WASHINGTON, May 29 — A new FDA report suggests that products containing acetaminophen carry stronger label warnings about the drug’s potential for liver damage.

Despite label changes and public awareness campaigns over the last decade, an FDA working group said patients still might not be aware of the danger and take multiple products that contain acetaminophen — or ingest the drug with alcohol.

“There is extensive evidence that hepatotoxicity caused by acetaminophen use may result from lack of consumer awareness that acetaminophen can cause severe liver injury,” the group’s report said.

The panel of outside advisers recommended to the FDA that the name “acetaminophen” be displayed prominently on package of any medicine containing it.

The group also suggested the label warn patients not to take more than one acetaminophen-containing product at a time, and that taking more than the recommended dose can cause severe liver injury.

Since 1998, over-the-counter acetaminophen products have carried the warning: “If you consume 3 or more alcoholic drinks every day, ask your doctor whether you should take acetaminophen or other pain relievers/fever reducers.”

The report says that should be strengthened to warn specifically about liver damage risk for those who have three or more drinks a day.

In a study combining data from 22 specialty medical centers in the U.S., acetaminophen-related liver injury was the leading cause of acute liver failure for the years 1998 through 2003. (See Acetaminophen Is Leading Cause of Acute Liver Failure)

According to the report, from 1991 to 2001, there were 56,000 emergency department visits, 26,000 hospitalizations, and 458 deaths annually from acetaminophen overdoses.

This week’s report was issued a month before a scheduled joint meeting of three advisory committees who will recommend to the FDA whether the warning labels for products such as Tylenol and Vicodin (acetaminophen with hydrocodone), should be updated.

The FDA working group also recommended the following steps to reduce risk:

• Enhance public education efforts by increasing partnerships with other government agencies, health professionals, industry and consumer groups.
• Lower the maximum adult daily dose to no more than 3,250 mg (the equivalent of 10 “regular strength” capsules or 6.5 “extra strength” capsules). The current maximum is dose 4,000 mg (eight “extra strength” capsules) per day. The dose should be even lower than this for people who consume three or more alcoholic drinks while on the medication.
• Limit immediate-release tablets to a maximum of 325 mg (now 500 mg), which may also reduce intentional overdose.
• Limit pediatric liquid formulations to one mid-strength dose, rather than the multiple strength doses currently available.

The joint advisory committee will meet June 29 and 30 to help the FDA craft a risk minimization strategy.

Primary source: Center for Drug Evaluation and Research Working Group

Source reference:
Recommendations for FDA Interventions to Decrease the Occurrence of Acetaminophen Hepatotoxicity

Related Article(s):

• Acetaminophen Is Leading Cause of Acute Liver Failure

Informa Healthcare - one of the world’s leading medical and scientific publishers- has announced that its peer-reviewed medical titles will be joining the company’s pharmaceutical science titles to form one, united platform for drug discovery and clinical medicine on http://www.Informahealthcare.com.

The combination of medicine and pharmaceutical science titles simplifies the customer experience in one new, easy to use, robust platform that will deliver online content and archive material from more than 170 journals.

All of the journals will utilize the online content management and delivery system provided by Atypon Systems, Inc. - a platform provider for over 70 information providers including JSTOR, New England Journal of Medicine and the American Chemical Society. The new platform offers the option of online trials, advanced searching, alerting, and single article purchases. In addition, the Atypon system enables Informa Healthcare to integrate the online content of over 170 journals with a comprehensive archive service, giving pharmaceutical and healthcare professionals one central, high-quality source of information spanning the fields of medicine and pharmaceutical science. The beta site on the new platform is scheduled for release in summer 2009 and the complete transition will continue through to the end of this calendar year.

“Our flexible technical architecture allows us to deploy functionally rich web sites tailored to the needs of particular information sectors. We are delighted to have delivered a cost-effective solution that addresses the specific needs of clinical medicine, pharmaceutical and allied markets for Informa Healthcare,” says Chris Beckett, Vice President of Sales and Marketing - Atypon Systems.

“We are excited to be able to offer this one-stop-shop hosting platform for our customers,” said Phil Garner, Publishing Director at Informa Healthcare. “This new platform means that healthcare, academic and corporate professionals will have one central, high-quality source of information spanning the drug discovery and clinical medicine fields from bench to bedside - including a comprehensive and easy-to-use archive service dating back to 1921.”

Informa Healthcare is encouraging customer feedback throughout the transition process. Subscribers will have a chance to send feedback and post questions about the beta site, and Informa is doing everything possible to make the transition as seamless and easy as possible. There will be a dual-hosting period with the informaworld platform, which currently hosts the content, through 2009 allowing for a gradual migration and the site will provide reports and statistics to help subscribers analyze usage.

“This new improved service provides users with outstanding navigation and functionality and is all about bringing together quality information and addressing the needs of our readers with the touch of a button,” explained Phil. “Until now, users had to duplicate their searches across the different platforms or miss out on coverage in their interest area because it was published elsewhere. Now, readers will be pointed from one article towards other articles of interest within the http://www.Informahealthcare.com site.

