Why Did France Wait To Pull A Weight Loss Drug?

It took years for France to pull Mediator (benfluorex) from its market.  But why did it take so long for the French Regulatory Authority, Afssaps, to force Servier to remove it from the Market in 2009?  The drug was being used for weight loss.  It was developed by the French pharma company, Servier, and approved by Regulators 35 years ago.  The drug, however was said to have been the cause of death for 2000 people.

In 1999 there was an official report that Mediator could cause heart disease, yet it stayed on the French market  for an additional 10 years.  What could be the reason?

In 2000, according to Martine Verdier, an attorney representing victims, "there was a scientific study that demonstrated the side effects."  Valvular heart disease was the issue.  This is not the first time that there was an association between a medication being used for weight loss and valvular heart disease and associated pulmonary hypertension.  In fact, according to The New York Times there were two other Servier wight-loss medications, which were closely related to Mediator that were at the center of the infamous fen-phen scandal in the late 1990s in the United States.

Mediator (benfluorex) is an amphetamine derivative.  Fenfluramine and dexfenfluramine  are amphetamine derivatives and were licensed to companies in the US and then marketed by Wyeth as the drug combination for wight loss.  In September 1997 the FDA announced the withdrawal of fenfluramine and dexfenfluramine.  Dexfenfluramine was manufactured for Interneuron Pharmaceuticals and marketed under the name of Redux by Wyeth, which also manufactured  and marketed fenfluramine under the brand name Pondimin. Both companies  agreed to voluntarily withdraw their drugs.  Nevertheless, Mediator remained available to the French public.


Servier stands accused of misleading the public over the ingredients of the Mediator.  The French government has accused the company of consumer fraud and manslaughter.  After Servier was granted a market approval for Mediator as a diabetes drug, it promoted the drug as a prescription for weight loss.  This was done to increase the sales of the drug, unfortunately it also increased the number of patients harmed.

Following this scandal, the head of the French equivalent to the FDA known as Afssaps resigned.  France has since implemented reforms to Afssaps, which is now known as Ansm.  The new French National Agency of Medicine and Health Products Safety is hoped to revamp the French Regulatory Agency and establish new trust and confidence following the scandal over Mediator.

Electronic Medical Records and Patient Safety

Electronic medical record (EMR) systems and electronic health records (EHR) have been purported to reduce patient mortality, reduce medical errors, increase health care savings and improve health.  This appears, in part, to be a result of decreased medication errors that could result in adverse drug reactions (ADRs).  One benefit is that electronic prescribing helps to save lives.  Could it be that there is less of a problem in reading the physicians' poor hand writing?


A study published in the Journal of Political Economy stated that a 10% increase in the use of electronic records in hospitals would save 16 newborns for every 100,000 live births.  This would result in the saving of 6,400 infants per year in the US.


According to the Centers for Disease Control and Prevention, in 2011, 57% of office-based physicians had EMR systems.

Adoption of EMR/EHR systems by office-based physicians has increased

According to a 2009 Harvard School of Public Health press release, the most commonly cited barriers to adoption of these systems were found to be:

• inadequate capital for purchase (73%)

• concerns about maintenance costs (44%)

• resistance from physicians (36%)

• unclear return on investment (32%)

• lack of staff with adequate IT expertise (30%)

The press release was based on an article published in the New England Journal of Medicine.  The first author of the NEJM article gave an interview discuss EHR which can be viewed here.

Statin-Associated Muscular and Renal Adverse Events

Using the US Food and Drug Administration (FDA) adverse event reports (AERs) system, a group of investigators were able to review muscular and renal adverse events (AEs) reported with the use of statins.

There were 1,644,220 signals in AERs from 2004 to 2009 related to 4 statins.  The signals detected were myalgia, rhabdomyolysis and elevated creatine phosphokinase.  The investigators also noted that signals were seen for acute renal failure.

Guns versus Opioids: Which is deadlier?

In 2007 there were 12,632 gun related homicide deaths in the US according to the National Vital Statistics Reports from 2010.  This is less than the 14,800 Americans who died of opioid overdoses in 2008.  But the number of overdose related deaths is increasing:  The Centers for Disease Control and Prevention reported that 15,597 Americans died from opioid overdoses in 2009.

The FDA estimated that there were 22.9 million prescriptions for extended-release and long-acting opioids in 2011.  This raises concerns that the number of Americans who will continue to die will only increase.

