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Systematic (IUPAC) name
CAS number 191114-48-4
ATC code J01FA15
PubChem 5462516
DrugBank APRD00483
Chemical data
Formula C43H65N5O10 
Mol. mass 812.004 g/mol
Pharmacokinetic data
Bioavailability 57%
Protein binding 60% to 70%
Metabolism Hepatic (50% CYP3A4-mediated)
Half life 10 hours
Excretion Biliary and renal
Therapeutic considerations
Pregnancy cat.

C (U.S.)

Legal status

POM (UK), ℞-only (U.S.)

Routes Oral

Telithromycin is the first ketolide antibiotic to enter clinical use. It is used to treat mild to moderate respiratory infections. Telithromycin is sold under the brand name of Ketek®.

Telithromycin is a semi-synthetic erythromycin derivative. It is created by substituting the cladinose sugar with a ketogroup and adding a carbamate ring in the lactone ring. An alkyl-aryl moiety is attached to this carbamate ring. Furthermore, the carbon at position 6 has been methylated, like in clarithromycin, to achieve better acid-stability.



French pharmaceutical company Hoechst Marion Roussel (later Sanofi-Aventis) started phase II/III trials of telithromycin (HMR-3647) in 1998. Telithromycin was approved by the European Commission in July 2001 and subsequently came on sale in October 2001. In USA, telithromycin gained FDA approval April 1, 2004 .

Available forms

Telithromycin is administered as tablets. Two 400mg tablets to be taken together, daily, with or without food.

Mechanism of action

Telithromycin prevents bacteria from growing, by interfering with their protein synthesis. Telithromycin binds to the subunit 50S of the bacterial ribosome, and blocks the progression of the growing polypeptide chain. Telithromycin has over 10 times higher affinity to the subunit 50S than erythromycin. In addition, telithromycin binds simultaneously to two domains of 23S RNA of the 50 S ribosomal subunit, where older macrolides bind only to one. Telithromycin can also inhibit the formation of ribosomal subunits 50S and 30S.


Unlike erythromycin, telithromycin is acid-stable and can therefore be taken orally while being protected from gastric acids. It is fairly rapidly absorbed, and diffused into most tissues and phagocytes. Due to the high concentration in phagocytes, telithromycin is actively transported to the site of infection. During active phagocytosis, large concentrations of telithromycin is released. The concentration of telithromycin in the tissues much higher than in plasma.


It is metabolized mainly in the liver, the main elimination route being the bile, a small portion is also excreted into the urine. About one third is excreted unchanged into the bile and urine, the biliary route being favoured. Telithromycin's half-life is approximately 10 hours.

Adverse effects

Most common side-effects are gastrointestinal; diarrhea, nausea, abdominal pain and vomiting. Headache and disturbances in taste also occur. Less common side-effects include palpitations, blurred vision and rashes.

Rare, but severe side effects reported in January 2006 involve damage to the liver. Three different incidents have been reported: one ending in death, one in a liver transplant and one case of drug-induced hepatitis.[1].

In the United States the FDA's Office of Epidemiology and Surveillance identified 12 cases of acute liver failure, resulting in four deaths, and an additional 23 cases of acute, serious liver injury in patients taking telithromycin up to April 2006.[4]

Telithromycin has been known to cause false positive readings in drug screenings for cocaine and amphetamines.[citation needed]

Safety controversies and fraud

FDA staffers publicly complained that safety problems were ignored, and congressional hearings were held to examine those complaints. Some of the data in clinical trials submitted to the FDA turned out to be fabricated, and one doctor went to prison. The House Committee on Energy and Commerce held hearings[2].

Study 3014 was a key clinical trial of more than 24,000 patients that Sanofi-Aventis submitted to the FDA seeking approval for Ketek.

The doctor who treated the most patients in Study 3014, Maria "Anne" Kirkman Campbell, is serving a 57-month sentence in federal prison after pleading guilty to defrauding Aventis and others. An indictment says Dr. Campbell fabricated data she sent to the company[3]. Documents including internal Sanofi-Aventis emails about show that Aventis was worried about Dr. Campbell early in study 3014 but didn't tell the FDA until the agency's own inspectors discovered the problem independently[4].

In July 2006, the New York Times[5] quoted E-mails from David Graham, an FDA safety official, arguing that telithromycin had not been proven safe, safer drugs were available for the same indications, the approval was a mistake and it should be immediately withdrawn. There were 14 cases of liver failure, including at least 4 deaths[1], vision problems, blackouts, syncope, and potentially fatal myasthenia gravis. Graham wrote, “It’s as if every principle governing the review and approval of new drugs was abandoned or suspended where telithromycin is concerned.” [5] The Times said that the FDA was having a "fierce battle" over the approval, fueled by the press attention. Three other FDA officials also criticized the approval: Dr. Charles Cooper, Dr. David Ross and Dr. Rosemary Johann-Liang, who wrote, "How does one justify balancing the risk of fatal liver failure against one day less of ear pain?". [5] Senator Charles E. Grassley (R-Iowa, chairman, Senate Finance Committee), Representatives Edward J. Markey (D-Mass) and Henry A. Waxman (D-Calif) held hearings.

FDA Warning

On February 12, 2007, the Food and Drug Administration announced a revision to the labeling of Ketek to improve patient safety. The changes included the removal of two of the three previously approved indications: acute bacterial sinusitis and acute bacterial exacerbations of chronic bronchitis. The agency determined that the balance of benefits and risks no longer supported approval of the drug for these indications. Ketek will remain on the market for the treatment of community acquired pneumonia of mild to moderate severity (acquired outside of hospitals or long-term care facilities). In addition, the FDA worked with the manufacturer to update the product labeling with a "boxed warning," FDA's strongest form of warning. The warning states that Ketek should not be used in patients with myasthenia gravis, a disease that causes muscle weakness. [5]


  1. ^ a b Clay KD et al. (2006). "Brief communication: severe hepatotoxicity of telithromycin: three case reports and literature review.". Annals of Internal Medicine 144(6): 415-420. PMID 16481451.
  2. ^ [1]House of Representatives, The House Committee on Energy and Commerce, Honorable John D. Dingell, Chairman, Subcommittee on Oversight and Investigations, "The Adequacy of FDA Efforts to Assure the Safety of the Drug Supply", February 13, 2007.
  4. ^ [3]Infected Data: Fraud, Errors Taint Key Study Of Widely Used Sanofi Drug Despite Some Faked Results, FDA Approves Antibiotic; One Doctor's Cocaine Use; Company Defends Safety, By ANNA WILDE MATHEWS, Wall Street Journal, May 1, 2006
  5. ^ a b c Harris, G . (2006). "Approval of Antibiotic Worried Safety Officials.". New York Times 19 July 2006.
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Telithromycin". A list of authors is available in Wikipedia.
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