Antinausea Drug Withdrawn From US Market

The FDA announced that the 32 mg dose of Zofran (ondansetron), an anti-nausea medication, will no longer be marketed in the US due to the potential the risk of Torsades de pointes, a serious cardiac rhythm abnormality.  The event occurs when there is a prolongation in the QTc interval, an important part of the electrical activity of the heart.  Prolongation of the QTc can be fatal.  Information from the FDA can be found here.

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.

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.

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.

FDA Gives Alert That Ampyra Has Seizure Risk for Multiple Sclerosis Patients

Today, July 23, 2012, the FDA warned that there is a risk of seizures in patients with multiple sclerosis (MS) who start treatment with Ampyra (dalfampridine).

This is based on data that the FDA reviewed from post-marketing reports.  Most of the seizures reported took place within days to weeks after patients with MS started Ampyra at the recommended dose.  The patients did not have a history of previous seizures.

The FDA also updated the drug label for Ampyra to clarify rcommendations that kidney function should be monitored in individuals before they begin treatment with Ampyra.  Patients should be monitored at least once a year.

More information can be found on the FDA website.

New Warnings for Aliskiren & FDA / Novartis to Pull Valturna

The FDA issued new warnings about antihypertensive medications which contain aliskiren (Tekturna, Amturnide, Takamio, and Valturna) when used in combination with ACE inhibitors or angiotensin receptor blockers (ARBs). The FDA indicates that the drug combinations are contraindicated in patients with diabetes, and it is adding a new warning to avoid the use of this combination in patients with moderate to severe renal impairment (GFR <60 mL/min).

Novartis has announced it will pull Valturna from the U.S. market.  Valturna contains aliskiren (Tekturna^®) as one of its ingredients.

Reporting A Safety Issue in the US

The U.S. Food and Drug Administration (FDA) is the agency that is accountable for protecting and promoting public heath in the United States. It does this by setting regulations, conducting inspections and analyzing adverse events (AEs). The FDA maintains a computerized database where information related to AEs is stored and then analyzed. This database is called the Adverse Event Reporting System (AERS). The FDA monitors the AEs in the database to determine if there are signals that could represent a health risk to the patients and public. The reporting of AEs is done on a voluntary basis by healthcare providers, patients and the public. Manufacturers of medications are required to report information related to AEs that they become aware of either through the conduct of clinical trials or that occur spontaneously in patients taking medicines that are marketed by the company. Reporting of Adverse Events can be done as follows: Consumers and Healthcare Providers can report Adverse Events online or using a form available through the FDA by clicking here or pasting the following URL into their web browser: https://www.accessdata.fda.gov/scripts/medwatch/medwatch-online.htm