Drug Profile

Telithromycin (KETEK) is approved by the Food and Drug Administration (FDA) to treat community-acquired pneumonia in adults due to certain bacteria germs, including multidrug-resistant Streptococcus pneumoniae (MDRSP).

Telithromycin underwent a long drug approval process with the FDA. The makers of telithromycin, Aventis Pharmaceuticals, submitted the new drug application (NDA) in March of 2000. In an unusual process for the FDA, the drug went through two advisory committee reviews because of problems concerning both efficacy and safety before it was approved in April of 2004.[2]

Aventis requested approval for four indications in the original application (tonsillitis, acute worsening of bronchitis, sinusitis and community-acquired pneumonia). The drug was not approved for tonsillitis because it failed to meet FDA standards of efficacy. The drug was approved for the three remaining indications, but this decision was later overturned for sinusitis and acute worsening of bronchitis due to concerns about the drug’s toxicity.[3],[4]

The drug may have been approved because some felt excited about the prospect of a “new” antibiotic and a “new” drug. These people typically argue that there is a need for more drugs. We would argue that we do not need more drugs, we need better drugs, and telithromycin is a drug that should not have been approved by the FDA.

We agree with the editors of Prescrire International, who stated in 2003, “Telithromycin is a needless addition to the other macrolides.”[5]

The chemical structure of telithromycin, which is classed as a ketolide, is similar to the macrolide drug family, which includes erythromycin (EES, ERYTHROCIN), clarithromycin (BIAXIN) and azithromycin (ZITHROMAX). In fact, telithromycin should not be taken by anyone with a history of hypersensitivity to any of the macrolide antibiotics. Most of the adverse effects for telithromycin are similar to those for macrolides (mainly headache, dizziness, nausea and diarrhea). But telithromycin also has additional risks for heart, liver and eye toxicity.[6] We recommend macrolide antibiotics as an alternative to telithromycin.

Studies say...

Telithromycin has not been shown to be more effective than the other antibiotics amoxicillin, cefuroxime, clarithromycin or trovafloxacin. Furthermore, the drug does not seem to have fewer adverse effects than macrolide antibiotics already on the market. Thus the drug does not have an important unique therapeutic benefit, and instead telithromycin is probably less safe (and has a higher risk for drug interactions) than other antibiotics. As a result, medical experts are not enthusiastic about telithromycin.

The only factor that sets telithromycin apart from the rest of the antibiotics is its FDA-approved use for treatment against macrolide-resistant Streptococcus pneumoniae. However, the clinical importance of macrolide resistance is up for debate: Although there is an increase in macrolide-resistant pneumococci in the United States, the number of clinical failures has not risen.[7]

Further, there has been no difference found in deaths for pneumonia patients infected with drug-sensitive or drug-resistant bacteria after controlling for other risk factors. However, patients with resistant bacteria have more prolonged hospital stays.[8]

The guidelines established by the Infectious Diseases Society of America state: “A macrolide plus a beta lactam is recommended for initial empiric treatment of outpatients in whom resistance is an issue and for hospitalized patients.”[7] In addition, experts believe the type of macrolide resistance found in the United States may be overcome by increasing the dose of the drug.

There was some debate about the effectiveness and safety of telithromycin at the Anti-infective Drug Advisory Committee. Some members felt the evidence to prove the effectiveness of telithromycin for the treatment of acute worsening of chronic bronchitis was insufficient, since the drug eradicated only 60-77% of one of the leading causes of the illness, the bacteria Haemophilus influenzae.[9],[10] One member questioned the effectiveness of the other drugs chosen for comparison to telithromycin in clinical studies, which led to her disapproval for all three indications:

The data at hand does not establish the efficacy of the comparators [drugs being compared to telithromycin]...without data in front of us establishing the efficacy of the comparators, the data in front of us does not establish efficacy of this drug [telithromycin].[11]

The committee also was split in its decision about the effectiveness of telithromycin against MDRSP. Telithromycin cure rates were 90% for erythromycin-resistant Streptococcus pneumoniae, 70% for penicillin-resistant Streptococcus pneumoniae, and 68.8% for penicillin plus erythromycin–resistant Streptococcus pneumoniae.[12] The evidence of its effectiveness for patients with MDRSP and severe infection was based on a small number of patients and demands further evaluation.[12] Drug-resistant Streptococcus pneumoniae infection frequently responds to drugs it is supposedly resistant to, even cases of bacterial pneumonia.

Adverse effects

Telithromycin causes a wide range of adverse effects. These adverse effects are sometimes shared by other antibiotics.

Heart problems: Telithromycin can cause a change in the electrical activity of the heart called QT prolongation. This prolongation increases with increasing doses of the drug. QT prolongation may develop into a life-threatening heart rhythm disturbance known as torsades de pointes. There have been reports of torsades de pointes which are suspected to be drug related.[13],[14] (QT prolongation is also reported with some other macrolides, fluoroquinolones and cephalosporin antibiotics.)

Liver toxicity: Another concern with telithromycin is liver toxicity, which has been reported with macrolide antibiotics as well. At the time of the Jan. 8, 2003, advisory committee meeting, the FDA had received 54 reports of liver problems with telithromycin from countries in which the drug had been marketed: 19 of the 54 were categorized as serious.[15] In addition, a report published in the March 21, 2006, issue of Annals of Internal Medicine described three cases of severe liver toxicity, including one death, in patients taking telithromycin.[16],[17]

Vision problems: Patients in clinical trials sometimes reported having blurred vision that significantly impaired their ability to perform daily activities.[18] The visual disturbances mainly occurred in women and younger people. Visual adverse effects occurred one to three hours after a dose and the effect lasted up to 20 hours.[18] The FDA has received more than 150 reports of visual adverse effects worldwide, of which about one-quarter have been categorized as serious. Telithromycin appears to cause more visual disturbances than macrolides already on the market. The FDA strengthened the drug's warning section to include visual disturbances in 2007.[19]

In 2010, Prescrire International published an article with information on a seven-year pharmacovigilance review by the Finnish drug regulatory agency on visual disorders associated with telithromycin use. According to the article, these visual disturbances occurred mainly in young patients (20 to 40 years of age) and in women.[20]

Dizziness: In addition to visual disturbances, users of telithromycin have reported fainting. In response to these adverse effects, the FDA revised the package insert of telithromycin, strengthening the warning section to include loss of consciousness in 2007.[19]

Other problems: Other concerns with telithromycin include vasculitis (inflammation of blood vessels) and worsening of myasthenia gravis (a disease of the muscles, immune system and nervous system), which can result in death. Increased muscle weakness, shortness of breath, difficulty breathing or severe acute respiratory failure can develop within hours of the first telithromycin dose.[5],[21]

In 2024, Scientific Reports published an article showing that macrolide antibiotics are associated with an increased risk of hearing loss.[22]

Regulatory actions surrounding telithromycin

2005: Suspected adverse reactions between telithromycin and anticoagulants, first reported in Canada, were the impetus behind a 2005 addition to the FDA package label of telithromycin. The label now lists interactions with anticoagulants in the precautions section.

2006: On June 29, the FDA announced that new warnings about liver toxicity, including the possibility of death, were added to the package insert for telithromycin.[23],[24]

2007: In February, the FDA announced that two of the three indications for which telithromycin was originally approved (acute worsening of bronchitis and sinusitis) would be removed from the label. The FDA found that the risks outweigh the benefits when used for these conditions.[25] The FDA also required that a medication guide be provided to patients when telithromycin is dispensed.[26]