Will FDA Restrict Use Of Ketek And Put Increased "Black Box" Warning On Sanofi-Aventis Antibiotic?

FDA Advisory Panel: Ketek Side Effects Risks Outweigh Benefits For Bronchitis And Sinusitis; Urges Patient Medication Guide When Used For Pneumonia

In mid-December 2006, after two days of hearings, an FDA advisory panel recommended that the antibiotic Ketek should not be used as treatment for acute bacterial exacerbation of chronic bronchitis nor acute bacterial sinusitis.  The same FDA panel, which included drug-safety experts and infectious-disease specialists, voted in favor of allowing Ketek to continue to be prescribed for community-acquired pneumonia, a more serious medical condition.

According to a December 16, 2006 article in The Wall Street Journal (WSJ) by Anna Wilde Mathews:

Several committee members said they worried that Ketek's use in the milder conditions wasn't justified. "The risk of the drug seems to me to make it not appropriate to keep on using" for those infections, said Carl Norden, a professor at the University of Medicine and Dentistry of New Jersey.

Furthermore, as regards Ketek remaining on the market, a majority of this advisory panel recommended that there be two conditions.  First, the addition of a so-called "black box" warning to the Ketek package insert, or label, addressing the serious side effects which have been associated with Ketek use in the past.  Second, the panel members recommended that Sanofi-Aventis develop a medication guide for patients prescribed Ketek in the future.

It is important understand that the recommendations made by this advisory panel are "nonbinding", i.e., the FDA is not required to follow this panel's guidance as regards the future prescribing and use of Ketek.  If, however, the FDA does adopt all of the Ketek advisory panel's recommendations -- namely, (a) withdraw approval of Ketek for bronchitis and sinusitis, (b) mandate a "black box" warning for Ketek regarding serious side effects such as liver damage and liver failure, and (c) require distribution of a patient medication guide with future Ketek prescriptions -- one must wonder whether Sanofi-Aventis will continue to market Ketek in the U.S.

As Andrew Bridges reported in a December 15, 2006 Associated Press article: "Doctors have prescribed the antibiotic more than 5.6 million times in the United States since the FDA approved it in 2004."  And from the December 16 WSJ article:  "Last year Ketek was prescribed 3.35 million times in the U.S. and brought in $193 million, according to IMS Health."

To be clear, the FDA advisory panel did not recommend a Ketek recall for safety reasons.  But if the FDA fully adopts their recommendations, Ketek sales may be greatly diminished going forward.  In turn, Sanofi-Aventis could follow the lead of another drug company when it experienced increasing scrutiny about the safety of its antibiotic.  Earlier in 2006, Bristol-Myers Squibb (BMS) announced that it would stop marketing Tequin in the U.S. for "business" reasons -- a move which was very similar to the method that was used by BMS during its withdrawal of their anti-depressant drug Serzone in 2004.

Moreover, the likelihood of there being a "soft" recall of Ketek is increased by the ongoing Congressional investigations being led by Senator Charles Grassley.  According to a December 13, 2006 report by CBS News, "there is a new Congressional probe under way to determine whether Ketek should remain on the market." 

The online version of this December 13 CBS report about Ketek includes a link for an extended interview with one patient, Chuck Gregg, who suffered liver failure in early 2006 after he took samples of Ketek for bronchitis.  This CBS interview with Mr. Gregg and his wife makes a compelling case for why we should be concerned if the FDA does not act so as to adopt all of this advisory panel's recommendations regarding Ketek use in the U.S.

(Posted by: Tom Lamb)