FDA Is Petitioned To Add Black Boxes For PPIs

Diagram depicting the major determinants of ga...Image via Wikipedia

nexium-flickrThe widely used class of drug known as proton pump inhibitors that are used to treat acid reflux can cause dependency and, therefore, are likely to increase various serious risks, some of which are not specified in product labeling, according to Public Citizen. And so the consumer watchdog is petitioning the FDA to upgrade labeling for these meds with Black Box warnings.
In making its case, Public Citizen notes that patients who use PPIs for at least a month, but then stop taking the med can have even more stomach acid, which is called rebound acid secretion. As a result, patients may return to the meds, creating what the watchdog group calls a “long-term dependence.” Yet some patients may not need the meds in the first place, Public Citizen argues.
“PPIs are often prescribed outside of their approved uses, for purposes such as stress ulcer prophylaxis in noncritical hospitalized patients and long-term treatment of conditions such as GERD past the approved time frame. It has been estimated that up to two-thirds of all people on PPIs do not have a verified indication for the drug. In addition, even in many people with presumed GERD on PPI therapy, less intense acid-suppressive therapies are effective in relieving symptoms, and in other cases, the medical problem does not even involve acid reflux,” the group writes in its petition.
“Compounding the problem of massive inappropriate use, recent evidence has documented several serious new safety problems with long-term PPI use. For some of these risks, current FDA-approved PPI labels do not mention the adverse effect at all, including the potential for developing dependence on the drugs, which results in rebound hypersecretion of stomach acid and recurrence of symptoms after stopping PPI use. For other risks, even if mentioned, the label does not adequately explain or emphasize them. There are currently no black box warnings in the label of any PPI” (you can read the petition here).
To bolster its cause, Public Citizen enlisted Helge Waldum, who heads of the Department of Digestive and Liver Diseases at Trondheim University Hospital in Norway and has authored dozens of medical journal articles on PPIs, including what is said to be the first trial to show patients could become dependent on the meds through the so-called rebound effect. He signed on as a co-petitioner (and you can read his statement here).
In response, a spokeswoman for AstraZeneca, which sells Nexium, Prilosec and Vimovo, wrote us this: “We work with the FDA to ensure the benefit/risk profile of our products are reflected appropriately in the prescribing information so that health care professionals can weigh the risk and benefit of medicines when making treatment decisions. PPIs have been available in the US for over 20 years and are among the most widely-studied class of medicines.
“The data referred to by Public Citizen is in the public domain and available to regulators and physicians across the world. Ultimately, it’s up to doctors to prescribe these medicines based on individual patient need. We encourage ongoing communication between physicians and patients concerning individual medical needs. AstraZeneca is confident in the positive benefit-riskand safety profiles of NEXIUM, PRILOSEC and VIMOVO.”

Delayed FDA Removal of Painkiller Propoxyphene

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Delayed FDA Removal of Painkiller Propoxyphene (Darvon, Darvocet) From U.S. Market Has Cost More Than 1,000 U.S. Lives

Statement by Dr. Sidney Wolfe, Director, Public Citizen’s Health Research Group

Note: Public Citizen petitioned the FDA in 1978 and 2006 to ban propoxyphene.

The announcement by the U.S. Food and Drug Administration (FDA) that propoxyphene-containing products are finally going to be taken off the market * because of dangers previously known and acted upon, with bans announced in the UK almost six years ago, and in Europe, almost 1½ years ago * is a serious indictment of the FDA’s long-lasting unwillingness to protect people in this country from a deadly but barely effective painkiller. In announcing the ban in 2005, the UK stated that the efficacy of propoxyphene (sold generically and under the brand name Darvon) “is poorly established and the risk of toxicity in overdose, both accidental and deliberate, is unacceptable” and that “[I]n relation to safety, there is evidence that fatal toxicity may occur with a small multiple of the normal therapeutic dose and a proportion of fatalities are caused by inadvertent overdose.” The FDA’s claim that this is the first evidence that the drug is dangerous at the “standard therapeutic dose” thus rings dangerously hollow.

