine dose adjusted accordingly.
Some azoles, including NOXAFIL, have been associated with prolongation of the QT interval on the electrocardiogram. In addition, cases of torsades de pointes have been reported in patients taking NOXAFIL. NOXAFIL should be administered with caution to patients with potentially proarrhythmic conditions. Do not administer with drugs that are known to prolong the QT interval and are metabolized through CYP3A4. Rigorous attempts to correct potassium, magnesium and calcium should be made in these patients before starting NOXAFIL.
Hepatic reactions (e.g., mild to moderate elevations in ALT, AST, alkaline phosphatase, total bilirubin and/or clinical hepatitis) have been reported in clinical trials. The elevations in liver function tests were generally reversible on discontinuation of therapy, and in some instances these tests normalized without drug interruption. Cases of more severe hepatic reactions including cholestasis or hepatic failure including deaths have been reported in patients with serious underlying medical conditions (e.g., hematologic malignancy) during treatment with NOXAFIL. Liver function tests should be evaluated at the start of and during the course of therapy. Patients who develop abnormal liver function tests during posaconazole therapy should be monitored for the development of more severe hepatic injury. Consider discontinuation of NOXAFIL (posaconazole) if clinical signs and symptoms consistent with liver disease develop that may be attributable to NOXAFIL.
Concomitant administration of NOXAFIL with midazolam increases the midazolam plasma concentrations by approximately 5-fold which could potentiate and prolong hypnotic and sedative effects. Concomitant use of NOXAFIL and other benzodiazepines metabolized by CYP3A4 (e.g., alprazolam, triazolam) could result in increased plasma concentrations of theses benzodiazepines. Patients must be monitored closely for adverse effects associated with high plasma concentrations of midazolam and other benzodiazepines metabolized by CYP3A4. In addition, benzodiazepine receptor antagonists must be available to reverse these effects.
Posaconazole is primarily metabolized via UDP glucuronidation and is a substrate of p-glycoprotein efflux. Therefore, inhibitors or inducers of these clearance pathways may affect posaconazole plasma concentrations. Coadministration of drugs that can decrease the plasma concentrations of posaconazole should generally be avoided unless the benefit outweighs the risk. If such drugs are necessary, patients should be monitored closely for breakthrough fungal infections. Posaconazole is also a strong inhibitor of CYP3A4. Therefore, plasma concentrations of drugs predominantly metabolized by CYP3A4 may be increased by posaconazole.
Coadministration of NOXAFIL with rifabutin, phenytoin and efavirenz should be avoided unless the benefit outweighs the risk. Monitoring for toxicity and/or adverse events is recommended when tacrolimus, cyclosporine, benzodiazepines, ritonavir, atazanavir, vinca alkaloids and calcium channel blockers and rifabutin are coadministered with NOXAFIL. Dosage adjustments should also be considered when tacrolimus, cyclosporine, vinca alkaloids, calcium channel blockers and phenytoin are administered with NOXAFIL. Monitor plasma concentrations when coadministering digoxin, phenytoin, tacrolimus and cyclosporine with NOXAFIL. Although no dosage adjustment of glipizide is required, it is recommended to monitor glucose concentrations when coadministering glipizide with NOXAFIL. Monitor for breakthrough fungal infections when coadministering fosamprenavir, rifabutin and phenytoin with NOXAFIL.
Coadministration of NOXAFIL oral suspension with cimetidine (an H2-receptor antagonist) and esomeprazole (a proton pump inhibitor) results in lower posaconazole plasma concentrations and should be avoided unless the benefit outweighs the risk. No clinically relevant effects were observed when posaconazole oral suspension is concomitantly used with antacids and H2-receptor antagonists other than cimetidine.
Coadministration of NOXAFIL oral suspension with metoclopramide decreases posaconazole plasma concentrations; however loperamide does not affect posaconazole plasma concentrations. Monitor for breakthrough fungal infections when coadministering cimetidine, esomeprazole and metoclopramide with NOXAFIL (posaconazole) oral suspension.
No clinically relevant effects on the pharmacokinetics of posaconazole delayed-release tablets were observed when concomitantly administered with drugs affecting gastric pH (i.e., antacids, H2-receptor antagonists, proton pump inhibitors). Concomitant administration of metoclopramide with posaconazole delayed-release tablets did not affect the pharmacokinetics of posaconazole.
The safety and effectiveness of NOXAFIL in patients below the age of 13 years old have not been established.
Patients weighing greater than 120 kg may have lower posaconazole plasma drug exposures. It is therefore, suggested to closely monitor for breakthrough fungal infections.
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