1: Ann Intern Med. 2004 Jan 6;140(1):73-4. Related Articles, Links
Gatifloxacin-induced hepatotoxicity and acute pancreatitis.
Cheung O, Chopra K, Yu T, Nalesnik MA, Amin S, Shakil AO.
Publication Types: Case Reports Letter
PMID: 14706991 [PubMed - indexed for MEDLINE]


Gatifloxacin-Induced Hepatotoxicity and Acute Pancreatitis

TO THE EDITOR: Background: Quinolones may induce transient abnormalities in serum aminotransferase levels. Severe hepatotoxicity and acute pancreatitis are rare. Gatifloxacin (Tequin, Bristol-Myers Squibb, New York, New York) is one of the newest members of the group (1). Increased serum bilirubin, aminotransferase, or amylase levels occur in less than 1% of patients exposed; 1 case of acute hepatitis has been reported (2). Objective: We describe 2 patients who developed acute cholestatic liver injury and acute pancreatitis while being treated with gati-
floxacin.

Case Reports: Patient 1, a 41-year-old woman, was treated for an upper respiratory tract infection with oral ciprofloxacin. After 2 doses, the drug was withdrawn because of nausea and vomiting.
Gatifloxacin was initiated orally at 400 mg/d. Two days later, skin rash appeared on the patient’s upper trunk, followed by dark urine, pale stools, and abdominal pain in the right upper quadrant. The
patient was not taking other medications. Laboratory studies revealed a total bilirubin level of 87.2
_mol/L (5.1 mg/dL) with conjugated fraction of 61.6 _mol/L (3.6 mg/dL), an aspartate aminotransferase level of 139 U/L, an alanine aminotransferase level of 145 U/L, an albumin level of 30 g/L, an
alkaline phosphatase level of 8.03 _kat/L, a _-glutamyl transpeptidase level of 8.62 _kat/L, an amylase level of 1.38 _kat/L, a lipase level of 6.5 _kat/L, and a prothrombin time of 6.1 seconds. Serologic
studies excluded viral and autoimmune hepatitis. Abdominal imaging (ultrasonography and computed tomography scan) revealed no evidence of biliary obstruction. Liver biopsy showed portal edema
and cholestasis with moderate macrovesicular steatosis. Two weeks after withdrawal of gatifloxacin, the patient’s abdominal pain resolved and prothrombin time returned to normal. The patient began taking and continues to take ursodeoxycholic acid. Over the next 3 months, the results of her liver tests remained abnormal (Figure). Results of endoscopic retrograde cholangiopancreatography were normal. Prednisone was started at 30 mg/d. A follow-up liver biopsy 8 months after her initial presentation showed increased portal fibrosis, early bridging fibrosis, and bile duct loss. A repeated serum antimitochondrial antibody measurement 10 months later was negative. The patient’s jaundice completely resolved 1 year later. However, she continues to have persistent elevation of alkaline phosphatase and aminotransferase levels.
 

Patient 2, a 49-year-old man, presented with jaundice and abdominal pain. He had received oral gatifloxacin, 400 mg/d, for an upper respiratory tract infection. Three days later, he developed severe
malaise, jaundice, pale stools, and abdominal discomfort. Laboratory studies revealed a bilirubin level of 94.05 _mol/L (5.5 mg/ dL), an aspartate aminotransferase level of 216 U/L, an alanine
aminotransferase level of 520 U/L, an alkaline phosphatase level of 4.47 _kat/L, a _-glutamyl transpeptidase level of 9.9 _kat/L, an amylase level of 5.12 _kat/L, and a lipase level of 60.01 _kat/L.
Results of abdominal ultrasonography and computed tomography scan and endoscopic retrograde cholangiopancreatography were nor- mal. Results of serologic studies for viral and autoimmune hepatitis were negative. Liver biopsy showed portal edema, bile ductular proliferation, and portal inflammatory infiltrate that included eosinophils with lobular cholestasis. At 3 months after initial presentation, serum bilirubin level had normalized but serum aminotransferase and alkaline phosphatase levels remained mildly elevated.
 

Discussion: Several characteristics in these 2 patients support gatifloxacin as the cause of liver injury, including the temporal relationship between the administration of gatifloxacin and injury onset.
Liver biopsies in both patients showed cholestasis with portal edema, bile duct injury, and eosinophilic infiltration. These changes are consistent with drug-induced hepatotoxicity, although it can be argued
that underlying steatohepatitis contributed to the disease process in patient 1. Following discontinuation of gatifloxacin, patient 2 improved but patient 1 developed progressive liver disease and ductopenia. Both patients also had concurrent acute pancreatitis, a complication that has not been described with gatifloxacin before to our knowledge. Of interest, only 3 cases of acute pancreatitis have been reported with other quinolones (3–5). Acute pancreatitis therefore appears to be a rare complication of quinolone-induced toxicity.

Conclusions: Gatifloxacin is a possible cause of severe hepatic and pancreatic injury. Although these complications appear to be infrequent, a heightened awareness is needed because gatifloxacin
and other quinolones are used extensively.

Onki Cheung, MD
Kapil Chopra, MD
Tina Yu, MD
Michael A. Nalesnik, MD
University of Pittsburgh School of Medicine
Pittsburgh, PA 15213
Shirish Amin, MD
A. Obaid Shakil, MD
Indiana Hospital
Indiana, PA 15701
References
1. Fish DN, North DS. Gatifloxacin, an advanced 8-methoxy fluoroquinolone. Pharmacotherapy.
2001;21:35-59. [PMID: 11191737]
2. Henann NE, Zambie MF. Gatifloxacin-associated acute hepatitis. Pharmacotherapy.
2001;21:1579-82. [PMID: 11765309]
3. Drabo YJ, Niakara A, Ouedraogo H. [Acute pancreatitis secondary to administration
or norfloxacin] [Letter]. Ann Fr Anesth Reanim. 2002;21:68-9. [PMID:
11878127]
4. Mann S, Thillainayagam A. Is ciprofloxacin a new cause of acute pancreatitis?
[Letter]. J Clin Gastroenterol. 2000;31:336. [PMID: 11129278]
5. Mennecier D, Thiolet C, Bredin C, Potier V, Vergeau B, Farret O. [Acute pancreatitis
after treatment by levofloxacin and methylprednisolone] [Letter]. Gastroenterol
Clin Biol. 2001;25:921-2. [PMID: 11852403]

Letters
www.annals.org 6 January 2004 Annals of Internal Medicine Volume 140 • Number 1 73