A Medication Guide should be considered as a means of informing patients about adverse events associated with Sanofi-Aventis' Ketek , FDA's Division of Drug Risk Evaluation suggests in a briefing paper prepared for an advisory committee meeting to discuss the risks and benefits of the antibiotic.

Citing the "potential seriousness" of side effects related to liver toxicity, exacerbation of myasthenia gravis and visual disorders/loss of consciousness, DDRE recommends that Sanofi-Aventis also develop a plan to inform and educate prescribers regarding the risks of Ketek (telithromycin).

The Anti-Infective Drug and Drug Safety and Risk Management Advisory Committees will meet Dec. 14-15 to consider "whether the overall risk/benefit profile supports continued marketing of Ketek for any of the three approved indications," according to a briefing package from FDA's Division of Anti-Infective and Ophthalmology Products.

Ketek is approved for treating acute exacerbation of chronic bronchitis, acute bacterial sinusitis and community-acquired pneumonia.

The product's safety profile has been the subject of extended scrutiny and has promoted an on-going congressional investigation into FDA's handling of the application.

Sanofi-Aventis revised labeling for Ketek, the first ketolide antibiotic, in June to move information about the risk of "acute hepatic failure and severe liver injury, in some cases fatal," from the Precautions to the Warnings section (¹ Also see "Ketek Risk Cannot Be Distinguished From Class, FDA Says" - Pink Sheet, 29 June, 2006.). At that time, FDA said the risk of liver toxicity with Ketek is not necessarily more dangerous than other macrolide antibiotics.

Sanofi-Aventis believes the "benefit does outweigh the risk," Chief Medical Officer Doug Greene said in an interview with "The Pink Sheet" DAILY. Because of Ketek's design, it is "a drug that meets an unmet medical need," he said. The product is designed to deal specifically with respiratory pathogens and attacks bacteria at two sites rather than one, enabling it to fight antibiotic-resistant microorganisms, he explained.

If continued marketing is recommended, FDA's anti-infective division also seeks committee discussion of whether additional communication strategies or risk management programs are necessary to ensure that Ketek is used safely, as well as whether any additional studies are needed to further assess risk/benefit.

The committees will review updated information on Ketek regarding liver toxicity, neurological and visual effects and muscle weakness associated with myasthenia gravis. Data used in an October 2006 review of telithromycin's effect on myasthenia gravis "suggest that exacerbation of MG may be more frequent with telithromycin than similar antibiotics," DDRE's briefing document says, even though no formal quantitative analysis of the drugs' reporting rates was conducted.

Senate Finance Committee Chairman Sen. Chuck Grassley (R-Iowa) released a report Dec. 13 saying that FDA previously kept adverse safety information from an advisory panel meeting during preapproval discussions about the drug. Grassley had placed a hold on Andrew von Eschenbach's nomination to be permanent FDA commissioner, citing the agency's failure to cooperate with the committee's investigation (² Also see "Grassley Places Hold On Von Eschenbach" - Pink Sheet, 17 November, 2006.).

-Cathy Dombrowski (c.dombrowski@elsevier.com)

Ketek Medication Guide Suggested By FDA Staff

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