Possible Gatifloxacin-Induced Fulminant Hepatic Failure

Coleman, Craig I.; Spencer, Jeffrey; Chung, Jenny

doi:10.1345/aph.1a414

Cited by 32 publications

(7 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Severe hepatocellular injury and cholestasis have been reported to occur in less than 1% of all fluoroquinolone recipients, excluding trovafloxacin, which was withdrawn due to its hepatotoxi-city (4,(134)(135)(136)(137). Clinically significant hepatotoxicity has been reported with ciprofloxacin, trovafloxacin, norfloxacin, ofloxacin, enoxacin, levofloxacin, and gatifloxacin, with large population denominators (138,139). Direct comparisons of rates of clinically significant hepatotoxicity are not available.…”

Section: Fluoroquinolonesmentioning

confidence: 99%

An Official ATS Statement: Hepatotoxicity of Antituberculosis Therapy

Saukkonen¹,

Cohn²,

Jasmer³

et al. 2006

Am J Respir Crit Care Med

962

786

View full text Add to dashboard Cite

Drug-induced liver injury (DILI) is a problem of increasing significance, but has been a long-standing concern in the treatment of tuberculosis (TB) infection. The liver has a central role in drug metabolism and detoxification, and is consequently vulnerable to injury. The pathogenesis and types of DILI are presented, ranging from hepatic adaptation to hepatocellular injury. Knowledge of the metabolism of anti-TB medications and of the mechanisms of TB DILI is incomplete. Understanding of TB DILI has been hampered by differences in study populations, definitions of hepatotoxicity, and monitoring and reporting practices. Available data regarding the incidence and severity of TB DILI overall, in selected demographic groups, and in those coinfected with HIV or hepatitis B or C virus are presented. Systematic steps for prevention and management of TB DILI are recommended. These include patient and regimen selection to optimize benefits over risks, effective staff and patient education, ready access to care for patients, good communication among providers, and judicious use of clinical and biochemical monitoring. During treatment of latent TB infection (LTBI) alanine aminotransferase (ALT) monitoring is recommended for those who chronically consume alcohol, take concomitant hepatotoxic drugs, have viral hepatitis or other preexisting liver disease or abnormal baseline ALT, have experienced prior isoniazid hepatitis, are pregnant or are within 3 months postpartum. During treatment of TB disease, in addition to these individuals, patients with HIV infection should have ALT monitoring. Some experts recommend biochemical monitoring for those older than 35 years. Treatment should be interrupted and, generally, a modified or alternative regimen used for those with ALT elevation more than three times the upper limit of normal (ULN) in the presence of hepatitis symptoms and/or jaundice, or five times the ULN in the absence of symptoms. Priorities for future studies to develop safer treatments for LTBI and for TB disease are presented.

show abstract

Section: Fluoroquinolonesmentioning

confidence: 99%

An Official ATS Statement: Hepatotoxicity of Antituberculosis Therapy

Saukkonen¹,

Cohn²,

Jasmer³

et al. 2006

Am J Respir Crit Care Med

962

786

View full text Add to dashboard Cite

show abstract

“…60 Isolated cases of significant hepatotoxicity have been reported with ciprofloxacin, 61 levofloxacin, 62 gatifloxacin. 63,64 The mechanism of hepatotoxicity is thought to be due to hypersensitivity reaction often associated with peripheral eosinophilia and fever. Introduction of fluoroquinolones didn't cause additional hepatotoxicity when used in patients with hepatitis induced by first line anti-TB drugs.…”

Section: Detoxification and Eliminationmentioning

confidence: 99%

Hepatotoxicity Related to Anti-tuberculosis Drugs: Mechanisms and Management

Ramappa

Aithal

2013

Journal of Clinical and Experimental Hepatology

407

310

View full text Add to dashboard Cite

Development of idiosyncratic hepatotoxicity is an intricate process involving both concurrent as well as sequential events determining the direction of the pathways, degree of liver injury and its outcome. Decades of clinical observation have identified a number of drug and host related factors that are associated with an increased risk of antituberculous drug-induced hepatotoxicity, although majority of the studies are retrospective with varied case definitions and sample sizes. Investigations on genetic susceptibility to hepatotoxicity have so far focused on formation and accumulation reactive metabolite as well as factors that contribute to cellular antioxidant defense mechanisms and the environment which can modulate the threshold for hepatocyte death secondary to oxidative stress. Recent advances in pharmacogenetics have promised the development of refined algorithms including drug, host and environmental risk factors that allow better tailoring of medications based on accurate estimates of risk-benefit ratio. Future investigations exploring the pathogenesis of hepatotoxicity should be performed using human tissue and samples whenever possible, so that the novel findings can be translated readily into clinical applications.

show abstract

“…5,32 This is frequently observed with amoxicillin/clavulanate and tetracycline, 32 and was reported for trovafloxacin, 33 although rapid onset is also seen. 33,34 Cholelithiasis associated with ceftriaxone–calcium precipitates typically occurs only after 9–11 days of treatment. 32 Physicians should therefore alert patients to the warning signs of antibiotic-induced hepatotoxicity and advise them to seek medical attention, even if symptoms appear sometime after completing their treatment.…”

Section: Identifying Antibiotic-induced Liver Injurymentioning

confidence: 99%

Hepatic safety of antibiotics used in primary care

Andrade

Tulkens

2011

Journal of Antimicrobial Chemotherapy

172

138

View full text Add to dashboard Cite

Antibiotics used by general practitioners frequently appear in adverse-event reports of drug-induced hepatotoxicity. Most cases are idiosyncratic (the adverse reaction cannot be predicted from the drug's pharmacological profile or from pre-clinical toxicology tests) and occur via an immunological reaction or in response to the presence of hepatotoxic metabolites. With the exception of trovafloxacin and telithromycin (now severely restricted), hepatotoxicity crude incidence remains globally low but variable. Thus, amoxicillin/clavulanate and co-trimoxazole, as well as flucloxacillin, cause hepatotoxic reactions at rates that make them visible in general practice (cases are often isolated, may have a delayed onset, sometimes appear only after cessation of therapy and can produce an array of hepatic lesions that mirror hepatobiliary disease, making causality often difficult to establish). Conversely, hepatotoxic reactions related to macrolides, tetracyclines and fluoroquinolones (in that order, from high to low) are much rarer, and are identifiable only through large-scale studies or worldwide pharmacovigilance reporting. For antibiotics specifically used for tuberculosis, adverse effects range from asymptomatic increases in liver enzymes to acute hepatitis and fulminant hepatic failure. Yet, it is difficult to single out individual drugs, as treatment always entails associations. Patients at risk are mainly those with previous experience of hepatotoxic reaction to antibiotics, the aged or those with impaired hepatic function in the absence of close monitoring, making it important to carefully balance potential risks with expected benefits in primary care. Pharmacogenetic testing using the new genome-wide association studies approach holds promise for better understanding the mechanism(s) underlying hepatotoxicity.

show abstract

Possible Gatifloxacin-Induced Fulminant Hepatic Failure

Cited by 32 publications

References 33 publications

An Official ATS Statement: Hepatotoxicity of Antituberculosis Therapy

An Official ATS Statement: Hepatotoxicity of Antituberculosis Therapy

Hepatotoxicity Related to Anti-tuberculosis Drugs: Mechanisms and Management

Hepatic safety of antibiotics used in primary care

Contact Info

Product

Resources

About