Telithromycin (Ketek) is a ketolide antimicrobial that was approved in April 2004 for the treatment of several common respiratory infections. In February 2007, in response to reports of adverse effects, the U.S. Food and Drug Administration (FDA) issued revised safety information and limited the marketing of telithromycin to the treatment of mild to moderate community-acquired pneumonia. Citing the increased risk/benefit ratio, the FDA removed the labeling for treatment of bacterial sinusitis and acute bacterial exacerbations of chronic bronchitis and further strengthened the safety warnings. This review is an update of the initial STEPS review on telithromycin.1
|Name||Dosage||Dose form||Approximate cost*|
|Telithromycin (Ketek)||800 mg (two tablets) daily for seven to 10 days||400-mg tablets||$80 to $115|
Changes to the telithromycin prescribing information include a warning that strengthens cautions about liver toxicity, a “black box” warning that contraindicates its use in patients with myasthenia gravis, and alerts about possible visual disturbance and loss of consciousness.2
Postmarketing surveillance documents a 3.5 to 11.0 times higher incidence of acute liver failure (including patients requiring transplantation) associated with telithromycin compared with other antimicrobials.3 This incidence translates into a rate of 167 cases of acute liver failure per one million person-years of telithromycin use.3 The manufacturer reports a telithromycin-induced hepatitis rate of seven per 10,000 persons treated.2
Blurred vision, difficulty focusing, and diplopia occurs in 0.3 to 2.1 percent of patients treated with telithromycin.5 Transient loss of consciousness has been reported, including cases associated with vagal syndrome.2 The concern over these adverse effects is great enough that the manufacturer recommends minimizing driving while taking telithromycin.
Telithromycin is a strong inhibitor of cytochrome P450 3A4, and it can increase serum concentrations of drugs metabolized via this pathway. It should not be used in patients taking pimozide (Orap), rifampin (Rifadin), or cisapride (not available in the United States), and should be avoided in combination with simvastatin (Zocor), lovastatin (Mevacor), or atorvastatin (Lipitor). Serum concentrations of digoxin and midazolam (Versed; brand not available in the United States) are increased by telithromycin. Telithromycin has not been studied in patients younger than 14 years. It is FDA pregnancy category C.
Side effects, such as nausea, vomiting, and diarrhea, are similar to those of other macrolides. Randomized controlled trials comparing telithromycin with clarithromycin (Biaxin), trovafloxacin (not available in the United States), or high-dose amoxicillin found telithromycin to be associated with more adverse events.2,6–8
Telithromycin is labeled only for the treatment of community-acquired pneumonia; however, fewer than one in 20 prescriptions were for this use before the change in labeling in 2007.9 Telithromycin has the same microbacterial activity as macrolides, and in addition, has activity against penicillin-resistant and macrolide-resistant Streptococcus pneumoniae. The relevance of the enhanced S. pneumoniae activity is unknown because in vitro activity does not always correlate with improved clinical results. Randomized controlled trials in the outpatient treatment of community-acquired pneumonia have found telithromycin to have similar effectiveness as clarithromycin 500 mg twice daily, amoxicillin 1,000 mg three times daily, and trovafloxacin 200 mg daily.6–8
A typical course of telithromycin (seven to 10 days) costs approximately $80 to $115. In contrast, a typical course of clarithromycin (seven days) costs about $59 to $63 for the generic version and $81 for the brand.
Telithromycin is dosed in adults as 800 mg orally once daily (administered as two 400 mg tablets at the same time) for seven to 10 days. It may be given without regard to meals. Dosage decreases are required in patients with renal insufficiency.
Telithromycin is similar to clarithromycin with regard to dosing, drug interactions, and effectiveness. It has more frequent and severe adverse effects and is more expensive than other macrolides. Telithromycin should only be used in patients with mild to moderate community-acquired pneumonia caused by penicillin- or macrolide-resistant S. pneumoniae. For other causes of community-acquired pneumonia, safer options are available. Telithromycin should not be used for the treatment of sinusitis, streptococcal pharyngitis, acute otitis media, bronchitis, or other common but non–life-threatening bacterial infections.