Benefit-risk assessment of telithromycin in the treatment of community-acquired pneumonia.

The purpose of this review is to assess the benefits and risks associated with the use of the ketolide antibacterial telithromycin, currently licensed for the treatment of adults with mild to moderate community-acquired pneumonia (CAP). Telithromycin is active against both the major (Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis) and atypical/intracellular (Chlamydophila pneumoniae, Legionella pneumophila and Mycoplasma pneumoniae) CAP pathogens. It is associated with a low potential to select for resistance and has maintained its in vitro activity against isolates of respiratory pathogens in countries where it has been in clinical use for several years. In randomized clinical trials, telithromycin has demonstrated efficacy comparable to the established antibacterial classes (macrolides, fluoroquinolones and beta-lactams) in the treatment of CAP.The safety profile of telithromycin is broadly similar to that of other antibacterials used to treat CAP. The most common adverse events are gastrointestinal adverse effects and headache; these are generally mild to moderate in severity and reversible. Telithromycin appears to be well tolerated by adult patients in all age groups, including those with co-morbid conditions. In common with other antibacterials, telithromycin has the potential to affect the corrected QT interval; the concomitant use of cisapride or pimozide with telithromycin is contraindicated, while telithromycin should be avoided in patients receiving Class IA or Class III antiarrhythmic drugs. Visual disturbances (usually transient) have occurred in a small proportion of patients treated with telithromycin; it is recommended that activities such as driving are minimized during treatment. Telithromycin is contraindicated in patients with myasthenia gravis. Hepatic dysfunction may occur in some patients taking telithromycin; rare cases of acute hepatic failure and severe liver injury, including deaths, have been reported. As telithromycin is an inhibitor of the cytochrome P450 (CYP) 3A4 system, coadministration of telithromycin with drugs metabolized by this pathway may require dose adjustments (e.g. with benzodiazepines) or a temporary hiatus in the use of the coadministered drug (e.g. HMG-CoA reductase inhibitors) metabolized by CYP3A4. Telithromycin may potentiate the effects of oral anticoagulants; careful monitoring is recommended in patients receiving telithromycin and oral anticoagulants simultaneously.Although serious and sometimes fatal events have occurred in patients receiving telithromycin therapy, current data indicate that telithromycin offers an acceptable benefit risk ratio in the treatment of mild to moderate CAP.