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Informa Healthcare

Cardium Therapeutics (NYSE Amex: CXM) and its subsidiary Tissue Repair Company (TRC) announced a presentation entitled “Phase 2b Study of GAM501 (Ad5PDGF-B/Collagen) in the Treatment of Diabetic Ulcers” at the Late Stage Industry Clinical Trials Symposium at the American Society of Gene Therapy (ASGT) Annual meeting in San Diego, California, on May 27, 2009. Dr. Barbara K. Sosnowski, Cardium’s Vice President of Biologics Development and the Chief Operating Officer of Cardium’s Tissue Repair Company Operating Unit, provided an update on TRC’s Phase 2b MATRIX clinical trial and the new formulation of the Excellarate(TM) product candidate, as well as an overview of the prior clinical study of Excellarate.

Excellarate Product Candidate

As explained by Dr. Sosnowski, Excellarate is a collagen-based topical gel employing TRC’s Gene Activated Matrix(TM) (GAM) technology to stimulate a patient’s cells to produce a sustained micro-release of platelet-derived growth factor-B (PDGF-B) protein directly within the patient’s wound where it is needed. The Excellarate product candidate is designed to require only one or two physician-administered treatments, in contrast to most diabetic wound healing agents or devices in use that require repeated administrations over a long term (weeks to months).

With regard to the biology underlying Excellarate, Dr. Sosnowski noted that PDGF-B is believed to stimulate angiogenesis and granulation tissue formation through the recruitment and proliferation of cells such as monocytes, fibroblasts and endothelial cells, which are critical for the effective stimulation of a variety of wound healing processes. The Excellarate product candidate represents a new class of advanced wound healing therapies designed to leverage the body’s own natural healing abilities. Normal wound healing proceeds in an ordered sequence of events that includes control of injury and inflammation, followed by repair and remodeling. These events are mediated by the complex interactions of specific growth factors and cytokines. In the diabetic patient, this wound healing process is often impaired, in part due to a deficiency of growth factors.

Placement of a gene encoding a therapeutic growth factor into the wound environment allows for sustained and localized production of micro quantities of the growth factor by the body’s own cells within the wound site, an approach designed to improve therapeutic responsiveness. To accomplish localized sustained production, Excellarate comprises an adenovector with a gene encoding human platelet-derived growth factor-B (Ad5PDGF-B), incorporated into a 3-dimensional biocompatible matrix of collagen, which can be applied as a topical gel directly to an ulcer site. The Excellarate biocompatible matrix is believed to have at least two key beneficial functions. First, the matrix can essentially hold the Ad5PDGF-B vector in place at the wound site until infiltrating wound-healing cells arrive. Second, the matrix can act as scaffolding to promote the migration and in-growth of cells that are responsible for accumulation of granulation tissue, a key part of the wound healing process. Studies using the Excellarate product candidate have shown that tissue repair cells such as macrophages, fibroblasts, endothelial cells and endothelial progenitor cells, which originate in viable tissue surrounding a wound site, naturally migrate into and proliferate within the gene-containing matrix.

Once in the matrix, cells that have taken up the PDGF-B gene act as local bioreactors that produce PDGF-B protein. PDGF-B is a known cyto-attractant and thus induces repair cells to migrate from the normal wound margins into the wound bed. PDGF-B is also known for its ability to stimulate repair cell proliferation so those cells that have migrated into the wound bed and are exposed to the protein can increase in number leading to a greater amount of granulation tissue. Studies have shown that the PDGF-B gene is expressed in tissue repair cells as early as one day following drug application and for as long as seven days. In the case of Excellarate, the PDGF-B protein that is expressed contains a collagen-binding domain, which further helps the protein to be retained in the wound bed environment where it is needed most. Although the protein is synthesized by wound repair cells only for as long as the gene is expressed, the duration of its availability is substantially prolonged relative to topical protein therapy, which must generally be re-applied daily.

Update on MATRIX Phase 2b Clinical Study

On May 6, 2009, Cardium announced the completion of recruitment for the Phase 2b MATRIX clinical trial to evaluate the safety and efficacy of Excellarate for the treatment of non-healing diabetic foot ulcers. The MATRIX Data and Safety Monitoring Board has reviewed safety data collected from study participants as of April 21, 2009 and reported that Excellarate appears to be both safe and well tolerated, with no serious adverse events attributable to the study product. Approximately 80% of the patients recruited in the MATRIX study have already completed their initial evaluation period. The Company expects to report on key efficacy data in September 2009, including the percentage of patients achieving complete wound closure, the rate of wound closure and the reduction of wound size at various time points. Patients with wounds that successfully closed are also followed up for an additional 12 weeks following closure to demonstrate durability.