Just like guns will probably always exist in America because it's a constitutional right, it is likely that the use of opioids will continue.

This month the FDA issued a safety measure to address the growing epidemic of opioid overdose.  Manufacturers of painkillers will now need to fund continuing educational programs for physicians and other healthcare providers.  This training will start in March 2013, but will be voluntary for healthcare providers.

The Obama administration's goal is to decrease abuse of prescription medications and the opioid overdoses leading to death by 15% in the next five years.  Not a lofty goal when one considers the increasing trend in deaths.

More than One in Four Medicare Beneficiaries Experience Some Degree of Harm While Hospitalized

This month the Office of Inspector General in the US Department of Health & Human Services has reported that more than one in four medicare beneficiaries experience some degree of harm while hospitalized.

Click here to see table in the report

The report noted that there were issues in the nation's hospital patient harm reporting system.

Findings included that half of States in the US had adverse event (AE) reporting systems in 2008, but only 12% of events met States requirements for reporting.

Of course, this means that half the States do not utilize a reporting system for AEs. This could be due in part to the fact that there are no Federal standards requiring States to have AE reporting systems.

Interestingly the report states that "hospital administrators indicated that staff often did not report events because they identified them not as patient harm, but rather as expected side effects."

Adverse Event Reporting of Lipitor, Lyrica, Viagra and Chantix

In May 2010, the FDA sent a letter to Pfizer's CEO, Jeffrey Kindler, warning the company that it had failed to report serious and unexpected adverse reactions to many of its widely known medications including Viagra (sildenafil), Lipitor (atorvastatin) and Lyrica (pregabalin) in a manner consistent with regulations.

The late reporting of adverse events was found to go back as far as 2004 and was noted to have increased over the six year period.  The FDA found that Pfizer did not report important cases within its 15-day period as a result of "misclassifying and/or downgrading reports to non-serious without reasonable justification."

In the past Pfizer had blamed issues with reporting on the lack of proper training of its employees with a new computerized adverse event reporting system.  Pfizer subsequently informed the FDA that this had been addressed, but the FDA called Pfizer's changes "inadequate" and "ineffective."  The FDA called for a revised "corrective action plan," also known as a CAP at the time.

A year later, in May 2011, the Institute for Safe Medication Practices (ISMP), a nonprofit organization, reported that "the risks of varenicline (CHANTIX) were underestimated in prior adverse event reporting." They outlined how Pfizer had failed to provide hundreds of reports through "the usual channels."  The ISMP noted that of the serious adverse event (SAE) reports, there were 150 patients who had completed suicides dating back to 2007.  As a result of the lapse in Pfizer's pharmacovigilance, more than half of the cases involving suicide were not sent to the FDA.  This meant that FDA analysts could not properly monitor this serious psychiatric issue.

Statins may help reduce bad memories

For a number of years there have been reports concerning the loss of memory, as well as muscle pains associated with the use of a group of medications called statins.  These drugs have been well known and widely prescribed to millions of people to help reduce cholesterol.  At least 32 million people in the US take these medications in the hopes that they will ward off a multitude of illnesses.  In the UK it is estimated that 5 million people take statins.

Cholesterol is associated with cardiovascular disease and can lead to myocardial infarctions, commonly called heart attacks.  Another risk associated with the build up of cholesterol in plaques is that of stroke.

In March of 2012 the U.S. Food and Drug Association (FDA) alerted the public that the entire class of statin drugs would be receiving new warnings in its labeling. The new label will warn that memory loss and confusion is associated with use of statins.  Additionally the labels will be updated to inform the public that statins can cause an increase in blood sugars called hyperglycemia and an increase in the risk of Type 2 diabetes.

With the above changes, the FDA is also removing its recommendation for routine and periodic monitoring of liver functioning.  Before patients start treatment with statins it is still recommended to get   liver enzyme tests (LFTs).

Cholesterol, however, is not all bad.  It is also not only from food; only 25% comes from diet.  The liver and other cells create approximately 75% of blood cholesterol.  There is good cholesterol, which is HDL and then bad cholesterol, also known as LDL.

Cholesterol is an important substance for normal functioning in the body.  Some people, however, have an increased risk of elevated cholesterol associated with genes that are inherited.  Others may have the ability to moderate their cholesterol through diet and exercise.

According to some investigators, a large number of patients do not achieve the desired goal of reduction in cholesterol levels after six months of treatment.