The FDA’s deadly delay in this case starkly illustrates how one of the most important public health concepts, the precautionary principle, was embraced by the UK and Europe, but was for too long recklessly rejected by the FDA.

Evidence going back more than 30 years indicates that propoxyphene is not very effective, is toxic at doses not much higher than the recommend dose because a heart-toxic metabolite accumulates in the body, and is somewhat addictive. It has been linked to many thousands of U.S. deaths since 1981, a large proportion of which were likely caused by cardiac toxicity, including the interruption of electrical conduction in the heart.

Since the time of the UK announcement in January 2005 of a phased, two-year withdrawal of this drug (which was followed by an immediate steep decline in use), approximately 120 million retail prescriptions have been filled in the U.S. for propoxyphene-containing drugs. These include Darvocet, which contains propoxyphene and acetaminophen and, primarily, the generic versions of the drug.

Due to FDA negligence, at least 1,000 to 2,000 or more people in the U.S. have died from using propoxyphene since time the UK ban was announced. The best forensic data, the kind relied upon in those countries for the UK and European bans, come from Florida where, because of routine drug testing required by the state medical examiner as part of many autopsies, deaths are categorized as being “caused” by certain drugs if the levels found are to be above a certain level. From 2005 through 2009, in Florida alone, 395 deaths were “caused” by propoxyphene. If data from 2007 are representative, in that year, 78 percent of the Florida deaths caused by propoxyphene were ruled accidental.

Our February 2006 petition to the FDA to ban the drug, following the UK ban announcement, did not even result in an FDA advisory committee hearing until we had sued the agency in 2008 to force them to respond to our petition. The subsequent January 2009 FDA advisory committee hearing resulted in a 14-12 vote in favour of banning propoxyphene, despite some FDA efforts to sway the committee against voting for a ban. In July 2009, several weeks after the European Medicines Agency announced its ban, the FDA denied our petition to ban the drug.

The FDA’s pitiful excuse that it needed to order a human study to find that “the drug puts patients at risk of potentially serious or even fatal heart rhythm abnormalities” before deciding whether to ban propoxyphene only emphasizes how out-of-step the agency is with the rest of the world * which already had enough human evidence of death and near-death in tens of thousands of people to act accordingly.

In a study on dogs published 31 years ago, researchers at Lilly, the discoverer of propoxyphene, stated that “cardiac conduction depression may be a factor in some of the [human] cardiac toxicities associated with propoxyphene overdose.” This study examined the same kind of function measured in the human study now being put forth by the FDA as a justification for belatedly banning propoxyphene.

We will ask for and support a congressional investigation into whom in the FDA, specifically in the Centre for Drug Evaluation and Research, was responsible for the loss of so many lives in this country. It is clear that long before today, many drug safety experts in the Office of Surveillance and Epidemiology had decided the drug should be removed from the market.

Note: For a chronology of events related to Darvon and Darvocet, go to

Public Citizen is a national, non-profit consumer advocacy organization based in Washington, D.C. For more information, please visit www.citizen.org.


Sidney M. Wolfe MD
Director, Health Research Group at Public Citizen
1600 20th St. NW
Washington, DC 20009
Phone: +1 202 588-7735

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:


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
*** 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

Public Citizen Sues FDA to Force Agency to Act on Petition Seeking Stricter Antibiotic Warnings

Public Citizen Sues FDA to Force Agency to Act on Petition Seeking Stricter Antibiotic Warnings

Fuente: Public Citizen
Despite long-standing evidence that fluoroquinolone antibiotics such as CIPRO and LEVAQUIN can cause tendon ruptures, the Food and Drug Administration (FDA) has failed to increase its warnings to patients and physicians about the dangers of the medicines, Public Citizen told a federal court Thursday.

Public Citizen, the authors of WorstPills.org, sued in the U.S. District Court for the District of Columbia, asking the court to force the FDA to act upon a petition the consumer group filed with the agency 16 months ago. The FDA has failed to respond to the petition, which Public Citizen contends is a violation of the Administrative Procedure Act.