Cardium announced on May 7, 2009, that in parallel with the Phase 2b study and in anticipation of a Phase 3 clinical study and future commercialization, the Company’s continuing process development activities have led to an important breakthrough in product formulation that not only significantly simplifies the use of Excellarate, but opens the door to additional potential applications. The product formulation that was used in the Phase 2b study required storage in a minus 70 degrees Celsius freezer and a two syringe mixing process prior to treatment. The new product formulation is designed to be maintained in a physician’s office using a standard refrigerator (at a temperature of about 4 degrees Celsius) and to have a shelf life of 12-18 months. It will also be formulated as an easy-to-use single syringe that is pre-mixed and ready to be applied to patients’ wounds.

About Cardium

Cardium Therapeutics, Inc. and its subsidiaries, InnerCool Therapies, Inc. and the Tissue Repair Company, are medical technology companies primarily focused on the development, manufacture and sale of innovative therapeutic products and devices for cardiovascular, ischemic and related indications.

Cardium’s InnerCool Therapies subsidiary is a San Diego-based medical technology company in the emerging field of temperature modulation therapy to rapidly and controllably cool the body in order to reduce cell death and damage following acute ischemic events such as cardiac arrest or stroke, and to potentially lessen or prevent associated injuries such as adverse neurological outcomes.

Cardium also has two biologic candidates in clinical development. Cardium’s Tissue Repair Company subsidiary (TRC) is focused on the development of growth factor therapeutics for the treatment of severe chronic diabetic wounds. TRC’s lead product candidate, Excellarate(TM), is a DNA-activated collagen gel for topical treatment formulated with an adenovector delivery carrier encoding human platelet-derived growth factor-B (PDGF-B). Excellarate(TM) is initially being developed to be administered once or twice for the potential treatment of non-healing diabetic foot ulcers. Other potential applications for TRC’s Gene Activated Matrix(TM) (GAM) technology include therapeutic angiogenesis (cardiovascular ischemia, peripheral arterial disease) and orthopedic products, including hard tissue (bone) and soft tissue (ligament, tendon, cartilage) repair. GAM technology can also be applied to a number of other approaches benefiting from sustained localized release of therapeutic proteins and other agents.

Cardium’s Generx product candidate (alferminogene tadenovec, Ad5FGF-4) is a DNA-based growth factor therapeutic designed for use by interventional cardiologists as a potential one-time treatment to promote and stimulate the growth of collateral circulation in the hearts of patients with ischemic conditions such as recurrent angina.

Forward-Looking Statements

Except for statements of historical fact, the matters discussed in this press release are forward-looking and reflect numerous assumptions and involve a variety of risks and uncertainties, many of which are beyond our control and may cause actual results to differ materially from stated expectations. For example, there can be no assurance that the MATRIX study or other human clinical trials can be conducted and completed in an efficient and successful manner, that product formulation enhancements will be successful or will effectively simplify or expand the use of product candidates or technologies, that the GAM technology can be successfully broadened or applied to additional wound healing or tissue repair opportunities, that Excellarate or our other candidates will prove to be sufficiently safe and effective, that results or trends observed in one clinical study or procedure will be reproduced in subsequent studies or procedures, that clinical studies even if successful will lead to product advancement or partnering, that our products or product candidates will not be unfavorably compared to competitive products that may be regarded as safer, more effective, easier to use or less expensive, that FDA, CE Mark or other regulatory clearances or UL or other certifications, or partnering or other distribution agreements or other commercialization efforts will be successful or will effectively accelerate the business or market, that product modifications or launches will be successful or that the resulting products will be favorably received in the marketplace, that our products or product candidates will prove to be sufficiently safe and effective after introduction into a broader patient population, or that third parties on whom we depend will perform as anticipated.

Actual results may also differ substantially from those described in or contemplated by this press release due to risks and uncertainties that exist in our operations and business environment, including, without limitation, risks and uncertainties that are inherent in the development of complex biologics and therapeutic hypothermia devices and in the conduct of human clinical trials, including the timing, costs and outcomes of such trials, our ability to obtain necessary funding, regulatory approvals and expected qualifications, our ability to successfully accelerate the commercialization of our therapeutic hypothermia devices and launch new devices within the timeframes contemplated, our dependence upon proprietary technology, our history of operating losses and accumulated deficits, our reliance on collaborative relationships and critical personnel, and current and future competition, as well as other risks described from time to time in filings we make with the Securities and Exchange Commission. We undertake no obligation to release publicly the results of any revisions to these forward-looking statements to reflect events or circumstances arising after the date hereof.

Copyright 2009 Cardium Therapeutics, Inc. All rights reserved.

Cardium Therapeutics(TM) and Generx(R) are trademarks of Cardium Therapeutics, Inc.

Tissue Repair(TM), Gene Activated Matrix(TM), GAM(TM), and Excellarate(TM) are trademarks of Tissue Repair Company.

InnerCool Therapies(R), InnerCool(R), RapidBlue(TM) and CoolBlue(TM) are trademarks of InnerCool Therapies, Inc.

Other trademarks are the property of their respective owners.

Source: Cardium Therapeutics