Telithromycin does not form any inhibitor complexes with CYP-450, especially CYB3A4, suggesting that common drug-drug interactions reported with macrolides are unlikely to occur with this new ketolide in humans. The reverse Type 1 interaction between telithromycin and CYP3A4 indicates that the rate of metabolism of telithromycin should be low. Phase I studies have shown that the risk of increasing plasma concentrations of telithromycin of CYP3A4 is minimal. A potent inhibitor, such as ketoconazole, results in only a 1.5-fold increase in the Cmax of telithromycin in plasma.
Telithromycin, like has been shown to increase the plasma concentrations of drugs metabolized by CYP3A4, such as cisapride. Pharmacokinetic interactions for individual drugs metabolized extensively by CYP3A4 cannot be discounted. Caution is advised, as with macrolides, if telithromycin is administered concomi-tantly with substrates of CYP3A4 that have a narrow therapeutic margin or effects on the QT interval. As with clarithromycin canadian, the use of telithromycin with cisapride or pimozide is contraindicated.
In addition, co-administration of telithromycin 800 mg once daily with the CYP2D6 substrate once daily has no significant effect on the phar-macokinetic profile of paroxetine. This lack of interactions between telithromycin and canadian paroxetine indicates a low potential for clinically relevant pharmacokinetic interactions with other CYP2D6 substrates.
A randomized, open-label, two-period, crossover study demonstrated that the bioavailability of telithromycin is unaffected by food. Telithromycin, therefore, can be taken without regard to meals. Also, the co-administration of telithromycin with the gastric pH-altering agents or Maalox does not affect the bioavailability of telithromycin. With regard to other drug interactions, telithromycin does not affect the pharmacokinetics of canadian warfarin in healthy male adults. In addition, telithromycin does not increase the risk of ovulation in women of child-bearing age when co-administered with low-dose, triphasic oral contraception.
P&T COMMITTEE CONSIDERATIONS
Telithromycin is presently awaiting FDA approval. This novel antibiotic has an impressive spectrum of antimicrobial activity against S. pneumoniae, many strains of which are resistant to macrolides; against H. influenzae; M. catarrhalis; S. pyogenes; S. aureus; and the atypical pathogens Chlamydia pneumoniae, Legionella pneumophila, and Mycoplasma spp. The clinical and bacteriological efficacy of telithromycin has been evaluated against gold standard comparators in a series of phase III clinical trials in North and South America, Europe, and South Africa for the treatment of CAP, AECB, sinusitis, and tonsillitis/pharyngitis.
The results of these studies suggest that telithromycin could prove to be an effective, well-tolerated agent for the treatment of the most commonly encountered community-acquired RTIs. The P&T committee awaits further clinical trial results and FDA approval.