FDA – Atencion Primaria

FDA sets draft rules for biotech drug copies

Via: Linkedin

By Deena Beasley

Thu Feb 9, 2012 4:46pm EST

(Reuters) – The Food and Drug Administration’s long-awaited guidelines for the sale of lower-cost versions of biotechnology drugs leave open the possibility that some products might not need to be tested in humans.

The proposed rules, issued on Thursday, require studies showing that the generic copies are “highly similar” to the originals, but there are several ways that might be proven.

Because of their complexity, generic copies of biotech drugs – first introduced in the 1980s – are known as “biosimilars.”

“We’re trying to send the signal that it’s not one-size-fits-all. It’s product-by-product,” Rachel Sherman, director of the FDA’s office of medical policy, said during a conference call with reporters.

The worldwide market for copies of biotech medicines will grow to $3.7 billion by 2015, from just $243 million in 2010, as more than 30 branded biologics with sales of $51 billion lose patent exclusivity, according to market analysis firm Datamonitor.

The FDA rules would set “an abbreviated pathway” to approval that would consider factors including a product’s complexity, formulation and stability, the agency said.

The proposal “reads largely as we expected, although a few points read as slightly more friendly to the generics industry,” ISI Group analyst Mark Schoenebaum said in a note to clients.

The FDA said it would decide on the “extent and scope of animal and clinical studies” needed for approval once it has considered other analytical data. The agency said it has yet to receive an application for a biosimilar drug, but nine applications have been filed for clinical trials.

Manufacturers will have the option of asking the FDA to deem their copies “interchangeable” with a brand-name drug, but the `agency said that would require additional clinical studies.

Makers of branded biotech drugs have argued that full-scale human trials need to be conducted before a rival version of an existing biologic drug should be allowed on the market.

Despite such qualms, biotech drug makers including Amgen Inc, Merck & Co and Biogen Idec are working to produce rival versions of biotech drugs made by competitors.

“While the documents provide a roadmap, they are sufficiently vague as to give FDA leeway for case by case assessments of each proposed biosimilar along their respective development paths,” said Wells Fargo analyst Brian Abrahams.

The Congressional Budget Office has estimated that the United States could save $25 billion from the use of biosimilars over 10 years.

European regulators have already approved cheaper versions of some biotech drugs.

The FDA said advances in science and manufacturing may facilitate fingerprint-like analysis of therapeutic protein products, which may allow for a more selective approach to any animal or human studies.

Unlike conventional, easy-to-replicate, chemical-based drug compounds, biotech drugs are derived from living organisms, such as proteins, and are often produced using recombinant DNA technologies.

Once a traditional pill loses patent protection, there is a quick regulatory pathway for generic drugmakers to sell much cheaper versions of the branded medicine. Similar U.S. guidelines for biotech drugs have been under negotiation for several years.

Biosimilar drugs are expected to sell at discounts of 25 to 45 percent to branded rivals, compared with generic versions of traditional pills that often sell for one-tenth the price of the branded product.

Under the U.S. healthcare reform law passed in 2010, brand-name biotech drugs – ranging from relatively simple molecules like insulin to complex antibodies used to treat cancer – were granted a 12-year period of market exclusivity, after which generic versions can be sold.

Opposing trade groups – the Biotechnology Industry Organization and the Generic Pharmaceutical Association – said they are reviewing the proposed rules.

The generic drugs group said it was pleased with the FDA’s action, which it called “an important step in getting these affordable, lifesaving medicines into the hands of doctors and patients.”

The FDA will require that biosimilar manufacturers provide a post-marketing safety monitoring program, which in some cases may include long-term clinical studies.

The agency is accepting public comment on the draft guidance documents for the next 60 days.

(Reporting by Deena Beasley in Los Angeles, Additional reporting by Bill Berkrot in New York and Anna Yukhananov in Washington; Editing by Gerald E. McCormick, John Wallace and Matthew Lewis)

Where The Boys Are: Merck, Gardasil And HPV

Pharmalot by Ed Silverman

In the midst of ongoing controversy over HPV vaccines, the Advisory Committee on Immunization Practices, which advises the US Centers for Disease Control and Prevention, voted unanimously to recommend routine use of Merck’s Gardasil in boys as young as 11 years old. The vaccine fights human papillomavirus, which causes genital warts and oral, penile and anal cancers in men and cervical cancers in women.

Two years ago, Gardasil was first approved for in males between ages 9 and 26 to combat two HPV strains that can cause genital warts, so the new recommendation greatly expands the population, although the ACIP previously suggested vaccination was suitable for boys. As for females, the Merck vaccine was originally approved in 2006 to protect against four HPV strains that can lead to cervical and other cancers in girls and women in the same age range.

The move comes just weeks after Gardasil took center stage in the Republican presidential primary campaign. Texas Governor and GOP candidate Rick Perry backpedaled on a 2007 decision to mandate Gardasil for school-age girls, and his ties to Merck at the time became campaign fodder. Later, rival candidate Michele Bachmann claimed Gardasil causes brain damage (see here and here).

The ruckus reflected concerns over side effects, long-term benefits and views of social conservatives, who fear vaccination will give teenagers a green light to premarital sex. This last issue was debated in California over the past several months, where a bill was introduced that removed parental consent for vaccinating children 12 and older against sexually transmitted diseases. Earlier this month, California Governor Jerry Brown signed it into law, but not before the debate raised charges that Merck engaged in the sort of surreptitious lobbying that was conducted when Gardasil was approved in 2006 (back story).

This is the second bit of good news that Merck has received this week about Gardasil. Early-stage research found evidence of a link between HPV infection and heart disease in women who have no other risk factors. The study appeared in the Journal of the American College of Cardiology (see here).

Last year, Gardasil sales slowed considerably, from $1.4 billion in 2008 to $988 million, although for the first half of this year, revenue climbed about 10 percent, to $490 million, from a year earlier. Besides controversy, cost has also been a factor – Gardasil costs about $360 for a three-course dose. The drugmaker will welcome the increased sales that come with the ACIP recommendation, given that 13,000 jobs are in the process of being eliminated. In fact, Merck employees in numerous locations this week are being notified of pending layoffs.

FDA Says Chantix Benefits Outweigh The Risks or were you expeting another end ?

Ed Silverman in Pharmalot

After reviewing the results of two epidemiological studies that compared the controversial Chantix smoking-cessation pill with NicoDerm patches, the FDA has decided that the benefits of the Pfizer pill continue to outweigh the risks. The decision comes three years after the drugmaker added warnings its anti-smoking drug is connected to suicidal thoughts and behavior (back story).

Due to the myriad reports linking Chantix to psychiatric side effects, the FDA had sponsored two observational studies of neuropsychiatric adverse events with Chantix. One was conducted by the Department of Veterans Affairs’ Center for Medication Safety and the other by the Department of Defense’s US Army Medical Command’s Pharmacovigilance Center.

The VA study population included 14,131 Chantix users and an equal number of NRT users. The DoD study was also a retrospective cohort study comparing 30-day rates of hospitalizations for neuropsychiatric adverse events among 19,933 new Chantix users and 15,867 NRT patch users who started therapy from August 1, 2006 to August 31, 2007 in the Military Health System. Patients were drawn from active duty military personnel, military retirees and their dependents.

“Neither study found a difference in risk of neuropsychiatric hospitalizations between Chantix and nicotine replacement therapy,” the FDA says in a statement. “However, both studies had a number of study design limitations, including only assessing neuropsychiatric events that resulted in hospitalization, and not having a large enough sample size to detect rare adverse events.

“Although these two studies did not suggest an increased risk of neuropsychiatric events that result in hospitalization, they do not rule out an increased risk of other neuropsychiatric events with Chantix…(But) based on FDA’s assessment of currently available data, the agency continues to believe that the drug’s benefits outweigh the risks and the current warnings in the Chantix drug label are appropriate.”

The verdict is a big win for Pfizer, which has struggled to promote Chantix against a rising mound of studies that its pill is more trouble than it’s worth. In addition to concerns about suicide, studies have suggested Chantix can be responsible for violent behavior and cause serious cardiovascular risks (see here, here and here). The European Medicines Agency, however, recently ruled that Chantix benefits outweigh any heart risks (see this).

Medical Device Innovation — Is “Better” Good Enough?

