FDA reports says Avandia can hurt heart: NY Times investigative report

From a report in Yahoo News, which is the source for this posting  – FDA reports says Avandia can hurt heart: report:

According to a report by the NY Times yesterday, February 19, 2010, Confidential U.S. government reports recommend that GlaxoSmithKline Plc’s diabetes drug Avandia be pulled from the market because it can hurt the heart.

Two authors of the report, Dr. David Graham and Dr. Kate Gelperin of the FDA, both concluded that it should be removed from the market.

According to Yahoo News, Sales of Avandia, once Glaxo’s second biggest-selling product, plummeted two years ago after a U.S. study linked it to an increased risk of heart attack in a conclusion disputed by Glaxo.

According to the Times reporter, Gardiner Harris, an FDA advisory board voted, 8-7, in 2007 to accept the advice of an independent committee that while Avandia might increase the risk of heart attack, it should stay on the market.

A U.S. Senate investigation into the product “said Glaxo failed to warn patients earlier that Avandia was potentially deadly” – according to the Times report.

The Times said the internal FDA findings reflected a fierce debate inside the agency about Avandia. The newspaper quoted Glaxo as saying it had studied Avandia extensively and that “scientific evidence simply does not establish that Avandia increases” heart attack risk.

At the end of last year, Dr. Janet Woodcock, director of the FDA’s drug center, wrote an internal memorandum that “there are multiple conflicting opinions” about Avandia and ordered officials to assemble another advisory committee to reconsider if the drug should be sold.

The Times quoted FDA Commissioner Margaret Hamburg as saying on Friday, “I await the recommendations of the advisory committee.”

FDA and International Serious Adverse Events Consortium Complete Third Data Release

Do you know what ‘adverse event reporting’ is all about?  Well, in case you don’t, here it is – as defined by the Food and Drug Administration (FDA):

The Adverse Event Reporting System (AERS) is a computerized information database designed to support the FDA’s post-marketing safety surveillance program for all approved drug and therapeutic biologic products. The FDA uses AERS to monitor for new adverse events and medication errors that might occur with these marketed products.

Yesterday, February 19, 2010, the FDA issued a news release –Regulatory Science Update: FDA and International Serious Adverse Events Consortium Complete Third Data Release – concerning data on the genetic basis of drug-induced liver injury (DILI) and serious skin reactions (SSRs).  This consortium report was the product of the combined efforts of the U.S. Food and Drug Administration and the International Serious Adverse Event Consortium (SAEC).

The concept behind their efforts is the identification of genetic factors  in a subset of patients and thereby assist researchers to better predict an individual’s risk of developing these serious complications.

Drug-induced liver injury occurs in a small subset of patients and is often associated with a drug that is an unpredictable liver toxin, and may be the cause of acute liver failure in some patients. Although the exact mechanism behind drug-induced liver injury is unknown, research suggests that a person’s genes contribute to their likelihood of developing this injury.                                                                                    

Drug-induced SSRs, such as Stevens-Johnson, present as allergic-like skin reactions (blistering and peeling of the skin) and are considered serious enough to discontinue treatment with the medication. These reactions can be fatal if the signs and symptoms are not quickly recognized.

“FDA is pleased with the Consortium’s progress,” said ShaAvhree Buckman, M.D., Ph.D., director of the Office of Translational Sciences in the FDA’s Center for Drug Evaluation and Research. “The continued accumulation of scientific information on the genetic basis of adverse drug events provides researchers with invaluable tools for understanding why some people respond to medicines differently than others.”

If you have ever seen or read about a person suffering from a condition such as Stevens-Johnson Syndrome (SJS), you can well appreciate the significance of this research project.

Use Of Acetaminophen In Pregnancy Associated With Increased Asthma Symptoms In Children

Medical News Today recently issued a report on a study, done by the Columbia Center for Children’s Environmental Health at Columbia University’s Mailman School of Public Health, in which children who were exposed to acetominophen (Tylenol) prenatally were at increased risk to have asthma symptoms by age 5.  Use Of Acetaminophen In Pregnancy Associated With Increased Asthma Symptoms In Children.

While the study involved 300 African-American and Dominican Republic children living in New York City, the potential relevance for broader concern for African-American and Hispanic children  is evident.

[The study] found that the relationship was stronger in children with a variant of a gene, glutathione S transferase, involved in detoxification of foreign substances. The variant is common among African-American and Hispanic populations. The results suggest that less efficient detoxification is a mechanism in the association between acetaminophen and asthma.

“These findings might provide an explanation for some of the increased asthma risk in minority communities and suggest caution in the use of acetaminophen in pregnancy,” says Matthew S. Perzanowski, PhD, assistant professor of Environmental Health Sciences at the Mailman School of Public Health.

What is of some related interest is the fact that online postings regarding acetaminophen suggest that this may be the drug of choice for conditions as short-term fever and minor pain during surgery.

For example, Medicinenet.com’s posting, (which certainly predates this study) states in pertinent part:

SIDE EFFECTS: When used appropriately, side effects with acetaminophen are rare.

This most recent study appears to have some similarity to a prior study, at least according to the article on Medical News Today:

In a similar study conducted in the UK, the frequency of acetaminophen use during pregnancy and the magnitude of association in the UK study were similar to that in New York City.

So – Moms-To-Be, consider discussing this study with your OB before reaching for that bottle of Tylenol.

Boston Anesthesiologist Charged with Fraud: The United States Department of Justice – United States Attorney’s Office – District of Massachusetts

This past Friday, January 15, 2010, the FDA issued an announcement regarding a criminal information/charge being filed by the United States Department of Justice against Dr. Scott Reuben.  The details of the charge are contained in the official announcement of the DOJ – The United States Department of Justice – United States Attorney’s Office – District of Massachusetts.

In essence, here is the nature of the charge:

The Information alleges that REUBEN solicited and obtained research grants from pharmaceutical companies to perform research studies on pain management, often associated with various surgical procedures, but that he did not actually perform the research studies. Instead he made up patient data, submitted it to medical journals and caused false articles to appear in a number of medical journals.

If convicted on this charge, REUBEN faces up to 10 years imprisonment, to be followed by 3 years of supervised release and a $250,000 fine.

As the DOJ correctly notes, this is only a charge against Dr. Reuben.  To use its words, “The details contained in the Information are allegations. The defendant is presumed to be innocent unless and until proven guilty beyond a reasonable doubt in a court of law.”

It does make you wonder, however, just how carefuly so-called ‘peer reviewed’ articles and research papers ARE scrutinized and ‘reviewed.’

FDA announces research program for prescription drugs in pregnancy

On December 30, 2009, the FDA announced that a new collaborative research program to study the effects of prescription medications taken by women during pregnancy.  This program is called the Medication Exposure in Pregnancy Risk Evaluation Program (MEPREP) and will be a collaborative effort among the FDA, and researchers at the HMO Research Network Center for Education and Research in Therapeutics (CERT), Kaiser Permanente’s multiple research centers and Vanderbilt University.

The FDA references in its announcement an article in the American Journal of Obstetrics and Gynecology, which states  that it estimates that two-thirds of women who are pregnant take at least one prescription medication during their pregnancy.

One might think that there had been a number of clinical trials relating to medications taken during pregnancy prior to this collaborative effort; however, this appears not to be the case since there were too many concerns about the health of the mother and fetus preventing such a study in the past.

For more details  on this long-overdue research study, see the FDA’s announcement.