A Cause of Pancreatitis in a Commonly Used Antibiotic: Metronidazole-induced Pancreatitis

Abstract

Metronidazole is a nitroimidazole antibacterial medication used in the treatment of anaerobic bacteria and protozoa. The main adverse effects include headache, nausea, vaginitis, metallic taste, neuropathy and rarely pancreatitis. Acute Pancreatitis is characterized by abdominal pain and elevated pancreatic enzymes including lipase. Here we present a case of elderly female who had pancreatitis associated with metronidazole therapy. The patient was an 85 year old female with medical history of colon cancer s/p resection, atrial fibrillation, hypertension, diabetes mellitus type 2 and hypothyroidism who presented with abdominal pain, nausea. One month prior to presentation she was treated for a urinary infection with cefpodoxime. She started having diarrhea and tested positive for Clostridium Difficile toxin. She was started on metronidazole. Two weeks later, she developed abdominal pain and nausea. Epigastric tenderness was present on exam with a negative murphy sign. Her lipase level was 17604 U/L. Liver function tests were unremarkable; ALT of 26 U/L, AST of 19 U/L, alkaline phosphatase of 46 U/L and a total bilirubin of 0.2 mg/dL. Serum triglycerides were 122. A right upper quadrant ultrasound was done which showed normal gallbladder size, wall thickness and normal common bile duct of 5.5mm. Metronidazole was stopped with resolution of abdominal pain and elevated lipase. No other obvious etiology of her pancreatitis was found. The Naranjo adverse drug reaction probability scale score was calculated to be a 4, indicating a possibility of adverse reaction from metronidazole. Approximately 2% of pancreatitis cases are drug-induced. Per our literature review there have been only 9 cases of pancreatitis associated with metronidazole. Although the mechanism is unknown, one possibility is redox cycling of metronidazole yielding hydrogen peroxide, superoxide and other free radicals which are toxic to pancreatic beta-cells. If metronidazole-induced pancreatitis is suspected, we recommend discontinuation of the medication and supportive care. In summary, physicians should be aware of the possibility of metronidazole as a possible etiology of pancreatitis, given that several million prescriptions of this medication dispensed every year in the United States.