Florida Suspends A Compounding Pharmacy

In the wake of the meningitis outbreak and controversy over compounding pharmacies, the Florida Department of Health late last week suspended a compounder in Boca Raton after determining the pharmacy had violated a number of statutes and rules. The move came following an inpsection earlier this month.

Florida Suspends A Compounding Pharmacy

octubre 29, 2012 under Compound Pharmacy, Rejuvi Pharmaceuticals

In reaching its decision, the department cited problems with cleanliness, dispensing and compounding medications, and record keeping. A review of previous inspections also found that Rejuvi Pharmaceuticals had previously been notified of the violations, but failed to correct them, according to a statement.
The suspension, which will be followed by a hearing, is the latest fallout from the scandal surrounding the New England Compounding Center – which has been identified as the source of contaminated vials of injectable steroids traced to the meningitis outbreak – and the role of regulators in overseeing compounding pharmacies.
Since the outbreak emerged this month, there has been a mixture of confusion and outrage over the extent to which the FDA and state regulators are responsible for enforcing regulations, and whether the appropriate actions were taken. NECC, for instance, received an FDA warning letter in 2006 and Massachusetts regulators had received complaints.
Although debate remains over FDA powers and whether Congress should clarify agency authority with additional legislation, the FDA last Friday issued the results of an inspection of NECC that found the compounding pharmacy had serious problems keeping its facilities free of mold and bacteria, notably in so-called clean rooms used for production (see this).
Meanwhile, state regulators are facing mounting pressure to ensure that compounders are adhering to local laws, a development reflected in the suspension in Florida. The state has, so far, tallied 22 cases of meningitis, including three deaths, accoring to the state health department (read here).
And in Massachusetts, regulators closed yet another compounder. In addition to shuttering NECC and a related operation called Ameridose, which voluntarily closed earlier this month, Infusion was closed after inspectors last week found “significant issues” and “expressed concerns for the sterility of products,” according to Madeleine Biondolillo, director of the Bureau for Health Care Safety and Quality.
In addition, “there was an adjacent space set up for giving patients intravenous medications onsite. Infusion Resource does not have an appropriate clinic license to conduct these activities, which is a violation of state regulations.” The pharmacy has now surrendered its license (here is the statement).
On a broader scale, the state is filing regulations to require compounding pharmacies in Masschusetts to submit frequent reports of production, volume and distribution of sterile, injectable medications. And a commission is being formed to examine best practices in other states and potential changes to state law or regulations.

Related articles

• Understanding the Regulatory Landscape for Compounding Pharmacies
• Compounding pharmacies have long evaded the tight oversight governing established drug makers
• Officials close another pharmacy since meningitis outbreak
• Fungal Meningitis and the End of Lackadaisical FDA Involvement in Compound Pharmacies
• Mass. shuts down another drug compounding pharmacy
• Massachusetts Cracks Down On Unregulated Compounding Pharmacies Linked To Deadly Meningitis Outbreak
• FDA Warned Mass. Pharmacy Linked To Meningitis Outbreak Of 'Possible Contamination' In 2006
• Meningitis Outbreak May Spur U.S. Oversight of Pharmacies - Bloomberg
• Compounding Pharmacies Come Under Scrutiny in Light of Meningitis Outbreak.
• Florida health department suspends compounding pharmacy

Delayed FDA Removal of Painkiller Propoxyphene

Image via Wikipedia

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
http://www.citizen.org/documents/chronologyofinactions.pdf

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

Regards

Sidney M. Wolfe MD
Director, Health Research Group at Public Citizen
1600 20th St. NW
Washington, DC 20009
Phone: +1 202 588-7735
Swolfe@citizen.org
www.worstpills.org
www.citizen.org/hrg

Related articles

• Darvon, Darvocet Banned (webmd.com)
• UPDATE 2-No more Darvon for U.S. market - FDA (reuters.com)
• "Propoxyphene: Darvon, Darvocet Pulled Off Market for Safety Risks" and related posts (commonlaw.findlaw.com)
• You: Painkillers Darvon, Darvocet withdrawn at FDA request (latimes.com)
• Manufacturer Pulls Darvon, Darvocet; FDA Wants Generic Makers to Do the Same - ABC News (news.google.com)
• FDA pulls Darvocet painkiller off the market over heart concerns (pennlive.com)
• You: F.D.A. Pulls Painkiller Due to Risks (nytimes.com)
• Darvon painkiller pulled for safety risks: FDA (cbc.ca)
• Darvon painkiller pulled off market due to heart risks (usatoday.com)