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Source: NEJM
Last year, the United States spent $95 billion on medical devices, nearly half of the $200 billion spent on devices worldwide.1 Our investment in devices has yielded impressive gains in length and quality of life from products such as implantable cardioverter–defibrillators, pacemakers, and artificial joints (cardiovascular and orthopedic devices account for more than 35% of the market1). Roughly 10 million Americans have symptomatic knee osteoarthritis,2 a leading cause of disability and the most common indication for total knee arthroplasty. More than 600,000 total knee arthroplasty procedures are performed annually in the United States; 85% of recipients report functional improvement, and the annual failure rate is 0.5 to 1.6%.3 Inspired by these successes, medical device innovation continues. Each year for the past decade, the Food and Drug Administration (FDA) has approved more than 35 new systems or components for total knee arthroplasty. Most are designed to improve durability, and their manufacturers cite laboratory studies showing reductions in wear. Advertising campaigns promote innovative implants for younger, more physically active patients, expanding the market for knee arthroplasty.
But oversight of device innovation is currently under scrutiny. Safety concerns have been raised over total joint components and other devices approved through the FDA’s 510(k) clearance process, whereby devices perceived as posing a low risk of complications are approved for marketing without clinical trials. These concerns led the Institute of Medicine to recommend eliminating the 510(k) process, calling it ineffective and unsalvageable.4 The current oversight system has been simultaneously faulted for inadequate assurance of safety and efficacy and for suppressing innovation. Since regulatory approval hinges on claims of similarity to previously approved devices, the process may encourage the development of devices that provide only small improvements at higher cost than their predecessors. The trade-offs between incremental improvement and the additional costs and technical complexity of the required procedure are poorly understood and seldom investigated rigorously.
When adequately powered randomized trials are not feasible, a model-based approach can offer insight into the interplay among device efficacy and durability, patient characteristics, costs, and long-term outcomes. We used a validated “state-transition” computer-simulation model of the natural history and management of knee osteoarthritis5 to forecast clinical outcomes associated with hypothetical “innovative” total knee implants as compared with existing implants. We considered cohorts of persons with end-stage, symptomatic knee osteoarthritis, stratified by age and presence of coexisting conditions at the time of arthroplasty. We used a range of values for the potential reduction in the likelihood of long-term implant failure with hypothetical innovative implants and estimated the proportion of each patient cohort that would remain alive with their original (standard or innovative) implant intact 20 years after surgery. We examined the effects of increasing the risk of short-term failure while simultaneously decreasing the rate of long-term failure, as might be expected from a device offering improved survival at the expense of greater technical complexity. (Details are presented in the Supplementary Appendix, available with the full text of this article at NEJM.org.)
According to our model, by 20 years after a standard total knee arthroplasty, 19% of people who were healthy and 50 to 59 years of age at the time of the surgery and 86% of those who were 70 to 79 years of age and had coexisting conditions would have died; 65% and 11% of these groups, respectively, would be alive with their original implant intact. In part because of the much higher risk of death among older patients, the cumulative risk of requiring revision surgery within 20 years after a primary total knee arthroplasty would be twice as high among younger, healthier patients than among older patients with coexisting conditions (18% vs. 9%; see graph
Cumulative Risk of Revision Surgery 20 Years after Total Knee Arthroplasty with a Standard Implant and with an Innovative Implant, According to Computer-Simulation Modeling.
). Innovative implants with long-term failure rates 70% lower than those of current implants (an improvement similar to those that some manufacturers have demonstrated in the laboratory) would reduce the cumulative risk of revision by 11% among healthy 50-to-59-year-olds and 6% among 70-to-79-year-olds with coexisting conditions. If short-term failure rates quintupled (as recent data on innovative orthopedic devices suggest they could), the reductions in cumulative risk of revision would be lessened by 35% among healthy 50-to-59-year-olds and 59% among 70-to-79-year-olds with coexisting conditions, potentially offsetting the benefits of decreases in long-term failure.
Our findings suggest that there can be no one-size-fits-all approach to the use of innovative devices. In the case of total knee arthroplasty, a patient’s life expectancy has a marked effect on his or her anticipated benefit from improvements in durability over existing implants, whose survival rates are already excellent. Given the low annual failure rate of existing implants, even significant reductions in long-term failure rates would have little effect on overall implant survival in older, sicker patients. This finding is even more significant when innovative implants have greater short-term failure rates (possibly attributable to the learning curve associated with new technology). There are also additional trade-offs that should be considered in evaluating and pricing innovative devices. For example, innovations are typically accompanied by cost increases, and devices providing small, incremental clinical benefits may be less likely to offer good value for any additional investment.
We believe that our approach and the insights it can offer extend well beyond knee implants. Total knee implants are similar to many medical devices — such as hip and spinal implants, other orthopedic hardware, and ophthalmologic implants — in that they improve quality of life rather than survival. Thus, our work has implications for the development and adoption of any medical device offering improved long-term clinical benefit at increased initial cost. These analyses demonstrate that even small decreases in long-term device failure can provide clinical value, but these innovations are unlikely to provide equal benefit to all patients. Innovative technologies may also increase the risk of short-term complications, owing to increased complexity of the procedure or the greater technical skill required to optimally implement such advances — a phenomenon that is rarely captured in laboratory-based testing. Furthermore, these technologies typically cost more than their predecessors. These considerations may further restrict the populations in which an innovative device offers good value.
Our goal is not to set limits on who receives which implants, but to illustrate a model-based approach to improving new-device evaluation. Decisions about the marketing, use, and pricing of medical devices are often made in the absence of robust outcomes data. As the current controversy over the 510(k) process attests, traditional approaches to clinical investigation and evaluation are poorly suited to exploring and balancing the competing considerations at play — for instance, estimating likely improvements in long-term efficacy and device durability, factoring in the competing risks when devices are used in older or higher-risk patients, and determining our willingness to pay for incremental improvements. A model-based assessment can help to define the circumstances under which the diffusion of medical device innovations to ever-expanding patient populations is clinically and economically justified.
Model-based evaluations could help define the thresholds for complication and efficacy rates and costs that would be required to improve on existing device performance while maintaining acceptable economic value. This information could then inform postmarketing surveillance efforts, triggering reviews at prespecified efficacy or complication thresholds and facilitating rapid application of new data as they become available. Manufacturers could use such data to improve device development; researchers could identify target populations for evaluating novel technologies; insurers could identify opportunities for value-based reimbursement; and consumers could be educated about what clinical benefits they are getting for their money. The complex trade-offs between short- and long-term health and economic consequences of technological innovation may not be captured by even the most sophisticated randomized trials. Model-based approaches may provide invaluable insights for evaluating medical device innovation and merit consideration as a standard component of the evaluation process.
Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.
SOURCE INFORMATION
From Yale School of Medicine (L.G.S.) and Yale School of Public Health (A.D.P.) — both in New Haven, CT; the Veterans Affairs Connecticut Healthcare System, West Haven, CT (L.G.S.); and Brigham and Women’s Hospital (B.N.R., D.H.S., I.G., H.G., J.N.K., E.L.), Harvard Medical School (D.H.S., E.L.), Harvard School of Public Health (J.N.K.), and Boston University School of Public Health (E.L.) — all in Boston.

OBJECIONES EN RELACION CON AMBAS VACUNAS DISPONIBLES CONTRA EL VIRUS DEL PAPILOMA HUMANO

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OBJECIONES EN RELACION CON AMBAS VACUNAS DISPONIBLES CONTRA EL VIRUS DEL PAPILOMA HUMANO
(especial para SIIC © Derechos reservados)

Se presenta un análisis del diseño, evaluación, aplicación y seguimiento de las 2 vacunas disponibles contra el HPV llevado a cabo por ambos laboratorios fabricantes para comentar sobre su aplicación. Se incluye una breve revisión bibliográfica sobre la historia natural del HPV, el comportamiento del sistema inmune y otros factores en el desarrollo del cáncer cervical uterino.

Autor:
Teresita Audisio
Columnista Experto de SIIC
Institución:
Hospital Materno-Neonatal Artículos publicados por Teresita Audisio

Coautores
Vainer Osvaldo*** Ramallo Rogelio* Vásquez Federico** Ringelheim Claudia**** Pelliza Palmes Maria Nuria****
Doctor, Clínica del Niño, Córdoba, Argentina*
Doctor, Clínica del Noreste, Córdoba, Argentina**
Doctor, Hospital Materno-Neonatal, Córdoba, Argentina***
Doctora, Hospital Materno-Neonatal, Córdoba, Argentina****

Recepción del artículo
10 de marzo, 2010

Aprobación
26 de junio, 2010

Primera edición
26 de agosto, 2011

Segunda edición, ampliada y corregida
21 de septiembre, 2011

Resumen
Las infecciones genitales por el virus papiloma humano (HPV) son altamente frecuentes tanto en adultos como en niños; varios estudios demuestran la relativa frecuencia en esta población de los serotipos oncogénicos del HPV (16 y 18), como sus proteínas tempranas (early proteins); por lo que se objeta que la vía de transmisión sexual sea la única. El comportamiento biológico de las neoplasias intraepiteliales cervicales (CIN) I y II en las adolescentes y adultos jóvenes es similar y presenta una alta tasa de regresión espontánea. Por lo tanto, la indicación de las dos vacunas para el HPV disponibles actualmente en el comercio no condice con la historia natural del HPV y las CIN. Los estudios realizados con ambas vacunas han demostrado la baja efectividad y el efecto contraproducente cuando los sujetos eran ADN-HPV positivos a los tipos de HPV que contiene la vacuna, por lo que sería peligroso vacunar si no está asegurado el control de los sitios donde se ubican los tipos de HPV, como el aparato genital. Además, el corto seguimiento de los estudios realizados con ambas vacunas no permitió observar la repercusión en el estado inmunitario, como también el remplazo por los serotipos de HPV que no contiene la vacuna. La rápida autorización de la US Food and Drug Administration (FDA) y de la European Medicines Agency (EMEA) llevó a la introducción de la vacuna en muchos países, sin tener en cuenta las indicaciones y las repercusiones mencionadas.

