Brands, Medical Use, Clinical Data
- Anti-bacterial Agents
Brands / Synonyms
Ketek; Ketek (TN)
For the treatment of Pneumococcal infection, acute sinusitis, acute bacterial tonsillitis, acute bronchitis and bronchiolitis, lower respiratory tract infection and lobar (pneumococcal) pneumonia.
Telithromycin is a macrolide antibiotic which has an antimicrobial spectrum similar or slightly wider to that of penicillin, and is often used for people who have an allergy to penicillins. For respiratory tract infections, it has better coverage of atypical organisms, including mycoplasma. It is also used to treat outbreaks of chlamydia, syphilis, and gonorrhea. Telithromycin prevents bacteria from growing, by interfering with their protein synthesis. Telithromycin binds to the subunit 50S of the bacterial ribosome, and thus inhibits the translocation of peptides.
Mechanism of Action
Telithromycin acts by binding to domains II and V of 23S rRNA of the 50S ribosomal subunit. By binding at domain II, telithromycin retains activity against gram-positive cocci (e.g., Streptococcus pneumoniae) in the presence of resistance mediated by methylases (erm genes) that alter the domain V binding site of telithromycin. Telithromycin may also inhibit the assembly of nascent ribosomal units.
LD50>2000 mg/kg (PO in rats)
Biotrnasformation / Drug Metabolism
Telithromycin is contraindicated in patients with a history of hypersensitivity to telithromycin and/or any components of Telithromycin tablets, or any macrolide antibiotic. Concomitant administration of Telithromycin with cisapride or pimozide is contraindicated.
Telithromycin is a strong inhibitor of the cytochrome P450 3A4 system. Co-administration of Telithromycin tablets and a drug primarily metabolized by the cytochrome P450 3A4 enzyme system may result in increased plasma concentration of the drug co-administered with telithromycin that could increase or prolong both the therapeutic and adverse effects. Therefore, appropriate dosage adjustments may be necessary for the drug co-administered with telithromycin.
The use of Telithromycin is contraindicated with cisapride.
The use of Telithromycin is contraindicated with pimozide. Although there are no studies looking at the interaction between Telithromycin and pimozide, there is a potential risk of increased pimozide plasma levels by inhibition of CYP 3A4 pathways by Telithromycin as with macrolides.
In a pharmacokinetic study, simvastatin levels were increased due to CYP 3A4 inhibition by telithromycin. Similarly, an interaction may occur with lovastatin or atorvastatin, but not with pravastatin or fluvastatin. High levels of HMG-CoA reductase inhibitors increase the risk of myopathy. Use of simvastatin, lovastatin, or atorvastatin concomitantly with Telithromycin should be avoided. If Telithromycin is prescribed, therapy with simvastatin, lovastatin, or atorvastatin should be suspended during the course of treatment.
Monitoring of digoxin side effects or serum levels should be considered during concomitant administration of digoxin and Telithromycin.
Patients should be monitored with concomitant administration of midazolam and dosage adjustment of midazolam should be considered if necessary. Precaution should be used with other benzodiazepines, which are metabolized by CYP 3A4 and undergo a high first-pass effect (e.g., triazolam).
Concomitant treatment of Telithromycin with rifampin, a CYP 3A4 inducer, should be avoided. Concomitant administration of other CYP 3A4 inducers such as phenytoin, carbamazepine, or phenobarbital is likely to result in subtherapeutic levels of telithromycin and loss of effect.
In patients treated with metoprolol for heart failure, the increased exposure to metoprolol, a CYP 2D6 substrate, may be of clinical importance. Therefore, co-administration of Telithromycin and metoprolol in patients with heart failure should be considered with caution.
Spontaneous post-marketing reports suggest that administration of Telithromycin and oral anticoagulants concomitantly may potentiate the effects of the oral anticoagulants. Consideration should be given to monitoring prothrombin times/INR while patients are receiving Telithromycin and oral anticoagulants simultaneously.
No specific drug interaction studies have been performed to evaluate the following potential drug-drug interactions with Telithromycin. However, these drug interactions have been observed with macrolide products.
Drugs metabolized by the cytochrome P450 system such as carbamazepine, cyclosporine, tacrolimus, sirolimus, hexobarbital, and phenytoin: elevation of serum levels of these drugs may be observed when co-administered with telithromycin. As a result, increases or prolongation of the therapeutic and/or adverse effects of the concomitant drug may be observed.
Ergot alkaloid derivatives (such as ergotamine or dihydroergotamine): acute ergot toxicity characterized by severe peripheral vasospasm and dysesthesia has been reported when macrolide antibiotics were co-administered. Without further data, the co-administration of Telithromycin and these drugs is not recommended.
Laboratory test interactions
There are no reported laboratory test interactions.