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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-.

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LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet].

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Last Update: August 10, 2017.



Telithromycin is a ketolide, a novel form of macrolide antibiotic that is recommended for treatment of community acquired pneumonia. Telithromycin was approved for use in the United States in 2004 and subsequently linked to several cases of severe drug induced liver injury.


Telithromycin (tel ith" roe mye' sin) is a ketolide antibiotic, a novel form of macrolide antibiotic that is used to treated community acquired pneumonia. Telithromycin differs from erythromycin by several substitutions that render it less susceptible to erythromycin-resistant strains of bacteria. Telithromycin is active against staphylococci, streptococci, S. pneumoniae, Haemophilus spp., Moraxella catarrhalis, mycoplasma, chlamydia and Legionella. Telithromycin was first approved for use in the United States in 2004 and initially had several clinical indications including sinusitis and bronchitis. Currently, because of the potential of serious side effects, the only approved indication for telithromycin is moderate-to-severe community acquired pneumonia due to sensitive organisms. Telithromycin is available in oral forms under the trade name Ketek in tablets of 300 mg (for reduced dosing in patients with renal disease) and 400 mg. The recommended dosage is 800 mg once daily for 7 to 10 days. Telithromycin is generally well tolerated, but side effects can include nausea, abdominal pain, diarrhea, dyspepsia, headache, dizziness and rash.


As with other macrolide antibiotics, telithromycin has been associated with a low rate (1% to 2%) of transient serum enzyme elevations during therapy. These elevations, however, are usually transient and resolve even with drug continuation and a similar rate of serum enzyme elevations can occur with comparator agents. More importantly, telithromycin has been linked to severe forms of acute, clinically apparent hepatotoxicity, first reported within a short time of its general approval for use in the United States. The typical latency to onset of liver injury is rapid, some cases presenting within a day or two of initiation of therapy, the average latency being 1 week. The liver injury is often abrupt in onset with fatigue, weakness, jaundice and fever. The pattern of enzyme elevations is typically hepatocellular and serum aminotransferase levels can be quite high (>1000 U/L). Mild and anicteric cases of liver injury attributed to telithromycin have been reported, but some cases are very severe and associated with rapid development of hepatic failure with ascites and hepatic encephalopathy. Eosinophilia and rash can occur, but are not common. Recurrence of injury with reexposure has been described.

Likelihood score: A (well known cause of clinically apparent liver injury).

Mechanism of Injury

The cause of hepatotoxicity from telithromycin is unknown, but the short latency period and abrupt onset of injury suggests hypersensitivity as the cause. Only a proportion of cases have been associated with eosinophilia, and rash, fever, adenopathy and facial edema are rarely described.

Outcome and Management

Severe cases of liver injury appearing within days of starting telithromycin have been described some of which have been associated with acute and rapid onset of ascites and liver failure requiring liver transplantation. Milder cases of injury and cases without jaundice have generally resolved rapidly over 4 to 6 weeks. Persons with a history of allergy or liver injury due to telithromycin or any macrolide antibiotic such as erythromycin, azithromycin or clarithromycin should not be reexposed to macrolide antibiotics.

Drug Class: Antiinfective Agents, Macrolide Antibiotics


Case 1. Mild hepatitis after telithromycin therapy.

[Modified from a case in the database of the Drug-Induced Liver Injury Network.]

A 31 year old man was treated with two 5-day courses of telithromycin for sinusitis. Five days after finishing the second course, he developed fever and chills and was found to have abnormal liver tests. On hospital admission, his ALT was 589 U/L but bilirubin was normal (Table). He had no previous history of liver disease or jaundice and drank little alcohol. He took antihistamines and used a nasal spray for his sinusitis, but took no medications chronically and had no drug allergies. Tests for hepatitis A, B and C were negative. Tests for anti-smooth muscle and antinuclear antibodies were weakly positive (1:80). A computed tomography scan of the abdomen showed no evidence of gallstone disease or obstruction. His serum aminotransferases fluctuated and peaked at levels of 15-25 times the upper limit of the normal range, but then gradually declined. Six weeks after admission, he was without symptoms and laboratory tests were completely normal.

Key Points

Medication:Telithromycin (800 mg daily for 5 days)
Pattern:Hepatocellular (R=43)
Severity:1+ (no jaundice)
Latency:2 weeks after starting second course
Recovery:Complete in 6 weeks
Other medications:Brompheniramine tannate, mometasone nasal spray, rarely acetaminophen

Laboratory Values

Time After StartingDays After StoppingAST* (U/L)Alk P* (U/L)Bilirubin *(mg/dL)Other
Second 5-day course of telithromycin (800 mg daily) – 1 week after the first
10 days5 days589430.7Admission
12 days7 days1091351.2INR 1.5
15 days10 days553350.8INR 1.3
19 days14 days768471.1
24 days19 days359591.1Discharge
31 days26 days151650.4
2 months7 weeks36400.7INR 1.0
Normal Values <42 <110 <1.2