Clasificación en siicsalud
Artículos originales > Expertos de Iberoamérica >
página www.siicsalud.com/des/expertocompleto.php/

Especialidades
Principal: Infectología, Obstetricia y Ginecología
Relacionadas: Atención Primaria, Educación Médica, Epidemiología, Farmacología, Medicina Farmacéutica, Inmunología, Medicina Familiar, Medicina Interna, Medicina Reproductiva, Pediatría

Enviar correspondencia a:
Teresita Audisio, 5000, Córdoba, Argentina

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Objections to the HPV Vaccine

Abstract
Genitals infection through human papilloma-virus (HPV) is frequently found in both adults and children, and several studies show the relative frequency of oncogenic HPV (16 and 18) in this population as well as their early proteins. This is why we object to the claim that this virus is exclusively sexually transmitted. The biological behavior of cervical intraepithelial neoplasia (CIN) I and II in teenagers and young adults is similar, presenting high spontaneous regression. Therefore, the indications for the two HPV vaccines do not match the natural history of HPV and CIN. The studies performed with both these vaccines have shown their low rate of efficacy and their counterproductive effect when the vaccinated subjects were HPV DNA positive to the HPV types in the vaccine, on account of this, vaccination without control of possible HPV type locations such as the genital apparatus would be dangerous. Besides, the short follow-up that has been made of the studies carried out with both vaccines has not allowed us to see their effects on immune system status nor on possible replacement by other types of HPV not contained in the vaccine. The fact of its rapid authorization by the U S Food and Drug Administration (FDA) and the European Medicines Agency (EMEA) led to the introduction of the vaccine in many countries without considering its indications and the repercussions mentioned above.

Key words
HPV, vaccine, pre-teenage

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2. Paavonen J, Jenkins D, Bosch FX, et al. Effi cacy of a prophylactic adjuvanted bivalent L1 virus-like-particle vaccine against infection with human papillomavirus types 16 and 18 in young women: an interim analysis of a phase III double-blind, randomized controlled
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Lesions do not substantiate the biologic relevance of the Bethesda System. Obstet Gynecol.
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12. Powell J , Strauss S, Gray J, Wojnarowska F. Genital Carriage of Human Papilloma Virus (HPV) DNA in Prepubertal Girls with and without Vulval Disease – Pediatric Dermatology. 2003. 20(3):191-4.
13. Rintala M, Grénman S, Puranen M, et al . Transmission of High-Risk Human Papillomavirus (HPV) between Parents and Infant: a Prospective Study of HPV in Families in Finland. Journal of Clinical Microbiology.2005; 43(1): 376-81,
14. Jenison S, Yu X,Valentine J, et al .Evidence of prevalent Genital-Type Human Papillomavirus Infections in Adults and Children.The Journal of Infections Diseases.1990;162:60-9
15. Cason J , Rice P , Best J.Transmission of Cervical Cancer-Associated Human
Papilloma Viruses from Mother to Child. Intervirology.1998; 41:213-18
16. De Palo Bergeron C., Ferenczy A., Richart R.: Underwear: contamination by human papillomavirus. Am. J. Obstet. Gynecol. 1990;162: 25.
17. Müller M, Viscidi R, Ulken V, et al .Antibodies to the E4, E6 and E7 proteins of Human Papillomavirus (HPV) type 16 in patients with HPV-associated diseases and the normal population.J Invest Dermatol.1995;104:138-41.
18. Hildesheim A, Herrero R, Wacholder S, et al. for the Costa Rican HPV Vaccine.Effect of Human Papillomavirus 16/18 L1Viruslike Particle Vaccine Among Young Women With Preexisting Infection- A Randomized Trial. JAMA. 2007; 298(7):743-53.
19. Pasqualini C.D. La etiología del cáncer .Vigencia de cinco paradigmas sucesivos. Medicina. 2003;63:757-60.
20. Pasqualini CD.Papel bivalente del sistema inmune en el crecimiento tumoral. Medicina. 2004; 64:277-80.
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25. Meyskens FL;Surwit E; Moon TE et al. Enhancement of regression of cervical intraepithelial neoplasia II with topically applied all -trans-retinoic acid: a randomized trial. Journal of the National Cancer Institute.1994; 86(7): 539-43.
26. Buckley DI, Mc Pherson RS, North CQ; Becker TM. Dietry micronutrients and cervical dysplasia en Southwestern American Indian women. Nutr and cancer.1992; 9: 179-85.
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28. Piyathilake CJ, Henao OL, Macaluso M, Cornwell PE, Meleth S, Heimburger DC, Partridge EE. Folate is associated with the natural history of high-risk human papillomavirus. Cancer Res. 2004; 64(23):8788-93.
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FDA Panel, Bayer Birth Control Pills & Blood Clots

By Ed Silverman in Pharmalot

Nearly six months after a pair of studies found that women taking birth control pills containing a hormone called drospirenone are more likely to develop blood clots than those who take an older oral contraceptive, the FDA has decided to hold an advisory panel meeting in December to review the risks and benefits.

Meanwhile, the agency is continuing to review a separate agency-funded study that evaluated the risk of blood clots in users of several different hormonal birth control products (contraceptives). Preliminary results suggest an approximately 1.5-fold increase in the risk of blood clots for women who use drospirenone-containing birth control pills compared to users of other hormonal contraceptives.

And so, the agency will convene the Reproductive Health Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee to examine the risk of blood clots of drospirenone-containing birth control pills. The most widely known oral contraceptives containing this hormone are the Yaz and Yasmin pills sold by Bayer.

The scrutiny is not good news for Bayer. Nearly 7,000 lawsuits are pending in the US over alleged injuries and deaths relating to Yaz and Yasmin, as well as generics. The lawsuits allege Yaz and Yasmin have risks beyond those of traditional birth control pills and Bayer too aggressively promoted the pills without disclosing higher risks. Bayer was warned by the FDA in 2008 that TV ads were misleading and did not disclose added risks (see here) and recently was chastised in the UK for running a Yasmin ad that boasted the pill could prove beneficial on the same problems it may cause (read this).

As to the data, the FDA says it reviewed six published epidemiologic studies that evaluated the risk of blood clots in women using birth control pills containing drospirenone, but generated conflicting findings. Two were postmarketing studies required by the FDA or European regulators, and did not report any difference in clot risk between the pills and products containing levonorgestrel or other progestins. But two studies in 2009 reported a 1.5- to 2-fold higher risk in women who use pills containing drospirenone as opposed to contraceptives containing levonorgestrel.

More recently, two articles published in 2011 in the British Medical Journal reported a 2- to 3-fold greater risk of clots in women using oral contraceptives containing drospirenone rather than levonorgestrel. However, the FDA notes these were epidemiological studies and, so far, has not reached a conclusion on the risk for blood clots, but remains concerned about a potential increased risk (here is the FDA statement).

Hodgin’s Lymphoma And A High-Priced Drug

Ed Silverman

When is a drug overpriced? The issue has come up repeatedly as various biologics treating cancer and assorted chronic conditions carry price tags in the tens of thousands of dollars. The debate was particularly vociferous last year when the Provenge prostate cancer vaccine was priced at $93,000 (read here). Now, a new entrant may become the focal point of controversy.

This morning, Seattle Genetics disclosed that the annual cost for Adcetris, which the FDAapproved late last week to combat Hodgkin’s disease and another rare lymphoma, will cost $13,500 per dose. In clinical trials, patients received an average of eight infusions, which works out to $108,000 a year, which Xconomy reports was in line with several Wall Street estimates.

There is reason, however, to argue the cost is justified. For one, chemotherapy is also expensive. More to the point, the data for Adcetris is impressive – 73 percent of Hodgkin’s patients had significant tumor shrinkage, including 32 percent showing complete remissions. And 86 percent of anaplastic large cell lymphoma patients also had significant tumor shrinkage.

And not only is Adcetris the first new Hodgkin’s treatment since 1977, but the medication may be a life-saving salve to relapsed patients, who are often young or in mid-life and facing uncertain life expectancy. The FDA approved the drug for patients whose cancer has progressed after autologous stem cell transplant or after two prior chemo treatments for those who cannot receive a transplant (here are the press releases from the biotech andthe FDA).

On the other hand, there is no survival data yet. And of course, insurers and patient advocates are likely to complain about the cost. Yet a price that fails to provide a return on investment will anger investors. This is a common conundrum now facing biotechs as they seek to balance R&D costs, profit targets and patient needs, which is the reason for their efforts in the first place.

