FDA Subtracts Two Indications for Ketek

ROCKVILLE, Md., Feb. 12 -- The FDA announced today that concerns about toxicity had led it to rescind two indications for the antibiotic Ketek (telithromycin).

The drug, said the agency, is no longer approved to treat:

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

Ketek, the first of the so-called ketolide antibiotics, is now approved only for community-acquired pneumonia of mild-to-moderate severity due to S. pneumoniae, H. influenzae, M. catarrhalis, Chlamydophila pneumoniae, or Mycoplasma pneumoniae.

It is indicated to treat patients 18 years and older.

The "balance of benefits and risks" doesn't support the use of the drug for the first two conditions, which are relatively mild, said John Jenkins, M.D., director of the FDA's Office of New Drugs.

On the other hand, community acquired pneumonia can be more serious and may need treatment with Ketek, he said during a telephone press conference.

The ruling comes in conjunction with a new boxed warning saying that Ketek is contraindicated in patients with myasthenia gravis because of the risk of fatal or life-threatening respiratory failure.

The new labeling also includes stronger warnings about visual disturbances -- including blurred vision, difficulty focusing, and diplopia -- and transient loss of consciousness, including some cases associated with vagal syndrome.

Because of those risks, patients treated with Ketek should minimize their driving or use of heavy machinery, the FDA said.

Warnings for liver toxicity were strengthened in June 2006, after a report earlier in the year of three patients who suffered serious damage - including one fatality and one transplant -- after taking the medication. (Three Severe Liver Damage Cases Linked to Ketolide Antibiotic)

In all three cases, the drug caused massive tissue necrosis in the liver, researchers reported.

The label changes come after "comprehensive scientific analysis and thoughtful public discussion of the data available for Ketek," according to Steven Galson, M.D., director of the FDA's Center for Drug Evaluation and Research.

The alterations were recommended by an FDA advisory committee in December. (FDA Advisers Recommend Limits for Ketek Antibiotic)

Ketek was approved by the FDA in 2004 for use in respiratory tract infections. The ketolides are semi-synthetic derivatives of the macrolide antibiotics, which are able to overcome most forms of macrolide resistance.

The agency said the changes were worked out in co-operation with the drug's maker, Sanofi-Aventis.