On February 12, 2007 the U.S. Food and Drug Administration (FDA) announced major revisions to the labeling for Ketek, an antibiotic manufactured and marketed by Sanofi-Aventis. The changes include the removal of two of the three approved indications of the drug and the addition of a “black-box” warning. While the FDA has not announced a Ketek recall, the changes may sharply limit the drug’s use in the U.S.

Ketek was approved for sale in the U.S. in 2004 for the treatment of certain severe respiratory ailments. Since its approval, the FDA has reported 13 cases of severe liver damage in patients on the drug, including five patients who died from liver failure. In December 2006, a joint advisory committee examining data acquired since the initial approval of Ketek concluded the benefits of Ketek did not outweigh the risks of such liver damage in patients taking Ketek for either acute bacterial sinusitis or acute bacterial exacerbation of chronic bronchitis, conditions which are considered relatively mild.

As a result, Ketek is no longer approved for the following conditions:

• Acute bacterial sinusitis due to Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis or Staphylococcus aureus; or
• Acute bacterial exacerbations of chronic bronchitis, due to S. pneumoniae, H. influenzae, or M. catarrhalis.

Ketek is now approved only for use by adults and for treatment of community-acquired pneumonia of mild-to-moderate severity due to S. pneumoniae, H. influenzae, M. catarrhalis, Chlamydophila pneumoniae, or Mycoplasma pneumoniae.

The FDA has also worked with Sanofi-Aventis to place a “black-box” warning on Ketek’s drug insert warning that Ketek should not be used in patients with myasthenia gravis because it is linked to the fatal worsening of that condition. Myasthenia gravis is an autoimmune disorder that attacks voluntary muscles such as those that control swallowing, speech, neck and limb movements. Symptoms include muscle weakness, impaired speech, drooping eyelids, and difficulty in speech, but can worsen to include generalized paralysis and eventual death from impaired breathing.

The “black-box” warning is considered the FDA’s strongest form of warning. The FDA has also worked with Sanofi-Aventis to provide a Patient Medication Guide informing the public about the risks of Ketek that will be given to all patients with each prescription. The new warnings also include information about potential vision damage and the potential for loss of consciousness.

Sources: FDA Release #P07-19, February 12, 2007; Michael Smith, “FDA Subtracts Two Indications for Ketek,” MedPage Today, February 12, 2007; Susan Heavey, “FDA limits use of risky Sanofi antibiotic Ketek,” ScientificAmerican.com, February 12, 2007; Anna Wilde Mathews, “FDA Limits Use of Sanofi Antibiotic,” Wall Street Journal,” February 13, 2007.