“We want to make sure we price this drug so that we can maximize the impact on patients, and maximize the effect for the company as well,” Seattle Genetics ceo Cory Siegall tellsXconomy while insisting months were spent chatting with insurers and doctors. “What we are excited about doing is making sure we can treat as many patients as possible, and also do well for our shareholders.”

Working in his favor are a couple of other points – there do not appear to be any out-of-the-ordinary side effects and a lab test can determine when a tumor expresses enough of the targets that Adcetris is designed to combat. And judging by the trial results, the med can hit anywhere from 73 percent to 85 percent, which are rather decent odds. What do you think? Do the odds justify the price?

Note: There is a poll embedded within this post, please visit the site to participate in this post’s poll.

benjamins pic thx to amagill on flickr

Reevaluating Studies: A CRO & A Coincidence?

Published 1 agosto, 2011 por Ed Silverman, via Pharmalot

Last week, the FDA announced that any clinical tests conducted between April 2005 and June 2010 by a contract research organization called Cetero Research may have to be reevaluated because two FDA inspections and an outside audit found falsified data and manipulated samples. In explaining its move, the agency maintained there were “significant instances” of misconduct.

The agency says Cetero failed to conduct an adequate internal investigation to determine the extent and impact of the violations, and did not take sufficient steps to assure data integrity during those five years. And so drugmakers must check their databases for trials that were used to support New Drug Applications and Abbreviated New Drug Applications – and may have to repeat or confirm results (back story).

For its part, Cetero subsequently issued a statement saying the CRO initiated its own internal investigation of its Houston bioanalytical laboratory in 2009 after discovering six chemists had misreported the date that samples were extracted prior to analysis. They did this to seek overtime pay for hours when they did not actually work. But the CRO insists reports were filed with the FDA and agency feedback was sought, although none was received. Cetero clients were also contacted.

“We leaned in roughly June 2009 and that’s the time at which we self reported the findings to the FDA,” Cetero ceo Troy McCall tells us. “We requested a meeting at the time that we originally provided them with our preliminary findings and during the course of our 18 month investigation. We were providing them with regular updates…They received all the information we provided to them on an interim basis.

“We took these issues so seriously that we not only terminated the employees who were responsible for these actions, but we also replaced management and ultimately the site leadership,” McCalls continues. “…That was probably another half dozen or so people.” He reiterated that all of the terminated employees were based in the Houston facility.

There is, however, an interesting tidbit concerning some other former and current Cetero employees – several of them have had experience suitable for dealing with the recent troubles. How so? They also once worked for MDS Pharma Services, another CRO that is now owned by INC Research and, notably, had rather similar problems with the validity and accuracy of test results. In fact, in January 2007, the FDAnotified drugmakers to reevaluate pharmacokinetic studies that were conducted for them by MDS from 2000 through 2004 (read here).

Which former and current Cetero employees worked at MDS? And when? Well, there wasJerry Merritt, who was MDS senior vice president and general manager from 2000 to 2006, when he left to run Cetero, although he was succeeded as ceo early last year by McCall. And Murray Ducharme, the chief scientific officer at Cetero, was previously an MDS vice president from 2000 to 2006, although his Cetera bio neglects to mention this (look here).

Then there was John Capicchioni, who was the MDS senior vice president of business development from 1994 to 2006, when he joined Cetero as vice president of business development, although his bio also overlooks time spent at MDS (see this).

There was also Herb Smith, who was MDS senior director of quality assurance from 1999 to 2007, when he became vp of quality assurance at Cetero, although he retired in April. Finally, there is April Johnson, who worked at MDS as a marketing manager from 1999 to 2005 and as a marketing director of early clinical research and bioanalysis from 2005 to 2007, when she joined Cetero as vp, business relationship management (see this). And, yes, her bio fails to mention MDS.

In other words, several current and former members of the Cetero managerial team arrived from another CRO that experienced similar breakdowns affecting the validity of bioequivalence data, which caused regulators to question the ability to conduct a proper audit (read a sample letter the FDA sent to drugmakers with pending ANDAs).

The problems at MDS, by the way, factored into growing concern a few years ago about oversight of CROs. The rise in the number of clinical trials prompted a corresponding growth in the number of such companies, along with complaints about quality and competency. In February 2007, for instance, Gilead reported that the FDA had found “certain irregularities” in studies conducted by MDS (read this).

We asked Cetero for comment about the experience some of their executives brought with them from MDS. Johnson, who also acts as the Cetero spokesperson, declined to comment

An Avastin Recommendation & Conflicts Of Interest

Bevacizumab = Avastin

Earlier this month, the National Comprehensive Cancer Network, a non-profit group of oncologists whose guidance is closely followed by leading treatment centers, voted overwhelmingly in favor of maintaining its recommendation that Avastin should be used to treat breast cancer. The vote came shortly after an FDA panel voted 6-to-0 to revoke the breast cancer indication for Avastin.

The endorsement is important because oncologists will likely continue to use Avastin even if FDA commish Margaret Hamburg rescinds the breast cancer indication. Roche and its Genentech unit had appealed a decision last December by the agency to pull the indication for their best-selling med after new studies showed the med does not prolong overall survival in breast cancer patients or provide a sufficient benefit in slowing disease progression to outweigh significant risks. This prompted the unusual two-day hearing last month (back stories here and here).

However, 10 of the 33 members of the NCCN breast cancer panel members have ties to Roche or Genentech, either as advisory board members, speakers, consultants, expert witnesses or having received clinical research support. These connections are disclosed on the NCCN web site (look here). And 25 members of the panel participated in the recent vote to maintain the recommendation.

Specifically, the NCCN panel voted 24 in favor, 0 against and 1 abstention. The simple math suggests that at least one panel member – and possibly two – with ties to Roche voted to support the metastatic breast cancer recommendation. Perhaps more panel members with connections voted, although there is now way to know ascertain this since the NCCN press release does not specify who participated in the voting.

As we have noted previously, the NCCN endorsement is likely to be a boon for Roche, since treatment for breast cancer has typically generated about $1 billion or more in annual sales. Avastin rings registers – worldwide sales last year totaled about $6.8 billion and rose 9 percent, which meant this one drug accounted for 14 percent of total Roche sales. In other words, much is at stake.

Meanwhile, the stated NCCN policy conflicts of interest requires “disclosure of external relationships and recusal of NCCN Guidelines Panel Members with conflicting interests so that the integrity of the NCCN Guidelines is not compromised or diminished by conflicts or by the perception of conflicts,” according to the NCCN web site.

The policy also states that a panel member with a significant and direct or indirect relationship with “an external entity” that constitutes a conflict shall not participate in NCCN Guidelines Panel discussions, when the panel’s action on the topic under discussion “may advantage or disadvantage an external entity.” An exception is granted when requested by the panel chair “to participate for the purpose of providing or presenting information to the NCCN Guidelines Panel.”

More specifically, certain “direct relationships,” such as a panel member who is a beneficial owner of stock in an “external” entity or a director of such an organization” would be considered to have a de facto conflict. The policy also defines “direct relationships” as anyone “who receives compensation for services including, but not limited to, management or consulting services to the organization” (here is the policy).

So we asked NCCN whether this policy was followed for the recent breast cancer panel, given that the vote tally suggested otherwise. The spokeswoman repeatedly declined to discuss specifics and referred us back to the recent press release which, again, offers no information on the topic. In fact, she refused to answer whether NCCN has a recusal policy, even though this exists on the web site. “I’m only allowed to discuss what is in the press release,” she told us over and over.

We also reached out to the 10 panel members who have ties to Roche and Genentech. One responded. Antonio Wolff wrote us to confirm that “Genentech provides funding to Johns Hopkins University (where I am employed as School of Medicine faculty) to support research costs associated with an ongoing early phase clinical trial, and I am the site PI for that study. As for your specific question regarding my activities within NCCN, I will ask (you) to contact it directly as NCCN requires all panel members to adhere to its confidentiality policy.”

And so, an influential panel with ties to a drugmaker – which has a lot of sales on the line – voted to maintain a key recommendation. In this instance, NCCN panel members fully disclosed their ties to Roche, but is this sufficient? Supposedly, there is a reason NCCN has a disclosure and recusal policy, but in this instance, there would appear to have been a breach. If none occurred, the organization should be willing to discuss specifics and defend its policy. Yet NCCN refused to do so. What do you think?

