Jane S. Ricciuti, RPh, MS


June 03, 2004

In This Article

Anti-infective Agents

(telithromycin) Tablets

Manufacturer: Aventis

Drug Approval Classification: Original New Drug Application (Approval Date: 04/01/2004)

Indication: Ketek (telithromycin) tablets are indicated for the treatment of infections caused by susceptible strains:

  • ABECB due to Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis

  • ABS due to Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, or Staphylococcus aureus

  • CAP due to Streptococcus pneumoniae, (including multidrug-resistant isolates), Haemophilus influenzae, Moraxella catarrhalis, Chlamydophila pneumoniae, or Mycoplasma pneumoniae.

Dosing: The dose of telithromycin tablets is 800 mg (2 400-mg tablets) taken orally once every 24 hours. The duration of treatment for ABECB and for ABS is 5 days. The duration of treatment for CAP is 7-10 days.

Clinical Summary: Telithromycin is a semisynthetic antibacterial in a new class called the ketolides. Telithromycin shares some of the properties of macrolide antibiotics, such as cross-hypersensitivity and prolongation of the QTc interval in some patients.

To assess telithromycin efficacy in the treatment of CAP, 4 randomized, double-blind, controlled studies and 4 open-label studies were conducted. A total of 2016 patients with mild to moderate CAP were enrolled. Clinical success for telithromycin against S pneumoniae was 312 (93.7%).

Telithromycin was also studied in 2 randomized, double-blind, comparative studies of ABS patients. Clinical cure rates for the 2 treatments (telithromycin vs amoxicillin/clavulanic or cefuroxime axetil) were similar (91.1% vs 91.0%).

Three randomized, double-blind, controlled studies of telithromycin for the treatment of ABECB yielded clinical cure rates ranging from 73.3% to 93.1%.

Adverse Effects: Telithromycin is contraindicated in patients with a history of hypersensitivity to any macrolide antibiotic. Telithromycin has the potential to prolong the QTc interval of the electrocardiogram.

Telithromycin may cause visual disturbances, particularly in slowing the ability to accommodate and the ability to release accommodation. Visual disturbances included blurred vision, difficulty focusing, and diplopia. Most events were mild to moderate; however, severe cases have been reported. Patients should be cautioned about the potential effects of these visual disturbances on driving a vehicle, operating machinery, or engaging in other potentially hazardous activities.

Pharmacokinetics: Telithromycin is 57% bioavailable and can be taken with or without food. Peak plasma concentrations are achieved at 1 hour post ingestion. Telithromycin's elimination half-life is 10 hours, and mean peak and trough plasma concentrations are 2.9 mcg/mL (± 1.55) and 0.2 mcg/mL (± 0.22), respectively, after 3-5 days of telithromycin 800 mg once daily.

Approximately 50% of the telithromycin concentration is metabolized by CYP 450 3A4 and 50% by CYP 450-independent pathways. Telithromycin is metabolized primarily by the liver, with the remaining drug unchanged in feces and renal excretion.

Drug-drug interactions are seen with digoxin, theophylline, sotalol, and rifampin. Other studies were performed in which the following interactions were noted:

  • CYP 3A4 inhibitors

    • Itraconazole

    • Ketoconazole

  • CYP 3A4 substrates

    • Cisapride

    • Simvastatin

    • Midazolam

  • CYP 2D6 substrates

    • Metoprolol

Ketek (telithromycin) Tablets Labeling