RxPRODUCT NEWS PROFILE: Ketek (telithromycin)

Background

Ketek is the first agent in a new class of antibiotics known as the ketolides. Manufactured by Aventis, Ketek was recently approved by the FDA for the treatment of acute bacterial exacerbation of chronic bronchitis (Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis), acute bacterial sinusitis (S pneumoniae, H influenzae, M catarrhalis, Staphylococcus aureus), and mild-to-moderate community-acquired pneumonia (CAP; S pneumoniae, H influenzae, M catarrhalis).

Pharmacology

Ketek inhibits protein synthesis by binding to domains II and V of 23S rRNA of the 50S ribosomal subunit. By binding to domain II, Ketek is active against gram-positive cocci (eg, S pneumoniae) in the presence of resistance mediated by methylases (erm genes) that change the domain V binding site of Ketek.^1,2 Following oral administration, Ketek reaches maximal concentration in ~1 hour (0.5-4 hours).

Safety

Adverse events noted in ?2% of patients in phase 3 clinical trials included diarrhea, nausea, dizziness, and vomiting.^1,2

Ketek is a strong inhibitor of the cytochrome P450 3A4 system. Coadministration of Ketek tablets and another agent that is primarily metabolized by the cytochrome P450 3A4 enzyme system may result in in-creased plasma concentration of that agent. Therefore, dosage adjustments may be necessary for that drug when coadministered with Ketek. Ketek is designated as a Pregnancy Category C drug.¹

Clinical Trials

Three clinical trials were performed to assess the efficacy of Ketek (5-day therapy) in acute exacerbations of chronic bronchitis (AECB) versus cefuroxime 500 mg bid for 10 days, clarithromycin 500 mg bid for 10 days, or amoxicillin/clavulanic acid 500/125 mg tid for 10 days. The Ketek 5-day dosing regimen was found to be as effective as 10-day comparator drug regimens for the treatment of AECB.

Two randomized, double-blind comparator studies were utilized to assess Ketek in acute sinusitis. These trials compared 5-day Ketek therapy with 10 days of amoxicillin/clavulanate 500/125 mg tid or cefuroxime 250 mg bid. An additional trial compared 5-day and 10-day dosing regimens. Results from controlled studies showed that Ketek 5-day therapy was equally efficacious as 10-day therapy of comparator drugs. Results from the additional trial also showed 5-day and 10-day Ketek therapy to be equally efficacious in terms of clinical cure rates (91.1% vs 91.0%, respectively).

Four randomized, double-blind studies and 4 open-label studies were performed to assess the efficacy of Ketek in CAP. The comparator drugs included amoxicillin 1000 mg tid for 10 days, clarithromycin 500 mg bid for 10 days, or trovafloxacin 200 mg qd for 7 to 10 days. After 7 to 10 days of Ketek therapy, a clinical cure rate of 83.0% to 95.7% bacterial eradication rate was observed. Ketek 7-day and 10- day dosing regimens were equally effective as those of comparator drugs, which had clinical cure rates ranging from 77.8% to 95.5% bacterial eradication. Ketek also showed 91.7% clinical success against multidrug-resistant S pneumoniae.

Outlook

Ketek is indicated for use in patients with bacterial infections: acute bacterial exacerbation of chronic bronchitis, acute bacterial sinusitis, and CAP. The recommended dose of Ketek tablets is 800 mg taken orally once every 24 hours. The duration of therapy depends on the infection type. Ketek tablets can be given without regard to food.¹

Dr. Hartman is medication safety officer at UMass Memorial Medical Center, Worcester, Mass. He also is a clinical assistant professor at Northeastern University and an adjunct assistant professor at Massachusetts College of Pharmacy. Dr. Faria is a senior research pharmacist at Brigham and Women's Hospital, Boston, Mass.

For a list of references, send a stamped, self-addressed envelope to: References Department, Attn. A. Stahl, Pharmacy Times, 241 Forsgate Drive, Jamesburg, NJ 08831; or send an e-mail request to: astahl@mwc.com.