The purpose of this guide is to provide a review of a new therapy to determine whether the Telithromycin drug should be considered a prior authorization drug, a clinical edit drug, or an open-access drug. While prescription expenditures are increasing at double-digit rates, payors are evaluating ways to control these costs by influencing prescriber behavior and guiding appropriate medication usage.

A new class of antibiotics has made its debut in the United States.  This new class of antibiotics is called Ketolides.  Their forte is enhanced activity against multidrug-resistant gram-positive pathogens and Haemophilus influenzae. 

Telithromycin Indication

Telithromycin is indicated for the treatment of infections caused by susceptible strains of the designated microorganisms in the conditions listed below for patients at least 18 years of age.

Mechanism of Action of Telithromycin

Telithromycin mechanism of action is similar to that of macrolides and is related to 50S-ribosomal subunit binding (domains II and V) with inhibition of bacterial protein synthesis.  Due to its binding at domain II, telithromycin retains activity against gram-positive cocci in the presence of resistance mediated by methylases that alter the domain V binding site of this antibiotic.  Ketolides are semisynthetic derivatives of 14-membered ring macrolides, and represent a new class of antibiotics with enhanced activity against multidrug-resistant gram-positive pathogens and Haemophilus influenza. 

Efficacy of Telithromycin

Numerous randomized, double-blind, controlled clinical trials have demonstrated the efficacy of once-daily telithromycin in the treatment of acute bacterial exacerbation of chronic bronchitis (AECB) with clinical cure rates of approximately 86%, acute bacterial sinusitis with clinical cure rates of 75-85%, and community-acquired pneumonia (CAP) with clinical cure rates of 88-95%, including multi-drug resistant Streptococcus pneumoniae (MDRSP) with an approximate 92% clinical success rate. 

Similarity With Other Antibiotics

Telithromycin appears to be similar in efficacy to cefuroxime, amoxicillin/clavulanic acid, or clarithromycin for the treatment of AECB; similar to cefuroxime or amoxicillin/clavulanic acid for the treatment of acute sinusitis; and similar to clarithromycin, trovafloxacin, or high dose amoxicillin for the treatment of CAP.  Comparative studies with other antimicrobial agents are not available.

Contraindication

• Hypersensitivity to telithromycin, macrolide antibiotics, or any product components.
• Concomitant administration with cisapride or pimozide (increased risk of QTc prolongation).

Warnings

• Telithromycin has the potential to prolong the QTc interval in some patients, which may lead to an increased risk for ventricular arrhythmias, including torsades de pointes.  Because of this, telithromycin should be avoided in patients with congenital prolongation of the QTc interval, and in patients with ongoing proarrhythmic conditions such as uncorrected hypokalemia or hypomagnesemia, a clinically significant bradycardia, and in patients receiving Class IA (e.g., quinidine and procainamide) or Class III (e.g., dofetilide) antiarrhythmic agents.
• Exacerbations of myasthenia gravis, including life-threatening acute respiratory failure, have been reported in patients with myasthenia gravis treated with telithromycin.

Drug Interactions

• Antiarrhythmic agents Class IA (e.g. quinidine and procainamide) or Class III (e.g., dofetilide)
• Cisapride
• Pimozide

Dosage And Administration

800 mg (2 tablets of 400 mg) orally once daily for 5 days in the treatment of AECB or acute bacterial sinusitis and for 7-10 days in the treatment of CAP.

Final Comments

Telithromycin is a once-daily ketolide antimicrobial agent that has demonstrated efficacy in the treatment of acute bacterial exacerbation of chronic bronchitis, acute bacterial sinusitis, and community-acquired pneumonia including multi-drug resistant Streptococcus pneumonia.  It is the first antibiotic available in this new class of antibiotics and may provide a useful option for the treatment of some multiresistant or difficult to treat infections.

Telithromycin has been available in numerous other countries but approval in the U.S. was delayed due to safety concerns.  Postmarketing commitments include pediatric use studies in acute bacterial sinusitis and CAP and a report on postmarketing vision-related adverse events.

Reference

Product Information:  Ketek^Ô, telithromycin tablets.  Aventis Pharmaceuticals, Kansas City, MO (03/2004) reviewed 05/2004.