The petition. asked the agency to put a “black box” warning on fluoroquinolone antibiotics to make doctors and patients more aware of the risk of serious tendon injury before tendons actually rupture. A “black box” is the strongest type of warning the FDA can request.

The petition also urged the FDA to send a warning letter to physicians, as well as require an FDA-approved medication guide to be dispensed when prescriptions are filled.

Stronger warnings could lead to earlier intervention and prevent needless injuries by allowing doctors to switch patients to other antibiotics, according to Dr. Sidney Wolfe, editor of WorstPills.org.

“While the FDA sits idly by and ignores the problem, more people will suffer serious tendon ruptures that could have been prevented,” Wolfe said. “The current warning is buried in a long list of possible side effects and is far too easy to miss.”

From November 1997 through December 2005, the FDA received 262 reports of tendon ruptures, mainly of the Achilles tendon, 258 cases of tendinitis and 274 cases of other tendon disorders in patients using fluoroquinolone antibiotics. An additional 74 tendon ruptures have subsequently been reported to the FDA for a total of 336. Because only a small fraction of cases are typically reported to the FDA, the actual number of ruptures and other tendon injuries attributable to the antibiotic is much higher.

LEARN more
VIEW the legal documents

Public Citizen y Rosiglitazona (Avandia).

Recibido de Worst Pills, Best Pills Drug Alert

In May, a study in the New England Journal of Medicine linked the diabetes drug rosiglitazone (AVANDIA, AVANDAMET and AVANDARYL) to heart attacks and heart-related deaths. But the heart risks of this drug should not have been a surprise.

Public Citizen has long warned about the dangers of using the glitazone class of diabetes drugs, beginning with our petition to the Food and Drug Administration (FDA) in 2000 for better warnings. We have classified rosiglitazone as a Do Not Use drug for the past three years.

Since the release of the New England Journal of Medicine study, the following actions have been taken:

1/ In October, the Department of Veterans Affairs, after conducting its own review, removed rosiglitazone from its formulary (the drugs that its doctors may prescribe), concluding that, “for some patients, rosiglitazone may not afford the same margin of safety as alternative drug therapies.”

2/  On November 6, 2007, Health Canada, the Canadian equivalent of the  U.S. FDA, issued broad new restrictions on the use of rosiglitazone. In Canada, rosiglitazone is now no longer approved either as a single treatment for diabetes (except for patients unable to take metformin), or for use in combination with a sulfonylurea* except when patients are unable to take metformin.
Furthermore, Health Canada warns that rosiglitazone should not be used in any of these situations: in patients taking insulin, in combination with metformin and a sulfonylurea drug, or in patients diagnosed with any degree of heart failure, either past or current, even that which is very mild (NYHA Classes I, II, III, or IV).

Health Canada advises patients to talk to their doctors about the benefits and risks of continuing therapy, especially those with heart disease or at a high risk for a heart attack or heart failure.

3/ Shortly after the Canadian warning, on November 14, the FDA modified its black box warning for rosiglitazone concerning heart attacks, but in a most confusing fashion: it cites four analyses. One of the four is a meta-analysis of 42 studies which showed an increased risk of heart attacks; the results of the three others “have not confirmed or  excluded this risk,” according to the FDA. This is inaccurate and provides no useful guidance to patients or their physicians.

The FDA needs to immediately publish an alert similar to that of Health Canada to warn U.S. citizens who are at increased risk from heart attacks and heart failure not to take rosiglitazone. Until then, Health Canada remains the sole source of this vital information.

We continue to label Avandia as a Do Not Use drug.

Learn more:
Read our July 2007 article about the risk of heart problems with
rosiglitazone: https://www.worstpills.org/member/newsletter.cfm?n_id=538

See the new Health Canada restrictions on rosiglitazone here:

*Examples of sulfonylurea drugs are glyburide, glimepiride, and
tolbutamide. Ask your doctor if you are taking these or any other drugs
in this class.

En Argentina:

AVANDIA • GlaxoSmithKline

Rosiglitazona mas metformina:

AVANDAMET • GlaxoSmithKline

Fuente: Alfabeta