Metoclopramide-Induced Acute Liver Injury

Hepatotoxins and ischemic hepatitis are the most common causes when transaminase levels exceed 1000 U/L. In recent years, drug-induced liver injury has been the leading cause of medication withdrawal from the market. Here we delineate a rare case of metoclopramide-induced liver injury. A 56-year-old lady with no known history of liver disease presented with biliary pancreatitis. On presentation, she had elevated AST (209 U/L) and ALT (205 U/L). She was managed with aggressive intravenous fluid hydration and symptomatic management with intravenous pantoprazole, ondansetron and hydromorphone. Her pain and vomiting improved and her AST and ALT levels down-trended to 28 U/L and 74 U/L respectively. However, she complained of worsening nausea on day 3 of admission. Oral metoclopramide 5 mg every 12 hours was started. She continued to improve clinically and metoclopramide was discontinued on day 4 after she received 3 doses. On day 5 she developed a worsening asymptomatic liver enzyme derangement. Her AST was 165 U/L (ref: 0-40 U/L), ALT was 1253 U/L (ref: 5-35 U/L), and LDH was 1195 (ref: 85-210 U/L). Total bilirubin and ALP were normal. On day 6, her AST and ALT reached to peaks of 1003 U/L and 2357 U/L respectively and then down-trended to 30 U/L and 255 U/L respectively by day 13. Secondary workup for acute hepatitis including viral-panel and immunological investigations were unremarkable. CT abdomen and liver ultrasound were unremarkable. No medications other than those aforementioned were administered. Per the Naranjo adverse drug reaction probability scale, the score was 6 which implied that Metoclopramide was most probably the etiology of acute AST/ALT elevation. The levels gradually down-trended once metoclopramide was held and the patient was safely discharged. Metoclopramide is a prokinetic agent and is commonly used as an antiemetic. Metoclopramide is largely excreted unchanged in the urine and has little active hepatic metabolism. Clinically apparent liver disease attributable to metoclopramide is usually caused by hypersensitivity reactions. The latency to onset of liver injury is usually less than 30 days and the pattern of liver enzyme elevations is either cholestatic or hepatocellular. Metoclopramide is seldom associated with acute drug-induced liver injury, with few such reported events. However in an appropriate clinical context, one must consider metoclopramide as a possible culprit for an unexplained severe elevation in transaminase levels.2181 Figure 1 No Caption available.