Tigecycline is a parenteral glycycline antibiotic used for treatment of serious infections due to susceptible organisms. Tigecycline therapy is sometimes accompanied by minor aminotransferase elevations, but has not been definitely associated with clinically apparent liver injury with jaundice.
Tigecycline (tye" ge sye' kleen) is new generation of tetracycline, known as a glycycline. Like other tetracyclines, tigecycline is a broad spectrum bacteriostatic agent that acts by binding to bacterial ribosomes inhibiting protein synthesis. Tigecycline has activity against both gram-positive and gram-negative bacteria and, importantly, it also has activity against many multidrug resistant organisms. Tigecycline was approved for use in the United States in 2005. Current indications inlcude treatment of community acquired pneumonia and complicated skin, tissue and intra-abdominal infections due to sensitive organisms. Tigecycline is available in vials of 50 mg for parenteral use under the brand name Tygacil. The recommended dose is 100 mg intravenously initially, followed by 50 mg every 12 hours for 5 to 14 days depending on the severity and site of the infection. A reduced dosage is recommended for patients with severe underlying liver disease. Because of its broad spectrum of activity, tigecycline is often reserved for patients with serious multidrug resistant infections and is recommended only for strongly suspected or proven susceptible bacteria. In 2010 an FDA analysis of randomized controlled trials suggested that tigecycline was associated with a higher mortality than comparator antibiotics. Several subsequent systematic reviews have reached conflicting conclusions. The higher mortality rate associated with tigecycline therapy does not seem to be due to adverse events, but rather lower success or cure rates. The most frequent side effects of tigecycline are diarrhea, nausea and vomiting.
Tigecycline is reported to cause mild, transient elevations in serum aminotransferase levels in 2% to 5% of recipients, rates similar to those in patients treated with comparator antibiotics. Cases of clinically apparent liver injury with jaundice must be very rare. Product labels for tigecycline mention isolated cases of significant hepatic dyfunction cholestasis and jaundice identified from postmarketing experience. No information is available on the latency, pattern, and duration of liver injury in cases of tigecycline induced hepatotoxicity. The reports of jaundice and deaths from hepatic dysfunction in large clinical trials of tigecycline may have reflected the complications of sepsis and multiorgan failure rather than drug hepatotoxicity. Tigecycline is minimally metabolized in the liver and most is excreted unchanged in the bile, feces and urine, which may explain its relative lack of liver injury. The structural similarity of tigecycline to minocycline suggests that patients with a history of minocycline hepatotoxicity should avoid exposure to tigecycline. In addition, patients with cirrhosis receiving tigecycline should be monitored during therapy for evidence of worsening hepatic function and coagulopathy.
Likelihood score: E* (unproven but suspected cause of clinically apparent liver injury).
REPRESENTATIVE TRADE NAMES
Tigecycline – Tygacil®
Product labeling at DailyMed, National Library of Medicine, NIH
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References updated: 20 June 2017
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Ellis-Grosse EJ, Babinchak T, Dartois N, Rose G, Loh E; Tigecycline 300 cSSSI Study Group; Tigecycline 305 cSSSI Study Group. The efficacy and safety of tigecycline in the treatment of skin and skin-structure infections: results of 2 double-blind phase 3 comparison studies with vancomycin-aztreonam. Clin Infect Dis 2005; 41 (Suppl 5): S341-53. PubMed Citation (Summary of two phase III trials comparing tigecycline [n=566] to vancomycin/aztreonam [n=550] for up to 14 days; ALT and AST elevations reported in 1.4-1.8% of tigecycline treated and 5.1-6.2% of vancomycin/aztreonam treated patients; no hepatitis with jaundice).
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(Controlled trial of tigecycline versus ceftriazone/metronidazole in 376 patients with complicated intra-abdominal infections; no mention of ALT elevations or liver injury).
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advanced liver cirrhosis. Eur J Gastroenterol Hepato 2014; 26: 681-4. PubMed Citation (A 43 year old woman with autoimmune hepatitis and advanced cirrhosis developed worsening jaundice, elevations in INR and fall in fibrinogen levels 5 days after starting tigecycline for a systemic infection, which then returned to baseline once tigecycline was stopped).
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