Source: Pharmalot

HiRes 90K Cochlear Implant Device: Recall – Malfunction

MedWatch logo MedWatch - The FDA Safety Information and Adverse Event Reporting Program HiRes 90K Cochlear Implant Device: Recall – Malfunction
[Posted 11/27/2010]
AUDIENCE: Audiology, Patients
ISSUE: Advanced Bionics (AB) announced that it will voluntarily recall its HiRes 90K cochlear implant device and is retrieving all unimplanted devices in distribution. This action is being taken in response to two confirmed instances where the product experienced a malfunction requiring explantation. These recipients experienced severe pain, overly loud sounds and/or shocking sensations at 8-10 days after initial activation of their device.
BACKGROUND: AB is continuing to evaluate the root cause(s) of the problem and is working closely with the FDA to address their questions and concerns, and institute changes to the product to ensure that the HiRes 90K has the highest quality for patients who use the device. This voluntary action is being taken to ensure continued patient safety and product quality. The risk of any significant adverse medical events appears to be remote at present.
RECOMMENDATION: Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA’s MedWatch Safety Information and Adverse Event Reporting Program:

Complete and submit the report Online: www.fda.gov/MedWatch/report.htm
Download form or call 1-800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178

Read the complete MedWatch Safety Alert at: : http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm235009.htm

Interaccion entre Clopidogrel y Omeprazol

FDA MEDWATCH:

La FDA informa hoy sobre la interacción entre Clopidogrel y Omeprazol. Nuevos datos informan que cuando los mismos son tomados en conjunto la efectividad del Clopidogrel se ve reducida. Aquellos pacientes con riesgo coronario o accidente cerebrovascular, que toman Clopidogrel pueden de esta manera reducido los efectos preventivos del clopidogrel. Tomar ambos medicamentos separados en el tiempo no ha probado reducir esta interacción.

Otros medicamentos también debieran ser evitados en combinación con clopidogrel, entre los que incluyen a la cimetidina, fluconazol, ketoconazol, voriconazol, etravirina, fluoxetina, fluvoxamina y ticlopidina. Mayor información puede encontrarse en el enlace de la propia FDA, con fecha 26 de Enero de 2009: en

http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm190848.htm

Efectos adversos del Tamiflu

Roche Laboratories has alerted healthcare professionals about neuropsychiatric events that have occurred in influenza patients taking Tamiflu (oseltamivir phosphate). Tamiflu is used to treat or prevent the flu in patients 1 year and older.

The company’s letter says that there have been reports of self-injury and delirium in flu patients who were taking Tamiflu. Most of these events occurred in Japan, and the majority were in children. The possible role of the drug in contributing to these events isn’t known. However, the labeling for Tamiflu now says that people with the flu, particularly children, may be at increased risk of self-injury and confusion shortly after taking Tamiflu, and so they should be closely monitored for signs of unusual behavior throughout the treatment period. Caregivers or patients should be told to contact a healthcare professional immediately if a patient taking Tamiflu shows any signs of unusual behavior.

The company’s letter also alerts practitioners to the potential interaction between Tamiflu and FluMist, the intranasal flu vaccine. It notes that if they are given together, Tamiflu may inhibit the desired replication of the live virus in the intranasal vaccine. Because of this, FluMist should not be administered within two weeks before, or 48 hours after administering Tamiflu. This potential interaction is not a problem with the injectable trivalent flu vaccine.

Additional Information:

FDA MedWatch Safety Alert. Tamiflu (oseltamivir phosphate). November 13, 2006.
http://www.fda.gov/medwatch/safety/20…

Efectos adversos del Tamiflu

Additional Information:

FDA MedWatch Safety Alert. Tamiflu (oseltamivir phosphate). November 13, 2006.
http://www.fda.gov/medwatch/safety/20…

Comite de seguridad de la FDA

Ciprian Jauca, de Therapeutics Initiative, nos da una buena noticia:
el Dr. Sidney Wolfe, editor en jefe de WorstPills.org y co-fundador del Grupo de Investigación en Salud “Public Citizen”, ha sido nombrado para un mandato de cuatro años en el Comité Asesor de la Seguridad de los Medicamentos y de Control del Riesgo, de la Administración de Medicamentos y Alimentos (FDA, por sus siglas en inglés), que asesora a la agencia sobre la seguridad de ciertos medicamentos.
En el contexto de este reciente nombramiento, la edición del 9 de enero de The Wall Street Journal en un artículo y un vídeo presentado en el sitio web del periódico, realiza una semblanza sobre Wolfe, destacando su papel como “cruzado de la seguridad de los medicamentos” y “rebelde farmacéutico con causa”. El artículo señala que “la industria farmacéutica tiene una pesadilla recurrente: el cruzado Sidney Wolfe se convierte en un actor de la Administración de Alimentos y Drogas”.

El artículo (A Wolfe in Regulator’s Clothing: Drug Industry Critic
Joins the FDA) está disponible en:

http://online.wsj.com/article/SB123145489435265929.html?mod=googlenews_wsj

El video de 4 minutos (Pharmaceuticals Rebel with a Cause) está disponible en::

http://online.wsj.com/article/SB123145489435265929.html?mod=googlenews_wsj # articleTabs% 3Dvideo

El articulo comienza recordando que durante más de tres décadas, el Dr. Wolfe, jefe del grupo de salud en la organización de defensa del consumidor Public Citizen, que fuera fundada por Ralph Nader, ha colaborado a que 16 medicamentos fueran retirados del mercado y a exigir restricciones en muchos productos multimillonarios

continuación, un vistazo a algunas de ellas.

algunas de ellas fueron
farmaco Fabricante

Atromid-S Wyeth
Bendectin Sanofi Aventis
Bextra Pfizer
Butazolidin Novartis
Cylert Abbott
Lotronex* Prometheus Labs
Oraflex Eli Lilly
Parlodel ** Novartis
Propulsid Johnson & Johnson
Rezulin Pfizer
Serzone *** Bristol-Myers Squibb
Tandearil Novartis
Trovan Pfizer

Notas: * retirado del mercado, luego reintroducido pero con restricciones
muy severas: poco uso
** Peticion logro la prohibicion de su uso principal, la supresion de la
lactancia
*** Despues de la peticion y demanda, Bristol-Myers Squibb retiro el
medicamento al igual que un fabricante de genericos. Otros fabricantes de
genericos lo siguen vendiendo.

Fuente: Martin Cañas

Revisa la FDA retiro de fármacos contra el asma por sus efectos

■ Pide retirar tratamientos con agonistas LABA en menores de 18 años y de Serevent y Foradil en pacientes de todas las edades

■ La semana próxima consultarán a un panel de expertos

Reuters

Washington, 5 de diciembre. Los reguladores sanitarios de Estados Unidos siguen preocupados por los graves riesgos causados por una clase de fármacos contra el asma, por lo que decidieron pedir asesoría a un grupo de especialistas externos, indicaron documentos publicados el viernes.
Los funcionarios del área de salud consultarán la semana próxima a un panel de asesores sobre si deberían revocar su aprobación para el tratamiento de la enfermedad, agregaron.
El personal de la oficina de seguridad de medicamentos de la Administración de Alimentos y Fármacos de Estados Unidos (FDA, por su siglas en inglés) recomendó de forma unánime retirar la autorización de tratamiento a menores de 18 años a todos los agonistas beta de larga duración (LABA, por sus siglas en inglés).
Las medidas se dan en medio de un aumento del riesgo de muertes y ataques relacionados con asma entre los consumidores de esos fármacos.
Entre los LABA se encuentran Advair y Serevent de GlaxoSmithKline Plc, Symbicort de Astra Zeneca Plc y Foradil de Novartis AG, que en Estados Unidos comercializa Schering-Plough Corp.
Riesgos contra beneficios
El personal de seguridad de medicamentos de la FDA, que controla los riesgos de los fármacos después de su aprobación, también instó a la remoción de la autorización de Serevent y Foradil para el tratamiento del asma en las personas de todas las edades.
Serevent y Foradil sólo contienen LABA, mientras Advair y Symbicort combinan LABA con esteroides inhalables.
Sumar el esteroide protegería contra las complicaciones graves, argumentó Glaxo.
Un “meta análisis” de varios estudios reveló que el riesgo “no se veía” en el caso de Advair o cuando el LABA se usaba con un esteroide, señalaron los documentos de la agencia federal estadunidense.
Un memorándum que resume los temas a tratar en el encuentro del panel asesor señaló que la FDA preguntará a los especialistas externos si las medicinas aún deberían tener aprobación para el tratamiento de asma. El panel se reunirá el miércoles y jueves próximos.
El doctor Badrul Chowdhury, director de la división de la FDA que revisa los fármacos pulmonares y antialérgicos, dijo que existe un “riesgo de seguridad grave e importante”, pero añadió que las muertes vinculadas con el asma eran “numéricamente escasas” y los beneficios no eran triviales.
“La remoción del mercado de los LABA inhalables como tratamiento para el asma es una forma de controlar el riesgo que implican estos medicamentos, pero se trataría de un enfoque extremo que podría resultar problemático”, escribió Chowdhury.
Los fármacos también están aprobados para el tratamiento de la enfermedad pulmonar obstructiva crónica (EPOC) y se mantendrían disponibles para los pacientes con esa dolencia.
Los fabricantes de las medicinas, en documentos separados preparados para el encuentro, indicaron que los beneficios superan a los riesgos cuando se utilizan como es indicado.