This patient developed anicteric but symptomatic hepatitis within 10 days of starting a second course of oral telithromycin. Worrisome was a slight increase in prothrombin time, but this reversed with time and after vitamin K injections. Serum aminotransferases remained elevated for several weeks, but recovery was complete. The finding of low levels of autoantibodies should lead to further follow up to exclude the possibility of autoimmune hepatitis with an onset marked by episodes of activity, but this is unlikely. The first course of telithromycin may have sensitized this patient; a history of previous exposure to macrolide antibiotics is not uncommon in patients presenting with liver injury. This patient should be strongly warned against future use of telithromycin, the indications for which have now been restricted to community acquired pneumonia. Recommendations regarding other macrolide antibiotics are not as clearly made, but use of a single test dose might be appropriate if these agents are considered necessary.



Telithromycin — Ketek®


Antiinfective Agents


Product labeling at DailyMed, National Library of Medicine, NIH


Telithromycin 173838-31-8 C43-H65-N5-O10
Telithromycin structure


References updated: 10 August 2017

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    (Expert review of macrolide antibiotic induced liver injury; telithromycin was impicated in at least 42 cases of clinically apparent liver injury with four deaths and one liver transplant; clinical features were short latency, abrupt onset and jaundice).
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    (Analysis of 42 cases of hepatotoxicity attributed to telithromycin reported to FDA between 2004-6; 26 were considered probable or highly likely and 16 as only possibly related to telithromycin, many cases were severe including 4 deaths and one liver transplant; onset in 2-43 days [median=10 days] with abrupt onset of symptoms or jaundice, usually hepatocellular with very high ALT, some developing ascites early, resolving with recovery; fever in 29% and eosinophilia in 19%).
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    (Among 300 cases of drug induced liver disease in the US collected from 2004 to 2008, 5 cases were attributed to telithromycin and 3 to azithromycin as single agents, but none to erythromycin or clarithromycin).
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    (Description of results of a semiautomated, sequential propensity score with a matched cohort approach for drug safety monitoring based upon electronic databases; among 106,658 new users of telithromycin and a similar number of users of azithromycin identified over a 5 year period, 41 cases of hepatitis were found, 23 due to telithromycin for a risk rate of 2 per 10,000 users, not appreciably greater than with azithromycin).
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    (In a population based study of drug induced liver injury from Iceland, 96 cases were identified over a 2 year period, of which none were attributable to telithromycin or other macrolide antibiotics).
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    (In a nested case control analysis of a health care network database of persons between 2001 and 2009, 8 selected antibiotics were assessed for association with risk of hospitalization for liver injury, adjusted relative risks being significantly elevated for levofloxacin [3.2], moxifloxacin [2.3], doxycycline [2.5], amoxicllin/clavulanate [2.5] and amoxicillin [2.3], but not for clarithromycin [1.8], telithromycin [1.7] or cefuroxime [0.9]).
  • Chalasani N, Bonkovsky HL, Fontana R, Lee W, Stolz A, Talwalkar J, Reddy KR, et al.; United States Drug Induced Liver Injury Network. Features and outcomes of 899 patients with drug-induced liver injury: The DILIN Prospective Study. Gastroenterology 2015; 148: 1340-52.e7. [PMC free article: PMC4446235] [PubMed: 25754159]
    (Among 899 cases of drug induced liver injury enrolled in a US prospective study between 2004 and 2013, 323 [36%] were attributed to antibiotics including 29 [3.2%] due to marolides of which 18 were linked to azithromycin, 2 to clarithromycin, 2 erythromycin and 7 telithromycin).
  • Ferrajolo C, Verhamme KM, Trifirò G, 't Jong GW, Picelli G, Giaquinto C, Mazzaglia G, et al. Antibiotic-induced liver injury in paediatric outpatients: a case-control study in primary care databases. Drug Saf 2017; 40: 305-15. [PMC free article: PMC5362651] [PubMed: 28025733]
    (In a health care database of 429,772 children in Italy and the Netherlands followed between 2008 and 2010, 938 cases of liver injury of uncertain cause were identified, the rate being higher in those with current use of antibiotics [12% vs 3.6%] for an adjusted odds rate ratio [aOR] of 3.2; specific antibiotics most commonly implicated were fluoroquinolones [19.0], cephalosporins [4.5], macrolides [3.5] and penicillins [2.6], but no cases were attributed to telithromycin).
  • Bonkovsky HL, Kleiner DE, Gu J, Odin JA, Russo MW, Navarro VM, Fontana RJ, et al.; U.S. Drug Induced Liver Injury Network Investigators. Clinical presentations and outcomes of bile duct loss caused by drugs and herbal and dietary supplements. Hepatology 2017; 65: 1267-77. [PMC free article: PMC5360519] [PubMed: 27981596]
    (Among 363 patients with drug induced liver injury who underwent liver biopsy, 26 [7%] had bile duct loss, including 2 cases attributed to azithromycin, but none to clarithromycin or other macrolides).


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