Revisa la FDA retiro de fármacos contra el asma por sus efectos

■ Pide retirar tratamientos con agonistas LABA en menores de 18 años y de Serevent y Foradil en pacientes de todas las edades

■ La semana próxima consultarán a un panel de expertos

Reuters

FDA y seguridad en medicamentos

Ahora tanto consumidores como profesionales de salud pueden acceder desde una sola pagina de la FDA (Agencia de Alimentos y Medicamentos de los EE.UU.) a una amplia variedad de información sobre seguridad de medicamentos de venta bajo receta. La página Web, http://www.fda.gov/cder/drugSafety.htm, ofrece enlaces a la información en diferentes categorías:

a.. Etiquetado de medicamentos, incluido el etiquetado para pacientes, para profesionales, y el prospecto incluido en el envase;
a.. Fármacos que están incluidos en la Estrategia de Evaluación y Minimización de Riesgo (REMS, por sus siglas en inglés) para garantizar que sus beneficios superan a sus riesgos;
a.. Una base de datos de estudios de post comercialización que han sido requeridos o acordados por las compañías farmacéuticas, para proporcionar información adicional acerca de la seguridad, la eficacia, o el uso óptimo de un medicamento, a la FDA;
a.. Clinicaltrials.gov, base de datos de ensayos clínicos, incluyendo información sobre cada propósito del ensayo, participantes y ámbito de desarrollo, así como números de teléfono útiles;
a.. Información de seguridad especifica para determinados fármacos, incluyendo hojas de información con las novedades más recientes, así como anuncios de prensa relacionados hojas de datos y podcasts de seguridad de los medicamentos de la FDA;
a.. Informes trimestrales del listado de medicamentos que están siendo evaluados por posibles problemas de seguridad, basados en las revisiones de la información del Sistema de Notificación de Eventos Adversos (AERS, por sus siglas en inglés) de la FDA;
a.. Cartas de advertencia, Recordatorios, Retiros del mercado, y alertas de seguridad;
a.. Regulación y documentos de orientación;
a.. Información para el consumidor sobre la utilización segura de medicamentos y eliminación de medicamentos no utilizados;
a.. Instrucciones de cómo notificar problemas a la FDA a través de su programa MedWatch;
a.. Artículos para el consumidor sobre seguridad de los medicamentos y
a.. La respuesta de la FDA al informe 2006 del Instituto de Medicina sobre el futuro de la seguridad de los medicamentos.
De acuerdo con Paul Seligman director asociado de Políticas y Comunicación de Seguridad del Centro de Evaluación e Investigación de Medicamentos, de la FDA “al colocar enlaces a estos recursos actualizados en una sola página, estamos ayudando a los consumidores y los profesionales de la salud a encontrar información de seguridad sobre medicamentos más rápida y fácilmente”.

El establecimiento de una página Web es uno de los requisitos de la Ley de Enmiendas de 2007 de la FDA.

http://www.fda.gov/cder/drugSafety.htm

FDA y seguridad en medicamentos

El establecimiento de una página Web es uno de los requisitos de la Ley de Enmiendas de 2007 de la FDA.

http://www.fda.gov/cder/drugSafety.htm

Medwatch: bifosfonatos y fibrilacion auricular,

Bisphosphonates marketed as Alendronate (Fosamax, Fosamax Plus D)
Etidronate (Didronel)
Ibandronate (Boniva)
Pamidronate (Aredia)
Risedronate (Actonel, Actonel W/Calcium)
Tiludronate (Skelid)
Zoledronic acid (Reclast, Zometa)

En Argentina se pueden ver los nombres comerciales desde la pagina de Alfabeta

Audience: Geriatricians, gynecologists, orthopedic surgeons, other healthcare professionals
FDA issued an update about the Agency’s review of safety data regarding the potential increased risk of atrial fibrillation in patients treated with a bisphosphonate drug. Bisphosphonates are a class of drugs used primarily to increase bone mass and reduce the risk for fracture in patients with osteoporosis, slow bone turnover in patients with Paget’s disease of the bone, and to treat bone metastases and lower elevated levels of blood calcium in patients with cancer. FDA reviewed data on 19,687 bisphosphonate-treated patients and 18,358 placebo-treated patients who were followed for 6 months to 3 years. The occurrence of atrial fibrillation was rare within each study, with most studies containing 2 or fewer events. Across all studies, no clear association between overall bisphosphonate exposure and the rate of serious or non-serious atrial fibrillation was observed. Additionally, increasing dose or duration of bisphosphonate therapy was not associated with an increase rate of atrial fibrillation. Healthcare professionals should not alter their prescribing patterns for bisphosphonates and patients should not stop taking their bisphosphonate medication.

Read the entire 2008 MedWatch Safety Summary, including a link to the FDA Update of Safety Review Follow-up to the October 1, 2007, Early Communication about the Ongoing Safety Review of Bisphosphonates, regarding this issue at:

http://www.fda.gov/medwatch/safety/2008/safety08.htm#bisphosphonates2

Medwatch: bifosfonatos y fibrilacion auricular,

En Argentina se pueden ver los nombres comerciales desde la pagina de Alfabeta

http://www.fda.gov/medwatch/safety/2008/safety08.htm#bisphosphonates2

Efalizumab y riesgos adversos

Como ya publique algo parecido el año pasado, le pido a los abogados de Serono que esta vez se ahorren el trabajo de mandar cartas documentos intimandome a bajar este post. Aunque aquel tambien tenia las referencias. Si el problema sigue siendo que el medicamento entro por presion dentro de nuestra canasta basica de servicios, y no por una evaluacion de tecnologias, ya esta, no se preocupen, la seguridad social argentina ya lo cubre, y la ONG que auspicio este mecanismo de aprobar medicamentos ya esta feliz, seguramente recibiendo alguno que otro viaje de la industria o donaciones para la fundacion.

La FDA anunció que se actualizará la etiqueta para el medicamento contra psoriasis Raptiva (efalizumab) para reflejar el hecho de que el medicamento puede incrementar el riesgo de infecciones oportunistas que pueden poner en riesgo la vida del paciente.
La nueva etiqueta hará declaración que Raptiva puede incrementar el riesgo de sepsis bacteriana, meningitis viral, infecciones fúngicas invasivas y leucoencefalopatía multifocal progresiva. De acuerdo con la FDA, hay varios reportes de pacientes tomando Raptiva que han sido hospitalizados por estos padecimientos.

Efalizumab y riesgos adversos

Medicamentos para la tos y el resfrio: reacciones adversas graves y recomendaciones de uso

Editado por Boletín Fármacos

En octubre de 2007 la FDA sostuvo una reunión de comité asesor que terminó en la recomendación de prohibir la utilización medicamentos para el resfriado en niños menores de dos años. Poco tiempo antes los fabricantes de docenas de remedios contra la tos y el resfriado destinados a bebés retiraron algunos de sus productos de manera voluntaria. En total, en EE.UU. se venden aproximadamente unos 800 medicamentos para la tos y el resfriado. Los expertos estiman que los estadounidenses gastan alrededor de US$2.000 millones cada año en estos tipos de medicamentos [1].

Un informe de los Centros Federales para el Control y la Prevención de Enfermedades (CDC) señala que anualmente 7.000 niños, menores de 11 años, reciben tratamiento en las salas de emergencia de los hospitales debido a reacciones a jarabes para la tos y el resfrío [2].

La Dra. Schaefer, autora líder del estudio del CDC, publicado de manera preliminar en la revista Pediatrics, señaló que los 7.000 casos representan menos del 6% de las visitas a las salas de emergencia por todos los demás medicamentos combinados, es decir que cualquier medicamento en manos de un niño de tres años es un problema [1].

Los investigadores usaron datos del proyecto del Sistema Electrónico Nacional de Vigilancia de Lesiones y Vigilancia Cooperativa de los Eventos Farmacológicos Adversos para analizar las visitas a emergencias debidas a fármacos contra la tos y los resfriados en 2004 y 2005. Encontraron que los niños entre los dos y los cinco años conformaban el 64% de todas las visitas a los departamentos de emergencia debidas a reacciones adversas a los medicamentos contra la tos y el resfriado. Entre esos niños más jóvenes, el 80% de los problemas se debieron a ingesta no supervisada. En general, aproximadamente dos tercios de todos los niños estudiados terminaron en emergencias debido a ingesta no supervisada.

La mayoría de los niños, el 93%, no necesitó ser hospitalizado. Pero una cuarta parte necesitó tratamiento adicional para eliminar el medicamento de sus sistemas, informaron los investigadores.

Entre los productos de venta sin receta para la tos y el resfriado que fueron incluidos en el estudio se encontraban descongestionantes, expectorantes y antitusivos. Los productos podrían también haber incluido antihistamínicos. Las etiquetas incluían los términos “descongestionantes nasales”, “supresores de la tos”, “expectorantes” y “antihistamínicos” [1].

Recomendaciones de la FDA sobre el uso de productos para la tos y el resfriado de venta sin receta
A mediados de enero, la FDA emitió una advertencia de salud pública para padres y cuidadores recomendando que los productos para la tos y el resfriado de venta sin receta (OTC, por sus siglas en inglés) no se utilizasen en bebés y niños menores de dos años porque se pueden producir efectos secundarios graves y potencialmente peligrosos para la vida. Los productos para la tos y el resfriado de venta sin receta incluyen descongestivos, expectorantes, antihistamínicos y antitusivos para el tratamiento del resfriado [3].

Se han notificado una gran variedad de efectos adversos graves e inusuales con productos para la tos y el resfriado, entre las que se incluyen la muerte, convulsiones, frecuencia cardiaca acelerada y disminución en los niveles de conciencia.

No se ha demostrado que estos medicamentos, que tratan los síntomas pero no la afición subyacente, sean seguros o eficaces en niños menores de dos años.

El anuncio no incluyó la recomendación final de la FDA acerca del uso de medicamentos para la tos y el resfriado de venta sin receta en niños de entre 2 y 11 años. La agencia está haciendo una revisión de datos de niños de estas edades y se ha comprometido a hacer una revisión oportuna e integral de la seguridad de la utilización de los medicamentos de venta sin receta para la tos y el resfriado en los niños. La agencia publicará sus recomendaciones tan pronto como esta revisión esté completa.

La declaración se basa en la revisión de la información que ha hecho la FDA y en el análisis que se realizó en una reunión conjunta de los Comités Asesores de Medicamentos de Venta sin Receta y de Pediatría realizada el 18 y 19 de octubre de 2007.

En espera de la finalización de la revisión en curso por la FDA, los padres y cuidadores que elijan usar medicamentos para la tos y el resfriado de venta sin receta en niños de entre 2 y 11 años deben [3]:

– seguir las indicaciones sobre la dosis que aparecen en la etiqueta;
– comprender que estos medicamentos NO curarán ni reducirán la duración de un resfrío común;
– revisar el prospecto para saber que ingredientes activos contiene el producto, ya que muchos productos para la tos y el resfriado de venta sin receta médica contienen múltiples ingredientes activos;
– usar solo las cucharas o tazas de medida que vienen con el medicamento o las que son hechas especialmente para medir medicamentos.

La FDA recomienda que en caso de duda se comunique con un médico, farmacéutico u otro profesional de la salud para analizar la forma de tratar a un niño que tiene tos o un resfrío. La FDA ha advertido contra efectos secundarios de estos medicamentos -poco comunes pero potencialmente graves en los niños- como convulsiones, aceleración del ritmo cardíaco y desmayos [4].

Recomendaciones de los CDC
Los CDC advirtieron que los padres tampoco deben usar productos destinados a niños mayores para tratar a niños pequeños y deberían mantener todos los medicamentos contra la tos y el resfriado lejos del alcance de los niños. Además, los padres deben eliminar los productos que pudieran tener que les fueron vendidos para usarlos en bebés de dos años o menos.

“Los padres deben guardar estos medicamentos fuera del alcance de los niños y no deberían alentarlos a tomar estos medicamentos diciendo que son bombones”’, comentó la funcionaria del CDC, Denise Cardo.

Entre estos medicamentos figuran descongestivos, expectorantes, anti-histamínicos, antitusígenos y productos anti-resfrío.

Referencias:
1. Reinberg S, Los medicamentos contra el resfriado envían a 7.000 niños de EE.UU. a emergencias cada año, Healthday, 28 de enero de 2008.
2. Cada año siete mil niños van a urgencias debido a reacciones por causa de jarabes para la tos,El Tiempo (Colombia), 29 de enero de 2008.
3. FDA, FDA Recommends that Over-the-Counter (OTC) Cough and Cold Products not be used for Infants and Children under 2 Years of Age, January 17, 2008. Disponible en:www.fda.gov/cder/drug/advisory/cough_cold_2008.htm
4. Miles de niños enferman por reacción a jarabes, El Nuevo Herald (EE.UU.), 30 de enero de 2008.

Medicamentos para la tos y el resfrio: reacciones adversas graves y recomendaciones de uso

Editado por Boletín Fármacos

La mayoría de los niños, el 93%, no necesitó ser hospitalizado. Pero una cuarta parte necesitó tratamiento adicional para eliminar el medicamento de sus sistemas, informaron los investigadores.

No se ha demostrado que estos medicamentos, que tratan los síntomas pero no la afición subyacente, sean seguros o eficaces en niños menores de dos años.

Entre estos medicamentos figuran descongestivos, expectorantes, anti-histamínicos, antitusígenos y productos anti-resfrío.

Efectos adversos: erlotinib e insuficiencia hepatica

Tarceva (erlotinib) Tablets
Audience: Oncological healthcare professionals
OSI and Genentech notified healthcare professionals that cases of hepatic failure and hepatorenal syndrome, including fatalities, have been reported during use of Tarceva, particularly in patients with baseline hepatic impairment. Patients with hepatic impairment receiving Tarceva should be closely monitored during therapy and the product should be used with extra caution in patients with total bilirubin >3x ULN. Dosing should be interrupted or discontinued if changes in liver function are severe, such as doubling of total bilirubin and/or tripling of transaminases in the setting of pretreatment values outside the normal range. New information from a pharmacokinetic study in patients with moderate hepatic impairment associated with significant liver tumor burden has been provided in the revised prescribing information, and other recommendations are included in the WARNINGS and DOSAGE AND ADMINISTRATION sections.

Read the entire 2008 MedWatch Safety Summary, including links to the manufacturer’s Dear Healthcare Provider Letter and the revised prescribing information for Tarceva, at: http://www.fda.gov/medwatch/safety/2008/safety08.htm#Tarceva.

Efectos adversos: erlotinib e insuficiencia hepatica

Rituximab: efectos neurologicos

Se ha identificado una especie de leucoencefalopatía multifocal progresiva fatal en pacientes tomando rituximab (Rituxan) para atritis reumatoide, según reporta la FDA.

La infección por virus JC anticipando a la leucoencefalopatía fué diagnósticada 18 meses depués de la última toma de rituximab.

El fabricante ha actualizado las etiquetas del medicamento para reflejar esta información. Previamente, la etiqueta avisaba sobre el riesgo de padecer leucoencefalopatía en pacientes con otras enfermedades autoinmunes o cáncer hematológico.

En una carta a profesionales de la salud, el fabricante advierte a los médicos a considerar leucoencefalopatía en cualquier paciente que use rituximab con manifestaciones neurológicas de inicio reciente. Si se diagnostica la leucoencefalopatía, rituximab debe ser suspendido.

Rituximab: efectos neurologicos

Se ha identificado una especie de leucoencefalopatía multifocal progresiva fatal en pacientes tomando rituximab (Rituxan) para atritis reumatoide, según reporta la FDA.

La infección por virus JC anticipando a la leucoencefalopatía fué diagnósticada 18 meses depués de la última toma de rituximab.

Exenatide (marketed as BYETTA): pancreatitis aguda

Exenatide (marketed as BYETTA): Acute PancreatitisFDA has been monitoring cases of acute pancreatitis in its postmarketing review of adverse event reports associated with the use of exenatide. Spontaneous adverse event reports of acute pancreatitis were described in the Adverse Reactions section of product labeling. Further postmarketing review of exenatide identified additional cases of acute pancreatitis associated with use of the drug. The product labeling has been updated to include information about acute pancreatitis in the Precautions section of the label, and information for healthcare professionals has been posted on FDA’s Web site.¹ This article, based on the review of 30 reports of acute pancreatitis, describes the postmarketing data that prompted the revision to product labeling and provides recommendations to healthcare professionals regarding this serious adverse event.

Exenatide, the first-in-class incretin mimetic, is a glucagon-like peptide-1 (GLP-1) analogue that stimulates insulin release from pancreatic beta-cells in a glucose-dependent manner, suppresses inappropriately elevated glucagon secretion, and slows gastric emptying.¹ Exenatide was approved by FDA on April 28, 2005, and is indicated as adjunctive therapy to improve glycemic control in patients with type 2 diabetes mellitus who are taking metformin, a sulfonylurea, a thiazolidinedione, a combination of metformin and a sulfonylurea, or a combination of metformin and a thiazolidinedione, but have not achieved adequate glycemic control.¹ Exenatide is administered by subcutaneous (SC) injection, initially as a 5 microgram (mcg) dose before the morning and evening meals, which can be increased to 10 mcg twice daily injections after 1 month of therapy. Commonly reported side effects of exenatide include nausea, vomiting, diarrhea, indigestion, and upper abdominal discomfort.

Exenatide was originally identified in the saliva of the poisonous Gila monster lizard. Pancreatitis has been reported with envenomation with Gila monster saliva due to overstimulation of the pancreas.²

From April 28, 2005, to December 31, 2006, FDA received 30 domestic reports of acute pancreatitis in patients who received exenatide treatment. Nineteen (63%) patients were female. The median age of patients described in the case reports was 60 years (range: 43-72 years).

The daily dose of exenatide was reported in 25 (83%) cases and ranged from 10-20 mcg. The median time to onset of symptoms of acute pancreatitis from the start of exenatide therapy was 34 days (range: 4-300 days). A dose-response relationship was observed in six patients who reported the onset or worsening of symptoms associated with acute pancreatitis soon after the dose of exenatide was increased from 5 mcg twice daily to 10 mcg twice daily.

Serum amylase, reported in 17 (57%) cases, ranged from 40-1,845 IU/L (normal range: 30-170 IU/L). The median serum amylase value was 384 IU/L. Serum lipase, reported in 25 (83%) cases, ranged from 62-16,970 (normal range: 7-60 IU/L). The median serum lipase value was 545 IU/L. The diagnosis of acute pancreatitis was confirmed by CT scan or ultrasound in 11 (37%) cases.

In 21 of the 30 cases (70%), the patients were hospitalized. There were no fatalities and no cases describing a hemorrhagic or necrotizing pancreatitis event. However, five patients developed serious complications, including dehydration and renal failure associated with dehydration (2), suspected ileus (2), ascites (1), and phlegmon (1) (these events are not mutually exclusive). Twenty-two patients improved after exenatide therapy was discontinued, and 15 reports described the event as resolved at the time of the report.

Twenty-seven cases (90%) reported one or more possible contributory factors, including concomitant use of medications that list pancreatitis among reported adverse events in product labeling, or confounding conditions such as obesity, gallstones, severe hypertriglyceridemia, and alcohol use. Twenty-two cases reported a positive dechallenge once the drug was discontinued; three of these cases reported recurrence of various symptoms (e.g., nausea and vomiting, abdominal pain) at re-initiation of exenatide. These findings suggested a strong temporal association between exenatide and acute pancreatitis.

Two cases reported to AERS that suggest a role for exenatide in the development of acute pancreatitis are summarized in Box 1. The first case is described in the medical literature.³ These cases were selected based on the temporal relationship between initiation of exenatide treatment or dose escalation and onset of symptoms associated with acute pancreatitis and the level of detail provided by the case reporter.

Box 1

Case 1

A 69-year-old obese man with a 15-year history of type 2 diabetes was started on exenatide 5 mcg SC twice a day due to poorly controlled blood glucose (HbA1c 10.5%). With the initiation of exenatide treatment, pioglitazone and metformin were stopped. Following the first exenatide injection, the patient developed midepigastric abdominal pain radiating to the back. The pain intensified over the next few days and he was admitted to the hospital. Admission laboratory results were significant for an elevated serum amylase of 384 IU/L, serum lipase of 346 IU/L, low serum sodium of 130 mg/dL, blood glucose of 309 mg/dL, and white blood cell count of 11,000 cells/mm³. His serum creatinine, aspartate aminotransferase (AST), and alanine aminotransferase (ALT), triglycerides, serum calcium, and hemoglobin were within normal limits. CT scan of the abdomen revealed no evidence of cholelithiasis, and the presumptive diagnosis of acute pancreatitis was made. The patient was treated with intravenous fluids, pain medication, pantoprazole, and insulin. The patient’s abdominal pain resolved, his serum lipase normalized, and he fully recovered.

The patient’s medical history was significant for diabetic neuropathy, retinopathy, hypertension, hyperlipidemia, coronary artery disease, gastroesoghageal reflux disease, colonic polyposis, depression, benign prostatic hypertrophy, convulsions, anxiety, stress, hypothyroidism, and rheumatoid arthritis. There was no previous history of pancreatitis, gallstones, or alcohol use. Concomitant medications included pioglitazone, metformin, Humulin NPH, rapid-acting insulin analogue, paroxetine, primidone, metoprolol, gabapentin, lovastatin, irbesartan, clopidogrel, infliximab, ezetimibe, and esomeprazole.

Case 2

A 51-year-old woman with a history of type 2 diabetes was started on exenatide 5 mcg SC twice a day. The patient experienced nausea, vomiting, and loss of appetite after starting the 5 mcg dose. One month later, the dose was increased to 10 mcg twice a day. Her symptoms increased, and she subsequently developed diarrhea and upper abdominal discomfort on the 10 mcg dose. Exenatide was discontinued. She was admitted to the hospital with a diagnosis of pancreatitis. She was treated with antibiotics, a liquid diet, and intravenous fluid. Diagnostic testing revealed a normal chest x-ray, normal sonogram of the gallbladder and kidneys, and an enlarged pancreas without a mass on abdominal ultrasound and CT scan. Admission laboratory results were significant for elevated serum amylase of 1,373 IU/L and serum lipase of 1,490 IU/L. During hospitalization, serum amylase and lipase decreased to 185 IU/L and 100 IU/L, respectively, and serum AST was 38 IU/L.

Nausea, vomiting, and diarrhea returned after the patient restarted exenatide therapy. At the time of the report, the pancreatitis was described as resolving, but the events of “nausea, vomiting, decreased appetite, and diarrhea were ongoing.”

Her medical history included depression, hyperlipidemia, urinary tract infections, and thalassemia diagnosed in childhood. The patient denied any history of pancreatitis. Her relevant concomitant medications included metformin/rosiglitazone, glimepiride, nateglinide, fenofibrate, and atorvastatin.

Subsequent to this review of 30 cases, additional cases of acute pancreatitis in association with exenatide use have been reported to FDA, including one case with serious complications resulting in pancreatic pseudocyst and sepsis leading to death. The cause of death was reported as metabolic acidosis from ischemic stomach, liver, and small intestines due to peripheral vascular disease.

FDA will continue to monitor AERS for reports of acute pancreatitis in association with the use of exenatide and carefully evaluate the data. Healthcare professionals are asked to report any suspected serious adverse reactions in association with exenatide therapy to the FDA MedWatch program.

FDA encourages:

Healthcare professionals to be aware of the potential for acute pancreatitis with exenatide and be alert to the signs and symptoms of acute pancreatitis. Symptoms include persistent, severe abdominal pain that can radiate to the back and may be accompanied by nausea and vomiting. Acute pancreatitis is typically confirmed by the presence of elevated levels of serum amylase and/or lipase and characteristic findings by radiological imaging.
Physicians to discontinue exenatide if pancreatitis is suspected. If pancreatitis is confirmed, exenatide should not be restarted unless an alternative etiology for the pancreatitis is identified.
Exenatide-treated patients to promptly seek medical care if they experience unexplained severe abdominal pain with or without nausea and vomiting.

Relevant Web Sites

http://www.fda.gov/cder/drug/infopage/exenatide/default.htm
http://www.fda.gov/cder/drug/InfoSheets/HCP/exenatideHCP.htm
http://www.fda.gov/medwatch/safety/2007/safety07.htm#Byetta

References

Exenatide (Byetta) product labeling.
Sherman M. Therapeutic Venoms. US Pharm. 2005;12:33-36.
Denker PS, Dimarco PE. Exenatide (exendin-4)-induced pancreatitis: a case report. Diabetes Care. 2006;29(2):471.

Novedades de la FDA

» News

— Food, Medical Product Safety Among Key FY ‘O9 FDA Budget Requests

— Doubled Risk of Suicidal Thoughts, Behaviors Seen With Antiepileptic Use

— FDA Approves New Drug-Eluting Stent for Opening Clogged Heart Arteries

» Safety Alerts/Recalls

» Upcoming Public Meetings

» Consumer Health Information

__________________________________________

NEWS

Food, Medical Product Safety Among Key FY ‘O9 FDA Budget Requests

FDA is requesting nearly $2.4 billion as part of the president’s fiscal year (FY) 2009 budget—a 5.7 percent increase over the current fiscal year budget. The budget proposal includes strategic increases to strengthen food protection, modernize drug safety, speed approval of generic drugs, and improve the safety and review of medical devices.

http://www.fda.gov/bbs/topics/NEWS/2008/NEW01789.html

Doubled Risk of Suicidal Thoughts, Behaviors Seen With Antiepileptic Use

FDA has alerted health care professionals about an increased risk of suicidal thoughts and behaviors (suicidality) in patients who take drugs called antiepileptics to treat epilepsy, bipolar disorder, migraine headaches, and other conditions. An FDA analysis of suicidality reports from placebo-controlled studies of 11 antiepileptic drugs shows that patients taking these drugs have about twice the risk of suicidal thoughts and behaviors (0.43 percent), compared with patients receiving a placebo (0.22 percent).

http://www.fda.gov/bbs/topics/NEWS/2008/NEW01786.html

FDA Approves New Drug-Eluting Stent for Opening Clogged Heart Arteries

FDA has approved the Endeavor Zotarolimus-Eluting Coronary Stent for use in treating patients with narrowed coronary arteries. The device

is a tiny metal mesh tube coated with a small amount of a new drug, zotarolimus, developed only for use on a stent. It is crimped around a balloon and delivered to a narrowed section of a coronary artery through a long, thin catheter. When the stent is positioned, the balloon is inflated, expanding into the vessel wall where it will remain in place, acting as a mechanical scaffold to keep the artery open.

http://www.fda.gov/bbs/topics/NEWS/2008/NEW01787.html

To view an archive of recent FDA news releases, go to

http://www.fda.gov/opacom/hpnews.html.

To access the RSS feed of FDA news releases, go to

http://www.fda.gov/bbs/topics/news/rssPress.xml.

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